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2.
Med J Aust ; 220(8): 417-424, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38613175

ABSTRACT

OBJECTIVES: To investigate the effectiveness of a school-based multiple health behaviour change e-health intervention for modifying risk factors for chronic disease (secondary outcomes). STUDY DESIGN: Cluster randomised controlled trial. SETTING, PARTICIPANTS: Students (at baseline [2019]: year 7, 11-14 years old) at 71 Australian public, independent, and Catholic schools. INTERVENTION: Health4Life: an e-health school-based multiple health behaviour change intervention for reducing increases in the six major behavioural risk factors for chronic disease: physical inactivity, poor diet, excessive recreational screen time, poor sleep, and use of alcohol and tobacco. It comprises six online video modules during health education class and a smartphone app. MAIN OUTCOME MEASURES: Comparison of Health4Life and usual health education with respect to their impact on changes in twelve secondary outcomes related to the six behavioural risk factors, assessed in surveys at baseline, immediately after the intervention, and 12 and 24 months after the intervention: binge drinking, discretionary food consumption risk, inadequate fruit and vegetable intake, difficulty falling asleep, and light physical activity frequency (categorical); tobacco smoking frequency, alcohol drinking frequency, alcohol-related harm, daytime sleepiness, and time spent watching television and using electronic devices (continuous). RESULTS: A total of 6640 year 7 students completed the baseline survey (Health4Life: 3610; control: 3030); 6454 (97.2%) completed at least one follow-up survey, 5698 (85.8%) two or more follow-up surveys. Health4Life was not statistically more effective than usual school health education for influencing changes in any of the twelve outcomes over 24 months; for example: fruit intake inadequate: odds ratio [OR], 1.08 (95% confidence interval [CI], 0.57-2.05); vegetable intake inadequate: OR, 0.97 (95% CI, 0.64-1.47); increased light physical activity: OR, 1.00 (95% CI, 0.72-1.38); tobacco use frequency: relative difference, 0.03 (95% CI, -0.58 to 0.64) days per 30 days; alcohol use frequency: relative difference, -0.34 (95% CI, -1.16 to 0.49) days per 30 days; device use time: relative difference, -0.07 (95% CI, -0.29 to 0.16) hours per day. CONCLUSIONS: Health4Life was not more effective than usual school year 7 health education for modifying adolescent risk factors for chronic disease. Future e-health multiple health behaviour change intervention research should examine the timing and length of the intervention, as well as increasing the number of engagement strategies (eg, goal setting) during the intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619000431123 (prospective).


Subject(s)
School Health Services , Humans , Adolescent , Male , Female , Australia/epidemiology , Child , School Health Services/organization & administration , Exercise , Telemedicine/methods , Health Behavior , Health Risk Behaviors , Health Education/methods , Health Promotion/methods , Chronic Disease/prevention & control , Adolescent Behavior/psychology , Life Style , Students/statistics & numerical data , Students/psychology
3.
Matern Child Nutr ; : e13650, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38547414

ABSTRACT

Parenting practices such as parental monitoring are known to positively impact dietary behaviours in offspring. However, links between adolescent-perceived parental monitoring and dietary outcomes have rarely been examined and never in an Australian context. This study investigated whether adolescent-perceived parental monitoring is associated with more fruit and vegetable, and less sugar-sweetened beverages (SSB) and junk food consumption in Australian adolescents. Cross-sectional data was collected as part of baseline measurement for a randomised controlled trial in 71 Australian schools in 2019. Self-reported fruit, vegetable, SSB and junk food intake, perceived parental monitoring and sociodemographic factors were assessed. Each dietary variable was converted to "not at risk/at risk" based on dietary guidelines, binary logistic regressions examined associations between dietary intake variables and perceived parental monitoring while controlling for gender and socio-economic status. The study was registered in ANZCTR clinical trials. The sample comprised 6053 adolescents (Mage = 12.7, SD = 0.5; 50.6% male-identifying). The mean parental monitoring score was 20.1/24 (SD = 4.76) for males and 21.9/24 (SD = 3.37) for females. Compared to adolescents who perceived lower levels of parental monitoring, adolescents reporting higher parental monitoring had higher odds of insufficient fruit (OR = 1.03; 95% CI = 1.02-1.05) and excessive SSB (OR = 1.07; 95% CI = 1.06-1.09) intake, but lower odds of excessive junk food (OR = 0.96; 95% CI = 0.95-0.98) and insufficient vegetable (OR = 0.97, 95% CI = 0.96-0.99) intake. Adolescent dietary intake is associated with higher perceived parental monitoring; however, these associations for fruit and SSB differ to junk food and vegetable intake. This study may have implications for prevention interventions for parents, identifying how this modifiable parenting factor is related to adolescent diet has highlighted how complex the psychological and environmental factors contributing to dietary intake are.

4.
Article in English | MEDLINE | ID: mdl-38224153

ABSTRACT

To identify proteins specific to the proximal ciliary axoneme, we used iTRAQ to compare short (~2 µm) and full-length (~11 µm) axonemes of Chlamydomonas. Known compoents of the proximal axoneme such as minor dynein heavy chains and LF5 kinase as well as the ciliary tip proteins FAP256 (CEP104) and EB1 were enriched in short axonemes whereas proteins present along the length of the axoneme were of similar abundance in both samples. The iTRAQ analysis revealed that FAP93, a protein of unknown function, and protein phosphatase 2A (PP2A) are enriched in the short axonemes. Consistently, immunoblots show enrichment of FAP93 and PP2A in short axonemes and immunofluorescence confirms the localization of FAP93 and enrichment of PP2A at the proximal axoneme. Ciliary regeneration reveals that FAP93 assembles continuously but more slowly than other axonemal structures and terminates at 1.03 µm in steady-state axonemes. The length of FAP93 assembly correlates with ciliary length, demonstrating ciliary length-dependent assembly of FAP93. Dikaryon rescue experiments show that FAP93 can assemble independently of IFT transport. In addition, FRAP analysis of GFP-tagged FAP93 demonstrates that FAP93 is stably anchored in axoneme. FAP93 may function as a scaffold for assembly of other specific proteins at the proximal axoneme.

5.
J Womens Health (Larchmt) ; 33(1): 20-27, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38016121

ABSTRACT

Background: Data documenting period product insecurity, or an inability to access products, in the United States have recently emerged. With multiple years of data now available, we assessed trends in period product insecurity among two nationally representative samples of U.S. adults. Materials and Methods: Data from nationally representative, cross-sectional online surveys conducted in January 2018 and April 2021 were used to run weighted logistic regressions. Those aged 18-49 years and who had menstruated in the past year (n = 922 in 2018; n = 1037 in 2021) were included. Results: In 2021, 59% experienced period product insecurity compared with 53% in 2018. In 2018 (adjusted odds ratio [aOR] 1.91, confidence interval [95% CI]: 1.29-2.83) and 2021 (aOR 1.53, 95% CI: 1.06-2.21), Hispanic respondents were more likely to find products unaffordable. Some college attainment was associated with finding products unaffordable in 2018 (aOR 1.53, 95% CI: 1.00-2.34) and 2021 (aOR 1.97, 95% CI: 1.35-2.88). Participants struggling to purchase products had higher odds of experiencing period product insecurity in 2018 (aOR 11.78, 95% CI: 8.07-17.20) and 2021 (aOR 7.71, 95% CI: 5.44-10.93). Conclusions: Hispanic ethnicity, lower educational attainment, and struggling to purchase period products were strong predictors of finding products unaffordable and experiencing product insecurity in both 2018 and 2021. Policies that improve access to or affordability of period products in the United States are needed to help those most vulnerable.


Subject(s)
Ethnicity , Menstrual Hygiene Products , Menstruation , Adult , Humans , Cross-Sectional Studies , Educational Status , Food Supply , Hispanic or Latino , United States , Female , Menstrual Hygiene Products/economics
6.
J Med Internet Res ; 25: e47849, 2023 11 28.
Article in English | MEDLINE | ID: mdl-38015600

ABSTRACT

BACKGROUND: Health technology innovation is increasingly supported by a bottom-up approach to priority setting, aiming to better reflect the concerns of its intended beneficiaries. Web-based forums provide parents with an outlet to share concerns, advice, and information related to parenting and the health and well-being of their children. They provide a rich source of data on parenting concerns and priorities that could inform future child health research and innovation. OBJECTIVE: The aim of the study is to identify common concerns expressed on 2 major web-based forums and cluster these to identify potential family health concern topics as indicative priority areas for future research and innovation. METHODS: We text-mined the r/Parenting subreddit (69,846 posts) and the parenting section of Mumsnet (99,848 posts) to create a large corpus of posts. A generative statistical model (latent Dirichlet allocation) was used to identify the most discussed topics in the corpus, and content analysis was applied to identify the parenting concerns found in a subset of posts. RESULTS: A model with 25 topics produced the highest coherence and a wide range of meaningful parenting concern topics. The most frequently expressed parenting concerns are related to their child's sleep, self-care, eating (and food), behavior, childcare context, and the parental context including parental conflict. Topics directly associated with infants, such as potty training and bottle feeding, were more common on Mumsnet, while parental context and screen time were more common on r/Parenting. CONCLUSIONS: Latent Dirichlet allocation topic modeling can be applied to gain a rapid, yet meaningful overview of parent concerns expressed on a large and diverse set of social media posts and used to complement traditional insight gathering methods. Parents framed their concerns in terms of children's everyday health concerns, generating topics that overlap significantly with established family health concern topics. We provide evidence of the range of family health concerns found at these sources and hope this can be used to generate material for use alongside traditional insight gathering methods.


Subject(s)
Infodemiology , Parents , Child , Infant , Humans , Parenting , Child Health , Food
7.
Cancers (Basel) ; 15(13)2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37444561

ABSTRACT

Uveal melanoma (UM) displays a high frequency of metastasis; however, effective therapies for metastatic UM are limited. Identifying unique metabolic features of UM may provide a potential targeting strategy. A lipid metabolism protein expression signature was induced in a normal choroidal melanocyte (NCM) line transduced with GNAQ (Q209L), a driver in UM growth and development. Consistently, UM cells expressed elevated levels of fatty acid synthase (FASN) compared to NCMs. FASN upregulation was associated with increased mammalian target of rapamycin (mTOR) activation and sterol regulatory element-binding protein 1 (SREBP1) levels. FASN and mTOR inhibitors alone significantly reduced UM cell growth. Concurrent inhibition of FASN and mTOR further reduced UM cell growth by promoting cell cycle arrest and inhibiting glucose utilization, TCA cycle metabolism, and de novo fatty acid biosynthesis. Our findings indicate that FASN is important for UM cell growth and co-inhibition of FASN and mTOR signaling may be considered for treatment of UM.

8.
Lancet Digit Health ; 5(5): e276-e287, 2023 05.
Article in English | MEDLINE | ID: mdl-37032200

ABSTRACT

BACKGROUND: Lifestyle risk behaviours are prevalent among adolescents and commonly co-occur, but current intervention approaches tend to focus on single risk behaviours. This study aimed to evaluate the efficacy of the eHealth intervention Health4Life in modifying six key lifestyle risk behaviours (ie, alcohol use, tobacco smoking, recreational screen time, physical inactivity, poor diet, and poor sleep, known as the Big 6) among adolescents. METHODS: We conducted a cluster-randomised controlled trial in secondary schools that had a minimum of 30 year 7 students, in three Australian states. A biostatistician randomly allocated schools (1:1) to Health4Life (a six-module, web-based programme and accompanying smartphone app) or an active control group (usual health education) with the Blockrand function in R, stratified by site and school gender composition. All students aged 11-13 years who were fluent in English and attended participating schools were eligible. Teachers, students, and researchers were not masked to allocation. Primary outcomes were alcohol use, tobacco use, recreational screen time, moderate to vigorous physical activity (MVPA), sugar-sweetened beverage intake, and sleep duration at 24 months, measured by self-report surveys, and analysed in all students who were eligible at baseline. Latent growth models estimated between-group change over time. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000431123). FINDINGS: Between April 1, 2019, and Sept 27, 2019, we recruited 85 schools (9280 students), of which 71 schools with 6640 eligible students (36 schools [3610 students] assigned to the intervention and 35 [3030 students] to the control) completed the baseline survey. 14 schools were excluded from the final analysis or withdrew, mostly due to a lack of time. We found no between-group differences for alcohol use (odds ratio 1·24, 95% CI 0·58-2·64), smoking (1·68, 0·76-3·72), screen time (0·79, 0·59-1·06), MVPA (0·82, 0·62-1·09), sugar-sweetened beverage intake (1·02, 0·82-1·26), or sleep (0·91, 0·72-1·14) at 24 months. No adverse events were reported during this trial. INTERPRETATION: Health4Life was not effective in modifying risk behaviours. Our results provide new knowledge about eHealth multiple health behaviour change interventions. However, further research is needed to improve efficacy. FUNDING: Paul Ramsay Foundation, the Australian National Health and Medical Research Council, the Australian Government Department of Health and Aged Care, and the US National Institutes of Health.


Subject(s)
Students , Telemedicine , United States , Humans , Adolescent , Australia , Life Style , Risk-Taking
9.
JMIR Pediatr Parent ; 6: e42272, 2023 Apr 04.
Article in English | MEDLINE | ID: mdl-37014696

ABSTRACT

BACKGROUND: Parents play an influential role in the health behaviors of their children, such as physical activity, dietary intake, sleep, screen time, and substance use. However, further research is needed to inform the development of more effective and engaging parent-based interventions targeting adolescent risk behaviors. OBJECTIVE: This study aimed to assess parents' knowledge about adolescent risk behaviors, barriers and facilitators to engaging in healthy behaviors, and preferences for a parent-based prevention intervention. METHODS: An anonymous web-based survey was conducted from June 2022 to August 2022. Eligible participants were parents of children aged 11 to 18 years and were residing in Australia at the time of this study. The survey assessed the parents' perceived and actual knowledge about Australian health guidelines for youth, parent and adolescent engagement in health behaviors, parenting style and attitudes, barriers and facilitators to engaging in healthy behaviors, and delivery and component preferences for a parent-based preventive intervention. Descriptive statistics and logistic regressions were conducted to analyze the data. RESULTS: A total of 179 eligible participants completed the survey. The mean age of the parents was 42.22 (SD 7.03) years, and 63.1% (101/160) were female. Parent-reported sleep duration was high for both parents (mean 8.31, SD 1.00 hours) and adolescents (mean 9.18, SD 0.94 hours). However, the proportion of parents who reported that their child met the national recommendations for physical activity (5/149, 3.4%), vegetable intake (7/126, 5.6%), and weekend recreational screen time (7/130, 5.4%) was very low. Overall, parents' perceived knowledge of health guidelines was moderate, ranging from 50.6% (80/158) for screen time to 72.8% (115/158) for sleep guidelines (for children aged 5-13 years). Actual knowledge was lowest for vegetable intake and physical activity, with only 44.2% (46/104) and 42% (31/74) of parents reporting correct guidelines for these behaviors, respectively. The key issues of concern reported by parents were excessive use of technology, mental health, e-cigarette use, and negative peer relationships. The top-rated delivery method for a parent-based intervention was via a website (53/129, 41.1%). The highest rated intervention component was opportunities for goal-setting (89/126, 70.7% rated very or extremely important), and other important program features were ease of use (89/122, 72.9%), paced learning (79/126, 62.7%), and appropriate program length (74/126, 58.8%). CONCLUSIONS: The findings suggest that such interventions should be brief and web based and should aim to increase parental knowledge of health guidelines; provide opportunities for skill-building, such as goal-setting; and include effective behavior change techniques, such as motivational interviewing and social support. This study will inform the development of future parent-based preventive interventions to prevent multiple lifestyle risk behaviors among adolescents.

10.
J Sch Health ; 93(7): 557-564, 2023 07.
Article in English | MEDLINE | ID: mdl-36893763

ABSTRACT

BACKGROUND: School nurses play a vital role in ensuring the health and well-being of their students, but little is known about menstrual products and resources available in schools. This study assessed period product resources and needs in Missouri schools from the perspective of school nurses and analyzed differences by district enrollment characteristics. METHODS: An electronic survey was emailed to public, charter, private, and parochial school nurses in Missouri who served fourth grade or older. From January through March 2022, 976 self-administered surveys were completed (40% response rate). Logistic regressions examined the associations between student needs and district characteristics. RESULTS: Among the sample, 70.7% knew students who could not afford period products, and 68.0% knew students who had missed school because of their period. When controlling for district size, race/ethnicity, and urban/rural classification, as the percentage free- or reduced-lunch (FRL) eligibility increases in a school, awareness of students struggling to afford products increases (AOR = 1.008, 95% confidence interval 1.000, 1.015). IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: School nurses need the resources and educational materials to support students to help reduce menstruation-related absences. CONCLUSIONS: Issues of period poverty cut across districts of differing enrollment characteristics, yet FRL percentage is an important predictor.


Subject(s)
Poverty , Schools , Female , Humans , Missouri , Surveys and Questionnaires , Students
11.
Cereb Cortex ; 33(5): 2101-2142, 2023 02 20.
Article in English | MEDLINE | ID: mdl-35667019

ABSTRACT

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar "horsetail" axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.


Subject(s)
Neocortex , Receptors, Metabotropic Glutamate , Humans , Neocortex/metabolism , Parvalbumins/metabolism , Receptors, Metabotropic Glutamate/metabolism , Interneurons/physiology , Synaptic Transmission/physiology , GABAergic Neurons/metabolism , Dendrites/metabolism
12.
Front Reprod Health ; 4: 1003040, 2022.
Article in English | MEDLINE | ID: mdl-36438906

ABSTRACT

Background: Prior to the COVID-19 pandemic, a few studies started to highlight the extent of period poverty in the U.S., especially among low-income women and girls. Preliminary data documenting the effects of the pandemic, subsequent economic downturn, and closure of schools and businesses on menstrual hygiene management are now emerging. Objective: This study explores the relationship between the effects of the COVID-19 pandemic and period poverty among a nationally representative sample of U.S. adults. Methods: Cross-sectional, secondary analyses of a 2021 nationwide, self-administered, online panel survey used weighted logistic regressions to assess the relationship between the COVID-19 pandemic making it more difficult to access products and missing work due to a lack of products. Responses from 1,037 menstruating individuals age 18-49 were included. Results: Overall, 30% of the sample indicated the COVID-19 pandemic made it more difficult to access period products, 29% struggled to purchase period products in the past year, and 18% missed work due to a lack of period products. Those who identified as Hispanic (aOR 2.06 95% CI 1.29-3.29) and had children under 18 (aOR 15.3 95% CI 1.03-2.26) were more likely to indicate that the pandemic made it harder to access period products. Subsequently, those who indicated that the pandemic made it more difficult to access period supplies were more likely to report missing work due to a lack of period products in the past 12 months (aOR 4.32 95% CI 4.69-6.94). Discussion: The COVID-19 pandemic exacerbated period poverty, especially among those in the U.S. who struggle with accessibility and affordability of products. Future pandemic response planning should consider period products as a basic need for vulnerable households. In addition, policies that increase the affordability and accessibility of period products for all should help reduce menstruation-related absenteeism from work.

13.
Prev Med ; 164: 107247, 2022 11.
Article in English | MEDLINE | ID: mdl-36075490

ABSTRACT

Lifestyle risk behaviors often co-occur and are prevalent among adolescents. Parent-based interventions addressing risk behaviors concurrently have the potential to improve youth and parent outcomes. This systematic review evaluated the efficacy of parent-based interventions targeting multiple lifestyle risk behaviors among adolescents and parents. MEDLINE (Ovid), Embase (Ovid), PsycInfo (Ovid), Scopus, CINAHL, the Cochrane Database of Systematic Reviews (CDSR) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 2010-May 2021. Eligible studies were randomised controlled trials (RCTs) of parent-based interventions addressing 2+ risk behaviors: alcohol use, smoking, poor diet, physical inactivity, sedentary behaviors, and poor sleep. Studies directly targeting parents, and that assessed adolescent outcomes (11-18 years) were eligible. Where possible, random-effects meta-analysis was conducted. From 11,975 identified records, 46 publications of 36 RCTs (n = 28,322 youth, n = 7385 parents) were eligible. Parent-based interventions were associated with improved adolescent moderate-to-vigorous physical activity (MVPA) [Odds Ratio (OR) = 1.82, 95% CI = 1.18, 2.81; p = 0.007], and reduced screen time (SMD = -0.39, 95% CI = -0.62, -0.16, p = 0.0009) and discretionary food intake (SMD = -0.18; 95% CI = -0.30, -0.06; p = 0.002) compared to controls. However, there was some evidence that interventions increased the odds of ever using tobacco in the medium-term (OR = 1.47, 95% CI = 0.99, 2.18, p = 0.06) and of past month tobacco use in the long-term (OR = 1.46, 95% CI = 1.12, 1.90; p = 0.005). Overall, the quality of evidence was moderate. Parent-based interventions targeting multiple risk behaviors improved adolescent MVPA, and reduced screen time discretionary food intake. Further research is needed to address sleep problems and increase intervention efficacy, particularly for alcohol and tobacco use.


Subject(s)
Life Style , Risk-Taking , Adolescent , Humans , Tobacco Use , Sedentary Behavior , Screen Time
15.
Oncogene ; 41(8): 1129-1139, 2022 02.
Article in English | MEDLINE | ID: mdl-35046531

ABSTRACT

Effective therapeutic options are still lacking for uveal melanoma (UM) patients who develop metastasis. Metastatic traits of UM are linked to BRCA1-associated protein 1 (BAP1) mutations. Cell metabolism is re-programmed in UM with BAP1 mutant UM, but the underlying mechanisms and opportunities for therapeutic intervention remain unclear. BAP1 mutant UM tumors have an elevated glycolytic gene expression signature, with increased expression of pyruvate dehydrogenase (PDH) complex and PDH kinase (PDHK1). Furthermore, BAP1 mutant UM cells showed higher levels of phosphorylated PDHK1 and PDH that was associated with an upregulated glycolytic profile compared to BAP1 wild-type UM cells. Suppressing PDHK1-PDH phosphorylation decreased glycolytic capacity and cell growth, and induced cell cycle arrest of BAP1 mutant UM cells. Our results suggest that PDHK1-PDH phosphorylation is a causative factor of glycolytic phenotypes found in BAP1 mutant UM and propose a therapeutic opportunity for BAP1 mutant UM patients.


Subject(s)
Melanoma , Uveal Neoplasms
16.
Pigment Cell Melanoma Res ; 35(1): 78-87, 2022 01.
Article in English | MEDLINE | ID: mdl-34347929

ABSTRACT

Metastatic uveal melanoma (UM) responds poorly to targeted therapies and immune checkpoint inhibitors. Loss of BRCA1-associated protein 1 (BAP1) via inactivating mutations in the BAP1 gene is associated with UM progression. Thus, molecular alterations caused by BAP1 dysfunction may be novel therapeutic targets for metastatic UM. Here, we found that phosphorylation of AMP-dependent kinase (AMPK) was elevated in BAP1-altered (or mutant) compared to BAP1-unaltered (or wild-type [WT]) UM tumors. As a readout of AMPK pathway activation, phosphorylation of an AMPK downstream effector, acetyl-CoA-carboxylase (ACC), was also elevated. BAP1 re-expression in BAP1-null UM cell lines decreased phospho-AMPK (pAMPK) and phospho-ACC (pACC) levels. AMPK phosphorylation is mediated by calcium/calmodulin dependent protein kinase kinase 2 (CaMKK2) and potentially liver kinase B1 (LKB1) in BAP1 mutant UM cells. Knockdown of AMPKα1/2 reduced the viability of BAP1 mutant UM cells, indicating a survival function of AMPK in BAP1 mutant UM. Our data suggest that the AMPK pathway is an important mechanism mediating the survival of BAP1 mutant UM. Targeting the AMPK pathway may be a novel therapeutic strategy for metastatic UM.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Melanoma/enzymology , Mutation , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Uveal Neoplasms/enzymology , AMP-Activated Protein Kinases/genetics , Acetyl-CoA Carboxylase/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism , Cell Line, Tumor , Cell Survival , Enzyme Activation , Humans , Melanoma/genetics , Melanoma/pathology , Phosphorylation , Signal Transduction , Uveal Neoplasms/genetics , Uveal Neoplasms/pathology
17.
J Neurosci ; 41(47): 9702-9719, 2021 11 24.
Article in English | MEDLINE | ID: mdl-34667071

ABSTRACT

Persistent anion conductances through GABAA receptors (GABAARs) are important modulators of neuronal excitability. However, it is currently unknown how the amplitudes of these currents vary among different cell types in the human neocortex, particularly among diverse GABAergic interneurons. We have recorded 101 interneurons in and near layer 1 from cortical tissue surgically resected from both male and female patients, visualized 84 of them and measured tonic GABAAR currents in 48 cells with an intracellular [Cl-] of 65 mm and in the presence of 5 µm GABA. We compare these tonic currents among five groups of interneurons divided by firing properties and four types of interneuron defined by axonal distributions; rosehip, neurogliaform, stalked-bouton, layer 2-3 innervating and a pool of other cells. Interestingly, the rosehip cell, a type of interneuron only described thus far in human tissue, and layer 2-3 innervating cells exhibit larger tonic currents than other layer 1 interneurons, such as neurogliaform and stalked-bouton cells; the latter two groups showing no difference. The positive allosteric modulators of GABAARs allopregnanolone and DS2 also induced larger current shifts in the rosehip and layer 2-3 innervating cells, consistent with higher expression of the δ subunit of the GABAAR in these neurons. We have also examined how patient parameters, such as age, seizures, type of cancer and anticonvulsant treatment may alter tonic inhibitory currents in human neurons. The cell type-specific differences in tonic inhibitory currents could potentially be used to selectively modulate cortical circuitry.SIGNIFICANCE STATEMENT Tonic currents through GABAA receptors (GABAARs) are a potential therapeutic target for a number of neurologic and psychiatric conditions. Here, we show that these currents in human cerebral cortical GABAergic neurons display cell type-specific differences in their amplitudes which implies differential modulation of their excitability. Additionally, we examine whether the amplitudes of the tonic currents measured in our study show any differences between patient populations, finding some evidence that age, seizures, type of cancer, and anticonvulsant treatment may alter tonic inhibition in human tissue. These results advance our understanding of how pathology affects neuronal excitability and could potentially be used to selectively modulate cortical circuitry.


Subject(s)
GABAergic Neurons/metabolism , Interneurons/metabolism , Neocortex/metabolism , Receptors, GABA-A/metabolism , Action Potentials/physiology , Adult , Aged , Female , GABAergic Neurons/cytology , Humans , Interneurons/cytology , Male , Middle Aged , Neocortex/cytology
18.
J Occup Health Psychol ; 26(5): 393-404, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34292018

ABSTRACT

The present study advances a within-person approach to the study of workaholism in line with whole trait theory, arguing that individuals have general workaholic tendencies as well as daily fluctuations in workaholism. We tested this model using an experience sampling study of 121 U.S. employees and their spouses who completed self-report surveys for 10 working days. Multilevel analyses supported the idea that workaholism varies at the daily level, and trait workaholism was significantly related to higher daily fluctuations in workaholism averaged across the 10 days. Consistent with whole trait theory (Fleeson, 2007), we found anticipated workload each morning positively related to daily fluctuations in workaholism. Moreover, individuals reported feeling more fatigued on days they report higher daily workaholism, and daily fluctuations in workaholism were related to stress crossover and spouse's relationship tension. Overall, results support a within-person conceptualization of workaholism, linking anticipated workload to daily fluctuations in workaholism, which in turn demonstrates negative spillover and crossover outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Spouses , Workload , Emotions , Humans , Surveys and Questionnaires
19.
Int Rev Educ ; 67(1-2): 9-29, 2021.
Article in English | MEDLINE | ID: mdl-33688100

ABSTRACT

The societal lockdown imposed in Canada in March 2020 to stem the spread of COVID-19 severed key points of connection for low-income Canadians who rely upon schools, libraries and even fast-food chains for internet connectivity. This has had dire implications for timely access to vital information and resources, and has revealed the extent to which women, transgender and racialised communities are bearing the brunt of the pandemic's effects. This article describes a study that investigated the pandemic-related work of community-based adult educators in the ethno-culturally diverse Canadian province of British Columbia. Interviews were conducted with 18 educators who were working on the "front lines" of the pandemic, to document their support of low-income and newcomer communities, to understand how these educators responded in terms of pedagogies and strategies, and to map how these pedagogies and practices might be leveraged for more equitable relationships in post-pandemic community-based education. The authors found that the educators developed a range of inventive and dynamic pedagogies oriented to social solidarity and to taking up intersectional oppressions. These "pandemic pedagogies" may contribute to more equitable and inclusive social-technology relationships in a post-pandemic future.


Pédagogies inventives et solidarité sociale : le travail des éducateurs communautaires d'adultes durant la pandémie de COVID-19 au Canada, en Colombie britannique ­ Le confinement social imposé en mars 2020 au Canada pour endiguer la propagation de la COVID-19 a rompu des liens essentiels pour des Canadiens à faibles revenus, qui ont besoin des écoles, des bibliothèques et même des chaînes de fast-food pour accéder à Internet. Il a eu des conséquences terribles pour ces personnes sur l'accès en temps voulu à des informations et ressources vitales, et révélé la mesure dans laquelle les femmes, les personnes transgenres et les communautés racisées essuyaient le plus fort des effets de la pandémie. Cet article présente une étude consacrée aux activités menées en lien avec la pandémie par des éducateurs d'adultes communautaires dans la province canadienne de Colombie britannique qui se caractérise par sa diversité ethnoculturelle. Les auteures ont interrogé 18 éducateurs qui ont travaillé « en première ligne ¼ pendant la pandémie. Elles voulaient documenter le soutien qu'ils ont apporté aux communautés à faibles revenus et aux nouveaux arrivants, et comprendre ainsi dans quelle mesure ils ont fourni des réponses pédagogiques et stratégiques. Elles entendaient par ailleurs schématiser la mesure dans laquelle on pourrait tirer parti de leurs pédagogies et pratiques pour établir des relations plus équitables dans l'éducation communautaire après la pandémie. Les auteures ont constaté que les éducateurs recouraient à tout un ensemble de pédagogies inventives et dynamiques, axées sur la solidarité sociale et tenant compte des oppressions intersectionnelles. Ces « pédagogies pandémiques ¼ pourraient contribuer à l'avenir, après la pandémie, à instaurer des relations socio-technologiques plus équitables.

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