PURPOSERunning and other strenuous sports activities are purported to increase osteoarthritis (OA) risk, more so than walking and less-strenuous activities. Analyses were therefore performed to test ...whether running, walking, and other exercise affect OA and hip replacement risk and to assess the role of body mass index (BMI) in mediating these relationships.
METHODSIn this article, we studied the proportional hazards analyses of patients’ report of having physician-diagnosed OA and hip replacement versus exercise energy expenditure (METs).
RESULTSOf the 74,752 runners, 2004 reported OA and 259 reported hip replacements during the 7.1-yr follow-up; whereas of the 14,625 walkers, 696 reported OA and 114 reported hip replacements during the 5.7-yr follow-up. Compared with running <1.8 MET·h·d, the risks for OA and hip replacement decreased as follows1) 18.1% (P = 0.01) and 35.1% (P = 0.03) for the 1.8- and 3.6-MET·h·d run, respectively; 2) 16.1% (P = 0.03) and 50.4% (P = 0.002) for the 3.6- and 5.4-MET·h·d run, respectively; and 3) 15.6% (P = 0.02) and 38.5% (P = 0.01) for the ≥5.4-MET·h·d run, suggesting that the risk reduction mostly occurred by 1.8 MET·h·d. Baseline BMI was strongly associated with both OA (5.0% increase per kilogram per square meter, P = 2 × 10) and hip replacement risks (9.8% increase per kilogram per square meter, P = 4.8 × 10), and adjustment for BMI substantially diminished the risk reduction from running ≥1.8 MET·h·d for OA (from 16.5%, P = 0.01, to 8.6%, P = 0.21) and hip replacement (from 40.4%, P = 0.005, to 28.5%, P = 0.07). The reductions in OA and hip replacement risk by exceeding 1.8 MET·h·d did not differ significantly between runners and walkers. Other (nonrunning) exercise increased the risk of OA by 2.4% (P = 0.009) and hip replacement by 5.0% per MET·h·d (P = 0.02), independent of BMI.
CONCLUSIONSRunning significantly reduced OA and hip replacement risk due to, in part, running’s association with lower BMI, whereas other exercise increased OA and hip replacement risk.
"Quantile-dependent expressivity" describes an effect of the genotype that depends upon the level of the phenotype (e.g., whether a subject's triglycerides are high or low relative to its population ...distribution). Prior analyses suggest that the effect of a genetic risk score (GRS) on fasting plasma triglyceride levels increases with the percentile of the triglyceride distribution. Postprandial lipemia is well suited for testing quantile-dependent expressivity because it exposes each individual's genotype to substantial increases in their plasma triglyceride concentrations. Ninety-seven published papers were identified that plotted mean triglyceride response vs. time and genotype, which were converted into quantitative data. Separately, for each published graph, standard least-squares regression analysis was used to compare the genotype differences at time t (dependent variable) to average triglyceride concentrations at time t (independent variable) to assess whether the genetic effect size increased in association with higher triglyceride concentrations and whether the phenomenon could explain purported genetic interactions with sex, diet, disease, BMI, and drugs.
Consistent with the phenomenon, genetic effect sizes increased (P≤0.05) with increasing triglyceride concentrations for polymorphisms associated with ABCA1, ANGPTL4, APOA1, APOA2, APOA4, APOA5, APOB, APOC3, APOE, CETP, FABP2, FATP6, GALNT2, GCKR, HL, IL1b, LEPR, LOX-1, LPL, MC4R, MTTP, NPY, SORT1, SULF2, TNFA, TCF7L2, and TM6SF2. The effect size for these polymorphisms showed a progressively increasing dose-response, with intermediate effect sizes at intermediate triglyceride concentrations. Quantile-dependent expressivity provided an alternative interpretation to their interactions with sex, drugs, disease, diet, and age, which have been traditionally ascribed to gene-environment interactions and genetic predictors of drug efficacy (i.e., personalized medicine).
Quantile-dependent expressivity applies to the majority of genetic variants affecting postprandial triglycerides, which may arise because the impaired functionalities of these variants increase at higher triglyceride concentrations. Purported gene-drug interactions may be the manifestations of quantile-dependent expressivity, rather than genetic predictors of drug efficacy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To examine the relationship between parental depression and cooperative coparenting among couples over the first 5 years after a birth.
Background
Previous research has considered how ...depression affects coparenting but has not focused on the association as a longitudinal and dyadic process. Understanding coparenting is important as it is linked to parents' and children's well‐being.
Method
Data from the Fragile Families and Child Wellbeing (FFCW) study were analyzed using actor–partner interdependence models. The FFCW follows families and their children as part of a birth cohort of children who were born in large urban cities of the United States in the late 1990s.
Results
The actor–partner interdependence models indicated that (a) parents' depression is associated with decreased coparenting perceptions for both mothers and fathers, and the effects endure over time; (b) fathers' depression was also associated with mothers' perceptions of cooperative coparenting over the later years; and (c) differences between mothers and fathers emerged only during the early years, with the effect of depression on coparenting being larger for fathers than mothers.
Conclusion
The results not only highlight the importance of both parents' mental health on coparenting but also the added role that fathers' depression plays in shaping their own and their partners' perceptions of coparenting.
Implications
Policy makers and family practitioners who are invested in building healthy families may find it valuable to screen for and treat mental illness in the context of creating programs to increase cooperative coparenting.
The Morris water maze (MWM) is a test of spatial learning for rodents that relies on distal cues to navigate from start locations around the perimeter of an open swimming arena to locate a submerged ...escape platform. Spatial learning is assessed across repeated trials and reference memory is determined by preference for the platform area when the platform is absent. Reversal and shift trials enhance the detection of spatial impairments. Trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol. Search-to-platform area determines the degree of reliance on spatial versus non-spatial strategies. Cued trials determine whether performance factors that are unrelated to place learning are present. Escape from water is relatively immune from activity or body mass differences, making it ideal for many experimental models. The MWM has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function. We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days.
The putative tumour suppressor and apoptosis-promoting gene,
growth arrest
-
specific 5
(
GAS5
), encodes long ncRNA (lncRNA) and snoRNAs. Its expression is down-regulated in breast cancer, which ...adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels.
GAS5
silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Reduced
GAS5
expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between
GAS5
expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of
GAS5
expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.
A recent paper by Nishiyama et al. (Earth, Planets, and Space 73:126) examined syntectonic quartz veins to constrain temporal variations in the recurrence intervals between slow slip and tremor ...events. The authors claim that by examining the liquid-volume fraction of syntectonic fluid inclusions in the veins, that they can accurately reconstruct pore-fluid pressures (and variations therein) that were operative during faulting at ~ 15 km depth in an exhumed subduction melange. From these observations, the authors infer that large (from lithostatic to hydrostatic) decreases in pore-fluid pressure occurred during faulting, and that these variations drove increases in supersaturation and rapid quartz precipitation over time scales consistent with the repeat times of seismologically observed slow slip and tremor events. Here, I show that Nishiyama et al.’s analysis neglects reasonable uncertainties in pore-fluid pressure reconstruction. When those uncertainties are included, the Nishiyama et al.’s results become ambiguous as to whether any variation in pore-fluid pressure during vein formation occurred at all, negating the validity of many of the subsequent conclusions.
Graphical Abstract
Opioids increase dopamine release in the brain through inhibition of GABA-A IPSCs onto dopamine cells. Immunolabeling indicates that GABA neurons in the rostromedial tegmental nucleus (RMTg), also ...known as the tail of the ventral tegmental area, send a dense projection to midbrain dopamine neurons stain for μ-opioid receptors. There is however, little functional evidence that these neurons play a role in the opioid-dependent increase in dopamine neuron activity. The present study used retrograde tracers injected into the ventral tegmental area and substantia nigra (VTA/SN) to identify RMTg neurons that project to the VTA/SN. Whole-cell current-clamp and cell-attached recordings from labeled RMTg neurons were performed in sagittal slices from rat. The rhythmic spontaneous firing rate of RMTg neurons was decreased and the membrane potential was hyperpolarized in response to application of μ-opioid agonist DAMGO. Agonists that act at κ- and δ-opioid receptors (U69593 and DPDPE) failed to hyperpolarize RMTg neurons. Whole-cell recordings made in dopamine neurons revealed rhythmic, large amplitude spontaneous IPSCs that had a similar frequency, pattern and opioid sensitivity to the firing of RMTg neurons. In addition, electrical and channelrhodopsin-2 stimulation within the RMTg evoked GABA-A IPSCs in dopamine neurons that were inhibited by μ-opioid agonists DAMGO, but not κ- and δ-opioid agonists. Thus, this study demonstrates functional connection from the RMTg to the VTA/SN mediated by a dense, opioid-sensitive GABA innervation, and that the RMTg is a key structure in the μ-opioid receptor-dependent regulation of dopamine neurons.
Student engagement is an important factor for learning outcomes in higher education. Engagement with learning at campus-based higher education institutions is difficult to quantify due to the variety ...of forms that engagement might take (e.g. lecture attendance, self-study, usage of online/digital systems). Meanwhile, there are increasing concerns about student wellbeing within higher education, but the relationship between engagement and wellbeing is not well understood. Here we analyse results from a longitudinal survey of undergraduate students at a campus-based university in the UK, aiming to understand how engagement and wellbeing vary dynamically during an academic term. The survey included multiple dimensions of student engagement and wellbeing, with a deliberate focus on self-report measures to capture students' subjective experience. The results show a wide range of engagement with different systems and study activities, giving a broad view of student learning behaviour over time. Engagement and wellbeing vary during the term, with clear behavioural changes caused by assessments. Results indicate a positive interaction between engagement and happiness, with an unexpected negative relationship between engagement and academic outcomes. This study provides important insights into subjective aspects of the student experience and provides a contrast to the increasing focus on analysing educational processes using digital records.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite renewed interest in studying the safety and efficacy of psychedelic-assisted psychotherapy for the treatment of psychological disorders, the enrollment of racially diverse participants and ...the unique presentation of psychopathology in this population has not been a focus of this potentially ground-breaking area of research. In 1993, the United States National Institutes of Health issued a mandate that funded research must include participants of color and proposals must include methods for achieving diverse samples.
A methodological search of psychedelic studies from 1993 to 2017 was conducted to evaluate ethnoracial differences in inclusion and effective methods of recruiting peopple of color.
Of the 18 studies that met full criteria (n = 282 participants), 82.3% of the participants were non-Hispanic White, 2.5% were African-American, 2.1% were of Latino origin, 1.8% were of Asian origin, 4.6% were of indigenous origin, 4.6% were of mixed race, 1.8% identified their race as "other," and the ethnicity of 8.2% of participants was unknown. There were no significant differences in recruitment methodologies between those studies that had higher (> 20%) rates of inclusion.
As minorities are greatly underrepresented in psychedelic medicine studies, reported treatment outcomes may not generalize to all ethnic and cultural groups. Inclusion of minorities in futures studies and improved recruitment strategies are necessary to better understand the efficacy of psychedelic-assisted psychotherapy in people of color and provide all with equal opportunities for involvement in this potentially promising treatment paradigm.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
