Maladaptive personality traits and older adult relationship satisfaction: A co-twin control approach to understanding associations.

OBJECTIVE: Maladaptive personality traits have been implicated in romantic relationship dissatisfaction, but the etiology of those links and the degree to which they extend to other types of relationships are unclear. The purpose of this study was to examine associations between maladaptive personality traits and satisfaction in various relationships using a co-twin control design to identify potential environmental contributions. METHOD: The sample consisted of 1340 older adult twin participants from the Minnesota Twin Registry (Mage = 70.3) that completed the Personality Inventory for DSM-5 Faceted Brief Form and Network of Relationships Inventory (Revised for Older Adults). RESULTS: Several maladaptive personality traits were phenotypically associated with relationship dissatisfaction, with detachment and negative affect having the largest effects. Further, within twin pair differences in detachment and negative affect were associated with greater relationship dissatisfaction, suggesting that observed associations were mediated partly by the unique environment, not solely the result of genetic and familial confounding. Both phenotypic and co-twin associations were strongest overall in the romantic partner relationship. CONCLUSION: These findings support the notion that maladaptive personality traits are implicated in interpersonal dysfunction across multiple domains.

Common conditions of use elements. Atomic concepts for consistent and effective information governance.

Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse 'use conditions'. We report a core lexicon of terms that are atomic, non-directional 'concepts of use', called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility. Seventy-six concepts were initially identified from diverse real-world settings, and via iterative rounds of deliberation and user-testing these were optimised and condensed down to 20 items. To validate utility, support software and training information was provided to biobanks and registries who were asked to create Sharing Policy Profiles. This succeeded and involved adding standardised directionality and scope annotations to the employed terms. The addition of free-text parameters was also explored. The approach is now being adopted by several real-world projects, enabling this standard to evolve progressively into a universal basis for representing and managing conditions of use.

A dynamic compositional equilibrium governs mRNA recognition by eIF3.

Eukaryotic translation initiation factor (eIF) 3 is a multi-subunit protein complex that binds both ribosomes and messenger RNAs (mRNAs) in order to drive a diverse set of mechanistic steps during translation. Despite its importance, a unifying framework explaining how eIF3 performs these numerous activities is lacking. Using single-molecule light scattering microscopy, we demonstrate that Saccharomyces cerevisiae eIF3 is an equilibrium mixture of the full complex, subcomplexes, and subunits. By extending our microscopy approach to an in vitro reconstituted eIF3 and complementing it with biochemical assays, we define the subspecies comprising this equilibrium and show that, rather than being driven by the full complex, mRNA binding by eIF3 is instead driven by the eIF3a subunit within eIF3a-containing subcomplexes. Our findings provide a mechanistic model for the role of eIF3 in the mRNA recruitment step of translation initiation and establish a mechanistic framework for explaining and investigating the other activities of eIF3.

Reduced cerebrospinal fluid motion in patients with Parkinson's disease revealed by magnetic resonance imaging with low b-value diffusion weighted imaging.

BACKGROUND: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation of α-synuclein protofibrils. New diagnostic methods assess α-synuclein aggregation characteristics from cerebrospinal fluid (CSF) and recent pathophysiologic mechanisms suggest that CSF circulation disruptions may precipitate α-synuclein retention. Here, diffusion-weighted MRI with low-to-intermediate diffusion-weightings was applied to test the hypothesis that CSF motion is reduced in Parkinson's disease relative to healthy participants. METHODS: Multi-shell diffusion weighted MRI (spatial resolution = 1.8 × 1.8 × 4.0 mm) with low-to-intermediate diffusion weightings (b-values = 0, 50, 100, 200, 300, 700, and 1000 s/mm2) was applied over the approximate kinetic range of suprasellar cistern fluid motion at 3 Tesla in Parkinson's disease (n = 27; age = 66 ± 6.7 years) and non-Parkinson's control (n = 32; age = 68 ± 8.9 years) participants. Wilcoxon rank-sum tests were applied to test the primary hypothesis that the noise floor-corrected decay rate of CSF signal as a function of b-value, which reflects increasing fluid motion, is reduced within the suprasellar cistern of persons with versus without Parkinson's disease and inversely relates to choroid plexus activity assessed from perfusion-weighted MRI (significance-criteria: p < 0.05). RESULTS: Consistent with the primary hypothesis, CSF decay rates were higher in healthy (D = 0.00673 ± 0.00213 mm2/s) relative to Parkinson's disease (D = 0.00517 ± 0.00110 mm2/s) participants. This finding was preserved after controlling for age and sex and was observed in the posterior region of the suprasellar cistern (p < 0.001). An inverse correlation between choroid plexus perfusion and decay rate in the voxels within the suprasellar cistern (Spearman's-r=-0.312; p = 0.019) was observed. CONCLUSIONS: Multi-shell diffusion MRI was applied to identify reduced CSF motion at the level of the suprasellar cistern in adults with versus without Parkinson's disease; the strengths and limitations of this methodology are discussed in the context of the growing literature on CSF flow.

Categorization of the amyotrophic lateral sclerosis population via the clinical determinant of post-onset ΔFS for study design and medical practice.

The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) has become the most widely utilized measure of disease severity in patients with ALS, with change in ALSFRS-R from baseline being a trusted primary outcome measure in ALS clinical trials. This is despite the scale having several established limitations, and although alternative scales have been proposed, it is unlikely that these will displace ALSFRS-R in the foreseeable future. Here, we discuss the merits of delta FS (ΔFS), the slope or rate of ALSFRS-R decline over time, as a relevant tool for innovative ALS study design, with an as yet untapped potential for optimization of drug effectiveness and patient management. In our view, categorization of the ALS population via the clinical determinant of post-onset ΔFS is an important study design consideration. It serves not only as a critical stratification factor and basis for patient enrichment but also as a tool to explore differences in treatment response across the overall population; thereby, facilitating identification of responder subgroups. Moreover, because post-onset ΔFS is derived from information routinely collected as part of standard patient care and monitoring, it provides a suitable patient selection tool for treating physicians. Overall, post-onset ΔFS is a very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design.

Characteristics of Clinicians Caring for Transgender Men and Nonbinary Individuals and Guideline Concordance of Clinicians' Cervical Cancer Screening Counseling for Cisgender Individuals Versus Transgender Men and Nonbinary Individuals with a Cervix.

Purpose: We examined characteristics of clinicians caring for transgender men and nonbinary (TMNB) individuals and guideline concordance of clinicians' cervical cancer screening recommendations. Methods: Using a survey of clinicians who performed ≥10 cervical cancer screenings in 2019, we studied characteristics of clinicians who do versus do not report caring for TMNB individuals and guideline concordance of screening recommendations for TMNB individuals with a cervix versus cisgender women. Results: In our sample (N = 492), 49.2% reported caring for TMNB individuals, and 25.4% reported performing cervical cancer screening for TMNB individuals with a cervix. Differences in guideline concordance of screening recommendations for TMNB individuals with a cervix versus cisgender women (45.8% vs. 50% concordant) were not statistically significant. Conclusion: Sizable proportions of clinicians cared for and performed cervical cancer screening for TMNB individuals. Research is needed to better understand clinicians' identified knowledge deficits to develop interventions (e.g., clinician trainings) to improve gender-affirming cervical cancer prevention.

Loneliness, epigenetic age acceleration, and chronic health conditions.

Having associations with a range of adverse physical health outcomes including mortality, loneliness is increasingly recognized as a pressing public health concern, but the mechanisms studied to date do not yet explain all loneliness-related health risk. We sought to evaluate whether epigenetic influences on DNA methylation could help explain the relationship between loneliness and health. To do so, we first estimated associations between loneliness and epigenetic age acceleration (EAA) in a subsample of participants in the study of midlife in the United States (n = 1,310), before testing whether EAA mediated and/or moderated the association between loneliness and the onset of chronic health conditions in older adulthood (n = 445 completing longitudinal follow-ups). Greater loneliness was weakly associated with greater EAA in the Horvath, DunedinPACE, and GrimAge measures after accounting for demographic (0.08 ≤ ß ≤ 0.11) and behavioral (0.06 ≤ ß ≤ 0.08) covariates. Loneliness also predicted increases in chronic condition counts and these effects were more pronounced for individuals with higher DunedinPACE EAA values (interaction term ß = 0.09, p = .009), suggesting possible synergistic impacts. EAA measures appear to be promising in helping to understand individual variations in the health impacts of loneliness, but the specific mechanisms involved require further research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Dragonflies and Damselflies (Insecta: Odonata) of Canada: species list, geographical distribution, status, and conservation ranks.

As of August 2023, 220 species in 57 genera and 10 families of damselflies and dragonflies (Insecta: Odonata) are recorded for Canada. Since the publication of the first edition in 2005, 14 species have been added to the list; one,Neurocordulia obsoleta (Say) has been removed because of a misidentification and another, Sympetrum occidentale, has been to synonymy. Conservation ranks are given for species in all 13 provinces and territories. English and French names for all listed species are included. Literature sources are discussed and presented, as is information on species status and the addition and exclusion of species. Sections on taxonomy and variation, subspecies, presumed hybrids, the introduction of exotic species, notable range extensions and observations, and conservation and protection are also provided.

Chronic and postprandial effect of blueberries on cognitive function, alertness, and mood in participants with metabolic syndrome - results from a six-month, double-blind, randomized controlled trial.

BACKGROUND: Anthocyanin and blueberry intakes positively associated with cognitive function in population-based studies and cognitive benefits in randomized controlled trials of adults with self-perceived or clinical cognitive dysfunction. To date, adults with metabolic syndrome (MetS) but without cognitive dysfunction are understudied. OBJECTIVES: Cognitive function, mood, alertness, and sleep quality were assessed as secondary end points in MetS participants, postprandially (>24 h) and following 6-mo blueberry intake. METHODS: A double-blind, randomized controlled trial was conducted, assessing the primary effect of consuming freeze-dried blueberry powder, compared against an isocaloric placebo, on cardiometabolic health >6 mo and a 24 h postprandial period (at baseline). In this secondary analysis of the main study, data from those completing mood, alertness, cognition, and sleep assessments are presented (i.e., n = 115 in the 6 mo study, n = 33 in the postprandial study), using the following: 1) Bond-Lader self-rated scores, 2) electronic cognitive battery (i.e., testing attention, working memory, episodic memory, speed of memory retrieval, executive function, and picture recognition), and 3) the Leeds Sleep Evaluation Questionnaire. Urinary and serum anthocyanin metabolites were quantified, and apolipoprotein E genotype status was determined. RESULTS: Postprandial self-rated calmness significantly improved after 1 cup of blueberries (P = 0.01; q = 0.04; with an 11.6% improvement compared with baseline between 0 and 24 h for the 1 cup group), but all other mood, sleep, and cognitive function parameters were unaffected after postprandial and 6-mo blueberries. Across the ½ and 1 cup groups, microbial metabolites of anthocyanins and chlorogenic acid (i.e., hydroxycinnamic acids, benzoic acids, phenylalanine derivatives, and hippuric acids) and catechin were associated with favorable chronic and postprandial memory, attention, executive function, and calmness. CONCLUSIONS: Although self-rated calmness improved postprandially, and significant cognition-metabolite associations were identified, our data did not support strong cognitive, mood, alertness, or sleep quality improvements in MetS participants after blueberry intervention. This trial was registered at clinicaltrials.gov as NCT02035592.

Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.

PURPOSE: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi. PATIENTS AND METHODS: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations. Paired pretreatment and day 15 tumor biopsies and serial cell-free (cf)DNA were analyzed. RESULTS: A total of 91 patients initiated treatment, with 38 in dose escalation. Fifty-eight percent had ≥3 prior therapies. A total of 15 patients (17%) had colorectal cancer, 19 (11%) pancreatic, 15 (17%) NSCLC, and 32 (35%) GYN cancers. The recommended phase II dose (RP2D) was established as trametinib 2 mg daily days 1 to 14 and navitoclax 250 mg daily days 1 to 28 of each cycle. Most common adverse events included diarrhea, thrombocytopenia, increased AST/ALT, and acneiform rash. At RP2D, 8 of 49 (16%) evaluable patients achieved partial response (PR). Disease-specific differences in efficacy were noted. In patients with GYN at the RP2D, 7 of 21 (33%) achieved a PR and median duration of response 8.2 months. No PRs occurred in patients with colorectal cancer, NSCLC, or pancreatic cancer. MAPK pathway inhibition was observed in on-treatment tumor biopsies. Reductions in KRAS/NRAS mutation levels in cfDNA correlated with clinical benefit. CONCLUSIONS: Navitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population.

Climate changes affecting global iodine status.

Global warming is now universally acknowledged as being responsible for dramatic climate changes with rising sea levels, unprecedented temperatures, resulting fires and threatened widespread species loss. While these effects are extremely damaging, threatening the future of life on our planet, one unexpected and paradoxically beneficial consequence could be a significant contribution to global iodine supply. Climate change and associated global warming are not the primary causes of increased iodine supply, which results from the reaction of ozone (O3) arising from both natural and anthropogenic pollution sources with iodide (I-) present in the oceans and in seaweeds (macro- and microalgae) in coastal waters, producing gaseous iodine (I2). The reaction serves as negative feedback, serving a dual purpose, both diminishing ozone pollution in the lower atmosphere and thereby increasing I2. The potential of this I2 to significantly contribute to human iodine intake is examined in the context of I2 released in a seaweed-abundant coastal area. The bioavailability of the generated I2 offers a long-term possibility of increasing global iodine status and thereby promoting thyroidal health. It is hoped that highlighting possible changes in iodine bioavailability might encourage the health community to address this issue.

A novel approach to model cumulative stress: Area under the s-factor curve.

OBJECTIVE: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes. METHOD: We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes. RESULTS: The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change. CONCLUSIONS: Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood.

Evaluation of models to estimate the bioaccumulation of organic chemicals in earthworms.

Modelling approaches to estimate the bioaccumulation of organic chemicals by earthworms are important for improving the realism in risk assessment of chemicals. However, the applicability of existing models is uncertain, partly due to the lack of independent datasets to test them. This study therefore conducted a comprehensive literature review on existing empirical and kinetic models that estimate the bioaccumulation of organic chemicals in earthworms and gathered two independent datasets from published literature to evaluate the predictive performance of these models. The Belfroid et al. (1995a) model is the best-performing empirical model, with 91.2% of earthworm body residue simulations within an order of magnitude of observation. However, this model is limited to the more hydrophobic pesticides and to the earthworm species Eisenia fetida or Eisenia andrei. The kinetic model proposed by Jager et al. (2003b) which out-performs that of Armitage and Gobas (2007), predicted uptake of PCB 153 in the earthworm E. andrei to within a factor of 10. However, the applicability of Jager et al.'s model to other organic compounds and other earthworm species is unknown due to the limited evaluation dataset. The model needs to be parameterised for different chemical, soil, and species types prior to use, which restricts its applicability to risk assessment on a broad scale. Both the empirical and kinetic models leave room for improvement in their ability to reliably predict bioaccumulation in earthworms. Whether they are fit for purpose in environmental risk assessment needs careful consideration on a case by case basis.

Measuring leadership in sport: Development and validation of the Identity Leadership Inventory - Youth (ILI-Y).

The social identity approach to leadership posits that leaders' effectiveness depends on their ability to represent, advance, create, and embed a shared sense of social identity among their followers. Although significant progress has been made in investigating the benefits of identity leadership in adult sports, research in youth sports is still in its infancy. One reason is the lack of a youth-centric inventory that adequately measures identity leadership in this population. To bridge this gap, we developed and validated a long (16 items) and short (5 items) version of the Identity Leadership Inventory for Youth Sport (ILI-Y or ILI-Y-Short-Form) through five studies conducted in three phases of research. Data were primarily collected in football in the United Kingdom, involving a total of 1096 participants. Results of Phase I of this study provided little to no evidence that the ILI - originally developed for adults - was understandable (Study 1) and had factor validity and internal consistency (Study 2) in a sample of youth athletes. Therefore, in Phase II, the ILI was revised, leading to the development of the ILI-Y, which was understandable for youth athletes (Study 3). Results from Phase II (Study 4) also indicated that the ILI-Y exhibited a unidimensional factor structure, which was subsequently confirmed in Phase III (Study 5). This last phase offered additional evidence for the discriminant, criterion, and incremental validity of the ILI-Y and its short form, along with their measurement invariance across genders and age groups, and internal consistency. This study provides sports psychology researchers and practitioners with a valid measure to assess identity leadership in youth sports.

Cycloaddition of Phenyltriazolinedione with Carbazole-Alkynes and Yne-Carbamates to Access Diazacyclobutenes.

Previously, we described the synthesis of stable, bicyclic examples of the rather rare diazacyclobutene (DCB) motif by means of a cycloaddition between triazolinediones and electron-rich thiolated alkynes. Here, we report the investigation of the cycloaddition of triazolinediones with related electron-rich yne-carbamates and carbazole-alkynes. Bicyclic DCBs arising from yne-carbamates were isolated in 8-65% yield, while those arising from carbazole-alkynes were isolated in 28-59% yield. Mechanistic studies and characterization of isolable byproducts shed light on the underlying issues leading to poor to moderate yields.

Genotype and ripening method affect carotenoid content and bio-accessibility in banana.

Bananas (Musa spp.) are a target crop for provitamin A carotenoids (pVACs) biofortification programs aiming at reducing the negative impact on health caused by vitamin A deficiency in vulnerable populations. However, studies to understand the effect of ripening methods and stages and the genotype on carotenoid content and bioaccessibility in the banana germplasm are scarce. This study evaluated carotenoid content and bioaccessibility in 27 different banana accessions at three maturation stages and two ripening methods (natural ripening and ethylene ripening). Across most accessions, total carotenoid content (TCC) increased from unripe to ripe fruit; only two accessions showed a marginal decrease. The ripening method affected carotenoid accumulation; 18 accessions had lower TCC when naturally ripened compared with the ethylene ripening group, while nine accessions showed higher TCC when ripened with exogenous ethylene, suggesting that treating bananas with exogenous ethylene might directly affect TCC accumulation, but the response is accession dependent. Additionally, carotenoid bioaccessibility varied across genotypes and was correlated with the amount of soluble starch and resistant starch. These findings highlight the importance of ripening methods and genotypes in maximizing banana carotenoid content and bioaccessibility, which could contribute to improving pVACs delivery in biofortification programs.

Cervical Spine Stenosis Causing Diaphragmatic Paralysis: A Case Study and Narrative Review of Clinical Presentations and Outcomes.

STUDY DESIGN: Case report and narrative review. OBJECTIVE: To explore the therapeutic role of surgical and nonsurgical treatment of diaphragmatic paralysis secondary to spinal cord and nerve root compression. SUMMARY OF BACKGROUND DATA: Phrenic nerve dysfunction due to central or neuroforaminal stenosis is a rare yet unappreciated etiology of diaphragmatic paralysis and chronic dyspnea. Surgical spine decompression, diaphragmatic pacing, and intensive physiotherapy are potential treatment options with varying degrees of evidence. METHODS: The case of a 70-year-old male with progressive dyspnea, reduced hemi-diaphragmatic excursion, and C3-C7 stenosis, who underwent a microscopic foraminotomy is discussed. Literature review (MEDLINE, PubMed, Google Scholar) identified 19 similar reports and discussed alternative treatments and outcomes. RESULTS AND CONCLUSIONS: Phrenic nerve root decompression and improvement in neuromonitoring signals were observed intraoperatively. The patient's postoperative course was uncomplicated, and after 15 months, he experienced significant symptomatic improvement and minor improvement in hemi-diaphragmatic paralysis and pulmonary function tests. All case reports of patients treated with spinal decompression showed symptomatic and/or functional improvement, while one of the 2 patients treated with physiotherapy showed improvement. More studies are needed to further describe the course and outcomes of these interventions, but early identification and spinal decompression can be an effective treatment. OCEBM LEVEL OF EVIDENCE: Level-4.

Deep learning segmentation of peri-sinus structures from structural magnetic resonance imaging: validation and normative ranges across the adult lifespan.

BACKGROUND: Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often requires exogenous contrast agents and manual delineation. METHODS: We propose a deep learning architecture to automatically delineate the peri-sinus space (e.g., PSD and intravenous AG structures) using two cascaded 3D fully convolutional neural networks applied to submillimeter 3D T2-weighted non-contrasted MRI images, which can be routinely acquired on all major MRI scanner vendors. The method was evaluated through comparison with gold-standard manual tracing from a neuroradiologist (n = 80; age range = 11-83 years) and subsequently applied in healthy participants (n = 1,872; age range = 5-100 years), using data from the Human Connectome Project, to provide exemplar metrics across the lifespan. Dice-Sørensen and a generalized linear model was used to assess PSD and AG changes across the human lifespan using quadratic restricted splines, incorporating age and sex as covariates. RESULTS: Findings demonstrate that the PSD and AG volumes can be segmented using T2-weighted MRI with a Dice-Sørensen coefficient and accuracy of 80.7 and 74.6, respectively. Across the lifespan, we observed that total PSD volume increases with age with a linear interaction of gender and age equal to 0.9 cm3 per year (p < 0.001). Similar trends were observed in the frontal and parietal, but not occipital, PSD. An increase in AG volume was observed in the third to sixth decades of life, with a linear effect of age equal to 0.64 mm3 per year (p < 0.001) for total AG volume and 0.54 mm3 (p < 0.001) for maximum AG volume. CONCLUSIONS: A tool that can be applied to quantify PSD and AG volumes from commonly acquired T2-weighted MRI scans is reported and exemplar volumetric ranges of these structures are provided, which should provide an exemplar for studies of neurofluid circulation dysfunction. Software and training data are made freely available online ( https://github.com/hettk/spesis ).