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Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
Adolescence is a critical developmental phase during which young people are vulnerable to the experiences of mental ill-health and social exclusion (consisting of various domains including education and employment, housing, finances and social supports and relationships). The aims of this study were to (i) obtain an understanding of the relationships between social exclusion, mental health and wellbeing of young people; and (ii) identify potentially modifiable targets, or population groups that require greater or targeted supports.
Methods
Data were obtained from the Mission Australia 2022 Youth Survey, Australia’s largest annual population-wide survey of young people aged 15–19 years (n = 18,800). Participants’ experiences of social exclusion in different domains were explored (e.g., prevalence, co-occurrence and controlling for differences in demographic characteristics). Multivariable linear regression models were used to map the relationships between social exclusion domains and mental health and wellbeing, controlling for confounding factors where necessary.
Results
Sixty per cent of all young people experienced social exclusion in at least one domain, 25% in multiple. Young people who identified as gender diverse, Indigenous, living in a remote/rural or socio-economically disadvantaged area and with a culturally diverse background were more likely to report social exclusion. A strong association was seen between all domains of social exclusion and poor mental health (e.g., higher psychological distress and loneliness, reduced personal wellbeing, reduced sense of control over their life and a more negative outlook on the future). Notably, difficulties in socialising and obtaining social support were critical factors linked to increased psychological distress and reduced wellbeing.
Conclusions
Findings underscore the need to address multiple domains of social exclusion concurrently, and in collaboration with youth mental healthcare. Prevention efforts aimed at early identification and intervention should be prioritised to support young people vulnerable to social exclusion. Screening approaches are needed to identify individuals and groups of young people in need of support, and to facilitate care coordination across multiple providers.
During the past 30 yr an impasse has developed in the discovery and commercialization of synthetic herbicides with new molecular targets and novel chemistries. Similarly, there has been little success with bioherbicides, both microbial and chemical. These bioherbicides are needed to combat fast-growing herbicide resistance and to fulfill the need for more environmentally and toxicologically safe herbicides. In response to this substantial and growing opportunity, numerous start-up companies are utilizing novel approaches to provide new tools for weed management. These diverse new tools broaden the scope of discovery, encompassing advanced computational, bioinformatic, and imaging platforms; plant genome–editing and targeted protein degradation technologies; and machine learning and artificial intelligence (AI)-based strategies. This review contains summaries of the presentations of 10 such companies that took part in a symposium held at the WSSA annual meeting in 2024. Four of the companies are developing microbial bioherbicides or natural product–based herbicides, and the other six are using advanced technologies, such as AI, to accelerate the discovery of herbicides with novel molecular target sites or to develop non-GMO, herbicide-resistant crops.
Attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with myriad adverse outcomes, including interpersonal difficulties, but factors that moderate the developmental course and functional impact of ADHD over time are not well understood. The present study evaluated developmental contributions of the triarchic neurobehavioral traits (boldness, meanness, and disinhibition) to ADHD symptomatology and its subdimensions from adolescence to young adulthood. Participants were twins and triplets assessed at ages 14, 17, and 19 (initial N = 1,185, 51.2% female). Path analyses using negative binomial regression revealed that boldness at age 14 was associated with more ADHD symptoms cross-sectionally (especially hyperactivity/impulsivity), but fewer symptoms (especially inattention) at age 19 in the prospective analysis. Notably, inclusion of interpersonal problems at ages 14 and 17 as covariates reduced the latter effect to nonsignificant. Disinhibition concurrently and prospectively predicted higher levels of ADHD symptoms, including both subdimensions, and the prospective effects were partially mediated by greater social impairment at age 17. Meanness prospectively (but not concurrently) predicted higher levels of hyperactivity/impulsivity symptoms. Sex moderated certain associations of meanness and disinhibition with ADHD symptoms. These findings highlight how fundamental neurobehavioral traits shape both psychopathology and adaptive outcomes in the developmental course of ADHD.
Higher education is strongly associated with better cognitive function in older adults. Previous research has also showed that positive psychosocial factors, such as selfefficacy and emotional and instrumental support, are beneficial for late-life cognition. There is prior evidence of a buffering effect of self-efficacy on the relationship between educational disadvantage and poor cognition in older adults, however it is not known if other psychosocial factors modify the schooling-cognition relationship. We hypothesized that higher levels of emotional and instrumental support will diminish the association between lower education and lower cognitive test scores among older adults.
Participants and Methods:
553 older adults without dementia (42.1% non-Latinx Black, 32.2% non-Latinx White, 25.7% Latinx; 63.2% women; average age 74.4 (SD 4.3)) from the Washington Heights-Inwood Columbia Aging Project. Neuropsychological tests assessed four cognitive domains (language, memory, psychomotor processing speed, and visuospatial function). Self-reported emotional and instrumental support were assessed with measures from NIH Toolbox. Linear regression estimated interactions between education and the two support measures on cognition in models stratified by cognitive domain and racial and ethnic group. Covariates included age, sex/gender, and chronic health conditions (e.g. heart disease, stroke, cancer, etc.).
Results:
Education was associated with cognition across racial and ethnic groups. For every one year of schooling, the processing speed z-score composite was 0.33 higher among Latinx participants, 0.10 among non-Latinx Black participants, and 0.03 higher among non-Latinx White participants. The education-cognition relationship was generally similar across cognitive domains with larger effects in non-Latinx Black and Latinx participants than in White participants. Low education was associated with slower processing speed among Black participants with low emotional support (B = 0.224, 95% CI [0.014, 0.096]), but there was no association between low education and processing speed among Black older adults with high levels of emotional support (beta for interaction = -.142, 95% CI [-0.061, -0.001]). A similar pattern of results was observed for instrumental support (beta for interaction = -.207, 95% CI [-0.064, 0.010]). There were no interactions between support and education on other cognitive domains or among Latinx and White participants.
Conclusions:
We found that higher levels of emotional and instrumental support attenuate the detrimental effect of educational disadvantages on processing speed in older Black adults. This may occur via benefits of social capital, which provides access to health resources and knowledge, increased social interaction, an emotional outlet allowing the ability to better cope with stress. Longitudinal analyses are needed to examine temporal patterns of associations. In addition, improving equitable access to high quality schools will improve later-life cognitive outcomes for future generations of older adults. However, for the growing number of Black older adults who will not experience the benefits of structural improvements in the education system, emotional and instrumental support may represent a modifiable psychosocial factor to reduce their disproportionate burden of cognitive morbidity.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
OBJECTIVES/GOALS: We aim to discover safer and more effective therapeutics for CNS disorders. Current therapeutic development is hindered by dosing out drugs for safe consumption. By identifying proteins with narrow functional roles in the brain (i.e., behavioral control), we can develop drugs targeting these proteins for improved treatment safety and efficacy. METHODS/STUDY POPULATION: We focused on an evolutionarily new, non-neuronal, non-synaptic glutamate signaling mechanism, system xc- (Sxc). Sxc activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc). To confirm Sxc mutation, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on behavioral control, such as impulse control and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on behavioral control were impaired. MSxc rats displayed deficits in impulse control and behavioral flexibility. We hypothesize that MSxc rats will also show deficits in response inhibition using the stop signal reaction time task, a common metric used in clinical populations. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on impulse control, without impacting development or simple brain function. These results show the potential of targeting Sxc to restore behavioral control without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.
Norway rats (Rattus norvegicus) are considered one of the most significant vertebrate pests globally, because of their impacts on human and animal health. There are legal and moral obligations to minimise the impacts of wildlife management on animal welfare, yet there are few data on the relative welfare impacts of rat trapping and baiting methods used in the UK with which to inform management decisions. Two stakeholder workshops were facilitated to assess the relative welfare impacts of six lethal rat management methods using a welfare assessment model. Fifteen stakeholders including experts in wildlife management, rodent management, rodent biology, animal welfare science, and veterinary science and medicine, participated. The greatest welfare impacts were associated with three baiting methods, anticoagulants, cholecalciferol and non-toxic cellulose baits (severe to extreme impact for days), and with capture on a glue trap (extreme for hours) with concussive killing (mild to moderate for seconds to minutes); these methods should be considered last resorts from a welfare perspective. Lower impacts were associated with cage trapping (moderate to severe for hours) with concussive killing (moderate for minutes). The impact of snap trapping was highly variable (no impact to extreme for seconds to minutes). Snap traps should be regulated and tested to identify those that cause rapid unconsciousness; such traps might represent the most welfare-friendly option assessed for killing rats. Our results can be used to integrate consideration of rat welfare alongside other factors, including cost, efficacy, safety, non-target animal welfare and public acceptability when selecting management methods. We also highlight ways of reducing welfare impacts and areas where more data are needed.
Make-at-home nasal irrigation solutions are often recommended for treating chronic rhinosinusitis. Many patients will store pre-made solution for convenient use. This study investigated the microbiological properties of differing recipes and storage temperatures.
Method
Three irrigation recipes (containing sodium chloride, sodium bicarbonate and sucrose) were stored at 5oC and 22oC. Further samples were inoculated with Staphylococcus aureus and Pseudomonas aeruginosa. Sampling and culturing were conducted at intervals from day 0–12 to examine for bacterial presence or persistence.
Results
No significant bacterial growth was detected in any control solution stored at 5oC. Saline solutions remained relatively bacterial free, with poor survival of inoculated bacteria, which may be related to either lower pH or lower osmolality. Storing at room temperature increased the risk of contamination in control samples, particularly from pseudomonas.
Conclusion
If refrigerated, pre-made nasal irrigation solutions can be stored safely for up to 12 days without risking cross-contamination to irrigation equipment or patients.
Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burdensome, rely on cutoff scores that reduce information, do not examine potential variations in task engagement across a battery, and are typically not well-suited to acquisition of large cognitive datasets. Here we describe the development of novel performance validity measures that could address some of these limitations by leveraging psychometric concepts using data embedded within the Penn Computerized Neurocognitive Battery (PennCNB).
Methods:
We first developed these validity measures using simulations of invalid response patterns with parameters drawn from real data. Next, we examined their application in two large, independent samples: 1) children and adolescents from the Philadelphia Neurodevelopmental Cohort (n = 9498); and 2) adult servicemembers from the Marine Resiliency Study-II (n = 1444).
Results:
Our performance validity metrics detected patterns of invalid responding in simulated data, even at subtle levels. Furthermore, a combination of these metrics significantly predicted previously established validity rules for these tests in both developmental and adult datasets. Moreover, most clinical diagnostic groups did not show reduced validity estimates.
Conclusions:
These results provide proof-of-concept evidence for multivariate, data-driven performance validity metrics. These metrics offer a novel method for determining the performance validity for individual neurocognitive tests that is scalable, applicable across different tests, less burdensome, and dimensional. However, more research is needed into their application.
To determine the proportion of hospitals that implemented 6 leading practices in their antimicrobial stewardship programs (ASPs). Design: Cross-sectional observational survey.
Setting:
Acute-care hospitals.
Participants:
ASP leaders.
Methods:
Advance letters and electronic questionnaires were initiated February 2020. Primary outcomes were percentage of hospitals that (1) implemented facility-specific treatment guidelines (FSTG); (2) performed interactive prospective audit and feedback (PAF) either face-to-face or by telephone; (3) optimized diagnostic testing; (4) measured antibiotic utilization; (5) measured C. difficile infection (CDI); and (6) measured adherence to FSTGs.
Results:
Of 948 hospitals invited, 288 (30.4%) completed the questionnaire. Among them, 82 (28.5%) had <99 beds, 162 (56.3%) had 100–399 beds, and 44 (15.2%) had ≥400+ beds. Also, 230 (79.9%) were healthcare system members. Moreover, 161 hospitals (54.8%) reported implementing FSTGs; 214 (72.4%) performed interactive PAF; 105 (34.9%) implemented procedures to optimize diagnostic testing; 235 (79.8%) measured antibiotic utilization; 258 (88.2%) measured CDI; and 110 (37.1%) measured FSTG adherence. Small hospitals performed less interactive PAF (61.0%; P = .0018). Small and nonsystem hospitals were less likely to optimize diagnostic testing: 25.2% (P = .030) and 21.0% (P = .0077), respectively. Small hospitals were less likely to measure antibiotic utilization (67.8%; P = .0010) and CDI (80.3%; P = .0038). Nonsystem hospitals were less likely to implement FSTGs (34.3%; P < .001).
Conclusions:
Significant variation exists in the adoption of ASP leading practices. A minority of hospitals have taken action to optimize diagnostic testing and measure adherence to FSTGs. Additional efforts are needed to expand adoption of leading practices across all acute-care hospitals with the greatest need in smaller hospitals.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Airway management is a controversial topic in modern Emergency Medical Services (EMS) systems. Among many concerns regarding endotracheal intubation (ETI), unrecognized esophageal intubation and observations of unfavorable neurologic outcomes in some studies raise the question of whether alternative airway techniques should be first-line in EMS airway management protocols. Supraglottic airway devices (SADs) are simpler to use, provide reliable oxygenation and ventilation, and may thus be an alternative first-line airway device for paramedics. In 2019, Alachua County Fire Rescue (ACFR; Alachua, Florida USA) introduced a novel protocol for advanced airway management emphasizing first-line use of a second-generation SAD (i-gel) for patients requiring medication-facilitated airway management (referred to as “rapid sequence airway” [RSA] protocol).
Study Objective:
This was a one-year quality assurance review of care provided under the RSA protocol looking at compliance and first-pass success rate of first-line SAD use.
Methods:
Records were obtained from the agency’s electronic medical record (EMR), searching for the use of the RSA protocol, advanced airway devices, or either ketamine or rocuronium. If available, hospital follow-up data regarding patient condition and emergency department (ED) airway exchange were obtained.
Results:
During the first year, 33 advanced airway attempts were made under the protocol by 23 paramedics. Overall, compliance with the airway device sequence as specified in the protocol was 72.7%. When ETI was non-compliantly used as first-line airway device, the first-pass success rate was 44.4% compared to 87.5% with adherence to first-line SAD use. All prehospital SADs were exchanged in the ED in a delayed fashion and almost exclusively per physician preference alone. In no case was the SAD exchanged for suspected dislodgement evidenced by lack of capnography.
Conclusion:
First-line use of a SAD was associated with a high first-pass attempt success rate in a real-life cohort of prehospital advanced airway encounters. No SAD required emergent exchange upon hospital arrival.
OBJECTIVES/GOALS: We aim to determine whether non-neuronal, non-synaptic glutamate signaling mechanisms can be targeted to produce highly specific, narrow changes in brain function that would benefit CNS disorders. To do this, we investigated cognitive changes produced through manipulating the activity of the astrocytic glutamate release mechanism system xc-. METHODS/STUDY POPULATION: System xc- (Sxc) activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc rats). To confirm a lack of Sxc activity, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on executive function, such as cognitive flexibility, impulse control, decision-making, and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on executive function were impaired. MSxc rats displayed deficits in cocaine reinstatement and attentional set-shifting. We anticipate MSxc rats to also show impairments in decision-making in the rat gambling task and response inhibition in the stop-signal reaction time task. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on executive function without impacting development or simple brain function. These results highlight the potential of targeting Sxc to enhance cognition without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.
Given the relatively small industry scale of cow-calf operations in New York to other regions of the country, little is known about differences in determinant values for feeder cattle. Using auction prices and quality characteristics over 7 years, differences in market, lot, and quality parameters suggest opportunities for improved marketing performance. A delta profit model is constructed to inform timing of marketing decisions for producers. The results indicate a relatively high potential for producers to increase farm returns by delaying sales of lighter-weight feeder cattle from the fall to spring auction months, given sufficient rates of gain and reasonable overwintering costs.
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Methods
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
Results
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
Conclusions
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
This chapter concerns itself with the fulfillment, or carrying out, of the work of art according to Gadamer. The chapter takes a cue from Gadamer and uses lyric poetry as the paradigm for such fulfillment. The experience of art is a hermeneutic experience that is a linguistic phenomenon with a speculative dimension. Poetic language is representative of language use in general, as it achieves a certain ideality. This chapter argues for the positive ontological stake of poetry. The essay considers the poetry of Rilke and Mallarme in relation to Hegel’s speculative thought and relates this to Gadamer’s hermeneutics. The concepts of contemporaneity and aesthetic nondifferentiation are explicated.