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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.
Partial remission after major depressive disorder (MDD) is common and a robust predictor of relapse. However, it remains unclear to which extent preventive psychological interventions reduce depressive symptomatology and relapse risk after partial remission. We aimed to identify variables predicting relapse and to determine whether, and for whom, psychological interventions are effective in preventing relapse, reducing (residual) depressive symptoms, and increasing quality of life among individuals in partial remission. This preregistered (CRD42023463468) systematic review and individual participant data meta-analysis (IPD-MA) pooled data from 16 randomized controlled trials (n = 705 partial remitters) comparing psychological interventions to control conditions, using 1- and 2-stage IPD-MA. Among partial remitters, baseline clinician-rated depressive symptoms (p = .005) and prior episodes (p = .012) predicted relapse. Psychological interventions were associated with reduced relapse risk over 12 months (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43–0.84), and significantly lowered posttreatment depressive symptoms (Hedges’ g = 0.29, 95% CI 0.04–0.54), with sustained effects at 60 weeks (Hedges’ g = 0.33, 95% CI 0.06–0.59), compared to nonpsychological interventions. However, interventions did not significantly improve quality of life at 60 weeks (Hedges’ g = 0.26, 95% CI -0.06 to 0.58). No moderators of relapse prevention efficacy were found. Men, older individuals, and those with higher baseline symptom severity experienced greater reductions in symptomatology at 60 weeks. Psychological interventions for individuals with partially remitted depression reduce relapse risk and residual symptomatology, with efficacy generalizing across patient characteristics and treatment types. This suggests that psychological interventions are a recommended treatment option for this patient population.
The aardvark (Oryecteropus afer) is a fossorial species with a widespread distribution across sub-Saharan Africa. It leaves distinctive tracks and traces of its presence, including large burrows. However, despite a substantial body fossil record, few trace fossils registered by aardvarks have been described. Its distribution range in southern Africa during historic and prehistoric times was probably broadly similar to that of today, with the addition of the currently submerged Palaeo-Agulhas Plain during much of the Pleistocene. Five new trace fossil sites have been identified in Pleistocene aeolianites on the Cape coast and are here interpreted with varying degrees of confidence as large burrows that were made by aardvarks. In addition, a possible aardvark tracksite has been identified. Together these add to the sparse paleoichnological evidence of aardvarks and add to the global ichnological record of large vertebrate burrows. While at this point the evidence does not warrant the proposal of new ichnotaxa, the findings may act to spur further identification of fossilized traces of aardvarks and other fossorial species on the Cape coast and beyond.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
OBJECTIVES/GOALS: The COVID-19 pandemic disrupted established social support networks (faith-based, community, family, friends), resulting in unprecedented health-related, financial, and employment challenges among African Americans (AAs). This study explores the psychosocial influences of the pandemic on the health and wellness of AAs. METHODS/STUDY POPULATION: The FAITH! (Fostering African-American Improvement in Total Health!) Program, an academic-community partnership with AA churches, shifted focus to COVID-19 prevention in AA communities. Funded by the Mayo Clinic Center for Clinical and Translation Sciences, this cross-sectional study recruited AA adults from FAITH!-affiliated churches and social media to complete a survey exploring the personal impact of the pandemic from hardships (e.g., food and housing insecurity, paying utilities) on healthy lifestyle (HL). The primary outcome was difficulty maintaining a HL during the pandemic. Logistic regression (odds ratios and associated 95% confidence intervals (CIs)) was used to examine the associations between difficulty maintaining a HL and factors including COVID-19 hardships and mental health. RESULTS/ANTICIPATED RESULTS: Participants (N=169, 71.4% female, 41.4% essential workers) had a mean age [SD] of 49.4 [14.9] years. Over half (91/169, 54%) reported difficulty maintaining a HL. Those reporting unemployment (OR 2.3; 95% CI [1.2,4.4]; p=0.008), difficulty paying rent (OR 4.1; 95% CI [2.1,8.6]; p<0.001), or food/utilities (OR 5.5; 95% CI [2.7,11.5]; p<0.001) all had greater odds of difficulty maintaining a HL. High stress (≥5/10, scale 1-10) was associated with difficulty maintaining a HL (OR 4.1; 95% CI [2.1,8.5]; p<0.001) compared to AAs with low stress. Negative mental health (depression (OR 3.4; 95% CI [1.0,13.7]; p<0.001), anger (OR 2.5; 95% CI [0.5,18.9]; p=0.005), and nervousness (OR 4.1; 95% CI [1.1,19.5]; p=0.003) was associated with difficulty maintaining a HL compared to AAs with positive mental health. DISCUSSION/SIGNIFICANCE: Our study findings revealed that COVID-19 hardships, stress, and negative mental health impacted the ability of AAs to maintain a HL. These issues should be considered in the design and implementation of community-based health programs to promote healthy living during future public health emergencies.
Several studies have shown the additional benefit of point-of-care ultrasound (POCUS) by prehospital Emergency Medical Services (EMS). Since organization of EMS may vary significantly across countries, the value of POCUS likely depends on the prehospital system in which it is used. In order to be able to optimally implement POCUS and develop a tailored training curriculum, it is important to know how often POCUS is currently used, for which indications it is used, and how it affects decision making. The aims of this study were: (1) to determine the percentage of patients in whom POCUS was used by Dutch Helicopter Emergency Medical Services (HEMS) crews; (2) to determine how often POCUS findings led to changes in on-scene management; and (3) what these changes were.
Methods:
Patients who received prehospital care from December 1, 2020 through March 31, 2021 by a single HEMS crew were included in this prospective cohort study. Clinical data and specific data on POCUS examination, findings, and therapeutic consequences were collected and analyzed.
Results:
During the study period, on-scene HEMS care was provided to 612 patients, of which 211 (34.5%) patients underwent POCUS. Of these, 209 (34.2%) patients with a median age of 45 years were included. There were 131 (62.7%) trauma patients, and 70 (33.7%) of the included patients underwent cardiopulmonary resuscitation (CPR). The median reported time of POCUS examination was three (P25-P75 2-5) minutes. Median prolongation of on-scene time was zero (P25-P75 0-1) minutes. In 85 (40.7%) patients, POCUS examination had therapeutic consequence: POCUS was found to impact treatment decisions in 34 (26.0%) trauma patients and 51 (65.4%) non-trauma patients. In patients with cardiac arrest, POCUS was most often used to aid decision making with regard to terminating or continuing resuscitation (28 patients; 13.4%).
Conclusion:
During the study period, POCUS examination was used in 34.5% of all prehospital HEMS patients and had a therapeutic consequence in 40.7% of patients. In trauma patients, POCUS seems to be most effective for patient triage and evaluation of treatment effectiveness. Moreover, POCUS can be of significant value in patients undergoing CPR. A tailored HEMS POCUS training curriculum should include ultrasound techniques for trauma and cardiac arrest.
OBJECTIVES/GOALS: Recent in vitro evidence suggests that diverse parasite protein families called RIFINs and STEVORs are displayed on the surface of infected red blood cells and may have a role in severe malaria, but they remain sparsely studied in natural infections. We measured the RNA expression of these antigens in Malian children with severe or mild malaria illness. METHODS/STUDY POPULATION: We collected blood samples from Malian children aged six months to five years, including 14 with cerebral malaria, 10 with severe malarial anemia, and demographic-matched controls with mild, uncomplicated malaria. We extracted total RNA from each patient and used a custom capture array to selectively enrich Plasmodium falciparum parasite RNA. We then performed Illumina next-generation RNA sequencing and reconstructed parasite transcriptomes using reference-free de novo assembly. We identified RNA encoding RIFINs and STEVORs using an in-house classifier, then measured the diversity and abundance of gene expression for each infection. Expression diversity was defined as the number of unique variants transcribed. Expression abundance was calculated as transcripts per million (TPM). RESULTS/ANTICIPATED RESULTS: Cerebral malaria cases, but not severe malarial anemia cases, had higher diversity and abundance of RIFIN expression compared to mild infections. Type A RIFINs predominated over Type B RIFINs, and the same two RIFINs were predominantly expressed in all disease phenotypes. We anticipate that predominantly expressed RIFINs share high sequence homology with variants previously shown to bind blood antigens or immune inhibitory receptors. STEVOR expression was also higher in cerebral malaria compared to mild malaria, but STEVOR transcripts were sparse overall. DISCUSSION/SIGNIFICANCE: Elevated RIFIN expression in cerebral malaria over mild malaria supports a role for these antigens in pathogenesis. Severe malarial anemia may progress through a different pathogenic mechanism. Predominantly expressed RIFIN variants may be promising targets for vaccines and therapeutics to protect children against cerebral malaria.
The giant Cape zebra (Equus capensis) is one of the extinct Quaternary large mammal species of southern Africa, and the largest equid from the Quaternary of Africa. Twenty-six Pleistocene equid tracksites have been identified in aeolianites on the Cape south coast of South Africa. An age range of 161 ± 12 ka to 43 ± 4 ka has been established through Optically Stimulated Luminescence. More than half of the sites contain large-equid tracks, representing the first ichnosites attributed to E. capensis. Smaller equid tracks may have been registered by the quagga (E. quagga quagga). The abundance of E. capensis tracksites on the Cape south coast contrasts with the paucity of body fossils of the species from the region, contrasting with the impression obtained from the body fossil record that E. capensis was predominantly a west coast species in the region. The new data illustrate the capacity of the body fossil and trace fossil records to complement each other. The loss of suitable habitat provided by the Palaeo-Agulhas Plain was probably a contributing factor in the extinction of this large-bodied grazer. A long trackway at Driefontein, attributed to E. capensis, adds to a sparse global record of fossil horse trackways.
Although tortoises (Testudinidae) are a familiar clade of reptiles, with a body fossil record extending to at least the Eocene, hitherto no tortoise ichnosites have been described. Here, a number of sites attributed to tortoise trackmakers are identified within Pleistocene aeolianites on South Africa's Cape south coast. These date from late Marine Isotope Stage 6 to Marine Isotope Stage 4. The findings indicate large trackmakers, with evidence of a trackmaker length of more than a meter—substantially longer than the largest extant tortoises in southern Africa. This suggests either the presence of an extinct very large tortoise species, or that Pleistocene leopard tortoises in the region were larger than their descendants. Variations in substrate properties are responsible for a variety of track and trace forms. A mismatch exists between the reported ichnological evidence for large tortoises, and the regional archaeological and body fossil records, which almost exclusively comprise smaller tortoises. The findings illustrate the potential of ichnology to complement and augment the paleontological and archaeological records.
In September 2021, a cluster of 6 patients with nosocomial coronavirus disease 2019 (COVID-19) were identified in a transplant unit. A visitor and 11 healthcare workers also tested positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). Genomic sequencing identified 3 separate introductions of SARS-CoV-2 with related transmission among the identified patients and healthcare workers.
The history of maize in Central America and surrounding areas has implications for the slow transition from hunting and gathering to agriculture. The spread of early forms of domesticated maize from southern Mexico across Mesoamerica and into South America has been dated to about 8,700–6,500 years ago on the basis of a handful of studies relying primarily on the analysis of pollen, phytoliths, or starch grains. Recent genomic data from southern Belize have been used to identify Archaic period south-to-north population movements from lower Central America, suggesting this migration pattern as a mechanism that introduced genetically improved maize races from South America. Gradually, maize productivity increased to the point that it was suitable for use as a staple crop. Here we present a summary of paleoecological data that support the late and uneven entry of maize into the Maya area relative to other regions of Central America and identify the Pacific coastal margin as the probable route by which maize spread southward into Panama and South America. We consider some implications of the early appearance of maize for Late Archaic populations in these areas; for example, with respect to the establishment of sedentary village life.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
A trackway and burrows of a small rodent-sized bounding mammal (attributed to the Cape gerbil, Gerbilliscus afra) and a traceway of a large arachnid (spider) from the Pleistocene Waenhuiskrans Formation represent two biological groups not previously reported from this track-rich dune facies, which is widely distributed along the Cape south coast of South Africa. This may be due to biases against the preservation of small tracks. Trackways of hopping or bounding rodent-sized mammals are rare in the fossil record, occurring at only two known Mesozoic sites and three Cenozoic sites. Where these occur in dune facies, they are commonly associated with arachnid and other arthropod surface trails. The arachnid trace fossils commonly include the spider traceway Octopodichnus, known from the Permian to Recent, which is also the temporal range of the eponymous Octopodichnus ichnofacies. The abundance of small-mammal tracks associated with dune ichnofaunas led to the naming of the late Palaeozoic and Mesozoic Chelichnus ichnofacies, which is largely co-extensive with the Octopodichnus ichnofacies at this time. However, the recognition of similar mammal–arthropod dune facies assemblages in the Cenozoic requires adjusting our understanding of their distribution in space and time, and extends the known distribution of dune ichnofacies.
Limited data exist on training of European paediatric and adult congenital cardiologists.
Methods:
A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries.
Results:
Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87–9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63–10.72 million), and one training centre per 4.29 million population (range 1.63–10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1–17), and duration of training was 3 years (range 2–5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41).
Conclusion:
Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Aeolianites and cemented foreshore deposits on South Africa's Cape south coast have the capacity to record and preserve events that transpired on them when they were composed of unconsolidated sand. Thirty-five Pleistocene elephant tracksites have been identified along this coastline. This abundance of sites along what was the margin of the vast Palaeo-Agulhas Plain allows for an appreciation of the forms that elephant tracks and traces can take in the context of the global proboscidean track record. They point to a significant regional elephant presence from Marine Isotope Stage (MIS) 11 (~400 ka) through MIS 5 (~130–80 ka) to MIS 3 (~35 ka) and also indicate repeated use of certain dune areas. They buttress Holocene and historical evidence that elephants made use of open areas in the region, and that the remaining “Knysna elephants” retreated into dense afrotemperate forest for protection in recent centuries. Analogies can be drawn between Pleistocene elephant tracks and Mesozoic dinosaur tracks, and some of the Cape south coast elephant tracks are among the largest Cenozoic (and hence, Quaternary) tracks ever to be described. A newly identified tracksite in this area may provide the first reported evidence of elephant trunk-drag impressions.
Adelges tsugae Annand (Hemiptera: Adelgidae), a nonindigenous insect pest of hemlock (Tsuga spp.) (Pinaceae) in eastern North America, spends most of its life cycle within an ovisac, which resembles a woolly white mass on twigs. We evaluated the probability of detecting adelgid wool with Velcro®-covered balls when taking an increasing number of samples per tree (field sampling) and number of trees per simulated stand. We examined the relationship between the detection of adelgid wool using this technique and the incidence of A. tsugae-infested twigs by sampling lower-crown branch tips of the same trees. We found that the probability of detecting wool with ball sampling increased with number of ball samples per tree, with number of trees per simulated stand, and with increasing incidence of ovisacs in the lower crown. When sampling an individual tree, we found that 20 ball samples per tree achieved a targeted precision level of 0.75, but when sampling a stand, we found that 10 ball samples per tree took the least time for the range of simulated A. tsugae infestations we tested. These sample sizes are recommended for detection of A. tsugae infestations on an individual tree and in a hemlock stand.