Prenatal exposure to maternal stress can have lifelong implications for psychological function, such as behavioral problems and even the development of mental illness. Previous research suggests that ...this is due to transgenerational epigenetic programming of genes operating in the hypothalamic-pituitary-adrenal axis, such as the glucocorticoid receptor (GR). However, it is not known whether intrauterine exposure to maternal stress affects the epigenetic state of these genes beyond infancy. Here, we analyze the methylation status of the GR gene in mothers and their children, at 10-19 years after birth. We combine these data with a retrospective evaluation of maternal exposure to intimate partner violence (IPV). Methylation of the mother's GR gene was not affected by IPV. For the first time, we show that methylation status of the GR gene of adolescent children is influenced by their mother's experience of IPV during pregnancy. As these sustained epigenetic modifications are established in utero, we consider this to be a plausible mechanism by which prenatal stress may program adult psychosocial function.
Recent empirical evaluations of replication in psychology have reported startlingly few successful replication attempts. At the same time, these programs have noted that the proper way to analyze ...replication studies is far from a settled matter and have analyzed their data in several different ways. This presents 2 challenges to interpreting the results of these programs. First, different analysis methods assess different operational definitions of replication. Second, the properties of these methods are not necessarily common knowledge; it is possible for a successful replication to be deemed a failure by nearly all of the metrics used, and it is not always immediately clear how likely such errors are to occur. In this article, we describe the methods commonly used in replication research and how they imply specific operational definitions of replication. We then compute the probability of false failure (i.e., a successful replication is concluded to have failed) and false success determinations. These are shown to be high (often over 50%) and in many cases uncontrolled. We then demonstrate that errors are probable in the data to which these methods have been applied in the literature. We show that the probability that some reported conclusions about replication are incorrect can be as high as 75-80%.
Translational Abstract
This article examines analysis methods for studying replications, and it finds that some of the commonly used methods have severe limitations. These limitations include the fact that a "replication failure" could arise by chance alone with a surprisingly high probability, even if the studies successfully replicate.
The goal of this work is to compare the outcome of a design for additive manufacturing (DfAM) heuristics lesson conducted in a virtual learning environment to the same in an in-person learning ...environment. Prior work revealed that receiving DfAM heuristics at different points in the design process impacts the quality and novelty of designs produced afterward, but this work may have been limited by the solely virtual format. In this work, an identical experiment was performed in a face-to-face learning environment. Results indicate that neither learning format presents an advantage over the other when it comes to the quality of designs produced during the intervention. Participants across all experimental groups reported an increase in self-efficacy after the intervention, with improved performance on quiz-type questions. However, the novelty and variety of the designs produced by the in-person experimental groups were significantly lower than that of the virtual experimental groups. In addition to validating the effectiveness of virtual instruction as a teaching method, these results also support the authors’ hypothesis that the priming effect is stronger in an in-person classroom than in a virtual classroom.
Esophagogastric junction (EGJ) outflow obstruction (EGJOO) per Chicago Classification v4.0 (CCv4.0) represents a high-resolution manometry (HRM) diagnosis with uncertain clinical significance. This ...study aimed to evaluate functional lumen imaging probe (FLIP) panometry among patients with EGJOO on HRM/CCv4.0 to assess clinical/manometric associations and treatment outcomes.
An observational cohort study was performed on patients who completed FLIP during endoscopy and had an HRM/CCv4.0 diagnosis of EGJOO, i.e., HRM-EGJOO (inconclusive). Abnormal FLIP panometry motility classifications were applied to identify FLIP-confirmed conclusive EGJOO. Rapid drink challenge on HRM and timed barium esophagram were also assessed. Clinical management plan was determined by treating physicians and assessed through chart review. Clinical outcome was defined using the Eckardt score (ES) during follow-up evaluation: ES < 3 was considered a good outcome.
Of 139 adult patients with manometric EGJOO (inconclusive per CCv4.0), a treatment outcome ES was obtained in 55 after achalasia-type treatment (i.e., pneumatic dilation, peroral endoscopic myotomy, laparoscopic Heller myotomy, or botulinum toxin injection) and 36 patients after other nonachalasia-type treatment. Among patients with conclusive EGJOO by HRM-FLIP complementary impression, 77% (33/43) had a good outcome after achalasia-type treatment, whereas 0% (0/12) of patients had a good outcome after nonachalasia-type treatment. Of patients with normal EGJ opening on FLIP, one-third of patients treated with achalasia-type treatment had a good outcome, while 9 of the 10 treated conservatively had a good outcome.
FLIP panometry provides a useful complement to clarify the clinical significance of an HRM/CCv4.0 EGJOO diagnosis and help direct management decisions.
To assess the odds of pregnancy after intrauterine insemination (IUI) timed by ultrasound monitoring and human chorionic gonadotropin (hCG) administration compared with monitoring luteinizing hormone ...(LH) levels.
We searched PubMed (MEDLINE), EMBASE (Elsevier), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov (National Institutes of Health), and the Cochrane Library (Wiley) from the inception until October 1, 2022. No language limitations were applied.
After deduplication, 3,607 unique citations were subjected to blinded independent review by three investigators. Thirteen studies (five retrospective cohort, four cross-sectional, two randomized controlled trials, and two randomized crossover studies) that enrolled women undergoing natural cycle, oral medication (clomid or letrozole), or both for IUI were included in the final random-effects model meta-analysis. Methodologic quality of included studies was assessed with the Downs and Black checklist.
Data extraction was compiled by two authors, including publication information, hCG and LH monitoring guidelines, and pregnancy outcomes. No significant difference in odds of pregnancy between hCG administration and endogenous LH monitoring was observed (odds ratio OR 0.92, 95% CI 0.69-1.22, P =.53). Subgroup analysis of the five studies that included natural cycle IUI outcomes also showed no significant difference in odds of pregnancy between the two methods (OR 0.88, 95% CI 0.46-1.69, P =.61). Finally, a subgroup analysis of 10 studies that included women who underwent ovarian stimulation with oral medications (clomid or letrozole) did not demonstrate a difference in odds of pregnancy between ultrasonography with hCG trigger and LH-timed IUI (OR 0.88, 95% CI 0.66-1.16, P =.32). Statistically significant heterogeneity was noted between studies.
This meta-analysis showed no difference between pregnancy outcomes between at-home LH monitoring and timed IUI.
PROSPERO, CRD42021230520.
Tetrabromobisphenol A (TBBPA) is widely used as a flame retardant and is suspected to be stable in the environment with possible widespread human exposures. This study reports the characterization of ...the toxicokinetics of TBBPA in human subjects and in rats. A single oral dose of 0.1 mg/kg TBBPA was administered to five human subjects. Rats were administered a single oral dose of 300 mg TBBPA/kg body weight. Urine and blood concentrations of TBBPA and its metabolites were determined by LC/MS-MS. TBBPA-glucuronide and TBBPA-sulfate were identified as metabolites of TBBPA in blood and urine of the human subjects and rats. In blood, TBBPA-glucuronide was detected in all human subjects, whereas TBBPA-sulfate was only present in blood from two individuals. Maximum plasma concentrations of TBBPA-glucuronide (16 nmol/l) were obtained within 4 h after administration. In two individuals where TBBPA-sulfate was present in blood, maximum concentrations were obtained at the 4-h sampling point; the concentrations rapidly declined to reach the limit of detection (LOD) after 8 h. Parent TBBPA was not present in detectable concentrations in any of the human plasma samples. TBBPA-glucuronide was slowly eliminated in urine to reach the LOD 124 h after administration. In rats, TBBPA-glucuronide and TBBPA-sulfate were also the major metabolites of TBBPA present in blood; in addition, a diglucuronide of TBBPA, a mixed glucuronide-sulfate conjugate of TBBPA, tribromobisphenol A, and the glucuronide of tribromobisphenol A were also present in low concentrations. TBBPA plasma concentrations peaked at 103 μmol/l 3 h after administration and thereafter declined with a half-life of 13 h; maximal concentrations of TBBPA-glucuronide (25 μmol/l) were also observed 3 h after administration. Peak plasma concentrations of TBBPA-sulfate (694 μmol/l) were reached within 6 h after administration. The obtained results suggest absorption of TBBPA from the gastrointestinal tract and rapid metabolism of the absorbed TBBPA by conjugation resulting in a low systemic bioavailability of TBBPA.
An association of eosinophilic esophagitis (EoE) with esophageal dysmotility has been described, however, the related mechanism remains unclear. We aimed to evaluate clinical and physiologic ...characteristics, including esophageal distensibility, associated with secondary peristalsis in patients with EoE.
A total of 199 consecutive adult patients with EoE (age, 18-78 y; 32% female) who completed a 16-cm functional luminal imaging probe (FLIP) during endoscopy were evaluated in a cross-sectional study. FLIP panometry contractile response (CR) patterns were classified as normal CR or borderline CR if antegrade contractions were present, and abnormal CRs included impaired/disordered CR, absent CR, or spastic-reactive CR. The distensibility plateau of the esophageal body and esophagogastric junction distensibility was measured with FLIP.
FLIP CR patterns included 68 (34%) normal CR, 65 (33%) borderline CR, 44 (22%) impaired/disordered CR, 16 (8%) absent CR, and 6 (3%) spastic-reactive CR. Compared with normal CRs, abnormal CRs more frequently had reduced esophageal distensibility (distensibility plateau <17 mm in 56% vs 32%), greater total EoE reference scores (median, 5; interquartile range IQR, 3-6 vs median, 4; IQR, 3-5) with more severe ring scores, and a greater duration of symptoms (median, 10 y; IQR, 4-23 y vs median, 7 y; IQR, 3-15 y). Mucosal eosinophil density, however, was similar between abnormal CRs and normal CRs (median, 34 eosinophils/high-power field hpf; IQR, 14-60 eosinophils/hpf vs median, 25 eosinophils/hpf; IQR, 5-50 eosinophils/hpf).
Although normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.
Stress, particularly when experienced early in life, can have profound implications for mental health. Previous research covering various tissues such as the brain, suggests that the detrimental ...impact of early-life stress (ELS) on mental health is mediated via epigenetic modifications including DNA methylation. Genes of the hypothalamic-pituitary-adrenal axis--in particular, the glucocorticoid receptor (hGR) gene--stand out as key targets for ELS. Even though the link between hGR methylation and either ELS or psychopathology is fairly well established, the mutually dependent relationships between ELS, DNA methylation and psychopathology remain to be uncovered. The specific psychopathology an individual might develop in the aftermath of stressful events can be highly variable, however, most studies investigating hGR methylation and psychopathology suffer from being limited to a single symptom cluster of mental disorders. Here, we screened volunteers for childhood maltreatment and analyzed whether it associates with hGR methylation in lymphocytes and a range of measures of psychological ill-health. hGR methylation in lymphocytes most likely reflects methylation patterns found in the brain and thus provides valuable insights into the etiology of psychopathology. We find the interaction between childhood maltreatment and hGR methylation to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions. Furthermore, our results indicate an additive effect of childhood maltreatment and hGR methylation in predicting borderline personality disorder (BPD)-associated symptoms, suggesting that the combination of both ELS and DNA methylation that possibly represents unfavorable events experienced even earlier in life poses the risk for BPD.
PDF
