Temporal changes in ewe vaginal microbiota throughout gestation.

Introduction: Numerous factors are known to influence reproductive efficiency in ewes, but few studies have investigated the potential role of vaginal microbiota in sheep reproductive success. The objective of this study was to thoroughly characterize the ewe vaginal microbiota throughout the course of pregnancy. Methods: Vaginal samples were collected from 31 pregnant Hampshire and Hampshire X Suffolk crossbred ewes on a weekly basis from pre-breeding to pregnancy testing and then biweekly until just after lambing. To characterize the vaginal microbial communities, DNA was extracted and 16S rRNA gene Illumina MiSeq amplicon sequencing was performed. Results and Discussion: Alpha diversity metrics indicated an increase in species richness, evenness, and overall diversity throughout gestation. Distinct shifts in the bacterial communities were observed during gestation and were segregated into three periods: early gestation, a transitional period and mid/late gestation. During early gestation, Actinobacillus, Histophilus, and unclassified Leptotrichiaceae were found in greater relative abundance. During the transitional period, a population shift occurred characterized by increasing relative abundance of Streptococcus and Staphylococcus. During mid/late gestation, Staphylococcus, Streptococcus, and Ureaplasma had the greatest relative abundance. These shifts in the microbial population throughout the ewe's gestation are likely related to hormonal changes triggered by the growing conceptus, specifically increasing blood concentration of progesterone. The transitional period shift in vaginal microbial communities potentially aligns with the placental take-over of progesterone production from the corpus luteum at approximately day 50 after conception (gestational week 7). Understanding the observed variability of the vaginal microbiota throughout pregnancy will allow for future comparison of ewes that did not become pregnant or had abnormal pregnancies, which could lead to the discovery of potential bacterial biomarkers for pregnancy outcome; this understanding could also lead to development of probiotics to improve sheep reproductive success.

Medical Misadventures as Errors and Mistakes and Motor Vehicular Accidents in the Disproportionate Burden of Childhood Mortality among Blacks/African Americans in the United States: CDC Dataset, 1968-2015.

PURPOSE: Racial disparities in infant mortality in the United States persist after adjustment for known confounders of race and mortality association, as well as heterogeneity assessment. Epidemiologic and clinical data continue to show the survival disadvantages of Black/AA children: when Black/AAs are compared to whites, they are three times as likely to die from all-cause mortality. The persistent inability to remove the variance in race-mortality association is partly due to unobserved, unmeasured, and residual confounding, as well as implicit biases in public health and clinical medicine in health equity transformation. This current epidemiologic-perspective explanatory model study aimed to examine the possible explanation of racial differences in U.S. infant mortality using medical misadventures as errors and mistakes, and infants' involvement in motor vehicular traffic accidents. MATERIALS AND METHOD: Using CDC WONDER ecologic data from 1968 to 2015, we assessed the infant mortality-rate ratio and percent change associated with medical misadventures as well as motor vehicular accidents or trauma. The rate ratio and percent change were estimated using stratification analysis and trend homogeneity, respectively. RESULTS: There was a Black-white racial difference in medical misadventures during the study period. Relative to the years 1968-1978 (rate ratio [RR], 1.43), there was a steady increase in the mortality-rate ratio in 1979-1998 (52%, RR = 1.52), and mortality was more than two times as likely in 1999-2015 (RR = 2.37). However, with respect to motor vehicular accident/trauma mortality, the mortality ratio, although lower among Blacks in 1968-1978 (RR, 0.92), increased in 1979-1998 by 27% (RR = 1.27) but decreased in 1999-2015 (RR, 1.17), though there was still an excess of 17% mortality among Black/AAs. The percent change for medical misadventures indicated an increasing trend from 9.3% in 1998 to 52% in 2015. However, motor vehicular-related mortality indicated a positive trend in 1998 (38.5%) but a negative trend in 2015 (-8.4%). CONCLUSIONS: There were substantial race differentials or variances in infant mortality associated with medical misadventures compared to traffic accidents, and Black/AA children relative to whites experienced a survival disadvantage. These comparative findings are suggestive of medical misadventures and motor vehicular trauma as potential explanations for some of the persistent Black-white disparities in overall infant mortality in the U.S. From these findings, we recommend a national effort to address these issues, thus narrowing the observed disparities in the U.S. infant mortality burden among Black/AAs.

Flow and outdoor adventure recreation: Using flow measures to re-examine motives for participation.

Adventure participants have traditionally been viewed as having thrill or risk-seeking motives, and this perception remains despite empirical research suggesting that other motives may drive participation. This study was conducted to extend understanding of participation motives of adventure recreation participants in relation to Csiksentmihalyi's nine-dimension model of flow and other proposed motivational constructs. Participants (n = 199) who had typically engaged in their adventure recreation activity (i.e., highlining, rock climbing, downhill mountain biking, freefalling, snow sports) regularly, and with considerable competence, took part in this investigation by completing self-report measures of dispositional flow (The Dispositional Flow Scale; DFS-2), state flow (The Short Flow State Scale; SFSS), and participation motives in their adventure recreation environments. Support was observed in confirmatory factor analytic procedures for the factorial validity of DFS-2 and SFSS data obtained from adventure recreation participants. Mean scores from measures on participant experience of flow in adventure recreation were generally found to be significantly higher than previously observed in other physical activity domains, with some differences also being observed among adventure recreation subgroups. Contrary to traditional explanations of adventure recreation participation, risk-seeking was not supported as a key underlying motive by participants in this study. Mastery of one's adventure recreation activity, perceived connection to one's activity, and trust in one's skills, were identified as important participation motives. This study demonstrated that the DFS-2 and SFSS were able to satisfactorily assess flow constructs in adventure recreation, and supported recent research demonstrating flow to be a relevant experience to this setting. The implications of these findings for theory, practice, and future research directions in adventure recreation are discussed.

The Variation of Withdrawal of Life Sustaining Therapy in Older Adults With Traumatic Brain Injury.

INTRODUCTION: The decision to withdraw life sustaining treatment (WDLST) in older adults with traumatic brain injury is subject to wide variability leading to nonbeneficial interventions and unnecessary use of hospital resources. We hypothesized that patient and hospital factors are associated with WDLST and WDLST timing. METHODS: All traumatic brain injury patients ≥65 with Glasgow coma scores (GCS) of 4-11 from 2018 to 2019 at level I and II centers were selected from the National Trauma Data Bank. Patients with head abbreviated injury scores 5-6 or death within 24 h were excluded. Bayesian additive regression tree analysis was performed to identify the cumulative incidence function (CIF) and the relative risks (RR) over time for withdrawal of care, discharge to hospice (DH), and death. Death alone (no WDLST or DH) served as the comparator group for all analyses. A subanalysis of the composite outcome WDLST/DH (defined as end-of-life-care), with death (no WDLST or DH) as a comparator cohort was performed. RESULTS: We included 2126 patients, of whom 1957 (57%) underwent WDLST, 402 (19%) died, and 469 (22%) were DH. 60% of patients were male, and the mean age was 80 y. The majority of patients were injured by fall (76%, n = 1644). Patients who were DH were more often female (51% DH versus 39% WDLST), had a past medical history of dementia (45% DH versus 18% WDLST), and had lower admission injury severity score (14 DH versus 18.6 WDLST) (P < 0.001). Compared to those who DH, those who underwent WDLST had a lower GCS (9.8 versus 8.4, P < 0.001). CIF of WDSLT and DH increased with age, stabilizing by day 3. At day 3, patients ≥90 y had an increased RR of DH compared to WDLST (RR 2.5 versus 1.4). As GCS increased, CIF and RR of WDLST decreased, while CIF and RR of DH increased (RR on day 3 for GCS 12: WDLST 0.42 versus DH 1.31).Patients at nonprofit institutions were more likely to undergo WDLST (RR 1.15) compared to DH (0.68). Compared to patients of White race, patients of Black race had a lower RR of WDLST at all timepoints. CONCLUSIONS: Patient and hospital factors influence the practice of end-of-life-care (WDLST, DH, and death), highlighting the need to better understand variability to target palliative care interventions and standardize care across populations and trauma centers.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection.

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs through BA.4/BA.5 in both pseudovirus-based and authentic virus assays. Three mAbs also retain potency to recently circulating VOCs XBB.1.5 and BQ.1.1 and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor-binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are unique in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.

Orthopaedic surgical documentation: pre-templated operation notes significantly improve documentation of surgical procedures.

OBJECTIVES: The Royal College of Surgeons of England (RCS) Good Surgical Practice guidance identifies essential criteria for surgical operation note documentation. The current quality improvement project aims to identify if using pre-templated operation notes for documenting fractured neck of femur surgery results in improved documentation when compared to freehand orthopaedic operation notes. METHODS: A total of fourteen categories were identified from the RCS guidance as required across all the operations identified in this study. All operations for the month of October 2021 were identified and the operation notes analysed. Pre-templated operation notes were compared to freehand operation notes. RESULTS: Ninety-seven cases were identified, of which 74 were freehand operation notes and 23 were pre-templated fractured neck of femur operation notes. All fourteen categories were completed in 13 (57%) of the templated operation notes versus 0 (0%) in the freehand operation notes (odds ratio 0.0052, 95% CI 0.0003 to 0.0945, p < 0.001). The median total number of completed categories was significantly higher in the templated op-note group compared to the freehand op-note group (templated median 14, range 12-14, vs. freehand median 11, range 9 to 13, p < 0.001). Logistic regression analysis of operation notes written by consultants or trainees identified trainees as more likely to document the antibiotic prophylaxis given (p = 0.025). CONCLUSIONS: Use of pre-templated operation notes results in significantly improved documentation. Adoption of generic pre-templated operation notes to improve surgical documentation should be considered across all operations.

Socioeconomic deprivation status predicts both the incidence and nature of Achilles tendon rupture.

PURPOSE: The aim of this study was to describe the epidemiology of Achilles tendon rupture (ATR) and its relationship with socioeconomic deprivation status (SEDS). The hypothesis was that ATR occurs more frequently in socioeconomically deprived patients. Secondary aims were to determine variations in circumstances of injury between more and less deprived patients. METHODS: A 6-year retrospective review of consecutive patients presenting with ATR was undertaken. The health-board population was defined using governmental population data and SEDS was defined using the Scottish Index of Multiple Deprivation. The primary outcome was an epidemiological description and comparison of incidence in more and less deprived cohorts. Secondary outcomes included reporting of the relationship between SEDS and patient and injury characteristics with univariate and binary logistic regression analyses. RESULTS: There were 783 patients (567 male; 216 female) with ATR. Mean incidence for adults (≥ 18 years) was 18.75/100,000 per year (range 16.56-23.57) and for all ages was 15.26/100,000 per year (range 13.51 to 19.07). Incidence in the least deprived population quintiles (4th and 5th quintiles; 18.07 per 100,000/year) was higher than that in the most deprived quintiles (1st and 2nd; 11.32/100,000 per year; OR 1.60, 95%CI 1.35-1.89; p < 0.001). When adjusting for confounding factors, least deprived patients were more likely to be > 50 years old (OR 1.97; 95%CI 1.24-3.12; p = 0.004), to sustain ATR playing sports (OR 1.72, 95%CI 1.11-2.67; p = 0.02) and in the spring (OR 1.65, 95%CI 1.01-2.70; p = 0.045) and to give a history of preceding tendinitis (OR 4.04, 95%CI 1.49-10.95; p = 0.006). They were less likely to sustain low-energy injuries (OR 0.44, 95%CI 0.23-0.87; p = 0.02) and to be obese (OR 0.25-0.41, 95%CI 0.07-0.90; p ≤ 0.03). CONCLUSIONS: The incidence of ATR was higher in less socioeconomically deprived populations and the hypothesis was therefore rejected. Significant variations in patient and predisposing factors, mechanisms of injury and seasonality were demonstrated between most and least deprived groups, suggesting that circumstances and nature of ATR may vary with SEDS and these are not a homogenous group of injuries. LEVEL OF EVIDENCE: Prognostic Study Level III.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection.

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs through BA.4/BA.5 in both pseudovirus-based and authentic virus assays. Three mAbs also retain potency to recently circulating VOCs XBB.1.5 and BQ.1.1 and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs, including recently circulating BA.4/BA.5, in both pseudovirus-based and live virus assays, and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.

Object play in the everyday home environment generates rich opportunities for infant learning.

Infants everywhere engage with objects throughout the day, even if the objects of play differ across cultures. Indeed, object play is a universal context for learning. Yet, the characteristics of object play at home remain largely unexamined, especially in infants from non-English-speaking backgrounds. Through frame-by-frame video coding, we documented Hispanic infants' object interactions based on 1-2 h of naturalistic home observations. Infants interacted with a wide variety of toys and household objects in brief bouts that summed to ~60% of their time. As infants transition among objects, they serendipitously generate opportunities for learning that support development across domains.

The epidemiology of Achilles tendon re-rupture and associated risk factors: male gender, younger age and traditional immobilising rehabilitation are risk factors.

PURPOSE: The aim of this study was to describe the epidemiology of Achilles tendon re-rupture. Secondary aims were to identify factors predisposing to increased Achilles tendon re-rupture risk, at the time of primary Achilles tendon rupture. METHODS: A retrospective review of all patients with primary Achilles tendon rupture and Achilles tendon re-rupture was undertaken. Two separate databases were compiled: the first included all Achilles tendon re-ruptures presenting during the study period and described epidemiology, mechanisms and nature of the re-rupture; the second was a case-control study analysing differences between patients with primary Achilles tendon rupture during the study period, who did, or did not, go on to develop re-rupture, with minimum review period of 1.5 years. RESULTS: Seven hundred and eighty-three patients (567 males, 216 females) attended with primary Achilles tendon rupture and 48 patients (41 males, 7 females) with Achilles tendon re-rupture. Median time to re-rupture was 98.5 days (IQR 82-122.5), but 8/48 re-ruptures occurred late (range 3 to 50 years) after primary Achilles tendon rupture. Males were affected more commonly (OR = 7.40, 95% CI 0.91-60.15; p = 0.034). Mean Achilles tendon re-rupture incidence was 0.94/100,000/year for all ages and 1.16/100,000/year for adults (≥ 18 years). Age distribution was bimodal for both primary Achilles tendon rupture and re-rupture, peaking in the fifth decade, with secondary peaks in older age. Incidence of re-rupture was higher in less socioeconomically deprived sub-populations (OR = 2.01, 95%CI 1.01-3.97, p = 0.04). The majority of re-ruptures were low-energy injuries. Greater risk of re-rupture was noted for patients with primary rupture aged < 45 years [adjusted odds ratio (aOR) 1.96; p = 0.037] and those treated with traditional cast immobilisation (aOR 2.20; p = 0.050). CONCLUSION: The epidemiology of Achilles tendon re-rupture is described and known trends (e.g. male predilection) are confirmed, while other novel findings are described, including incidence of a small but significant number of late re-ruptures, occurring years after the primary injury and an increased incidence of re-rupture in less socioeconomically deprived patients. Younger age and traditional immobilising cast treatment of primary Achilles tendon rupture were independently associated with Achilles tendon re-rupture. LEVEL OF EVIDENCE: III.

Association of antenatal steroids with surfactant administration in moderate preterm infants born to women with diabetes mellitus and/or hypertension.

BACKGROUND: Randomized trials of antenatal steroid administration (ANS) for extreme or moderate preterm pregnancies excluded women with diabetes mellitus (DM) and included few with preeclampsia. METHODS: Cohort study (n = 1,813) including moderate preterm births [290/7-336/7wks' gestational age GA)] before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with hypertensive disorders (HTN) and/or DM. We compared surfactant administration in Group-1 (neither HTN nor DM), Group-2a (HTN not DM), Group-2b (DM not HTN) and Group-2c (DM and HTN). RESULTS: Surfactant administration was less frequent after ANS in Group-1 [adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.31, 0.93, P = 0.03], Group-2a (aOR 0.36, CI 0.22, 0.58, P < 0.001) and Group-2c (aOR 0.29, CI 0.12, 0.71, P = 0.007) but not Group-2b (P = 0.64). CONCLUSIONS: ANS administration was independently associated with less surfactant administration in moderately preterm neonates whose mothers had neither HTN nor DM, and those with HTN, but not those with DM without HTN.

Infant study of hemispheric asymmetry after long-gap esophageal atresia repair.

OBJECTIVES: Previous studies have demonstrated that infants are typically born with a left-greater-than-right forebrain asymmetry that reverses throughout the first year of life. We hypothesized that critically ill term-born and premature patients following surgical and critical care for long-gap esophageal atresia (LGEA) would exhibit alteration in expected forebrain asymmetry. METHODS: Term-born (n = 13) and premature (n = 13) patients, and term-born controls (n = 23) <1 year corrected age underwent non-sedated research MRI following completion of LGEA treatment via Foker process. Structural T1- and T2-weighted images were collected, and ITK-SNAP was used for forebrain tissue segmentation and volume acquisition. Data were presented as absolute (cm3 ) and normalized (% total forebrain) volumes of the hemispheres. All measures were checked for normality, and group status was assessed using a general linear model with age at scan as a covariate. RESULTS: Absolute volumes of both forebrain hemispheres were smaller in term-born and premature patients in comparison to controls (p < 0.001). Normalized hemispheric volume group differences were detected by T1-weighted analysis, with premature patients demonstrating right-greater-than-left hemisphere volumes in comparison to term-born patients and controls (p < 0.01). While normalized group differences were very subtle (a right hemispheric predominance of roughly 2% of forebrain volume), they represent a deviation from the expected pattern of hemispheric brain asymmetry. INTERPRETATION: Our pilot quantitative MRI study of hemispheric volumes suggests that premature patients might be at risk of altered expected left-greater-than-right forebrain asymmetry following repair of LGEA. Future neurobehavioral studies in infants born with LGEA are needed to elucidate the functional significance of presented anatomical findings.

Association of antenatal steroids with neonatal mortality and morbidity in preterm infants born to mothers with diabetes mellitus and hypertension.

BACKGROUND: Randomized trials of antenatal steroids (ANS) included women at 24-33 weeks gestational age (GA); however, few women had preeclampsia and women with diabetes mellitus (DM) were excluded. METHODS: Cohort study including preterm births at 230/7-286/7 weeks GA before (Epoch-1) and after (Epoch-2) expansion of ANS administration to women with DM and hypertensive disorders (HTN). We compared Group-A (neither DM nor HTN) and Group-B (DM and/or HTN). RESULTS: Among 747 neonates the adjusted odds ratio (aOR) for surfactant administration, in-hospital mortality, severe intraventricular hemorrhage (IVH) and death or severe IVH were lower in ANS-exposed neonates than unexposed neonates. In Group-B, ANS administration was independently associated with less severe IVH and less death or severe IVH, but not less surfactant use or mortality. CONCLUSIONS: Increased ANS administration in women with DM and/or HTN was independently associated with less severe IVH and less death or severe IVH but without decrease in surfactant administration.

Traumatic Events Are Associated with Diverse Psychological Symptoms in Typically-Developing Children.

Childhood traumatic events are significant risk factors for psychopathology according to adult retrospective research; however, few studies examine trauma exposure and psychological symptoms in pre-adolescent children. Typically-developing children, aged 9-12 years (N = 114), were recruited from the community and selected from the Developmental Chronnecto-Genomics (Dev-CoG) study examining child development. Children completed questionnaires about traumatic life events, posttraumatic stress, anxiety, depression, dissociation, anger, and internalizing and externalizing behaviors. Parents also completed internalizing and externalizing measures. The number of traumatic events significantly correlated with symptom severity across all child-report psychological measures, but surprisingly, trauma was not correlated with any parent-report scores. Follow-up analyses revealed a significant trauma effect for internalizing and externalizing behaviors according to child self-report, but not for parent-report measures. Results indicate that childhood trauma may be a non-specific risk factor for sub-clinical psychopathology in otherwise typically-developing children. Moreover, children appear to be the most appropriate reporters of their own psychological distress.

Attention bias variability and posttraumatic stress symptoms: the mediating role of emotion regulation difficulties.

Growing literature has linked attention bias variability (ABV) to the experience and treatment of posttraumatic stress disorder (PTSD). Unlike assessments of attention bias in only one direction, ABV captures dynamic fluctuations in attention toward and away from threat. While mechanisms underlying the ABV-PTSD relations are unclear, some research implicates emotion regulation difficulties. The current study examined in community women with varying PTSD symptom severity, the amount of variance in the association between ABV and PTSD accounted for by emotion regulation difficulties. The full sample (N = 74) was comprised of 59% community women with PTSD due to domestic and/or sexual violence, and 41% community women without PTSD. All participants completed self-report questionnaires including the Difficulties in Emotion Regulation Scale-16, which assessed emotion regulation. ABV was calculated following a computerised dot probe task. The indirect effect of ABV on PTSD symptom severity through emotion regulation difficulties was statistically significant, while the direct effect between ABV and PTSD symptom severity was not significant. Findings replicated after controlling for total trauma exposure. Clinical implications and literature suggesting how ABV may perpetuate emotion regulation difficulties associated with PTSD symptomology are discussed.

Cognitive appraisal in fish: stressor predictability modulates the physiological and neurobehavioural stress response in sea bass.

The role of cognitive factors in triggering the stress response is well established in humans and mammals (aka cognitive appraisal theory) but very seldom studied in other vertebrate taxa. Predictability is a key factor of the cognitive evaluation of stimuli. In this study, we tested the effects of stressor predictability on behavioral, physiological and neuromolecular responses in the European sea bass (Dicentrarchus labrax). Groups of four fish were exposed to a predictable (signalled) or unpredictable (unsignalled) stressor. Stressor predictability elicited a lower behavioural response and reduced cortisol levels. Using the expression of immediate early genes (c-fos, egr-1, bdnf and npas4) as markers of neuronal activity, we monitored the activity of three sea bass brain regions known to be implicated in stressor appraisal: the dorsomedian telencephalon, Dm (putative homologue of the pallial amygdala); and the dorsal (Dld) and ventral (Dlv) subareas of the dorsolateral telencephalon (putative homologue of the hippocampus). The activity of both the Dm and Dlv significantly responded to stressor predictability, suggesting an evolutionarily conserved role of these two brain regions in information processing related to stressor appraisal. These results indicate that stressor predictability plays a key role in the activation of the stress response in a teleost fish, hence highlighting the role of cognitive processes in fish stress.

Hippocampal and parahippocampal volumes vary by sex and traumatic life events in children

Background: Childhood trauma is reliably associated with smaller hippocampal volume in adults; however, this finding has not been shown in children, and even less is known about how sex and trauma interact to affect limbic structural development in children. Methods: Typically developing children aged 9 to 15 years who completed a trauma history questionnaire and structural T1-weighted MRI were included in this study (n = 172; 85 female, 87 male). All children who reported 4 or more traumas (n = 36) composed the high trauma group, and all children who reported 3 or fewer traumas (n = 136) composed the low trauma group. Using multivariate analysis of covariance, we compared FreeSurfer-derived structural MRI volumes (normalized by total intracranial volume) of the amygdalar, hippocampal and parahippocampal regions by sex and trauma level, controlling for age and study site. Results: We found a significant sex × trauma interaction, such that girls with high trauma had greater volumes than boys with high trauma. Follow-up analyses indicated significantly increased volumes for girls and generally decreased volumes for boys, specifically in the hippocampal and parahippocampalregions for the high trauma group; we observed no sex differences in the low trauma group. We noted no interaction effect for the amygdalae. Limitations: We assessed a community sample and did not include a clinical sample. We did not collect data about the ages at which children experienced trauma. Conclusion: Results revealed that psychological trauma affects brain development differently in girls and boys. These findings need to be followed longitudinally to elucidate how structural differences progress and contribute to well-known sex disparities in psychopathology.

Comparative analysis of lung and blood transcriptomes in mice exposed to multi-walled carbon nanotubes.

Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) causes inflammation, fibroproliferation, immunotoxicity, and systemic responses in rodents. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identification of novel disease biomarkers. We asked if the whole blood transcriptome reflects pathology-specific changes in lung gene expression caused by MWCNT. To answer this question, we performed mRNA sequencing analysis of the whole blood and lung in mice administered MWCNT or vehicle solution via pharyngeal aspiration and sacrificed 56 days later. The pattern of lung mRNA expression as determined using Ingenuity Pathway Analysis (IPA) was indicative of continued inflammation, immune cell trafficking, phagocytosis, and adaptive immune responses. Simultaneously, innate immunity-related transcripts (Plunc, Bpifb1, Reg3g) and cancer-related pathways were downregulated. IPA analysis of the differentially expressed genes in the whole blood suggested increased hematopoiesis, predicted activation of cancer/tumor development pathways, and atopy. There were several common upregulated genes between whole blood and lungs, important for adaptive immune responses: Cxcr1, Cd72, Sharpin, and Slc11a1. Trim24, important for TH2 cell effector function, was downregulated in both datasets. Hla-dqa1 mRNA was upregulated in the lungs and downregulated in the blood, as was Lilrb4, which controls the reactivity of immune response. "Cancer" disease category had opposing activation status in the two datasets, while the only commonality was "Hypersensitivity". Transcriptome changes occurring in the lungs did not produce a completely replicable pattern in whole blood; however, specific systemic responses may be shared between transcriptomic profiles.