Post-Roe v Wade psychiatry: legal, clinical, and ethical challenges in psychiatry under abortion bans.

In recent history, the world has witnessed a trend towards liberalization of abortion laws driven by an increasing understanding of the negative personal and public health consequences of criminalizing abortion. By contrast, several countries have recently implemented restrictive reproductive laws, joining the 112 countries where access to abortion care is banned completely or with narrow exceptions. On June 24, 2022, the US Supreme Court ruling in Dobbs v Jackson Women's Health Organization overturned its landmark decisions in Roe v Wade that established abortion until the point of viability of the fetus as a constitutional right. After Roe v Wade having been overturned, it is projected that many women in the USA will be prevented from accessing safe abortion care. Importantly, abortion bans not only impose constraints on patient autonomy, they also restrict physicians' ability to practice evidence-based medicine, which will negatively impact psychiatric care. It is therefore crucial for the practicing psychiatrist to be familiar with this new legal landscape. In this Personal View, we aim to provide a topical overview to help clinicians gain a clear understanding of legal, clinical, and ethical responsibilities, focusing on the USA. We also discuss the reality that psychiatrists might be called upon to determine medical necessity for an abortion on psychiatric grounds, which is new for most US psychiatrists. We predict that psychiatrists will be confronted with very difficult situations in which lawful and ethical conduct might be incongruent, and that abortion bans will result in greater numbers of patients needing psychiatric care from a system that is ill-prepared for additional demands.

Anterior Cruciate Ligament Return to Sport after Injury Scale (ACL-RSI) Scores over Time After Anterior Cruciate Ligament Reconstruction: A Systematic Review with Meta-analysis.

BACKGROUND: Psychological readiness is an important consideration for athletes and clinicians when making return to sport decisions following anterior cruciate ligament reconstruction (ACLR). To improve our understanding of the extent of deficits in psychological readiness, a systematic review is necessary. OBJECTIVE: To investigate psychological readiness (measured via the Anterior Cruciate Ligament-Return to Sport after Injury scale (ACL-RSI)) over time after ACL tear and understand if time between injury and surgery, age, and sex are associated with ACL-RSI scores. METHODS: Seven databases were searched from the earliest date available to March 22, 2022. Articles reporting ACL-RSI scores after ACL tear were included. Risk of bias was assessed using the ROBINS-I, RoB-2, and RoBANS tools based on the study design. Evidence certainty was assessed for each analysis. Random-effects meta-analyses pooled ACL-RSI scores, stratified by time post-injury and based on treatment approach (i.e., early ACLR, delayed ACLR, and unclear approach). RESULTS: A total of 83 studies were included in this review (78% high risk of bias). Evidence certainty was 'weak' or 'limited' for all analyses. Overall, ACL-RSI scores were higher at 3 to 6 months post-ACLR (mean = 61.5 [95% confidence interval (CI) 58.6, 64.4], I2 = 94%) compared to pre-ACLR (mean = 44.4 [95% CI 38.2, 50.7], I2 = 98%), remained relatively stable, until they reached the highest point 2 to 5 years after ACLR (mean = 70.7 [95% CI 63.0, 78.5], I2 = 98%). Meta-regression suggests shorter time from injury to surgery, male sex, and older age were associated with higher ACL-RSI scores only 3 to 6 months post-ACLR (heterogeneity explained R2 = 47.6%), and this reduced 1-2 years after ACLR (heterogeneity explained R2 = 27.0%). CONCLUSION: Psychological readiness to return to sport appears to improve early after ACL injury, with little subsequent improvement until ≥ 2-years after ACLR. Longer time from injury to surgery, female sex and older age might be negatively related to ACL-RSI scores 12-24 months after ACLR. Due to the weak evidence quality rating and the considerable importance of psychological readiness for long-term outcomes after ACL injury, there is an urgent need for well-designed studies that maximize internal validity and identify additional prognostic factors for psychological readiness at times critical for return to sport decisions. REGISTRATION: Open Science Framework (OSF), https://osf.io/2tezs/ .

Dysmaturation of sleep state and electroencephalographic activity after hypoxia-ischaemia in preterm fetal sheep.

Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion (UCO, n = 9) or sham occlusion (controls, n = 9), and recovered for 21 days. HI was associated with a shift to lower frequency EEG activity for the first 5 days with persisting loss of EEG power in the delta and theta bands, and initial loss of power in the alpha and beta bands in the first 14 days of recovery. In the final 3 days of recovery, there was a marked rhythmic shift towards higher frequency EEG activity after UCO. The UCO group spent less time in high-voltage sleep, and in the early evening (7:02 pm ± 47 min) abruptly stopped cycling between sleep states, with a shift to a high frequency state for 2 h 48 min ± 40 min, with tonic electromyographic activity. These findings demonstrate persisting EEG and sleep state dysmaturation after severe hypoxia-ischaemia. Loss of fetal or neonatal sleep state cycling in the early evening may be a useful biomarker for evolving cystic WMI.

Nutrition delivery across hospitalisation in critically ill patients with COVID-19: An observational study of the Australian experience.

BACKGROUND: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting. OBJECTIVES: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices. METHODS: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020. Data were extracted on baseline characteristics and clinical outcomes. Nutrition practice data from the ICU and weekly in the post-ICU ward (up to week four) included route of feeding, presence of nutrition-impacting symptoms, and nutrition support received. RESULTS: A total of 103 patients were included (71% male, age: 58 ± 14 years, body mass index: 30±7 kg/m2), of whom 41.7% (n = 43) received mechanical ventilation within 14 days of ICU admission. While oral nutrition was received by more patients at any time point in the ICU (n = 93, 91.2% of patients) than enteral nutrition (EN) (n = 43, 42.2%) or parenteral nutrition (PN) (n = 2, 2.0%), EN was delivered for a greater duration of time (69.6% feeding days) than oral and PN (29.7% and 0.7%, respectively). More patients received oral intake than the other modes in the post-ICU ward (n = 95, 95.0%), and 40.0% (n = 38/95) of patients were receiving oral nutrition supplements. In the week after ICU discharge, 51.0% of patients (n = 51) had at least one nutrition-impacting symptom, most commonly a reduced appetite (n = 25; 24.5%) or dysphagia (n = 16; 15.7%). CONCLUSION: Critically ill patients during the COVID-19 pandemic in Australia were more likely to receive oral nutrition than artificial nutrition support at any time point both in the ICU and in the post-ICU ward, whereas EN was provided for a greater duration when it was prescribed. Nutrition-impacting symptoms were common.

Circadian patterns of heart rate variability in fetal sheep after hypoxia-ischaemia: A biomarker of evolving brain injury.

Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury. KEY POINTS: Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury.

Optimizing team science in an academic medical center: A qualitative examination of investigator perspectives.

Introduction: Optimizing the effectiveness of a team-based approach to unite multiple disciplines in advancing specific translational areas of research is foundational to improving clinical practice. The current study was undertaken to examine investigators' experiences of participation in transdisciplinary team science initiatives, with a focus on challenges and recommendations for improving effectiveness. Methods: Qualitative interviews were conducted with investigators from twelve multidisciplinary teams awarded pilot research funding by the University of Kentucky College of Medicine to better understand the barriers and facilitators to effective team science within an academic medical center. An experienced qualitative researcher facilitated one-on-one interviews, which lasted about one hour. Structured consensus coding and thematic analysis were conducted. Results: The sample was balanced by gender, career stage (five were assistant professor at the time of the award, seven were senior faculty), and training (six were PhDs; six were MD physicians). Key themes at the team-level centered on the tension between clinical commitments and research pursuits and the limitations for effective team functioning. Access to tangible support from home departments and key university centers was identified as a critical organizational facilitator of successful project completion. Organizational barriers centered on operationalizing protected time for physicians, gaps in effective mentoring, and limitations in operational support. Conclusions: Prioritizing tailored mentoring and career development support for early career faculty, and particularly physician faculty, emerged as a key recommendation for improving team science in academic medical centers. The findings contribute to establishing best practices and policies for team science in academic medical centers.

Collaborative team dynamics and scholarly outcomes of multidisciplinary research teams: A mixed-methods approach.

Introduction: Impactful, transdisciplinary scientific discoveries are created by teams of researchers spanning multiple disciplines, but collaboration across disciplines can be challenging. We examined how team dynamics and collaboration are related to successes and barriers faced by teams of researchers from multiple disciplines. Methods: A mixed-methods approach was used to examine 12 research teams granted multidisciplinary pilot awards. Team members were surveyed to assess their team dynamics and individual views about transdisciplinary research. Forty-seven researchers (59.5%) responded, including two to eight members from each funded team. Associations were examined between collaborative dynamics and scholarly product outcomes, including manuscripts, grant proposals, and awarded grants. One member from each team was selected for an in-depth interview to contextualize and extend information about collaborative processes, successes, and barriers to performing transdisciplinary research. Results: Quality of team interactions was positively associated with achievement of scholarly products (r = 0.64, p = 0.02). Satisfaction with team members (r = 0.38) and team collaboration scores (r = 0.43) also demonstrated positive associations with achievement of scholarly products, but these were not statistically significant. Qualitative results support these findings and add further insight into aspects of the collaborative process that were particularly important to foster success on multidisciplinary teams. Beyond scholarly metrics, additional successes from the multidisciplinary teams were identified through the qualitative portion of the study including career development and acceleration for early career researchers. Conclusions: Both the quantitative and qualitative study results indicate that effective collaboration is critical to multidisciplinary research team success. Development and/or promotion of team science-based trainings for researchers would promote these collaborative skills.

Ability of Countermovement Jumps to Detect Bilateral Asymmetry in Hip and Knee Strength in Elite Youth Soccer Players.

Clinicians frequently assess asymmetry in strength, flexibility, and performance characteristics as a method of screening for potential musculoskeletal injury. The identification of asymmetry in countermovement jumps may be an ideal method to reveal asymmetry in other lower extremity characteristics such as strength that otherwise may require additional testing, potentially reducing the time and burden on both the athlete and clinicians. The present study aims to examine the ability of asymmetry in both the single-leg and two-leg countermovement jump tests to accurately detect hip abduction, hip adduction, and eccentric hamstring strength asymmetry. Fifty-eight young male elite soccer players from the same professional academy performed a full battery of functional performance tests which included an assessment of hip adductor and abductor strength profiles, eccentric hamstring strength profiles, and neuromuscular performance and asymmetries during countermovement jumps. Bilateral variables attained from both the single-leg and two-leg countermovement jump tests included concentric impulse (Ns), eccentric mean force (N), and concentric mean force (N) computed by the VALD ForceDecks software. Average maximal force (N) was calculated bilaterally for the strength assessments. Asymmetry was calculated for each variable using 100 × |(right leg - left leg)/(right leg)| and grouped into three categories: 0 to <10%, 10% to <20%, and 20% or greater. Analyses were performed for the two higher asymmetry groups. The accuracy to detect strength asymmetry was assessed as the sensitivity, specificity, and predictive values for positive and negative tests. The outcomes from the accuracy assessments suggest that the single-leg countermovement jump concentric impulse variable at the 20% threshold is indicative of a youth male soccer player having hip adduction strength asymmetry while also demonstrating more accuracy and applicability than the two-leg countermovement jump concentric impulse variable.

Nutrition care processes across hospitalisation in critically ill patients with COVID-19 in Australia: A multicentre prospective observational study.

BACKGROUND: The COVID-19 pandemic highlighted major challenges with usual nutrition care processes, leading to reports of malnutrition and nutrition-related issues in these patients. OBJECTIVE: The objective of this study was to describe nutrition-related service delivery practices across hospitalisation in critically ill patients with COVID-19 admitted to Australian intensive care units (ICUs) in the initial pandemic phase. METHODS: This was a multicentre (nine site) observational study in Australia, linked with a national registry of critically ill patients with COVID-19. Adult patients with COVID-19 who were discharged to an acute ward following ICU admission were included over a 12-month period. Data are presented as n (%), median (interquartile range [IQR]), and odds ratio (OR [95% confidence interval {CI}]). RESULTS: A total of 103 patients were included. Oral nutrition was the most common mode of nutrition (93 [93%]). In the ICU, there were 53 (52%) patients seen by a dietitian (median 4 [2-8] occasions) and malnutrition screening occurred in 51 (50%) patients most commonly with the malnutrition screening tool (50 [98%]). The odds of receiving a higher malnutrition screening tool score increased by 36% for every screening in the ICU (1st to 4th, OR: 1.39 [95% CI: 1.05-1.77] p = 0.018) (indicating increasing risk of malnutrition). On the ward, 51 (50.5%) patients were seen by a dietitian (median time to consult: 44 [22.5-75] hours post ICU discharge). The odds of dietetic consult increased by 39% every week while on the ward (OR: 1.39 [1.03-1.89], p = 0.034). Patients who received mechanical ventilation (MV) were more likely to receive dietetic input than those who never received MV. CONCLUSIONS: During the initial phases of the COVID-19 pandemic in Australia, approximately half of the patients included were seen by a dietitian. An increased number of malnutrition screens were associated with a higher risk score in the ICU and likelihood of dietetic consult increased if patients received MV and as length of ward stay increased.

Fetal growth restriction and stillbirth: Biomarkers for identifying at risk fetuses.

Fetal growth restriction (FGR) is a major cause of stillbirth, prematurity and impaired neurodevelopment. Its etiology is multifactorial, but many cases are related to impaired placental development and dysfunction, with reduced nutrient and oxygen supply. The fetus has a remarkable ability to respond to hypoxic challenges and mounts protective adaptations to match growth to reduced nutrient availability. However, with progressive placental dysfunction, chronic hypoxia may progress to a level where fetus can no longer adapt, or there may be superimposed acute hypoxic events. Improving detection and effective monitoring of progression is critical for the management of complicated pregnancies to balance the risk of worsening fetal oxygen deprivation in utero, against the consequences of iatrogenic preterm birth. Current surveillance modalities include frequent fetal Doppler ultrasound, and fetal heart rate monitoring. However, nearly half of FGR cases are not detected in utero, and conventional surveillance does not prevent a high proportion of stillbirths. We review diagnostic challenges and limitations in current screening and monitoring practices and discuss potential ways to better identify FGR, and, critically, to identify the "tipping point" when a chronically hypoxic fetus is at risk of progressive acidosis and stillbirth.

Kinesiophobia, Knee Self-Efficacy, and Fear Avoidance Beliefs in People with ACL Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: To improve the understanding of the psychological impacts of anterior cruciate ligament (ACL) injury, a systematic review synthesizing the evidence on knee self-efficacy, fear avoidance beliefs and kinesiophobia following ACL injury is needed. OBJECTIVE: The aim of this systematic review was to investigate knee self-efficacy, fear avoidance beliefs and kinesiophobia following ACL injury, and compare these outcomes following management with rehabilitation alone, early and delayed ACL reconstruction (ACLR). METHODS: Seven databases were searched from inception to April 14, 2022. Articles were included if they assessed Tampa Scale of Kinesiophobia (TSK), Knee Self-Efficacy Scale (KSES), or Fear Avoidance Beliefs Questionnaire (FABQ). Risk of bias (RoB) was assessed using domain-based RoB tools (ROBINS-1, RoB 2, RoBANS), and GRADE-assessed certainty of evidence. Random-effects meta-analyses pooled outcomes, stratified by time post-injury (pre-operative, 3-6 months, 7-12 months, > 1-2 years, > 2-5 years, > 5 years). RESULTS: Seventy-three studies (70% high RoB) were included (study outcomes: TSK: 55; KSES: 22; FABQ: 5). Meta-analysis demonstrated worse kinesiophobia and self-efficacy pre-operatively (pooled mean [95% CI], TSK-11: 23.8 [22.2-25.3]; KSES: 5.0 [4.4-5.5]) compared with 3-6 months following ACLR (TSK-11: 19.6 [18.7-20.6]; KSES: 19.6 [18.6-20.6]). Meta-analysis suggests similar kinesiophobia > 3-6 months following early ACLR (19.8 [4.9]) versus delayed ACLR (17.2 [5.0]). Only one study assessed outcomes comparing ACLR with rehabilitation only. CONCLUSIONS: Knee self-efficacy and kinesiophobia improved from pre-ACLR to 3-6 months following ACLR, with similar outcomes after 6 months. Since the overall evidence was weak, there is a need for high-quality observational and intervention studies focusing on psychological outcomes following ACL injury.

Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia.

Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing of evolution of injury is vital to guide treatment. Post-HI recovery is associated with a typical neurophysiological profile, with stereotypic changes in cerebral perfusion and oxygenation. After the initial recovery, there is a delayed, prolonged reduction in cerebral perfusion related to metabolic suppression, followed by secondary deterioration with hyperperfusion and increased cerebral oxygenation, associated with altered neurovascular coupling and impaired cerebral autoregulation. These changes in cerebral perfusion are associated with the stages of evolution of injury and injury severity. Further, iatrogenic factors can also affect cerebral oxygenation during the early period of deranged metabolism, and improving clinical management may improve neuroprotection. We will review recent evidence that changes in cerebral oxygenation and metabolism after HI may be useful biomarkers of prognosis.

Contrasting Frontoparietal Network Connectivity in Antipsychotic Medication-Naive First-Episode Psychosis Patients Who Do and Do Not Display Features of the Deficit Syndrome.

BACKGROUND: The deficit syndrome is a clinical subtype of schizophrenia that is characterized by enduring negative symptoms. Several lines of evidence point to frontoparietal involvement, but the frontoparietal control network (FPCN) and its subsystems (FPCNA and FPCNB) proposed by Yeo et al. have not been systematically characterized at rest in patients with the deficit syndrome. METHODS: We used resting-state fMRI to investigate the FPCN and its subnetworks in 72 healthy controls and 65 antipsychotic medication-naive, first-episode psychosis patients (22 displayed deficit syndrome features, 43 did not). To assess whole-brain FPCN connectivity, we used the right posterior parietal cortex as the seed region. We then performed region of interest analyses in FPCN subsystems. RESULTS: We found that patterns of FPCN dysconnectivity to the whole brain differed in patients who displayed deficit syndrome features compared with those who did not. Examining the FPCN on a more granular level revealed reduced within-FPCN(A) connectivity only in patients displaying deficit features. FPCNB connectivity did not differ between patient groups. DISCUSSION: Here, we describe a neurobiological signature of aberrant FPCN connectivity in antipsychotic-naive, first-episode patients who display clinical features of the deficit syndrome. Importantly, frontoparietal subnetwork connectivity differentiated subgroups, where the FPCNA is selectively involved in patients with deficit features. Our findings add to the growing body of literature supporting a neurobiological distinction between two clinical subtypes of schizophrenia, which has the potential to be leveraged for patient stratification in clinical trials and the development of novel treatments.

Conservative or liberal oxygen therapy for mechanically ventilated adults with acute brain pathologies: A post-hoc subgroup analysis.

PURPOSE: To compare the effect of conservative vs. liberal oxygen therapy in mechanically ventilated adults in the intensive care unit (ICU) with non-hypoxic ischemic encephalopathy (HIE) acute brain pathologies. MATERIALS AND METHODS: Post-hoc analysis of data from 217 patients with non-HIE acute brain pathologies included in the ICU Randomized Trial Comparing Two Approaches to OXygen therapy (ICU-ROX). RESULTS: Patients allocated to conservative oxygen spent less time with oxygen saturation ≥ 97% (50.5 [interquartile range (IQR), 18.5-119] vs. 82 h [IQR, 38-164], absolute difference, -31.5 h; 95%CI, -59.6 to -3.4). At 180 days, 38 of 110 conservative oxygen patients (34.5%) and 28 of 104 liberal oxygen patients (26.9%) had died (absolute difference, 7.6 percentage points; 95%CI, -4.7 to 19.9 percentage points; P = 0.23; interaction P = 0.02 for non-HIE acute brain pathologies vs. HIE; interaction P = 0.53 for non-HIE acute brain pathologies vs. non-neurological conditions). CONCLUSIONS: In this post-hoc analysis, patients admitted to the ICU with non-HIE acute brain pathologies treated with conservative oxygen therapy did not have significantly lower mortality than those treated with liberal oxygen. A trial with adequate statistical power is needed to determine whether our day 180 mortality point estimate of treatment effect favoring liberal oxygen therapy indicates a true effect.

Protocol summary and statistical analysis plan for Intensive Nutrition Therapy comparEd to usual care iN criTically ill adults (INTENT): a phase II randomised controlled trial.

INTRODUCTION: It is plausible that a longer duration of nutrition intervention may have a greater impact on clinical and patient-centred outcomes. The Intensive Nutrition care Therapy comparEd to usual care iN criTically ill adults (INTENT) trial will determine if a whole hospital nutrition intervention is feasible and will deliver more total energy compared with usual care in critically ill patients with at least one organ system failure. METHODS AND ANALYSIS: This study is a prospective, multicentre, unblinded, parallel-group, phase II randomised controlled trial (RCT) conducted in 23 hospitals in Australia and New Zealand. Mechanically ventilated critically ill adult patients with at least one organ failure who have been in intensive care unit (ICU) for 72-120 hours and meet all of the inclusion and none of the exclusion criteria will be randomised to receive either intensive or usual nutrition care. INTENT started recruitment in October 2018 and a sample size of 240 participants is anticipated to be recruited in 2022. The study period is from randomisation to hospital discharge or study day 28, whichever occurs first, and the primary outcome is daily energy delivery from nutrition therapy. Secondary outcomes include daily energy and protein delivery during ICU and in the post-ICU period, duration of ventilation, ventilator-free days, total bloodstream infection rate and length of hospital stay. All other outcomes are considered tertiary and results will be analysed on an intention-to-treat basis. ETHICS AND DISSEMINATION: Ethics approval has been received in Australia (Alfred Hospital Ethics Committee (HREC/18/Alfred/101) and Human Research Ethics Committee of the Northern Territory Department of Health (2019-3372)) and New Zealand (Northern A Health and Disability Ethics Committee (18/NTA/222). Results will be disseminated in an international peer-reviewed journal(s), at scientific meetings and via social media. TRIAL REGISTRATION NUMBER: NCT03292237.

Fetal heart rate variability is a biomarker of rapid but not progressive exacerbation of inflammation in preterm fetal sheep.

Perinatal infection/inflammation can trigger preterm birth and contribute to neurodevelopmental disability. There are currently no sensitive, specific methods to identify perinatal infection. We investigated the utility of time, frequency and non-linear measures of fetal heart rate (FHR) variability (FHRV) to identify either progressive or more rapid inflammation. Chronically instrumented preterm fetal sheep were randomly assigned to one of three different 5d continuous i.v. infusions: 1) control (saline infusions; n = 10), 2) progressive lipopolysaccharide (LPS; 200 ng/kg over 24 h, doubled every 24 h for 5d, n = 8), or 3) acute-on-chronic LPS (100 ng/kg over 24 h then 250 ng/kg/24 h for 4d plus 1 µg boluses at 48, 72, and 96 h, n = 9). Both LPS protocols triggered transient increases in multiple measures of FHRV at the onset of infusions. No FHRV or physiological changes occurred from 12 h after starting progressive LPS infusions. LPS boluses during the acute-on-chronic protocol triggered transient hypotension, tachycardia and an initial increase in multiple time and frequency domain measures of FHRV, with an asymmetric FHR pattern of predominant decelerations. Following resolution of hypotension after the second and third LPS boluses, all frequencies of FHRV became suppressed. These data suggest that FHRV may be a useful biomarker of rapid but not progressive preterm infection/inflammation.

KIF21A regulates breast cancer aggressiveness and is prognostic of patient survival and tumor recurrence.

PURPOSE: Invasion of carcinoma cells into surrounding tissue affects breast cancer staging, influences choice of treatment, and impacts on patient outcome. KIF21A is a member of the kinesin superfamily that has been well-studied in congenital extraocular muscle fibrosis. However, its biological relevance in breast cancer is unknown. This study investigated the functional roles of KIF21A in this malignancy and examined its expression pattern in breast cancer tissue. METHODS: The function of KIF21A in breast carcinoma was studied in vitro by silencing its expression in breast cancer cells and examining the changes in cellular activities. Immunohistochemical staining of breast cancer tissue microarrays was performed to determine the expression patterns of KIF21A. RESULTS: Knocking down the expression of KIF21A using siRNA in MDA-MB-231 and MCF7 human breast cancer cells resulted in significant decreases in tumor cell migration and invasiveness. This was associated with reduced Patched 1 expression and F-actin microfilaments. Additionally, the number of focal adhesion kinase- and paxillin-associated focal adhesions was increased. Immunohistochemical staining of breast cancer tissue microarrays showed that KIF21A was expressed in both the cytoplasmic and nuclear compartments of carcinoma cells. Predominance of cytoplasmic KIF21A was significantly associated with larger tumors and high grade cancer, and prognostic of cause-specific overall patient survival and breast cancer recurrence. CONCLUSION: The data demonstrates that KIF21A is an important regulator of breast cancer aggressiveness and may be useful in refining prognostication of this malignant disease.

The Disparities Researchers Equalizing Access for Minorities (DREAM) Scholars program: career development for underrepresented health equity researchers.

Diversity remains low among US colleges faculty, with only 3% identifying as Black or Hispanic. Moreover, underrepresented racial minority faculty often face unique challenges and are less likely than their white counterparts to earn higher academic rank, tenure, and funding, especially those who study health equity. We developed a novel program for health-equity focused pre-docs and junior faculty. The Disparities Researchers Equalizing Access for Minorities (DREAM) Scholars is a 24-month career development program led by the Center for Clinical and Translational Science (CCTS) that provides pilot and travel funding, career development seminars, mentoring, and writing retreats. We report the outcomes of the first Scholar cohort (N = 10), pre-docs n = 6; assistant professors, n = 4; seven were Black, one Hispanic, two White, one who identified as non-binary. At the end of the program, Scholars coauthored 34 manuscripts, 9 abstracts and 8 grants. Semi-structured interviews revealed seven major program strengths: funding, support and sense of community, accountability, exposure to translational science, network expansion, and exposure to multidisciplinary peers. Scholars provided feedback useful for subsequent cohorts. The DREAM program provided accountability and fostered a sense of community, expanded professional networks and enhanced scholarly productivity. The program serves as a model for implementation throughout the CCTSs.

Using transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex to promote long-term foreign language vocabulary learning.

Transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex (DLPFC) was used to improve foreign-langue learning while using mental imagery. Participants underwent two sessions of 1 mA, 1.5 mA, or sham stimulation prior to learning Swahili-English word pairs two consecutive days. During learning, participants were encouraged to create a mental image of the associated English word. Twenty-four hours after learning and one week later, participants received a cued recall test. A linear dose-response effect of stimulation was found across both tests that occurred long after the immediate effects of stimulation. Follow-up comparisons revealed that only the 1.5 mA condition differed from the sham group. Exploratory moderating effects revealed interactions with sleep quality and handedness. Those with poorer sleep and who were left-handed showed greater recall after 1.5 mA of stimulation than those with better sleep and right-handers. A follow-up behavioral study probing strategy usage indicated that mental imagery strategy use did not strongly impact learning but point to other possible mechanisms including the importance of attending to multimodal perceptual details and memory consolidation. This preliminary evidence supports the role of the DLPFC or connected regions in foreign language vocabulary learning and verbal memory encoding.