Animal cells have a remarkable capacity to adopt durable and heritable gene expression programs or epigenetic states that define the physical properties and diversity of somatic cell types. The ...maintenance of epigenetic programs depends on poorly understood pathways that prevent gain or loss of inherited signals. In the germline, epigenetic factors are enriched in liquid-like perinuclear condensates called nuage. Here, we identify the deeply conserved helicase-domain protein, ZNFX-1, as an epigenetic regulator and component of nuage that interacts with Argonaute systems to balance epigenetic inheritance. Our findings suggest that ZNFX-1 promotes the 3′ recruitment of machinery that propagates the small RNA epigenetic signal and thus counteracts a tendency for Argonaute targeting to shift 5′ along the mRNA. These functional insights support the idea that recently identified subdomains of nuage, including ZNFX-1 granules or “Z-granules,” may define spatial and temporal zones of molecular activity during epigenetic regulation.
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•Genetic identification of ZNFX-1, a conserved epigenetic inheritance factor•ZNFX-1 balances the transgenerational inheritance of epigenetic information•ZNFX-1 interacts with RdRP and three distinct Argonaute systems in germline nuage•ZNFX-1 promotes balanced amplification of small RNA signals along germline mRNAs
Ishidate et al. identify ZNFX-1, a highly conserved helicase protein, as a factor required for epigenetic inheritance in C. elegans. Their findings indicate that ZNFX-1 localizes within nuage, where it interacts with Argonaute systems and RNA-dependent RNA polymerase (RdRP) to ensure balanced amplification of small RNA signals along germline mRNAs.
Background Preoperative brain injury is common in neonates with complex congenital heart disease. Increasing evidence suggests a complex interaction of prenatal and postnatal risk factors for ...development of brain white matter injury, called periventricular leukomalacia (PVL), in neonates with complex congenital heart disease. To date, there remains a limited understanding of the risk factors contributing to preoperative PVL in hypoplastic left heart syndrome (HLHS). Methods Neonates with HLHS or HLHS variants from 3 prospective magnetic resonance imaging studies (2003-2010) were selected for this cohort. Preoperative brain magnetic resonance imaging was performed the morning of the surgery. Stepwise multilogistic regression of patient characteristics, mode of delivery (cesarean section vs vaginal), time of diagnosis (prenatal vs postnatal), HLHS subtypes, brain total maturation score, time to surgery, individual averaged daily preoperative blood gases, and complete blood cell count values was used to determine significant associations. Results A total of 57 neonates with HLHS were born at 38.7 ± 2.3 weeks; 86% (49/57) had a prenatal diagnosis, with 31% (18/57) delivered by cesarean section. HLHS with aortic atresia (AA) was common in this cohort, 71% (41/57). Preoperative PVL was identified in 19% (11/57). Male patients with AA ( P = .004) were at higher risk for PVL. Lower total brain maturation score was also identified as a strong predictor for preoperative PVL ( P = .005). Conclusions In neonates with HLHS, nonmodifiable patient-related factors, including male sex with AA (lack of antegrade blood flow) and lower total brain maturation score, placed neonates at the greatest risk for preoperative white matter injury.
Traditional quality metrics do not adequately represent the clinical work done by residents and, thus, cannot be used to link residency training to health care quality. This study aimed to determine ...whether electronic health record (EHR) data can be used to meaningfully assess residents' clinical performance in pediatric emergency medicine using resident-sensitive quality measures (RSQMs).
EHR data for asthma and bronchiolitis RSQMs from Cincinnati Children's Hospital Medical Center, a quaternary children's hospital, between July 1, 2017, and June 30, 2019, were analyzed by ranking residents based on composite scores calculated using raw, unadjusted, and case-mix adjusted latent score models, with lower percentiles indicating a lower quality of care and performance. Reliability and associations between the scores produced by the 3 scoring models were compared. Resident and patient characteristics associated with performance in the highest and lowest tertiles and changes in residents' rank after case-mix adjustments were also identified.
274 residents and 1,891 individual encounters of bronchiolitis patients aged 0-1 as well as 270 residents and 1,752 individual encounters of asthmatic patients aged 2-21 were included in the analysis. The minimum reliability requirement to create a composite score was met for asthma data (α = 0.77), but not bronchiolitis (α = 0.17). The asthma composite scores showed high correlations ( r = 0.90-0.99) between raw, latent, and adjusted composite scores. After case-mix adjustments, residents' absolute percentile rank shifted on average 10 percentiles. Residents who dropped by 10 or more percentiles were likely to be more junior, saw fewer patients, cared for less acute and younger patients, or had patients with a longer emergency department stay.
For some clinical areas, it is possible to use EHR data, adjusted for patient complexity, to meaningfully assess residents' clinical performance and identify opportunities for quality improvement.
Post-operative oral feeding difficulties in neonates and infants with CHD is common. While pre-operative oral feeding may be normal, oral feeding challenges manifest in the post-operative period ...without a clearly defined aetiology. The objective of this scoping review was to examine post-operative oral feeding in full-term neonates and infants with a CHD. Electronic databases query (1 January 1975–31 May 2021), hand-search of the reference lists of included studies, contact with experts, and review of relevant conferences were performed to identify quantitative studies evaluating post-operative oral feeding in full-term neonates and infants with a CHD. Associations with additional quantitative variables in these studies were also examined. Twenty-five studies met inclusion criteria. Eighty per cent were cohort studies that utilised retrospective chart review from a single institution. The primary variable of interest in all studies was oral feeding status upon discharge from neonatal hospitalisation. The most common risk factors evaluated with poor feeding at time of discharge were birth weight (36% of included studies), gestational age (44%), duration of post-operative intubation (48%), cardiac diagnosis (40%), and presence of genetic syndrome or chromosomal anomaly (36%). The most common health-related outcomes evaluated were length of hospital stay (40%) and length of ICU stay (16%). Only the health-related outcomes of length of hospital stay and length of ICU stay were consistently significantly associated with poor post-operative oral feeding across studies in this review. A clear aetiology of poor post-operative oral feeding remains unknown.
We employ a hybrid diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) monitor for neonates with congenital heart disease (n=33). The NIRS-DCS device measured changes during ...hypercapnia of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations; cerebral blood flow (rCBF
); and oxygen metabolism (rCMRO
). Concurrent measurements with arterial spin-labeled magnetic resonance imaging (rCBF
, n=12) cross-validate rCBF
against rCBF
, showing good agreement (R=0.7, p=0.01). The study demonstrates use of NIRS-DCS on a critically ill neonatal population, and the results indicate that the optical technology is a promising clinical method for monitoring this population.
Impaired neurodevelopmental outcome represents a major morbidity for survivors of infant heart surgery for congenital heart defects. Previous studies in these neonates have reported preoperative ...microcephaly, periventricular leukomalacia, and other findings. The hypothesis of this study is that preoperative cerebral blood flow is substantially diminished and might relate to preoperative neurologic conditions.
Preoperative brain magnetic resonance imaging was performed. Cerebral blood flow measurements in infants with congenital heart defects were obtained by using a novel noninvasive magnetic resonance imaging technique, pulsed arterial spin-label perfusion magnetic resonance imaging. Cerebral blood flow was measured before the operation under standard ventilation and repeated after increased carbon dioxide.
A total of 25 term infants were studied. The average age at the time of the operation was 4.4 ± 4.6 days. Congenital heart defects varied widely. Microcephaly occurred in 24% (6/25). Baseline cerebral blood flow was 19.7 ± 9.2 mL · 100 g
−1 · min
−1 (8.0-42.2 mL · 100 g
−1 · min
−1). Five patients had cerebral blood flow measurements of less than 10 mL · 100 g
−1 · min
−1. Mean hypercarbic cerebral blood flow increased to 40.1 ± 20.3 mL · 100 g
−1 · min
−1 (11.4-94.0 mL · 100 g
−1 · min
−1,
P < .001). Pairwise analyses found that low hemoglobin levels were associated with higher baseline cerebral blood flow values (
P = .04). Periventricular leukomalacia occurred in 28% (7/25) and was associated with decreased baseline cerebral blood flow values (
P = .05) and a smaller change in cerebral blood flow with hypercarbia (
P = .003).
Structural brain abnormalities are common in these neonates before surgical intervention. Preoperative cerebral blood flow for this cohort was low and drastically reduced in some patients. Low cerebral blood flow values were associated with periventricular leukomalacia. Carbon dioxide reactivity was preserved but might be compromised by some aspects of the cardiac anatomy. The full spectrum of cerebral blood flow measurements with this technique in congenital heart defects and their long-term significance require continued investigation.
An evidence-based approach to assessment is critical for ensuring the development of clinical reasoning (CR) competence. The wide array of CR assessment methods creates challenges for selecting ...assessments fit for the purpose; thus, a synthesis of the current evidence is needed to guide practice. A scoping review was performed to explore the existing menu of CR assessments.
Multiple databases were searched from their inception to 2016 following PRISMA guidelines. Articles of all study design types were included if they studied a CR assessment method. The articles were sorted by assessment methods and reviewed by pairs of authors. Extracted data were used to construct descriptive appendixes, summarizing each method, including common stimuli, response formats, scoring, typical uses, validity considerations, feasibility issues, advantages, and disadvantages.
A total of 377 articles were included in the final synthesis. The articles broadly fell into three categories: non-workplace-based assessments (e.g., multiple-choice questions, extended matching questions, key feature examinations, script concordance tests); assessments in simulated clinical environments (objective structured clinical examinations and technology-enhanced simulation); and workplace-based assessments (e.g., direct observations, global assessments, oral case presentations, written notes). Validity considerations, feasibility issues, advantages, and disadvantages differed by method.
There are numerous assessment methods that align with different components of the complex construct of CR. Ensuring competency requires the development of programs of assessment that address all components of CR. Such programs are ideally constructed of complementary assessment methods to account for each method's validity and feasibility issues, advantages, and disadvantages.
The relationship between professionalism and distress among medical students is unknown.
To determine the relationship between measures of professionalism and burnout among US medical students.
...Cross-sectional survey of all medical students attending 7 US medical schools (overall response rate, 2682/4400 61%) in the spring of 2009. The survey included the Maslach Burnout Inventory (MBI), the PRIME-MD depression screening instrument, and the SF-8 quality of life (QOL) assessment tool, as well as items exploring students' personal engagement in unprofessional conduct, understanding of appropriate relationships with industry, and attitudes regarding physicians' responsibility to society.
Frequency of self-reported cheating/dishonest behaviors, understanding of appropriate relationships with industry as defined by American Medical Association policy, attitudes about physicians' responsibility to society, and the relationship of these dimensions of professionalism to burnout, symptoms of depression, and QOL.
Of the students who responded to all the MBI items, 1354 of 2566 (52.8%) had burnout. Cheating/dishonest academic behaviors were rare (endorsed by <10%) in comparison to unprofessional conduct related to patient care (endorsed by up to 43%). Only 14% (362/2531) of students had opinions on relationships with industry consistent with guidelines for 6 scenarios. Students with burnout were more likely to report engaging in 1 or more unprofessional behaviors than those without burnout (35.0% vs 21.9%; odds ratio OR, 1.89; 95% confidence interval CI, 1.59-2.24). Students with burnout were also less likely to report holding altruistic views regarding physicians' responsibility to society. For example, students with burnout were less likely to want to provide care for the medically underserved than those without burnout (79.3% vs 85.0%; OR, 0.68; 95% CI, 0.55-0.83). After multivariable analysis adjusting for personal and professional characteristics, burnout was the only aspect of distress independently associated with reporting 1 or more unprofessional behaviors (OR, 1.76; 95% CI, 1.45-2.13) or holding at least 1 less altruistic view regarding physicians' responsibility to society (OR, 1.65; 95% CI, 1.35-2.01).
Burnout was associated with self-reported unprofessional conduct and less altruistic professional values among medical students at 7 US schools.
Clinical reasoning is essential to physicians' competence, yet assessment of clinical reasoning remains a significant challenge. Clinical reasoning is a complex, evolving, non-linear, ...context-driven, and content-specific construct which arguably cannot be assessed at one point in time or with a single method. This has posed challenges for educators for many decades, despite significant development of individual assessment methods.
Programmatic assessment is a systematic assessment approach that is gaining momentum across health professions education. Programmatic assessment, and in particular assessment for learning, is well-suited to address the challenges with clinical reasoning assessment. Several key principles of programmatic assessment are particularly well-aligned with developing a system to assess clinical reasoning: longitudinality, triangulation, use of a mix of assessment methods, proportionality, implementation of intermediate evaluations/reviews with faculty coaches, use of assessment for feedback, and increase in learners' agency. Repeated exposure and measurement are critical to develop a clinical reasoning assessment narrative, thus the assessment approach should optimally be longitudinal, providing multiple opportunities for growth and development. Triangulation provides a lens to assess the multidimensionality and contextuality of clinical reasoning and that of its different, yet related components, using a mix of different assessment methods. Proportionality ensures the richness of information on which to draw conclusions is commensurate with the stakes of the decision. Coaching facilitates the development of a feedback culture and allows to assess growth over time, while enhancing learners' agency.
A programmatic assessment model of clinical reasoning that is developmentally oriented, optimizes learning though feedback and coaching, uses multiple assessment methods, and provides opportunity for meaningful triangulation of data can help address some of the challenges of clinical reasoning assessment.
Many medical students experience distress during medical school. If matriculating medical students (MMSs) begin training with similar or better mental health than age-similar controls, this would ...support existing concerns about the negative impact of training on student well-being. The authors compared mental health indicators of MMSs versus those of a probability-based sample of the general U.S. population.
In 2012 all MMSs at six U.S. medical schools were invited to participate in a survey during orientation. The research team surveyed a probability-based sample of U.S. individuals using the same questions in 2011. Individuals from the population sample who completed a four-year college degree and matched within the appropriate age strata (< 30, 31-35, 36-40, > 40) were compared with MMSs. Surveys included demographics and validated instruments to measure burnout; depression symptoms; and mental, emotional, physical, and overall of quality of life (QOL).
Demographic characteristics of the 582/938 (62%) responding MMSs were similar to U.S. MMSs. Relative to 546 age-similar college graduates, MMSs had lower rates of burnout (27.3% versus 37.3%, P < .001) and depression symptoms (26.2% versus 42.4%, P < .0001) and higher scores across the four QOL domains assessed relative to controls (all P < .0001). These findings persisted on multivariate analysis after adjusting for age, sex, relationship status, and race/ethnicity.
These findings, along with high rates of distress reported in medical students and residents, support concerns that the training process and environment contribute to the deterioration of mental health in developing physicians.
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