Investigation of health inequities in maternal and neonatal outcomes of patients with placenta accreta spectrum: a multicenter study.

BACKGROUND: Placenta accreta spectrum (PAS) is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in outcomes of patients with PAS. OBJECTIVE: To investigate health inequities in maternal and neonatal outcomes of pregnancies with PAS. STUDY DESIGN: This multicentered retrospective cohort study included patients with histopathological diagnosis of PAS at four regional perinatal centers between 1/1/2013 - 6/30/2022. Maternal race and/or ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. Primary outcome was a composite adverse maternal outcome: transfusion of 4+ units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury or mortality. Secondary outcomes were composite adverse neonatal outcome (APGAR < 7 at 1-minute, morbidity, or mortality), gestational age at PAS diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race/ethnicity with maternal and neonatal outcomes. RESULTS: 408 pregnancies with PAS were included. In 218 patients (53%), the diagnosis of PAS was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, BMI, income and parity, there was no difference in composite adverse maternal outcome among racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team and cesarean hysterectomy were similar between groups. CONCLUSION: In our multicenter PAS cohort, race and/or ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis and planned multi-disciplinary care. We hypothesize that comparable incidence of individual risk factors for perinatal morbidity as well as geographic proximity reduce potential inequities that may exist in the larger population.

Acute hypoxia impairs posterior cerebral bioenergetics and memory in man.

Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7 h) on central executive (Go/No-Go) and non-executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2 ). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2 ), in a randomized block cross-over single-blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No-Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No-Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. NEW FINDINGS: What is the central question of this study? We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non-executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery. What is the main finding and its importance? Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia.

Epigenetic dynamics during capacitation of naïve human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine. Naïve hPSCs hold promise to overcome some of the limitations of conventional (primed) hPSCs, including recurrent epigenetic anomalies. Naïve-to-primed transition (capacitation) follows transcriptional dynamics of human embryonic epiblast and is necessary for somatic differentiation from naïve hPSCs. We found that capacitated hPSCs are transcriptionally closer to postimplantation epiblast than conventional hPSCs. This prompted us to comprehensively study epigenetic and related transcriptional changes during capacitation. Our results show that CpG islands, gene regulatory elements, and retrotransposons are hotspots of epigenetic dynamics during capacitation and indicate possible distinct roles of specific epigenetic modifications in gene expression control between naïve and primed hPSCs. Unexpectedly, PRC2 activity appeared to be dispensable for the capacitation. We find that capacitated hPSCs acquire an epigenetic state similar to conventional hPSCs. Significantly, however, the X chromosome erosion frequently observed in conventional female hPSCs is reversed by resetting and subsequent capacitation.

Lower systemic nitric oxide bioactivity, cerebral hypoperfusion and accelerated cognitive decline in formerly concussed retired rugby union players.

NEW FINDINGS: What is the central question of this study? What are the molecular, cerebrovascular and cognitive biomarkers of retired rugby union players with concussion history? What is the main finding and its importance? Retired rugby players compared with matched controls exhibited lower systemic nitric oxide bioavailability accompanied by lower middle cerebral artery velocity and mild cognitive impairment. Retired rugby players are more susceptible to accelerated cognitive decline. ABSTRACT: Following retirement from sport, the chronic consequences of prior-recurrent contact are evident and retired rugby union players may be especially prone to accelerated cognitive decline. The present study sought to integrate molecular, cerebrovascular and cognitive biomarkers in retired rugby players with concussion history. Twenty retired rugby players aged 64 ± 5 years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex-, age-, cardiorespiratory fitness- and education-matched controls with no prior concussion history. Concussion symptoms and severity were assessed using the Sport Concussion Assessment Tool. Plasma/serum nitric oxide (NO) metabolites (reductive ozone-based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light-chain (ELISA and single molecule array) were assessed. Middle cerebral artery blood velocity (MCAv, doppler ultrasound) and reactivity to hyper/hypocapnia ( CVR CO 2 hyper ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hyper}}}$ / CVR CO 2 hypo ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hypo}}}$ ) were assessed. Cognition was determined using the Grooved Pegboard Test and Montreal Cognitive Assessment. Players exhibited persistent neurological symptoms of concussion (U = 109(41) , P = 0.007), with increased severity compared to controls (U = 77(41) , P < 0.001). Lower total NO bioactivity (U = 135(41) , P = 0.049) and lower basal MCAv were apparent in players (F2,39  = 9.344, P = 0.004). This was accompanied by mild cognitive impairment (P = 0.020, 95% CI, -3.95 to -0.34), including impaired fine-motor coordination (U = 141(41) , P = 0.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non-concussed, non-contact controls.

Acute high-intensity interval exercise is less pro-oxidative/thrombotic compared to isovolumic moderate-intensity steady-state exercise

While high-intensity interval training (HIIT) has emerged as a more time-efficient alternative to moderate-intensity steady-state exercise (MISS), the impact on systemic free radical formation and link to activated coagulation remains unknown. We recruited sixteen healthy males aged 21 ± 3 y who performed incremental cycle ergometry to determine peak oxygen uptake (V˙O2 PEAK). Participants were randomly assigned single blind to two separate groups (MISS: n = 8; HIIT: n = 8) matched for V˙O2 PEAK. HIIT participants completed five exercise cycles, each consisting of 3 min at 80%V˙O2 PEAK alternating with 3 min at 40% V˙O2 PEAK, whereas MISS participants performed an isovolumic bout of 30 min at 60% V˙O2 PEAK. Cephalic venous blood was assayed for ascorbate free radical (A•−, electron paramagnetic resonance spectroscopy) and clot fractal dimension (df, rheometry) at rest every hour over a 6-h period to determine critical difference (CD) and before/after submaximal/peak exercise. Submaximal MISS increased A• − and df to a greater extent compared to HIIT (P = 0.039 to 0.057) although elevations generally fell within CD boundaries (54.2% and 5.5% respectively). No further elevations were observed during peak exercise (P = 0.508 to 0.827) and no relationships were observed between A•− and df (r = 0.435 to − 0.121, P = 0.092 to 0.655). Collectively, these findings suggest that HIIT is less pro-oxidative/thrombotic compared to more traditional MISS, advocating its prescription in patients given the potential for superior vascular adaptive benefit. (AU)

Acute high-intensity interval exercise is less pro-oxidative/thrombotic compared to isovolumic moderate-intensity steady-state exercise.

While high-intensity interval training (HIIT) has emerged as a more time-efficient alternative to moderate-intensity steady-state exercise (MISS), the impact on systemic free radical formation and link to activated coagulation remains unknown. We recruited sixteen healthy males aged 21 ± 3 y who performed incremental cycle ergometry to determine peak oxygen uptake ([Formula: see text] PEAK). Participants were randomly assigned single blind to two separate groups (MISS: n = 8; HIIT: n = 8) matched for [Formula: see text] PEAK. HIIT participants completed five exercise cycles, each consisting of 3 min at 80%[Formula: see text] PEAK alternating with 3 min at 40% [Formula: see text] PEAK, whereas MISS participants performed an isovolumic bout of 30 min at 60% [Formula: see text] PEAK. Cephalic venous blood was assayed for ascorbate free radical (A•-, electron paramagnetic resonance spectroscopy) and clot fractal dimension (df, rheometry) at rest every hour over a 6-h period to determine critical difference (CD) and before/after submaximal/peak exercise. Submaximal MISS increased A• - and df to a greater extent compared to HIIT (P = 0.039 to 0.057) although elevations generally fell within CD boundaries (54.2% and 5.5% respectively). No further elevations were observed during peak exercise (P = 0.508 to 0.827) and no relationships were observed between A•- and df (r = 0.435 to - 0.121, P = 0.092 to 0.655). Collectively, these findings suggest that HIIT is less pro-oxidative/thrombotic compared to more traditional MISS, advocating its prescription in patients given the potential for superior vascular adaptive benefit.

Effects of continuous hypoxia on flow-mediated dilation in the cerebral and systemic circulation: on the regulatory significance of shear rate phenotype.

Emergent evidence suggests that cyclic intermittent hypoxia increases cerebral arterial shear rate and endothelial function, whereas continuous exposure decreases anterior cerebral oxygen (O2) delivery. To examine to what extent continuous hypoxia impacts cerebral shear rate, cerebral endothelial function, and consequent cerebral O2 delivery (CDO2), eight healthy males were randomly assigned single-blind to 7 h passive exposure to both normoxia (21% O2) and hypoxia (12% O2). Blood flow in the brachial and internal carotid arteries were determined using Duplex ultrasound and included the combined assessment of systemic and cerebral endothelium-dependent flow-mediated dilatation. Systemic (brachial artery) flow-mediated dilatation was consistently lower during hypoxia (P = 0.013 vs. normoxia), whereas cerebral flow-mediated dilation remained preserved (P = 0.927 vs. normoxia) despite a reduction in internal carotid artery antegrade shear rate (P = 0.002 vs. normoxia) and CDO2 (P < 0.001 vs. normoxia). Collectively, these findings indicate that the reduction in CDO2 appears to be independent of cerebral endothelial function and contrasts with that observed during cyclic intermittent hypoxia, highlighting the regulatory importance of (hypoxia) dose duration and flow/shear rate phenotype.

Parental Guidance Suggested: Engaging Parents as Partners in Research Studies of Genomic Screening for a Pediatric Population.

Recent advances in genomic sequencing and genomic medicine are reshaping the landscape of clinical care. As a screening modality, genetic sequencing has the potential to dramatically expand the clinical utility of newborn screening (NBS), though significant barriers remain regarding ethical, legal, and social implications (ELSI) and technical and evidentiary challenges. Stakeholder-informed implementation research is poised to grapple with many of these barriers, and parents are crucial stakeholders in this process. We describe the formation and activities of a Community Research Board (CRB) composed of parents with diverse backgrounds assembled to participate in an ongoing research partnership with genomic and public health researchers at the University of North Carolina. The mission of the CRB is to provide insight into parental perspectives regarding the prospect of adding genomic sequencing to NBS and collaboratively develop strategies to ensure its equitable uptake. We describe how these contributions can improve the accessibility of research and recruitment methods and promote trust and inclusivity within diverse communities to maximize the societal benefit of population genomic screening in healthy children.

Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition.

Recurrent contact and concussion in rugby union remains a significant public health concern given the potential increased risk of neurodegeneration in later life. This study determined to what extent prior-recurrent contact impacts molecular-hemodynamic biomarkers underpinning cognition in current professional rugby union players with a history of concussion. Measurements were performed in 20 professional rugby union players with an average of 16 (interquartile range [IQR] 13-19) years playing history reporting 3 (IQR 1-4) concussions. They were compared to 17 sex-age-physical activity-and education-matched non-contact controls with no prior history of self-reported concussion. Venous blood was assayed directly for the ascorbate free radical (A•- electron paramagnetic resonance spectroscopy) nitric oxide metabolites (NO reductive ozone-based chemiluminescence) and select biomarkers of neurovascular unit integrity (NVU chemiluminescence/ELISA). Middle cerebral artery blood flow velocity (MCAv doppler ultrasound) was employed to determine basal perfusion and cerebrovascular reactivity (CVR) to hyper/hypocapnia ( CVR CO 2 Hyper / Hypo ). Cognition was assessed by neuropsychometric testing. Elevated systemic oxidative-nitrosative stress was confirmed in the players through increased A•- (p < 0.001) and suppression of NO bioavailability (p < 0.001). This was accompanied by a lower CVR range ( CVR CO 2 Range ; p = 0.045) elevation in neurofilament light-chain (p = 0.010) and frontotemporal impairments in immediate-memory (p = 0.001) delayed-recall (p = 0.048) and fine-motor coordination (p < 0.001). Accelerated cognitive decline subsequent to prior-recurrent contact and concussion history is associated with a free radical-mediated suppression of CVR and neuronal injury providing important mechanistic insight that may help better inform clinical management.

Contact events in rugby union and the link to reduced cognition: evidence for impaired redox-regulation of cerebrovascular function.

NEW FINDINGS: What is the central question of this study? How does recurrent contact incurred across a season of professional rugby union impact molecular, cerebrovascular and cognitive function? What is the main findings and its importance? A single season of professional rugby union increases systemic oxidative-nitrosative stress (OXNOS) confirmed by a free radical-mediated suppression in nitric oxide bioavailability. Forwards encountered a higher frequency of contact events compared to backs, exhibiting elevated OXNOS and lower cerebrovascular function and cognition. Collectively, these findings provide mechanistic insight into the possible cause of reduced cognition in rugby union subsequent to impairment in the redox regulation of cerebrovascular function. ABSTRACT: Contact events in rugby union remain a public health concern. We determined the molecular, cerebrovascular and cognitive consequences of contact events during a season of professional rugby. Twenty-one male players aged 25 (mean) ± 4 (SD) years were recruited from a professional rugby team comprising forwards (n = 13) and backs (n = 8). Data were collected across the season. Pre- and post-season, venous blood was assayed for the ascorbate free radical (A•- , electron paramagnetic resonance spectroscopy) and nitric oxide (NO, reductive ozone-based chemiluminescence) to quantify oxidative-nitrosative stress (OXNOS). Middle cerebral artery velocity (MCAv, Doppler ultrasound) was measured to assess cerebrovascular reactivity (CVR), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Notational analysis determined contact events over the season. Forwards incurred more collisions (Mean difference [MD ] 7.49; 95% CI, 2.58-12.40; P = 0.005), tackles (MD 3.49; 95% CI, 0.42-6.56; P = 0.028) and jackals (MD 2.21; 95% CI, 0.18-4.24; P = 0.034). Forwards suffered five concussions while backs suffered one concussion. An increase in systemic OXNOS, confirmed by elevated A•- (F2,19  = 10.589, P = 0.004) and corresponding suppression of NO bioavailability (F2,19  = 11.492, P = 0.003) was apparent in forwards and backs across the season. This was accompanied by a reduction in cerebral oxygen delivery ( cDO2 , F2,19  = 9.440, P = 0.006) and cognition (F2,19  = 4.813, P = 0.041). Forwards exhibited a greater decline in the cerebrovascular reactivity range to changes in PETCO2 ( CVRCO2RANG compared to backs (MD 1.378; 95% CI, 0.74-2.02; P < 0.001).

Absence of carbonic anhydrase in chloroplasts affects C3 plant development but not photosynthesis.

The enzyme carbonic anhydrase (CA), which catalyzes the interconversion of bicarbonate with carbon dioxide (CO2) and water, has been hypothesized to play a role in C3 photosynthesis. We identified two tobacco stromal CAs, ß-CA1 and ß-CA5, and produced CRISPR/Cas9 mutants affecting their encoding genes. While single knockout lines Δß-ca1 and Δß-ca5 had no striking phenotypic differences compared to wild type (WT) plants, Δß-ca1ca5 leaves developed abnormally and exhibited large necrotic lesions even when supplied with sucrose. Leaf development of Δß-ca1ca5 plants normalized at 9,000 ppm CO2 Leaves of Δß-ca1ca5 mutants and WT that had matured in high CO2 had identical CO2 fixation rates and photosystem II efficiency. Fatty acids, which are formed through reactions with bicarbonate substrates, exhibited abnormal profiles in the chloroplast CA-less mutant. Emerging Δß-ca1ca5 leaves produce reactive oxygen species in chloroplasts, perhaps due to lower nonphotochemical quenching efficiency compared to WT. Δß-ca1ca5 seedling germination and development is negatively affected at ambient CO2 Transgenes expressing full-length ß-CA1 and ß-CA5 proteins complemented the Δß-ca1ca5 mutation but inactivated (ΔZn-ßCA1) and cytoplasm-localized (Δ62-ßCA1) forms of ß-CA1 did not reverse the growth phenotype. Nevertheless, expression of the inactivated ΔZn-ßCA1 protein was able to restore the hypersensitive response to tobacco mosaic virus, while Δß-ca1 and Δß-ca1ca5 plants failed to show a hypersensitive response. We conclude that stromal CA plays a role in plant development, likely through providing bicarbonate for biosynthetic reactions, but stromal CA is not needed for maximal rates of photosynthesis in the C3 plant tobacco.

Impaired cerebral blood flow regulation and cognition in male football players.

Football players are at increased risk of neurodegeneration, the likely consequence of repetitive mechanical trauma caused by heading the ball. However, to what extent a history of heading the ball affects cerebral blood flow (CBF) regulation and its potential relationship to cognitive impairment is unknown. To address this, we recruited 16 concussion-free male amateur football players (age: 25 ± 6 y) with a history of heading the ball (18 ± 6 y) and 18 sex, age, education, and activity-matched controls with no prior history of contact sport participation or concussion. Cerebral perfusion was measured at rest and in response to both hyper/hypocapnia to determine cerebrovascular reactivity to carbon dioxide (CVRCO2HYPER/HYPO ) using transcranial Doppler ultrasound and capnography, with the sum reflecting the cerebral vasomotor range. Cognition and visuomotor coordination were assessed using the Montreal cognitive assessment (MoCA) and the Grooved Pegboard Dexterity Test (GPD), respectively. While no differences in cerebral perfusion were observed (p = 0.938), CVRCO2HYPER/HYPO (p = 0.038/p = 0.025), cerebral vasomotor range (p = 0.002), MoCA (p = 0.027), and GPD performance (dominant hand, P ≤ 0.001) were consistently lower in the players compared to controls. These findings are the first to demonstrate that CBF regulation and cognition are collectively impaired in male football players with history of heading the ball, which may contribute to neurodegeneration.

Integrated respiratory chemoreflex-mediated regulation of cerebral blood flow in hypoxia: Implications for oxygen delivery and acute mountain sickness.

NEW FINDINGS: What is the central question of this study? To what extent do hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness. ABSTRACT: The aim of the present study was to determine the extent to which hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2 ), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2 ) and hypoxia (12% O2 ). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P < 0.001), whereas the central respiratory chemoreflex remained unchanged (P > 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546-0.709, P = 0.004-0.043; Environmental Symptoms Questionnaires-Cerebral symptoms score, r = 0.587-0.771, P = 0.001-0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.

Long-term Exercise Confers Equivalent Neuroprotection in Females Despite Lower Cardiorespiratory Fitness.

Females are more prone to cognitive decline, stroke and neurodegenerative disease, possibly due to more marked reductions in cerebral blood flow and cerebrovascular reactivity to CO2 (CVRCO2HYPER) in later life. To what extent regular exercise confers selective neuroprotection in females remains unestablished. To examine this, 73 adults were prospectively assigned to 1 of 4 groups based on sex (male, ♂ vs. female, ♀) and physical activity status (trained, ≥150 min of moderate-vigorous intensity aerobic exercise/week; n = 18♂ vs. 18♀ vs. untrained, no formal exercise; n = 18♂ vs. 19♀). Middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound), mean arterial pressure (MAP, finger photoplethysmography) and end-tidal CO2 (capnography) were assessed at rest during normocapnea and hypercapnea (5% CO2) enabling CVRCO2HYPER to be assessed. Cerebrovascular resistance/conductance indices (CVRi/CVCi) were calculated as MAP/MCAv and MCAv/MAP. Maximal oxygen uptake (VO2MAX) was determined during incremental semi-recumbent cycling ergometry to volitional exhaustion. Despite having a lower VO2MAX, females were characterized by selective elevations in MCAv, CVRCO2HYPER and lower CVRi (P < 0.05), but the training responses were similar across sexes. Linear relationships were observed between VO2MAX and CVRCO2HYPER (pooled untrained and trained data; ♂ r = 0.70, ♀ r = 0.51; both P < 0.05) with a consistent elevation in the latter equivalent to ∼1.50%.mmHg-1 compared to males across the spectrum of cardiorespiratory fitness. These findings indicate that despite having comparatively lower levels of cardiorespiratory fitness, the neuroprotective benefits of regular exercise translate into females and may help combat cerebrovascular disease in later life.

The relationship between genetic counseling student self-efficacy and clinical training.

Clinical experience is an important part of the training required in genetic counseling graduate programs, but little evidence exists for the number of clinical cases a student may need in order to confidently perform skills. The purpose of this study was to further describe the relationship between genetic counseling student self-efficacy and the number of core cases students log during their training. In this study, second year genetic counseling students nearing the end of their training completed a questionnaire that included the Genetic Counseling Self-efficacy Scale (GCSES) and questions related to the students' clinical experiences. Genetic counseling student self-efficacy was found to be positively associated with the number of core cases the student accumulated during training, with a plateau in GCSES scores between 80 and 100 core cases. These data suggest that 50 cases may not be enough for the average student, but over 100 may be more than needed in order to feel confident in their skills. Genetic counseling programs may benefit from increased flexibility in clinical training to meet the different needs of their trainees. Further studies characterizing the relationship between genetic counseling student self-efficacy and clinical competency, and well as the effectiveness of clinical training by genetic counseling programs, may aid in better understanding the clinical training specifications that best meet the needs of genetic counseling trainees.