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Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk., Methods: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging., Results: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (β, -0.67 [95% CI, -1.21 to -0.13]; P =0.016), lower stress myocardial blood flow (β, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P =0.001), and higher stress coronary vascular resistance (β, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P =0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery ( P =0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow ( r =0.71; P <0.001), independent of hemodynamics., Conclusions: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease., Competing Interests: Disclosures M.C. Honigberg reports consulting fees from CRISPR Therapeutics and Comanche Biopharma, the advisory board service for Miga Health, and grant support from Genentech. J.M. Brown reports consulting fees from Bayer AG and AstraZeneca. B.N. Weber reports advisory board service for Novo Nordisk, Horizon Therapeutics, Kinsika Pharmaceuticals, and Aegpha. E.S. Lau reports previous advisory board service for Astellas Pharma. P. Natarajan reports research grants from Allelica, Apple, Amgen, Boston Scientific, Genentech/Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, equity in Preciseli and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals and is a scientific co-founder of TenSixteen Bio, all unrelated to the present work. N.M. Hamburg reports consulting fees from Merck, Boston Scientific, and Novo Nordisk, all unrelated to the present work. M.F. Di Carli reports grant support from Gilead Sciences, in-kind research support from Amgen, and consulting fees from Sanofi, MedTrace Pharma, and Vale Health. The other authors report no conflicts.

Importance: Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease., Objective: To identify proteins in the circulation associated with HDPs., Design, Setting, and Participants: Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023., Exposures: Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs)., Main Outcomes and Measures: Gestational hypertension and preeclampsia., Results: Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins., Conclusions and Relevance: Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.

Maternal Cardiovascular Health Post-DobbsPregnancy is associated with increasing morbidity and mortality in the United States. In the post-Dobbs era, many pregnant patients at highest risk no longer have access to abortion, which has been a crucial component of standard medical care.

Animals move smoothly and reliably in unpredictable environments. Models of sensorimotor control, drawing on control theory, have assumed that sensory information from the environment leads to actions, which then act back on the environment, creating a single, unidirectional perception-action loop. However, the sensorimotor loop contains internal delays in sensory and motor pathways, which can lead to unstable control. We show here that these delays can be compensated by internal feedback signals that flow backward, from motor toward sensory areas. This internal feedback is ubiquitous in neural sensorimotor systems, and we show how internal feedback compensates internal delays. This is accomplished by filtering out self-generated and other predictable changes so that unpredicted, actionable information can be rapidly transmitted toward action by the fastest components, effectively compressing the sensory input to more efficiently use feedforward pathways: Tracts of fast, giant neurons necessarily convey less accurate signals than tracts with many smaller neurons, but they are crucial for fast and accurate behavior. We use a mathematically tractable control model to show that internal feedback has an indispensable role in achieving state estimation, localization of function (how different parts of the cortex control different parts of the body), and attention, all of which are crucial for effective sensorimotor control. This control model can explain anatomical, physiological, and behavioral observations, including motor signals in the visual cortex, heterogeneous kinetics of sensory receptors, and the presence of giant cells in the cortex of humans as well as internal feedback patterns and unexplained heterogeneity in neural systems.

Objective: Greater parity has been associated with cardiovascular disease risk. We sought to find whether the effects on cardiac remodeling and heart failure risk are clear., Methods: We examined the association of number of live births with echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction using a Fine-Gray subdistribution hazards model in a pooled analysis of n = 12,635 participants in the FHS, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular Endstage Disease. Secondary analyses included major cardiovascular disease, myocardia infarction and stroke., Results: Among n = 3931 FHS participants (mean age 48 ± 13 years), higher numbers of live births were associated with worse left ventricular fractional shortening (multivariable β -1.11 (0.31); P = 0.0005 in ≥ 5 live births vs nulliparous women) and worse cardiac mechanics, including global circumferential strain and longitudinal and radial dyssynchrony (P < 0.01 for all comparing ≥ 5 live births vs nulliparity). When examining HF subtypes, women with ≥ 5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19-3.12; P = 0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37-0.91; P = 0.02)., Conclusions: Greater numbers of live births are associated with worse cardiac structure and function. There was no association with overall HF, but a higher number of live births was associated with greater risk for incident HFrEF., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Previously we reported evidence that a regenerative response in the appendages of moon jellyfish, fruit flies, and mice can be promoted by nutrient modulation (Abrams et al., 2021). Sustar and Tuthill subsequently reported that they had not been able to reproduce the induced regenerative response in flies (Sustar and Tuthill, 2023). Here we discuss that differences in the amputation method, treatment concentrations, age of the animals, and stress management explain why they did not observe a regenerative response in flies. Typically, 30-50% of treated flies showed response in our assay., Competing Interests: YL, AS, IL, ZC, MR, JD, DG No competing interests declared, FT, MA, MH, LG Has applied for a patent related to the findings reported in this manuscript (US Patent Application No. 17/355,727), (© 2023, Li et al.)

Objective: Whether biomarkers may enable early identification of women who develop peripartum cardiomyopathy (PPCM) prior to disease onset remains a question of interest., Study Design: A retrospective nested case-control study was conducted to determine whether first trimester N -terminal pro-B type natriuretic peptide (NT-proBNP) or high sensitivity cardiac troponin I (hs-cTnI) differed among women who developed PPCM versus unaffected pregnancies. Cases were matched to unaffected women by age, race, parity, and gestational age of sample (control A) and then further by blood pressure and pregnancy weight gain (control B)., Results: First trimester NT-proBNP concentrations were numerically higher among women who subsequently developed PPCM (116 pg/mL [83-177]) as compared with women in control A (56.1 pg/mL [38.7-118.7], p  = 0.3) or control B (37.6 [23.3 - 53.8], p <0.05). A higher proportion of women who subsequently developed PPCM (50%) had detectable levels of hs-cTnI as compared with control A (0%, p  = 0.03) or control B (18.8%, p  = 0.52). Among both cases and controls, hs-cTnI values were low and often below the limit of detection., Conclusion: There were differences in first trimester NT-proBNP and hs-cTnI concentrations between women who subsequently developed PPCM and those who did not, raising the possibility the early pregnancy subclinical myocardial dysfunction may be associated with this late-pregnancy disease., Key Points: · First trimester NT-proBNP is numerically higher among women who subsequently develop PPCM.. · First trimester hs-cTnI was nominally higher among women who developed PPCM versus those who did not.. · A significant proportion of normal pregnant women have undetectable hs-cTnI.., Competing Interests: A.A.S. and I.T.G. are supported by an Institutional CRICO Patient Safety Award. J.L.J. reports being a trustee of the American College of Cardiology, receipt of grant support from Novartis Pharmaceuticals and Abbott Diagnostics and honoraria from Abbott, Janssen, Novartis, and Roche Diagnostics, and participation in clinical end point committees and data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, and Takeda; he is also supported in part by the Hutter Family Professorship. R.T. reports consultancy agreements with Fresenius Medical Care North America, Thermo Fisher, Moderna, Alnylum, Bayer, Genzyme/Sanofi, Kaneka, FDA, and Novartis; ownership interest in Aggamin LLC and Tvardi; researching funding from National Institutes of Health, Kaneka Corporation, and Genzyme/Sanofi; honoraria from Thermo Fisher, Roche Diagnostics, Pfizer, Merc, Amgen, Genzyme/Sanofi, Bayer, Alnylum, and maternal; patents and inventions with Thermo Fisher and Up-To-Date; and being a scientific advisor or member with Aggamin LLC and Vifor Pharma. M.J.W. reports being a trustee of the American College of Cardiology and on a clinical events committee for Abbvie. C.E.P. is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDKK) grant K23-DK-113218 and the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program. There are no other author disclosures., (Thieme. All rights reserved.)

Cardiac biomarkers are widely used in the nonpregnant population when acute cardiovascular (CV) pathology is suspected; however, the behavior of these biomarkers in the context of pregnancy is less well understood. Pregnant individuals often have symptoms that mimic those of cardiac dysfunction, and complications of pregnancy may include CV disease. This paper will summarize our current knowledge on the use of cardiac biomarkers in pregnancy and provide suggestions on how to use these tools in clinical practice based on the available evidence. Natriuretic peptides and troponin should not be measured routinely in uncomplicated pregnancy, where values should remain low as in the nonpregnant population. In the context of pre-existing or suspected CV disease, these biomarkers retain their negative predictive value. Elevations of both natriuretic peptides and troponin may occur without clear clinical significance in the immediate postpartum period. Elevations of these markers should always prompt further investigation into possible CV pathology., Competing Interests: Dr Sarma has received the CRICO patient safety award and the MGH Department of Medicine Innovation grant. Dr Januzzi has received the Hutter Family Professorship; is a trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from 10.13039/100014386Abbott Diagnostics, Applied Therapeutics, Innolife, and 10.13039/100004336Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Jana Care, Janssen, Novartis, Prevencio, and Roche Diagnostics; and participates in clinical end point committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr Quesada has received support from the 10.13039/100000002NIH (K23-HL151867). Dr Briller is an unpaid consultant for the Illinois Maternal Mortality Committee; and is on the Steering committee for the REBIRTH trial of bromocriptine in Peripartum Cardiomyopathy (NCT05180773). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Importance: A growing body of evidence suggests that adverse pregnancy outcomes (APOs), including hypertensive disorders of pregnancy, gestational diabetes (GD), preterm birth, and intrauterine growth restriction, are associated with increased risk of cardiometabolic disease and cardiovascular disease (CVD) later in life. Adverse pregnancy outcomes may therefore represent an opportunity to intervene to prevent or delay onset of CVD. The objective of this review was to summarize the current evidence for targeted postpartum interventions and strategies to reduce CVD risk in women with a history of APOs., Observations: A search of PubMed and Ovid for English-language randomized clinical trials, cohort studies, descriptive studies, and guidelines published from January 1, 2000, to April 30, 2021, was performed. Four broad categories of interventions were identified: transitional clinics, lifestyle interventions, pharmacotherapy, and patient and clinician education. Observational studies suggest that postpartum transitional clinics identify women who are at elevated risk for CVD and may aid in the transition to longitudinal primary care. Lifestyle interventions to increase physical activity and improve diet quality may help reduce the incidence of type 2 diabetes in women with prior GD; less is known about women with other prior APOs. Metformin hydrochloride may prevent development of type 2 diabetes in women with prior GD. Evidence is lacking in regard to specific pharmacotherapies after other APOs. Cardiovascular guidelines endorse using a history of APOs to refine CVD risk assessment and guide statin prescription for primary prevention in women with intermediate calculated 10-year CVD risk. Research suggests a low level of awareness of the link between APOs and CVD among both patients and clinicians., Conclusions and Relevance: These findings suggest that transitional clinics, lifestyle intervention, targeted pharmacotherapy, and clinician and patient education represent promising strategies for improving postpartum maternal cardiometabolic health in women with APOs; further research is needed to develop and rigorously evaluate these interventions. Future efforts should focus on strategies to increase maternal postpartum follow-up, improve accessibility to interventions across diverse racial and cultural groups, expand awareness of sex-specific CVD risk factors, and define evidence-based precision prevention strategies for this high-risk population.

Competing Interests: Competing Interests Statement: P.N. reports grant support from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis, personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech, and Novartis, and spousal employment at Vertex, all unrelated to the present work. All other authors do not report any disclosures.

Although some progress has been made in the last 3 decades to increase the number of women in clinical cardiology trials, review of recent cardiovascular literature demonstrates that women and underrepresented minority women are still underrepresented in most clinical cardiology trials. This is especially notable in trials of patients with coronary artery disease, heart failure with reduced ejection fraction, and arrhythmia studies, especially those involving devices and procedures. Despite the call from National Institutes of Health, Food and Drug Administration, Institute of Medicine, and various professional societies, the gap remains. This paper seeks to identify the barriers for low enrollment and retention from patient, clinician, research team, study design, and system perspectives, and offers recommendations to improve recruitment and retention in the current era., Competing Interests: Funding Support and Author Disclosures Dr Cho has received institutional research grants from Esperion, Novartis, AstraZeneca, and Amgen; and has been a consultant for Esperion, Amgen, and AstraZeneca. Dr Vest has received institutional research grants from Boehringer Ingelheim, CareDx, and Corvia. Dr O’Donoghue has received institutional research grants from Amgen, Novartis, AstraZeneca, Medimmune, Intarcia, and Merck; and has received honoraria from Amgen, Novartis, Janssen, AstraZeneca, and CRICO. Dr Ogunniyi has received institutional research grants from AstraZeneca, Boehringer Ingelheim, and Zoll; and has been a consultant for Pfizer. Dr Sarma has received an institutional research grant from CRICO. Dr Poole has received institutional research grants from AtriCure, Kestra, and Biotronic. Dr Mehran has received institutional research grants from Abbott Laboratories, Abiomed, Applied Therapeutics, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and Zoll; has received consultant fees from Boston Scientific, Cine-Med Research, Janssen Scientific Affairs, Medscape/WebMD; has had consultant fees paid to the institution from Abbott Laboratories, Abiomed (spouse), Bayer (spouse), Beth Israel Deaconess, Bristol Myers Squibb, CardiaWave, Chiesi, Concept Medical, DSI, Duke University, Idorsia Pharmaceuticals, Medtronic, Novartis, and Spectranetics/Philips/Volcano Corp; holds equity in Applied Therapeutics, Claret Medical, Elixir Medical, STEL, CONTROLRAD (spouse); and has been consultant (no fee) for Regeneron Pharmaceutical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We investigated the effect of galectin-3 (Gal-3) inhibition with modified citrus pectin on markers of collagen metabolism in a proof-of-concept randomized placebo-controlled trial of participants with elevated Gal-3 levels and hypertension. Although higher Gal-3 levels were associated with female sex, diabetes, and reduced glomerular filtration rate in cross-sectional analyses, treatment with modified citrus pectin did not change collagen markers. The effect of Gal-3 inhibition among individuals with heart failure warrants further investigation., Competing Interests: This work was supported by National Institutes of Health Grant Nos. NIH-5T32HL094301-07 (to Dr. Lau), R01-HL134893 (to Dr. Ho), R01-HL140224 (to Dr. Ho), and K24-HL153669 (to Dr. Ho) and a Gilead Sciences Research Scholar Award (to Dr. Ho). Dr. Ho has received research grants from Gilead Sciences and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Purpose of Review: Pregnancy is associated with significant hemodynamic changes, making it a potentially high-risk period for women with underlying cardiovascular disease. Echocardiography remains the preferred modality for diagnosis and monitoring of pregnant women with cardiovascular disease as it is widely available and does not require radiation. This paper reviews the role of echocardiography along the continuum of pregnancy in at-risk patients, with a focus on key cardiac disease states in pregnancy., Recent Findings: In the preconception stage, risk stratification scores such as CARPREG II, ZAHARA and the modified WHO remain central to counseling and planning. As such, echocardiography serves an important role in assessing the severity of pre-existing structural disease. Among women with pre-existing cardiovascular disease who become pregnant-as well as those who develop cardiovascular symptoms during pregnancy-echocardiography is a key imaging tool for assessment of hemodynamic and structural changes and is recommended as the first-line imaging modality when appropriate by both the American College of Obstetricians and Gynecologists (ACOG) and the Food and Drug Administration (FDA). However, routine screening intervals during pregnancy for various cardiac lesions are not well defined, resulting in clinical heterogeneity in care., Summary: Echocardiography is the imaging modality of choice for defining, risk stratifying, and monitoring cardiovascular changes throughout pregnancy. Once identified, at-risk patients should receive careful individual counseling and follow-up with a multidisciplinary team. Echocardiography serves as a widely available tool for serial monitoring of pregnant women with cardiovascular disease throughout pregnancy and the postpartum period., Competing Interests: Conflict of InterestHenrietta A. Afari declares that she has no conflict of interest. Esther F. Davis declares that she has no conflict of interest. Amy A. Sarma declares that she has no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Background: It remains disputed whether women are at excess risk of adverse outcomes versus men after non-ST-segment elevation acute coronary syndromes (NSTEACS) or whether differences are explained by discordant risk factors., Objectives: A sex-specific analysis of cardiovascular outcomes after NSTEACS across trials conducted by the Thrombolysis In Myocardial Infarction (TIMI) Study Group was performed to determine the impact of sex on cardiovascular outcomes in this dataset., Methods: Ten TIMI trials were identified that enrolled >2,500 patients with NSTEACS within 30 days of hospitalization. Cox proportional hazards models were used to examine the association of sex with major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, or stroke) after adjusting for relevant risk factors in individual trials; point estimates were then combined by using random effects models. Individual components of the composite outcome and all-cause mortality were also analyzed., Results: Among 68,730 patients with NSTEACS, 19,827 (29%) were women. Women were older and more frequently had hypertension, diabetes, prior heart failure, and renal impairment than men. Before considering relevant confounders, women were at similar risk of MACE compared with men (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 0.99 to 1.09; p = 0.16) but at higher risk of all-cause death (HR: 1.12; 95% CI: 1.01 to 1.24; p = 0.03). After adjustment for baseline differences, risks of MACE (HR: 0.93; 95% CI: 0.88 to 0.98; p < 0.01) and all-cause death (HR: 0.84; 95% CI: 0.78 to 0.90; p < 0.0001) were lower among women compared with men., Conclusions: After accounting for cardiovascular risk factors, women enrolled in clinical trials were at lower risk of MACE than men after NSTEACS. Women, however, remain undertreated with many evidence-based therapies., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Intracortical brain-computer interfaces (BCIs) can enable individuals to control effectors, such as a computer cursor, by directly decoding the user's movement intentions from action potentials and local field potentials (LFPs) recorded within the motor cortex. However, the accuracy and complexity of effector control achieved with such "biomimetic" BCIs will depend on the degree to which the intended movements used to elicit control modulate the neural activity. In particular, channels that do not record distinguishable action potentials and only record LFP modulations may be of limited use for BCI control. In contrast, a biofeedback approach may surpass these limitations by letting the participants generate new control signals and learn strategies that improve the volitional control of signals used for effector control. Here, we show that, by using a biofeedback paradigm, three individuals with tetraplegia achieved volitional control of gamma LFPs (40-400 Hz) recorded by a single microelectrode implanted in the precentral gyrus. Control was improved over a pair of consecutive sessions up to 3 days apart. In all but one session, the channel used to achieve control lacked distinguishable action potentials. Our results indicate that biofeedback LFP-based BCIs may potentially contribute to the neural modulation necessary to obtain reliable and useful control of effectors. NEW & NOTEWORTHY Our study demonstrates that people with tetraplegia can volitionally control individual high-gamma local-field potential (LFP) channels recorded from the motor cortex, and that this control can be improved using biofeedback. Motor cortical LFP signals are thought to be both informative and stable intracortical signals and, thus, of importance for future brain-computer interfaces.

Restoring communication for people with locked-in syndrome remains a challenging clinical problem without a reliable solution. Recent studies have shown that people with paralysis can use brain-computer interfaces (BCIs) based on intracortical spiking activity to efficiently type messages. However, due to neuronal signal instability, most intracortical BCIs have required frequent calibration and continuous assistance of skilled engineers to maintain performance. Here, an individual with locked-in syndrome due to brain stem stroke and an individual with tetraplegia secondary to amyotrophic lateral sclerosis (ALS) used a simple communication BCI based on intracortical local field potentials (LFPs) for 76 and 138 days, respectively, without recalibration and without significant loss of performance. BCI spelling rates of 3.07 and 6.88 correct characters/minute allowed the participants to type messages and write emails. Our results indicate that people with locked-in syndrome could soon use a slow but reliable LFP-based BCI for everyday communication without ongoing intervention from a technician or caregiver. NEW & NOTEWORTHY This study demonstrates, for the first time, stable repeated use of an intracortical brain-computer interface by people with tetraplegia over up to four and a half months. The approach uses local field potentials (LFPs), signals that may be more stable than neuronal action potentials, to decode participants' commands. Throughout the several months of evaluation, the decoder remained unchanged; thus no technical interventions were required to maintain consistent brain-computer interface operation.

Purpose of Review: To educate clinicians on cardiovascular considerations and management strategies surrounding pregnancy in childhood cancer survivors., Recent Findings: With advances in oncologic treatment, growing numbers of childhood cancer survivors are now able to consider pregnancy. A significant proportion of survivors have received cardiotoxic therapy, particularly anthracyclines, and/or chest radiation. Cardiomyopathy is the most common cardiac complication of cancer-directed therapy; pericardial disease, valvular disease, premature coronary artery disease, and conduction abnormalities are other potential sequelae. In female survivors of childhood malignancy, cardiac evaluation should be performed prior to pregnancy as subclinical disease has the potential to be unmasked by the hemodynamic stress of pregnancy. However, limited data exist on pregnancy outcomes after cancer survivorship. With appropriate management, maternal and fetal outcomes in pregnancy following childhood cancer are generally favorable. Further research is needed to understand the incidence of cardiac complications among childhood cancer survivors, strategies to prevent these complications, optimal cardiovascular management during pregnancy and the postpartum period, and on the impact of pregnancy itself on the natural history of treatment-related cardiotoxicity.

Objective: Brain-computer interfaces (BCIs) can enable individuals with tetraplegia to communicate and control external devices. Though much progress has been made in improving the speed and robustness of neural control provided by intracortical BCIs, little research has been devoted to minimizing the amount of time spent on decoder calibration., Approach: We investigated the amount of time users needed to calibrate decoders and achieve performance saturation using two markedly different decoding algorithms: the steady-state Kalman filter, and a novel technique using Gaussian process regression (GP-DKF)., Main Results: Three people with tetraplegia gained rapid closed-loop neural cursor control and peak, plateaued decoder performance within 3 min of initializing calibration. We also show that a BCI-naïve user (T5) was able to rapidly attain closed-loop neural cursor control with the GP-DKF using self-selected movement imagery on his first-ever day of closed-loop BCI use, acquiring a target 37 s after initiating calibration., Significance: These results demonstrate the potential for an intracortical BCI to be used immediately after deployment by people with paralysis, without the need for user learning or extensive system calibration.

Women are a consistent minority in the field of cardiology, with concerns regarding balancing career and parenting responsibilities often cited as a contributing factor to this under-representation. To investigate the impact that a career in cardiology may have on the family planning decisions of female cardiologists, the Women in Cardiology section of the American College of Cardiology conducted a voluntary anonymous survey. The following perspective highlights lessons learned from the survey, and potential solutions to the issues surrounding maternity leave, radiation exposure during pregnancy, and breastfeeding accommodations raised by these data. Given that most female cardiologists are pregnant at some point during their careers, particularly during the vulnerable periods of training and early career, improving the experience of pregnancy and early parenthood for all cardiologists may secure the best possible candidates to the field of cardiology., (Copyright © 2017 American College of Cardiology Foundation. All rights reserved.)

Brain-computer interfaces (BCIs) aim to restore independence to people with severe motor disabilities by allowing control of acursor on a computer screen or other effectors with neural activity. However, physiological and/or recording-related nonstationarities in neural signals can limit long-term decoding stability, and it would be tedious for users to pause use of the BCI whenever neural control degrades to perform decoder recalibration routines. We recently demonstrated that a kinematic decoder (i.e. a decoder that controls cursor movement) can be recalibrated using data acquired during practical point-and-click control of the BCI by retrospectively inferring users' intended movement directions based on their subsequent selections. Here, we extend these methods to allow the click decoder to also be recalibrated using data acquired during practical BCI use. We retrospectively labeled neural data patterns as corresponding to "click" during all time bins in which the click log-likelihood (decoded using linear discriminant analysis, or LDA) had been above the click threshold that was used during real-time neural control. We labeled as "non-click" those periods that the kinematic decoder's retrospective target inference (RTI) heuristics determined to be consistent with intended cursor movement. Once these neural activity patterns were labeled, the click decoder was calibrated using standard supervised classifier training methods. Combined with real-time bias correction and baseline firing rate tracking, this set of "retrospectively labeled" decoder calibration methods enabled a BrainGate participant with amyotrophic lateral sclerosis (T9) to type freely across 11 research sessions spanning 29days, maintaining high-performance neural control over cursor movement and click without needing to interrupt virtual keyboard use for explicit calibration tasks. By eliminating the need for tedious calibration tasks with prescribed targets and pre-specified click times, this approach advances the potential clinical utility of intracortical BCIs for individuals with severe motor disability., (Published by Elsevier Ltd.)

Neuromodulation systems based on electrical stimulation can be used to investigate, probe, and potentially treat a range of neurological disorders. The effects of ongoing neural state and dynamics on stimulation response, and of stimulation parameters on neural state, have broad implications for the development of closed-loop neuro-modulation approaches. We describe the development of a modular, low-latency platform for pre-clinical, closed-loop neuromodulation studies with human participants. We illustrate the uses of the platform in a stimulation case study with a person with epilepsy undergoing neuro-monitoring prior to resective surgery. We demonstrate the efficacy of the system by tracking interictal epileptiform discharges in the local field potential to trigger intracranial electrical stimulation, and show that the response to stimulation depends on the neural state.

Brain-computer interfaces (BCIs) promise to restore independence for people with severe motor disabilities by translating decoded neural activity directly into the control of a computer. However, recorded neural signals are not stationary (that is, can change over time), degrading the quality of decoding. Requiring users to pause what they are doing whenever signals change to perform decoder recalibration routines is time-consuming and impractical for everyday use of BCIs. We demonstrate that signal nonstationarity in an intracortical BCI can be mitigated automatically in software, enabling long periods (hours to days) of self-paced point-and-click typing by people with tetraplegia, without degradation in neural control. Three key innovations were included in our approach: tracking the statistics of the neural activity during self-timed pauses in neural control, velocity bias correction during neural control, and periodically recalibrating the decoder using data acquired during typing by mapping neural activity to movement intentions that are inferred retrospectively based on the user's self-selected targets. These methods, which can be extended to a variety of neurally controlled applications, advance the potential for intracortical BCIs to help restore independent communication and assistive device control for people with paralysis., (Copyright © 2015, American Association for the Advancement of Science.)

Neural prostheses have the potential to improve the quality of life of individuals with paralysis by directly mapping neural activity to limb- and computer-control signals. We translated a neural prosthetic system previously developed in animal model studies for use by two individuals with amyotrophic lateral sclerosis who had intracortical microelectrode arrays placed in motor cortex. Measured more than 1 year after implant, the neural cursor-control system showed the highest published performance achieved by a person to date, more than double that of previous pilot clinical trial participants.

The prevailing view of motor cortex holds that motor cortical neural activity represents muscle or movement parameters. However, recent studies in non-human primates have shown that neural activity does not simply represent muscle or movement parameters; instead, its temporal structure is well-described by a dynamical system where activity during movement evolves lawfully from an initial pre-movement state. In this study, we analyze neuronal ensemble activity in motor cortex in two clinical trial participants diagnosed with Amyotrophic Lateral Sclerosis (ALS). We find that activity in human motor cortex has similar dynamical structure to that of non-human primates, indicating that human motor cortex contains a similar underlying dynamical system for movement generation.

This proof-of-concept study demonstrates the application of a novel nucleic acid detection platform to detect Clostridium difficile in subjects presenting with acute diarrheal symptoms. This method amplifies three genes associated with C. difficile infection, including genes and deletions (cdtB and tcdC) associated with hypervirulence attributed to the NAP1/027/BI strain. Amplification of DNA from the tcdB, tcdC, and cdtB genes was performed using a droplet-based sandwich platform with quantitative real-time PCR in microliter droplets to detect and identify the amplified fragments of DNA. The device and identification system are simple in design and can be integrated as a point-of-care test to help rapidly detect and identify C. difficile strains that pose significant health threats in hospitals and other health-care communities., (Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Rapid diagnostic identification of the human H5 influenza virus is a strategic cornerstone for outbreak prevention. We recently reported a method for direct detection of viral RNA from a highly pathogenic human H5 influenza strain (A/Hanoi/30408/2005(H5N1)), which necessarily was transcribed in vitro from non-viral sources. This article provides an in-depth analysis of the reaction conditions for in vitro transcription (IVT) of full-length influenza H5 RNA, which is needed for diagnostic RNA production, for the T7 and SP6 phage promoter systems. Gel analysis of RNA transcribed from plasmids containing the H5 sequence between a 5' SP6 promoter and 3' restriction site (BsmBI) showed that three sequence-verified bands at 1,776, 784, and 591 bases were consistently produced, whereas only one 1,776-base band was expected. These fragments were not observed in H1 or H3 influenza RNA transcribed under similar conditions. A reverse complement of the sequence produced only a single band at 1,776 bases, which suggested either self-cleavage or early termination. Aliquots of the IVT reaction were quenched with EDTA to track the generation of the bands over time, which maintained a constant concentration ratio. The H5 sequence was cloned with T7 and SP6 RNA polymerase promoters to allow transcription in either direction with either polymerase. The T7 transcription product from purified, restricted plasmids in the vRNA direction only produced the 1,776-base full-length sequence and the 784-base fragment, instead of the three bands generated by the SP6 system, suggesting an early termination mechanism. Additionally, the T7 system produced a higher fraction of full-length vRNA transcripts than the SP6 system did under similar reaction conditions. By sequencing we identified a type II RNA hairpin loop terminator, which forms in a transcription direction-dependent fashion. Variation of the magnesium concentration produced the greatest impact on termination profiles, where some reaction mixtures were unable to produce full-length transcripts. Optimized conditions are presented for the T7 and SP6 phage polymerase systems to minimize these early termination events during in vitro transcription of H5 influenza vRNA.

The piriform cortex (PCX) is a trilaminar paleocortex that is of interest for its role in odor coding and as a model for studying general principles of cortical sensory processing. While the structure of the mature PCX has been well characterized, its development is poorly understood. Notably, the kinetics as well as the cellular and morphological basis of the postnatal events that shape the PCX remain unknown. We followed the cellular fates of early- versus late-born cells in layer II of the anterior PCX, with a focus on the molecular maturation of pyramidal cells and the kinetics of their differentiation. We showed that: 1) early-born pyramidal cells differentiate more rapidly than late-born cells and 2) the position of pyramidal cells within the thickness of layer II determines the kinetics of their molecular maturation. We then examined the postnatal development of cortical lamination and showed that the establishment of inhibitory networks in the PCX proceeds through an increase in the density of inhibitory synapses despite a decrease in the number of interneurons. Together, our results provide a more comprehensive view of the postnatal development of the anterior PCX and reveal both similarities and differences in the development of this paleocortex versus the neocortex.