The ciliopathy Joubert syndrome is marked by cerebellar vermis hypoplasia, a phenotype for which the pathogenic mechanism is unclear1–3. In order to investigate Joubert syndrome pathogenesis, we have examined mice with mutated Ahi1, the first identified Joubert syndrome gene4,5. These mice exhibit cerebellar hypoplasia with a vermis/midline fusion defect early in development. This defect is concomitant with expansion of the roof plate and is also evident in a mouse mutant for another Joubert syndrome gene, Cep2906,7. Further, fetal magnetic resonance imaging (MRI) from human subjects with Joubert syndrome reveals a similar midline cleft suggesting parallel pathogenic mechanisms. Previous evidence has suggested a role for Jouberin (Jbn), the protein encoded by Ahi1, in canonical Wnt signaling8. Consistent with this, we found decreased Wnt reporter activity at the site of hemisphere fusion in the developing cerebellum of Ahi1 mutant mice. This decrease was accompanied by reduced proliferation at the site of fusion. Finally, treatment with lithium, a Wnt pathway agonist9, partially rescued this phenotype. Our findings implicate a defect in Wnt signaling in the cerebellar midline phenotype seen in Joubert syndrome, which can be overcome with Wnt stimulation.

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Heart disease affects 1 in 3 individuals in the United States, and the prevalence of heart failure (HF) is increasing exponentially. Although our understanding of the disease progression of congestive HF (CHF) has advanced, refining the areas of diagnosis, risk stratification, prognosis, and treatment is still needed. The natriuretic peptides, specifically B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have shown promise in clinical practice. Brain natriuretic peptide is released from cardiac ventricular myocytes in response to volume or pressure overload. Rapid measurement of plasma BNP or NT-proBNP has been shown to increase the diagnostic accuracy of HF exacerbations. A cutoff value of 100 pg/mL has a sensitivity and specificity of 90% and 73%, respectively, according to the Breathing Not Properly Study. In addition, BNP and NT-proBNP have been considered independent predictors of adverse outcome. One study calculated a 35% increase in risk of death due to HF for every 100-pg/mL increase in BNP level. Lastly, natriuretic peptides have been known to decrease following medical therapy of HF, suggesting the role of their measurement in monitoring inpatient disease progression and outpatient medical programs. The future of natriuretic peptides lies in risk stratification in other cardiac diseases, such as acute coronary syndrome, and possibly determining severity of valvular disease. Although there is substantial work done in elucidating the power of natriuretic peptides in clinical practice, more research is necessary to reach a consensus regarding how to appropriately utilize them in treatment regimens.

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Background Lipomatous hypertrophy of the interatrial septum (LHIAS) is a common finding on transthoracic echocardiogram (TTE). Occasionally, the appearance of LHIAS is atypical and multimodality imaging is helpful to make the diagnosis. We present a case of atypical LHIAS to highlight the potential aetiologies for an interatrial septal mass and review features on multimodality imaging that help decrease uncertainty and establish a diagnosis. Case summary A 64-year-old man with a history of hypertension, diabetes mellitus, and coronary artery disease with multiple percutaneous coronary interventions presented to the emergency room with chest pain. Transthoracic echocardiogram showed a homogenous echo-dense, intracardiac mass present within the interatrial septum. Computed tomography (CT) angiogram of the chest showed a homogenous mass similar in radiodensity to extracardiac and pericardial fat. Cardiac magnetic resonance (CMR) confirmed LHIAS by homogenous signal that was nulled on fat suppression images. Discussion This case highlights that while most LHIAS has the standard ‘dumbbell’ appearance on TTE, there are instances where it can appear more like an adherent mass prompting a wider differential. Unenhanced CT of the heart can be used to confirm LHIAS by the presence of low attenuation values for tissue. Alternatively, CMR can be used for tissue characterization and confirmation of LHIAS. Precontrast T2/T1-weighted CMR images with steady-state free precession show high signal intensity in the area of LHIAS and produce a black/hypointense boundary effect between fat and myocardium. A multimodality approach is crucial in arriving at the appropriate diagnosis using the tissue characterization capabilities of CT and CMR.

Background Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality among women, with younger women being disproportionately affected by traditional cardiovascular risk factors such as dyslipidemia. Despite recommendations for lipid screening in early adulthood and the risks associated with maternal dyslipidemia during pregnancy, many younger women lack access to and utilization of early screening. Accordingly, our objective was to assess the prevalence of and disparities in lipid screening and awareness of high cholesterol as an atherosclerotic cardiovascular disease risk factor among pregnant women receiving prenatal care. Methods and Results We invited 234 pregnant women receiving prenatal care at 1 of 3 clinics affiliated with the University of Pennsylvania Health System to complete our survey. A total of 200 pregnant women (86% response rate) completed the survey. Overall, 59% of pregnant women (mean age 32.2 [±5.7] years) self‐reported a previous lipid screening and 79% of women were aware of high cholesterol as an atherosclerotic cardiovascular disease risk factor. Stratified by racial/ethnic subgroups, non‐Hispanic Black women were less likely to report a prior screening (43% versus 67%, P =0.022) and had lower levels of awareness (66% versus 92%, P <0.001) compared with non‐Hispanic White women. Non‐Hispanic Black women were more likely to see an obstetrician/gynecologist for their usual source of non‐pregnancy care compared with non‐Hispanic White women (18% versus 5%, P =0.043). Those seeing an obstetrician/gynecologist for usual care were less likely to report a prior lipid screening compared with those seeing a primary care physician (29% versus 63%, P =0.007). Conclusions Significant racial/ethnic disparities persist in lipid screening and risk factor awareness among pregnant women. Prenatal care may represent an opportunity to enhance access to and uptake of screening among younger women and reduce variations in accessing preventive care services.

Heart failure is extremely prevalent and is associated with significant mortality, morbidity and cost. Studies have already established mortality benefit with the use of neurohormonal blockade therapy in systolic failure. Unfortunately, physical signs and symptoms of heart failure lack diagnostic sensitivity and specificity, and medication doses proven to improve mortality in clinical trials are often not achieved. Brain natriuretic peptide (BNP) has proven to be of clinical use in the diagnosis and prognosis of heart failure, and recent efforts have been taken to further elucidate its role in guiding heart failure management. Multiple studies have been conducted on outpatient guided management, and although still controversial, there is a trend towards improved outcomes. Inpatient studies are lacking, but preliminary data suggest various BNP cut-off values, as well as percentage changes in BNP, that could be useful in predicting outcomes and improving mortality. In the future, heart failure management will probably involve an algorithm using clinical assessment and a multibiomarker-guided approach.