Is our initial evaluation of patients admitted for syncope guideline-directed and cost-effective?

INTRODUCTION: Recent American College of Cardiology and European Society of Cardiology guidelines for syncope evaluation help distinguish high-cardiac risk patients from those with low-risk orthostatic and neurogenic syncope. Inpatient evaluation is recommended if at least one high-risk feature is present. OBJECTIVE: To assess guideline adherence and its impact on hospitalization in patients who presented with syncope before and after the introduction of guideline-based syncope protocol in the emergency department (ED). METHODS: All adult patients admitted to general medicine from the ED with the primary diagnosis of syncope in the months of October 2016 and October 2018 (before and after the introduction of syncope protocol in 2017). Electronic charts were retrospectively reviewed for high-risk cardiac features and orthostatic blood pressure measurement. RESULTS: Sixty patients were admitted for syncope in October 2016 (n = 32) and October 2018 (n = 28), out of which 33 (55%) were female and 47 (78.3%) were over age 50. Forty-five patients had at least one high-risk feature. Excluding one patient with an alternate diagnosis at discharge, 14 out of 60 patients (23.3%) admitted for syncope did not have any high-risk feature. Orthostatic blood pressure was measured in 3 patients (5%) in the ED and 27 patients (45%) later in the hospitalization. Six out of eight patients with implanted cardioverter-defibrillator or pacemaker had their devices interrogated. After the introduction of syncope protocol, there was an improvement in the proportion of high-risk patients admitted [68.7% (22/32) in October 2016 vs. 82.1% (23/28) in October 2018]. CONCLUSION: Utilizing syncope protocol in the ED may improve guideline adherence, direct appropriate disposition, and reduce healthcare expenses.

Strain Modulated Superlattices in Graphene.

Numerous theoretically proposed devices and novel phenomena have sought to take advantage of the intense pseudogauge fields that can arise in strained graphene. Many of these proposals, however, require fields to oscillate with a spatial frequency smaller than the magnetic length, while to date only the generation and effects of fields varying at a much larger length scale have been reported. Here, we describe the creation of short wavelength, periodic pseudogauge-fields using rippled graphene under extreme (>10%) strain and study of its effects on Dirac electrons. Combining scanning tunneling microscopy and atomistic calculations, we find that spatially oscillating strain generates a new quantization different from the familiar Landau quantization. Graphene ripples also cause large variations in carbon-carbon bond length, creating an effective electronic superlattice within a single graphene sheet. Our results thus also establish a novel approach of synthesizing effective 2D lateral heterostructures by periodically modulating lattice strain.

Coronary Revascularization in High-Risk Stable Patients With Significant Comorbidities: Challenges in Decision-Making.

PURPOSE OF REVIEW: There is a growing cohort of complex high-risk patients with stable ischemic heart disease (SIHD) who present for coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). These patients are older, have complex coronary disease, and a substantial comorbidity burden including frailty. The procedural risks and outcomes of CABG and PCI in these patients are more difficult to assess based on the available literature, which has generally studied a younger population with a lower comorbidity burden. RECENT FINDINGS: There have been initiatives to recalibrate and expand risk models derived from procedural registries to inform the care of complex higher-risk patients, including patients "turned down" for CABG. There is greater recognition of the need for improved assessment of risk, quality, and benefits of coronary revascularization in higher-risk SIHD patients with a substantial comorbidity burden. Clinicians and patients should be aware that there are significant evidence gaps regarding revascularization in complex high-risk patients. The limitations of procedural-derived risk scores should be understood when presenting treatment options. Future randomized controlled trials and expanded registries are greatly desired and should be achievable. Meanwhile, a multidisciplinary heart team approach should be employed for proper decision-making.

RAB-10-GTPase-mediated regulation of endosomal phosphatidylinositol-4,5-bisphosphate.

Caenorhabditis elegans RAB-10 and mammalian Rab10 are key regulators of endocytic recycling, especially in the basolateral recycling pathways of polarized epithelial cells. To understand better how RAB-10 contributes to recycling endosome function, we sought to identify RAB-10 effectors. One RAB-10-binding partner that we identified, CNT-1, is the only C. elegans homolog of the mammalian Arf6 GTPase-activating proteins ACAP1 and ACAP2. Arf6 is known to regulate endosome-to-plasma membrane transport, in part through activation of type I phophatidylinositol-4-phosphate 5 kinase. Here we show that CNT-1 binds to RAB-10 through its C-terminal ankyrin repeats and colocalizes with RAB-10 and ARF-6 on recycling endosomes in vivo. Furthermore, we find that RAB-10 is required for the recruitment of CNT-1 to endosomal membranes in the intestinal epithelium. Consistent with negative regulation of ARF-6 by RAB-10 and CNT-1, we found overaccumulation of endosomal phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] in cnt-1 and rab-10 mutants and reduced endosomal PI(4,5)P2 levels in arf-6 mutants. These mutants produced similar effects on endosomal recruitment of the PI(4,5)P2-dependent membrane-bending proteins RME-1/Ehd and SDPN-1/Syndapin/Pacsin and resulted in endosomal trapping of specific recycling cargo. Our studies identify a RAB-10-to-ARF-6 regulatory loop required to regulate endosomal PI(4,5)P2, a key phosphoinositide in membrane traffic.

EHBP-1 functions with RAB-10 during endocytic recycling in Caenorhabditis elegans.

Caenorhabditis elegans RAB-10 functions in endocytic recycling in polarized cells, regulating basolateral cargo transport in the intestinal epithelia and postsynaptic cargo transport in interneurons. A similar role was found for mammalian Rab10 in MDCK cells, suggesting that a conserved mechanism regulates these related pathways in metazoans. In a yeast two-hybrid screen for binding partners of RAB-10 we identified EHBP-1, a calponin homology domain (CH) protein, whose mammalian homolog Ehbp1 was previously shown to function during endocytic transport of GLUT4 in adipocytes. In vivo we find that EHBP-1-GFP colocalizes with RFP-RAB-10 on endosomal structures of the intestine and interneurons and that ehbp-1 loss-of-function mutants share with rab-10 mutants specific endosome morphology and cargo localization defects. We also show that loss of EHBP-1 disrupts transport of membrane proteins to the plasma membrane of the nonpolarized germline cells, a defect that can be phenocopied by codepletion of RAB-10 and its closest paralog RAB-8. These results indicate that RAB-10 and EHBP-1 function together in many cell types and suggests that there are differences in the level of redundancy among Rab family members in polarized versus nonpolarized cells.

Regulation of endosomal clathrin and retromer-mediated endosome to Golgi retrograde transport by the J-domain protein RME-8.

After endocytosis, most cargo enters the pleiomorphic early endosomes in which sorting occurs. As endosomes mature, transmembrane cargo can be sequestered into inwardly budding vesicles for degradation, or can exit the endosome in membrane tubules for recycling to the plasma membrane, the recycling endosome, or the Golgi apparatus. Endosome to Golgi transport requires the retromer complex. Without retromer, recycling cargo such as the MIG-14/Wntless protein aberrantly enters the degradative pathway and is depleted from the Golgi. Endosome-associated clathrin also affects the recycling of retrograde cargo and has been shown to function in the formation of endosomal subdomains. Here, we find that the Caemorhabditis elegans endosomal J-domain protein RME-8 associates with the retromer component SNX-1. Loss of SNX-1, RME-8, or the clathrin chaperone Hsc70/HSP-1 leads to over-accumulation of endosomal clathrin, reduced clathrin dynamics, and missorting of MIG-14 to the lysosome. Our results indicate a mechanism, whereby retromer can regulate endosomal clathrin dynamics through RME-8 and Hsc70, promoting the sorting of recycling cargo into the retrograde pathway.