Complications associated with use of the Wolverine cutting balloon: insights from the Manufacturer and User Facility Device Experience (MAUDE) database.

Objectives: The Wolverine cutting balloon (CB) (Boston Scientific) is a specialized balloon catheter with microsurgical blades that is used for balloon-resistant lesions. The Manufacturer and User Facility Device Experience (MAUDE) database serves as a repository for reports of medical device complications. The aim of this study was to analyze complications associated with CB use during percutaneous coronary intervention in real-world contemporary practice.

PFO Leading to Concomitant Platypnea-Orthodeoxia Syndrome and Stroke.

Platypnea-orthodeoxia syndrome is a rare entity seen in patients with patent foramen ovale, characterized by dyspnea and arterial desaturation in the upright position. We describe a case of a patient who presented with cryptogenic stroke, evidence of right-to-left interatrial shunting, and refractory hypoxemia necessitating closure of his patent foramen ovale.

Atrial Fibrillation Following Esophageal Stent Placement: A Rare but Important Complication to Recognize.

There is a risk of new-onset atrial fibrillation (AF) in patients with esophageal cancer treated with neoadjuvant chemotherapy/radiotherapy followed by esophagectomy. However, the occurrence of AF after stent placement for esophageal cancer is less explored. Here, we present a case of esophageal cancer where AF developed poststent placement.

The tether function of the anoctamins.

The core functions of the anoctamins are Cl channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites.

OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage.

Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which is effectively prevented when the cell is at rest. Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca2+ directly released from acidic Ca2+ stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by Tmem63a) as an organellar Ca2+ regulator protein integral to the membrane of secretory granules that controlled Ca2+ release via inhibition of TPC1 and TPC2 currents.

PtdSer as a signaling lipid determined by privileged localization of ORP5 and ORP8 at ER/PM junctional foci to determine PM and ER PtdSer/PI(4)P ratio and cell function.

The membrane contact site ER/PM junctions are hubs for signaling pathways, including Ca signaling. Phosphatidylserine (PtdSer) mediates various physiological functions; however, junctional PtdSer composition and the role of PtdSer in Ca signaling and Ca-dependent gene regulation are not understood. Here, we show that STIM1-formed junctions are required for PI(4)P/PtdSer exchange by ORP5 and ORP8, which have reciprocal lipid exchange modes and function as a rheostat that sets the junctional PtdSer/PI(4)P ratio.

Prevalence and Safety of Prescribing PPIs with Clopidogrel in Palestine.

Background: Proton pump inhibitors (PPIs) are commonly prescribed medications that are thought to increase the risk of cardiovascular events because they reduce the effectiveness of clopidogrel via shared hepatic pathways.

Objective: This study examined the prevalence of concomitant prescribing of clopidogrel/PPI among patients diagnosed with acute coronary syndrome and the adverse cardiovascular event associated with this interaction.

Methods: A retrospective cohort study was conducted by retrieving patient data from the Nat Health Insurance claims processor database in Palestine.

Assessment of Volume Status in Hospitalized Patients With Chronic Heart Failure.

Assessment of volume status in hospitalized patients with heart failure is a critically important diagnostic skill that clinicians utilize frequently. However, accurate assessment is challenging and there is often significant inter-provider disagreement. This review serves as an appraisal of current methods of volume assessment amongst different categories of evaluation including patient history, physical exam, laboratory analysis, imaging, and invasive procedures.

Hydrophobic interactions within the C terminus pole helices tunnel regulate calcium-dependent inactivation of TRPC3 in a calmodulin-dependent manner.

Recent structural studies have shown that the carboxyl-terminus of many TRP channels, including TRPC3, are folded into a horizontal rib helix that is connected to the vertical pole helix, which play roles in inter-structural interactions and multimerization. In a previous work we identified I807 located in the pole helix with a role in regulation of TRPC3 by STIM1 (Lee et al., 2014, Liu et al.

The intracellular Ca channel TRPML3 is a PI3P effector that regulates autophagosome biogenesis.

Autophagy is a multiple fusion event, initiating with autophagosome formation and culminating with fusion with endo-lysosomes in a Ca-dependent manner. The source of Ca and the molecular mechanism by which Ca is provided for this process are not known. The intracellular Ca permeable channel transient receptor potential mucolipin 3 (TRPML3) localizes in the autophagosome and interacts with the mammalian autophagy-related protein 8 (ATG8) homolog GATE16.

The sun, cholesterol and Orai1 conspire in melanoma.

How does skin cancer become metastatic? A recent study by Gross et al (2022) reports a novel pathway by which UV radiation acts on cholesterol biosynthesis to control Ca influx by Orai1, causing protein O-GlcNAcylation that promotes transformation to invasive melanoma.

TRPC3 channel gating by lipids requires localization at the ER/PM junctions defined by STIM1.

TRPC3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a lipid-regulated, Ca2+-permeable channel that mediates essential components of the receptor evoked Ca2+ signal. The modes and mechanisms by which lipids regulate TRPC3 and other members of the TRPC channel family are not well understood. Here, we report that PI(4,5)P2 regulates TRPC3 in three independent modes.

Letter to the editor to update the article "Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials".

Our recently published systematic review and meta-analysis of heart failure (HF) remote monitoring using implantable devices (Hajduczok et al. in HF Reviews 1-20, 1) has been updated to reflected new data from the GUIDE-HF trial (Lindenfeld et al. in Lancet 398(10304):991-1001, 2).

Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

In heart failure (HF) patients, remote monitoring using implantable devices may be used to predict and reduce HF exacerbations and mortality. Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. A systematic review and meta-analysis of RCTs testing remote monitoring versus standard of care for management of HF patients was performed.

Cl as a bona fide signaling ion.

Cl is the major extracellular (Cl) and intracellular (Cl) anion whose concentration is actively regulated by multiple transporters. These transporters generate Cl gradients across the plasma membrane and between the cytoplasm and intracellular organelles. [Cl] changes rapidly in response to cell stimulation and influences many physiological functions, as well as cellular and systemic homeostasis.

Ca Signaling in Exocrine Cells.

Calcium (Ca) and cyclic AMP (cAMP) signaling cross talk and synergize to stimulate the cardinal functions of exocrine cells, regulated exocytosis, and fluid and electrolyte secretion. This physiological process requires the organization of the two signaling pathways into complexes at defined cellular domains and close placement. Such domains are formed by membrane contact sites (MCS).

Ca Influx Channel Inhibitor SARAF Protects Mice From Acute Pancreatitis.

Background & Aims: Pancreatitis is characterized by increased influx of Ca into acinar cells, by unknown mechanisms. Inhibitors of Ca influx channels could be effective in treating acute pancreatitis, but these have deleterious side effects that can result in death. We investigated the expression patterns and functions of acinar cell Ca channels and factors that regulate them during development of acute pancreatitis, along with changes in the channel inactivator store-operated calcium entry-associated regulatory factor (SARAF).

Homer2 and Homer3 modulate RANKL-induced NFATc1 signaling in osteoclastogenesis and bone metabolism.

The receptor activator of nuclear factor-kappa B ligand (RANKL) induces osteoclastogenesis by induction of Ca2+ oscillation, calcineurin activation and translocation into the nucleus of nuclear factor of activated T cells type c1 (NFATc1). Homer proteins are scaffold proteins. They regulate Ca2+ signaling by modulating the activity of multiple Ca2+ signaling proteins.

Anoctamin 8 tethers endoplasmic reticulum and plasma membrane for assembly of Ca signaling complexes at the ER/PM compartment.

Communication and material transfer between membranes and organelles take place at membrane contact sites (MCSs). MCSs between the ER and PM, the ER/PM junctions, are the sites where the ER Ca sensor STIM1 and the PM Ca influx channel Orai1 cluster. MCSs are formed by tether proteins that bridge the opposing membranes, but the identity and role of these tethers in receptor-evoked Ca signaling is not well understood.

Oncogenes calling on a lysosomal Ca channel.

Oncogene‐dependent cancers upregulate and use lysosomal biogenesis for nutrient supply. It is unclear which lysosomal proteins and functions are essential for cell proliferation and tumor growth. A study by Jung in this issue of shows that increased levels of the lysosomal Ca release channel TRPML1 and its activator PI(3,5)P in HRAS ‐dependent tumors are essential for cell proliferation and tumor growth 1.

Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate Lithogenesis.

Background: In the kidney, low urinary citrate increases the risk for developing kidney stones, and elevation of luminal succinate in the juxtaglomerular apparatus increases renin secretion, causing hypertension. Although the association between stone formation and hypertension is well established, the molecular mechanism linking these pathophysiologies has been elusive.

Methods: To investigate the relationship between succinate and citrate/oxalate levels, we assessed blood and urine levels of metabolites, renal protein expression, and BP (using 24-hour telemetric monitoring) in male mice lacking slc26a6 (a transporter that inhibits the succinate transporter NaDC-1 to control citrate absorption from the urinary lumen).

Exosomal release through TRPML1-mediated lysosomal exocytosis is required for adipogenesis.

The lysosomal Ca permeable channel TRPML1 (MCOLN1) plays key roles in lysosomal membrane trafficking, including the fusion of late endosomes to lysosomes and lysosomal exocytosis, both of which are essential for release of exosomes into the extracellular milieu. Multiple lines of evidence indicate that the contents of adipocyte-derived exosomes mediate diverse cellular responses, including adipogenic differentiation. In this study, we aimed to define the potential roles of TRPML1 in lysosomal membrane trafficking during adipogenesis and in exosomal release.