Common and distinct risk profiles of asymptomatic extra- and intracranial atherosclerosis in the Nagahama cohort.

BACKGROUND AND PURPOSE: Atherosclerotic burden increases the risk of both extracranial internal carotid artery stenosis (ICS) and intracranial large artery disease (ICAD). However, the differences in risk profiles have not been thoroughly investigated. METHODS: Participants were recruited from the Nagahama study cohort in Japan. Individuals over 60 years old who underwent 1.5-T head and neck magnetic resonance angiography (MRA) between July 2013 and February 2017 were included. ICAD was defined as WASID ≥ 50 %, and ICS was defined as NSCET ≥ 30 %. The prevalence and association of risk factors, including proatherogenic and proinflammatory factors, and the p.R4810K variant in the RNF213 gene, were investigated. Multivariable logistic regression analyses were performed. RESULTS: A total of 3089 individuals participated in the study, with a mean age of 68.1 ± 5.3 years, and 36.0 % were males. Among them, 52 (1.7 %) had ICS, 119 (3.8 %) had ICAD, and 15 (0.49 %) had both conditions. Alopecia areata was an independent predictor for both ICS (Odds ratio [OR] 3.5; 95 % CI 1.3-8.3) and ICAD (OR 2.1; 95 % CI 1.0-3.9). Diabetes (OR 3.7; 95 % CI 2.0-7.0) and older age (OR 2.4; 95 % CI 1.2-4.5) were associated only with ICS, while the RNF213 variant was associated with only ICAD (OR 5.7; 95 % CI 1.6-16.0). ICS and ICAD were also independently associated with each other. CONCLUSIONS: In this MRA-based large scale study, alopecia areata, known as a systemic inflammatory disease, was shown to be a common risk factor for ICS and ICAD. While conventional atherosclerotic factors were associated with ICS, non-atherosclerotic factors appear to contribute to ICAD in Japan.

Sequestration of microRNA-mediated target repression by the Ago2-associated RNA-binding protein FAM120A.

Argonaute (Ago) proteins interact with various binding partners and play a pivotal role in microRNA (miRNA)-mediated silencing pathways. By utilizing immunoprecipitation followed by mass spectrometry to determine cytoplasmic Ago2 protein complexes in mouse embryonic stem cells (mESCs), we identified a putative RNA-binding protein FAM120A (also known as OSSA/C9ORF10) as an Ago2 interacting protein. Individual nucleotide resolution cross-linking and immunoprecipitation (iCLIP) analysis revealed that FAM120A binds to homopolymeric tracts in 3'-UTRs of about 2000 mRNAs, particularly poly(G) sequences. Comparison of FAM120A iCLIP and Ago2 iCLIP reveals that greater than one-third of mRNAs bound by Ago2 in mESCs are co-bound by FAM120A. Furthermore, such FAM120A-bound Ago2 target genes are not subject to Ago2-mediated target degradation. Reporter assays suggest that the 3'-UTRs of several FAM120A-bound miRNA target genes are less sensitive to Ago2-mediated target repression than those of FAM120A-unbound miRNA targets and FAM120A modulates them via its G-rich target sites. These findings suggest that Ago2 may exist in multiple protein complexes with varying degrees of functionality.

Differences of Extracellular Cues and Ca2+ Permeable Channels in the Signaling Pathways for Inducing Amphibian Sperm Motility.

Low osmolality of freshwater and/or sperm motility-initiating substance (SMIS) induce amphibian sperm motility through increases in intracellular Ca2+. In the internally fertilizing newt Cynops pyrrhogaster, the sperm motility-initiating substance engages T type voltage-dependent Ca2 + channels and N-methyl D-aspartate-type glutamate receptors to initiate sperm motility and L type voltage-dependent Ca2+ channels to enhance motility. In the present study, differences in the usages of SMIS and Ca2+ permeable channels for sperm motility regulation were examined in amphibians that undergo different reproductive modes. Proteins of 14-17 kDa were detected by antibody against the active site peptide of SMIS in the oviduct secretion of internal fertilizers (C. pyrrhogaster, Cynops ensicauda, and Ambystoma mexicanum) and arboreal fertilizers (Rhacophorus arboreus and Rhacophorus schlegelii), but not in Buergeria japonica, an external fertilizer in freshwater. In the pharmacological study, a blocker of some transient receptor potential channels (RN1734) additionally suppressed enhancement of sperm motility in C. pyrrhogaster. In R. schlegelii, blockers of four types of channels differently suppressed sperm motility induced by low osmolality with or without the active site peptide of SMIS. Notably, blockers of L type voltage-dependent Ca2+ channels (nifedipine) and N-methyl D-aspartate-type glutamate receptors (MK801) suppressed sperm motility in the presence and the absence of the peptide, respectively. Low osmolality-induced sperm motility was suppressed by RN1734 and MK801 in B. japonica, but not in Xenopus laevis. These results reveal complex differences in the signaling pathways for inducing sperm motility that may be partly related to reproductive modes in amphibians.

Prevalence of carotid artery stenosis with coronary artery disease in Japanese patients: A single-center study.

There are a few reports of the prevalence of extracranial internal carotid artery stenosis (ICAS) in Asian patients with coronary artery disease (CAD). This was a prospective registry study of 157 consecutive Japanese patients undergoing coronary angiography that aimed to determine the prevalence of extracranial ICAS in recent Japanese patients. The associations between ICAS and the extent or the maximal stenosis of CAD were also investigated. The 131 eligible patients with suspected CAD were prospectively analyzed. Their mean age was 69.0 ± 8.2 years, and 75.6% were males. A total of 111 patients (84.7%) were angiographically diagnosed with CAD. ICAS (area stenosis ≥50% on ultrasonography) was present in 9 patients, and the prevalence in patients with CAD was 8.1%. All patients in the ICAS group had CAD, and this group was significantly more likely to have a history of stroke (p = 0.03). Although no significant relationships were found between the severity of ICAS and the maximal stenosis of CAD, the severity of ICAS increased gradually with the extent of CAD. The prevalence of ICAS in patients with CAD treated with current medical treatment was relatively low (8.1%) compared to previous reports, and the severity of ICAS was significantly associated with the extent of CAD.

Carotid Endarterectomy for Medical Therapy-Resistant Symptomatic Low-Grade Stenosis.

BACKGROUND: Plaque characteristics play pivotal roles in ischemic events, but stenosis severity does not accurately reflect carotid plaque volume due to expansive remodeling in some patients with low-grade stenosis (LGS). This study aimed to assess the safety, efficacy, and durability of carotid endarterectomy (CEA) for symptomatic LGS. METHODS: Study participants comprised 61 consecutive patients who underwent CEA for symptomatic carotid stenosis. Patients were divided into an LGS group (<50%, n = 17) and a non-LGS group (≥50%, n = 44). Patient characteristics and short-term (within 30 days of CEA) and long-term outcomes were compared between groups for selective usage of internal shunt and known complications of CEA. RESULTS: Magnetic resonance imaging-detected intraplaque hemorrhage was more significant in LGS than in non-LGS (P = 0.04). For short-term outcomes, no symptomatic infarcts, hyperperfusion syndrome, or acute myocardial infarction was confirmed in either group. Internal shunts were used in 4 LGS (23.5%) and 6 non-LGS (13.6%). Asymptomatic diffusion-weighted imaging-positive lesions were confirmed in 2 LGS patients (11.8%) and 5 non-LGS patients (11.4%), neck hematoma in 1 LGS patient, and transient cranial nerve palsy in 1 LGS patient and 2 non-LGS patients, with no significant differences apparent between groups. For long-term outcomes, 5 non-LGS patients showed restenosis (P = 0.17). Hemorrhagic stroke was not observed in either group. No significant differences were seen for infarct in the ipsilateral carotid territory, any ischemic stroke, AMI, or mortality. CONCLUSIONS: CEA represents a safe and feasible therapeutic option for a subset of patients with symptomatic LGS.

A local excitation magnetic resonance imaging method for intracranial unruptured aneurysm at the distal internal carotid artery.

It is often difficult to diagnose an intracranial aneurysm at the distal internal carotid artery by conventional magnetic resonance imaging. PURPOSE: We assessed the effectiveness of the local excitation technique, a new application for magnetic resonance imaging, to clarify the geometric structure of aneurysm and adjacent branches at the distal internal carotid artery. STUDY DESIGN: Two independent evaluators diagnosed 10 cases of suspected aneurysms at the distal internal carotid artery by T2-weighted magnetic resonance imaging with application of local excitation, adding it to conventional time-of-flight-magnetic resonance angiography. FINDINGS: We successfully distinguished the aneurysm from infundibular dilatation in five of 10 cases. CONCLUSION: Our results suggested that addition of local excitation to conventional magnetic resonance angiography was effective to diagnose unruptured aneurysm at the distal internal carotid artery, to clarify the configuration of the prominent lesion or whether the location of the adjacent branch orifice on the parent vessel was symmetric or asymmetric.

Spontaneous Resolution of Cerebral Pial Arteriovenous Fistula After Angiography: Report of Two Cases.

BACKGROUND: Cerebral pial arteriovenous fistula (AVF) is a rare disorder, and its natural course is uncertain. The present article reports 2 rare cases of pial AVF that underwent spontaneous cure after diagnostic cerebral angiogram. CASE DESCRIPTIONS: A 73-year-old man presented with generalized seizure and reported severe but intermittent headache in the right temporo-occipital area. Single-photon emission computed tomography (SPECT) showed hyperperfusion in that area. The main finding of a cerebral angiogram was an arteriovenous shunt at the cortical surface of the right temporal area. Soon after this diagnostic angiogram, the symptoms vanished. A further cerebral angiogram showed the disappearance of this pial AVF, and a SPECT study showed resolution of the hyperperfusion of the affected area. A 69-year-old man, with a history of intracerebral hemorrhage on the left parietal area 3 years earlier, presented with speech disturbance and headache on his left side. SPECT showed hyperperfusion in the left temporoparietal area. A cerebral angiogram showed an arteriovenous shunt at the surface of the left parietal area. During the same cerebral angiogram session, the pial AVF disappeared after the third injection of a contrast medium with magnification. Two days after the cerebral angiogram, the patient's headache disappeared and speech disturbance gradually improved. SPECT also showed disappearance of the hyperperfusion. CONCLUSIONS: It is possible that pial AVF is a cause of headache and neurologic symptoms in association with focal hyperperfusion. Diagnostic cerebral angiography should be performed to make a definite diagnosis; after this, pial AVF sometimes disappears.