Interpretation and classification of FBN1 variants associated with Marfan syndrome: consensus recommendations from the Clinical Genome Resource's FBN1 variant curation expert panel.

Background: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) developed standardized variant curation guidelines for Mendelian disorders. Although these guidelines have been widely adopted, they are not gene- or disease-specific. To mitigate classification discrepancies, the Clinical Genome Resource FBN1 variant curation expert panel (VCEP) was established in 2018 to develop adaptations to the ACMG/AMP criteria for FBN1 in association with Marfan syndrome.

Inflammasome regulation by the cell surface ecto-5'-nucleotidase of the oral commensal, Streptococcus oralis.

Streptococcus oralis is a commensal oral bacterium that acts as an opportunistic pathogen, causing systemic diseases, such as infective endocarditis and aspiration pneumonia. However, the specific molecular mechanisms underlying its transition from commensal to pathogenic state remain unclear. In this study, to further elucidate the mechanisms underlying virulence expression, we identified and characterized the cell surface-associated ecto-5'-nucleotidase (Nt5e) in S.

Variations in echocardiographic findings in patients with Loeys-Dietz syndrome type 4 with 2 types of variant mutations in TGFB.

Unlabelled: Loeys-Dietz syndrome (LDS) type 4 is a rare connective tissue disorder caused by mutations in the transforming growth factor β 2 gene. It is well-documented that LDS4 shares clinical features of Marfan syndrome (MFS), and vascular involvement is less significant compared to other types of LDS. However, information on the valvular characteristics is scarce due to the small number of reported cases.

Neuraxial anesthesia for patients with severe pulmonary arterial hypertension undergoing urgent open abdominal surgeries: two case reports.

Background: There is no consensus regarding the choice of anesthetic method for patients with pulmonary hypertension (PH). We report two cases in which neuraxial anesthesia was safely performed without general anesthesia during open abdominal surgery in patients with severe PH.

Case Presentation: Case 1: A 59-year-old woman had an atrial septal defect and a huge abdominal tumor with a mean pulmonary arterial pressure (PAP) of 39 mmHg and pulmonary vascular resistance (PVR) of 3.

Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.

Aim: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD.

Methods: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.

Meflin/ISLR is a marker of adipose stem and progenitor cells in mice and humans that suppresses white adipose tissue remodeling and fibrosis.

Identifying specific markers of adipose stem and progenitor cells (ASPCs) in vivo is crucial for understanding the biology of white adipose tissues (WAT). PDGFRα-positive perivascular stromal cells represent the best candidates for ASPCs. This cell lineage differentiates into myofibroblasts that contribute to the impairment of WAT function.

Association between parental decisions regarding abortion and severity of fetal heart disease.

The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes.

Hereditary Aortic Aneurysms and Dissections: Clinical Diagnosis and Genetic Testing.

Hereditary aortic aneurysms and dissections, such as Marfan syndrome, differ in that they occur in younger patients without generally recognized risk factors, have a predilection for the thoracic rather than the abdominal aorta, and are at risk for dissection even at smaller aortic diameters. Early diagnosis, careful follow-up, and early intervention, such as medication to reduce aortic root growth and prophylactic aortic replacement to prevent fatal aortic dissection, are essential for a better prognosis. Molecular genetic testing is extremely useful for early diagnosis.

The Klebsiella mannose phosphotransferase system promotes proliferation and the production of extracellular polymeric substances from mannose, facilitating adaptation to the host environment.

Objectives: Klebsiella spp., an opportunistic infectious organism, is commensal in the nasal and oral cavities of humans. Recently, it has been reported that oral Klebsiella spp.

Aortic Dissection and a Previously Unreported Missense Variant Mutation in a Young Patient: A Case Report.

Hereditary connective tissue disease is known to cause aortic lesions at an early age. Familial aortic aneurysm/dissection is caused due to an mutation that affects smooth muscle structure. We present a case of a 15-year-old boy with a mild developmental disorder in whom no abnormalities were identified on previous physical examinations.

Computational and Experimental Analyses for Pathogenicity Prediction of Missense Variants in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a vascular disease caused by the defects of ALK1/ACVRL1 receptor signaling. In this study, we evaluated 25 recently identified ACVRL1 missense variants using multiple computational pathogenicity classifiers and experimentally characterized their signal transduction capacity. Three extracellular residue variants showed no detectable cell surface expression and impairment of bone morphogenetic protein 9 (BMP9) responsiveness of SMAD-dependent transcription in luciferase assays.

AMPD2 plays important roles in regulating hepatic glucose and lipid metabolism.

Dysregulation of hepatic glucose and lipid metabolism can instigate the onset of various metabolic disorders including obesity, dyslipidemia, insulin resistance, type 2 diabetes, and fatty liver disease. Adenosine monophosphate (AMP) deaminase (AMPD), which converts AMP to inosine monophosphate, plays a key role in maintaining adenylate energy charge. AMPD2 is the major isoform present in the liver.

Levels of preoperative cerebrospinal fluid pro-inflammatory mediators and chronic pain after total knee arthroplasty surgery.

Background: Patients undergoing total knee arthroplasty (TKA) surgery are at high risk of chronic postsurgical pain (CPSP). Accumulating evidence suggests an active role of neuroinflammation in chronic pain. However, its role in the progression to CPSP following TKA surgery remains unanswered.

Decreased Interoceptive Awareness as a Risk Factor for Moderate to Severe Pain in Japanese Full-Time Workers: A Longitudinal Cohort Study.

Interoceptive awareness, the conscious perception of internal bodily states, is a key construct of mind-body interaction. Decreases in interoceptive awareness, as measured by the Multidimensional Assessment of Interoceptive Awareness (MAIA), are found in chronic pain patients. In this study, we explored whether a specific aspect of interoceptive awareness is a risk for the onset and chronicity of pain.

The potential of dynamic Tc-sestamibi cadmium zinc telluride-single-photon emission computed tomography camera assessing myocardial flow reserve in patients with heart failure with preserved ejection fraction.

Aims: Coronary microvascular dysfunction (CMD) is related to the pathophysiology, mortality, and morbidity of heart failure with preserved ejection fraction (HFpEF). A novel single-photon emission computed tomography (SPECT) camera with cadmium zinc telluride (CZT) detectors allows for the quantification of absolute myocardial blood flow and myocardial flow reserve (MFR) in patients with coronary artery disease. However, the potential of CZT-SPECT assessing for CMD has never been evaluated in patients with HFpEF.

Pharmacological Ischemic Conditioning with Roxadustat Does Not Affect Pain-Like Behaviors but Mitigates Sudomotor Impairment in a Murine Model of Deep Hind Paw Incision.

Purpose: The involvement of hypoxic response mechanisms in local functional impairments in surgical wounds is unclear. In the present study, we characterized tissue hypoxia in surgical wounds and investigated the role of pharmacological ischemic conditioning (PIC) using roxadustat, an oral prolyl hydroxylase domain enzyme inhibitor, in postoperative local functional impairments in a murine model of deep hind paw incision.

Methods: Male BALB/cAJcl mice aged 9-13 weeks were used in all experiments.

Effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles of diabetic and non-diabetic patients with low back pain.

Purpose: We aimed to investigate the effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles and pituitary-adrenal axis functions of diabetic and non-diabetic patients with low back pain.

Methods: A total of 28 patients (ten diabetic [DM group] and 18 non-diabetic patients [non-DM group]) with low back pain were followed-up. Transforaminal epidural low-dose dexamethasone (1.

Oral commensal bacterial flora is responsible for peripheral differentiation of neutrophils in the oral mucosa in the steady state.

Objectives: Commensal bacteria in the host body play a fundamental role in the differentiation and maintenance of the immune system. Studies on intestinal immunity have revealed that, under steady-state conditions, microflora have an important role in the maintenance of health. However, the role of oral commensal bacteria on the oral immune system is still unclear.

Melatonin suppresses the antiviral immune response to EMCV infection through intracellular ATP deprivation caused by mitochondrial fragmentation.

Melatonin, a sleep hormone derived from the pineal gland, has an anti-inflammatory effect on the immune system in addition to modulating the brain nervous system. Previous studies have shown that melatonin suppresses signaling pathways downstream of multiple pattern recognition receptors on the innate immune cells during pathogen infection, but the specific mechanism of suppression has not been well understood. Using an encephalomyocarditis virus (EMCV) infection model in macrophages, we investigated the effects of melatonin on the antiviral response in innate immunity and found that melatonin attenuated the uptake of viral particles into macrophages.