Hepatovirus translation requires PDGFA-associated protein 1, an eIF4E-binding protein regulating endoplasmic reticulum stress responses.

The overexpression and misfolding of viral proteins in the endoplasmic reticulum (ER) may cause cellular stress, thereby inducing a cytoprotective, proteostatic host response involving phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). Here, we show that hepatitis A virus, a positive-strand RNA virus responsible for infectious hepatitis, adopts a stress-resistant, eIF2α-independent mechanism of translation to ensure the synthesis of viral proteins within the infected liver. Cap-independent translation directed by the hepatovirus internal ribosome entry site and productive hepatovirus infection of mice both require platelet-derived growth factor subunit A (PDGFA)-associated protein 1 (PDAP1), a small phosphoprotein of unknown function with eIF4E-binding activity.

Delayed Trastuzumab-induced Cardiotoxicity Leading to Severe Left Ventricular Dysfunction.

An 81-year-old woman presented to our hospital with dyspnea. She had been treated with trastuzumab for nine years. Chest radiography revealed pleural effusion.

Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology.

Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen, herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (), both the IFN-λ and the IFN-α/β receptors (), or IFN-λ cytokines () and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions without affecting viral loads.

Mice with FVB-derived sequence on chromosome 17 succumb to disseminated virus infection due to aberrant NK cell and T cell responses.

Zoonotic arenavirus infections can result in viral hemorrhagic disease, characterized by platelet loss, petechia, and multi-organ injury. The mechanisms governing these outcomes are likely impacted by virus strain and infection dose, as well as an individual's genetic background and immune constitution. To better understand the processes leading to severe pathogenesis, we compared two strains of inbred mice, C57BL/6J (B6) and FVB/NJ (FVB), that have diametrically opposed outcomes during disseminated lymphocytic choriomeningitis virus (LCMV) infection.

Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology.

Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (), both the IFN-λ and the IFN-αβ receptor ( ), or IFN-λ cytokines () and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions, independent of a direct effect on viral load.

Advent of paradoxical flow after antihypertensive treatment in mid-ventricular obstructive hypertrophic cardiomyopathy - A case report.

Unlabelled: A 69-year-old woman was admitted our hospital due to acute cerebral infarction. Transthoracic echocardiography showed massive left ventricular (LV) hypertrophy with small ventricles and normal LV ejection fraction. Apical 4-chamber and longitudinal images showed mild LV obstruction.

Severe hypotension during junctional rhythm in a patient with multiple cerebral infarcts.

Unlabelled: An 82-year-old woman with parkinsonism and Lewy body dementia was re-admitted to our hospital due to convulsions and the recurrence of cerebral infarction. Parasternal transthoracic echocardiography showed normal left ventricular wall thickness and wall motion. To treat marked bradycardia and hypotension, she underwent temporary pacing.

Mid-ventricular Obstructive Cardiomyopathy after Takotsubo Cardiomyopathy.

A 93-year-old woman was transferred to our hospital for lightheadedness. She had had Takotsubo cardiomyopathy for seven years. Transthoracic apical four-chamber echocardiography showed a large apical aneurysm.

Viral protease cleavage of MAVS in genetically modified mice with hepatitis A virus infection.

Background & Aims: Consistent with its relatively narrow host species range, hepatitis A virus (HAV) cannot infect C57BL/6 mice. However, in Mavs mice with genetic deficiency of the innate immune signaling adaptor MAVS, HAV replicates robustly in the absence of disease. The HAV 3ABC protease cleaves MAVS in human cells, thereby disrupting virus-induced IFN responses, but it cannot cleave murine MAVS (mMAVS) due to sequence differences at the site of scission.

The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis.

Despite excellent vaccines, resurgent outbreaks of hepatitis A have caused thousands of hospitalizations and hundreds of deaths within the United States in recent years. There is no effective antiviral therapy for hepatitis A, and many aspects of the hepatitis A virus (HAV) replication cycle remain to be elucidated. Replication requires the zinc finger protein ZCCHC14 and noncanonical TENT4 poly(A) polymerases with which it associates, but the underlying mechanism is unknown.

Recurrent Syncope in a Case with Mediastinal Lymphoma.

An 83-year-old man suddenly lost consciousness, and his blood pressure dropped. Results of blood analysis were within normal range. A chest radiograph showed enlargement of the left mediastinum.

Constrictive pericarditis following mRNA COVID-19 vaccination in a patient with systemic sclerosis.

Unlabelled: A 59-year-old man with systemic sclerosis and interstitial pneumonia was referred to our department because he developed dyspnea and leg edema after receiving a first shot of coronavirus disease 2019 (COVID-19) vaccine. Transthoracic echocardiography showed moderate pericardial effusion with conspicuous fibrin deposition. Prednisolone was increased from 6 mg/day for systemic sclerosis to 20 mg/day.

Incidence, clinical characteristics, and diagnostic approach in transthyretin amyloid cardiomyopathy: The Kumamoto Cardiac Amyloidosis Survey.

Background: In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has received increasing attention; however, the epidemiology of ATTR-CM in Japan is not yet understood. In the Kumamoto Cardiac Amyloid Survey, we evaluated the current incidence, clinical characteristics, diagnostic approaches, and treatment strategies for ATTR-CM and compared tafamidis-prescription hospitals with regional hospitals.

Methods: We conducted a retrospective multicenter observational cohort study.

A case of malignant hypertension with multi-organ injury.

A 33-year-old woman visited our hospital due to visual loss. Her BP was 280/150 mm Hg and pulse rate was 111 beats per minute. A urinalysis showed protein in urine, suggesting kidney injury.

IRF3-mediated pathogenicity in a murine model of human hepatitis A.

HAV-infected Ifnar1-/- mice recapitulate many of the cardinal features of hepatitis A in humans, including serum alanine aminotransferase (ALT) elevation, hepatocellular apoptosis, and liver inflammation. Previous studies implicate MAVS-IRF3 signaling in pathogenesis, but leave unresolved the role of IRF3-mediated transcription versus the non-transcriptional, pro-apoptotic activity of ubiquitylated IRF3. Here, we compare the intrahepatic transcriptomes of infected versus naïve Mavs-/- and Ifnar1-/- mice using high-throughput sequencing, and identify IRF3-mediated transcriptional responses associated with hepatocyte apoptosis and liver inflammation.

Current Awareness and Status of Venous Ultrasonography in Kumamoto Prefecture - A Report of the Kumamoto Cardiovascular Echocardiography Standardization Project.

There are few reports on the current awareness and status of venous ultrasonography, including the number of specialists who perform this procedure, in a specific regional area in Japan. This cross-sectional survey study was conducted in Kumamoto Prefecture from October 2018 to March 2019. Of the 366 medical institutions providing cardiology services in Kumamoto Prefecture, 259 (101 general hospitals, 158 small clinics) responded to our questionnaire.

T cells protect against hepatitis A virus infection and limit infection-induced liver injury.

Background & Aims: Hepatitis A virus (HAV) is a common cause of enterically transmitted viral hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant and fatal inflammatory liver injury. Virus-specific T cell frequencies peak when liver damage is at its zenith, leading to the prevalent notion that T cells exacerbate liver disease, as suspected for other hepatotropic virus infections.

A Coronary Artery-left Ventricular Fistula through the Sinusoid.

A 78-year-old woman was referred to our hospital because of repetitive suppurative arthritis at the artificial left knee joint. Her plasma brain natriuretic peptide level was 122 pg/mL. A 12-lead electrocardiogram showed a QS pattern in the inferior leads.

Iminosugar Glucosidase Inhibitors Reduce Hepatic Inflammation in Hepatitis A Virus-Infected Mice.

Iminosugar compounds are monosaccharide mimetics with broad but generally weak antiviral activities related to inhibition of enzymes involved in glycobiology. Miglustat (-butyl-1-deoxynojirimycin), which is approved for the treatment of lipid storage diseases in humans, and UV-4 [-(9-methoxynonyl)-1-deoxynojirimycin] inhibit the replication of hepatitis A virus (HAV) in cell culture (50% inhibitory concentrations [ICs] of 32.13 μM and 8.

Left Ventricular Apical Thrombus Mimicking Hypertrabeculation.

A 73-year-old man visited our hospital due to dyspnea and epigastralgia. His plasma brain natriuretic peptide level was 1,205 pg/mL. A 12-lead electrocardiogram showed ST segment depression in leads I, V5, and V6.