Interpretation of Flood-Illuminated Adaptive Optics Images in Subjects with Retinitis Pigmentosa.

The purpose of this study was to correlate features on flood-illuminated adaptive optics (AO) images with color fundus, fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) images in patients with retinitis pigmentosa (RP). We imaged 39 subjects diagnosed with RP using the rtx1™ flood-illuminated AO camera from Imagine Eyes (Orsay, France). We observed a correlation between hyper-autofluoresence changes on FAF, disruption of the interdigitation zone (IZ) on SD-OCT and loss of reflective cone profiles on AO.

A Case of Clozapine-Induced Myocarditis in a Young Patient with Bipolar Disorder.

We present a case of drug-induced myocarditis manifesting as acute heart failure in a young patient with bipolar disorder being treated for depression. The case describes a 20-year-old man being treated in the psychiatry ward for worsening depression when he started complaining of chest pain and shortness of breath. His list of medications included clozapine, lithium, lorazepam, and haloperidol.

RIG-I Signaling Is Essential for Influenza B Virus-Induced Rapid Interferon Gene Expression.

Unlabelled: Influenza B virus causes annual epidemics and, along with influenza A virus, accounts for substantial disease and economic burden throughout the world. Influenza B virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza A virus. Influenza B virus has been less studied than influenza A virus, and thus, a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions.

Takotsubo Cardiomyopathy in the Setting of Tension Pneumothorax.

Background. Takotsubo cardiomyopathy is defined as a transient left ventricular dysfunction, usually accompanied by electrocardiographic changes. The literature documents only two other cases of Takotsubo cardiomyopathy in the latter setting.

Class A Scavenger Receptor-Mediated Double-Stranded RNA Internalization Is Independent of Innate Antiviral Signaling and Does Not Require Phosphatidylinositol 3-Kinase Activity.

dsRNA is a potent trigger of innate immune signaling, eliciting effects within virally infected cells and after release from dying cells. Given its inherent stability, extracellular dsRNA induces both local and systemic effects. Although the class A scavenger receptors (SR-As) mediate dsRNA entry, it is unknown whether they contribute to signaling beyond ligand internalization.

Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission.

Hepatitis C virus (HCV) is the world's most common blood-borne viral infection for which there is no vaccine. The rates of vertical transmission range between 3 and 6% with odds 90% higher in the presence of HIV coinfection. Prevention of vertical transmission is not possible because of lack of an approved therapy for use in pregnancy or an effective vaccine.

Assessment of Different Sampling Methods for Measuring and Representing Macular Cone Density Using Flood-Illuminated Adaptive Optics.

Purpose: To describe a standardized flood-illuminated adaptive optics (AO) imaging protocol suitable for the clinical setting and to assess sampling methods for measuring cone density.

Methods: Cone density was calculated following three measurement protocols: 50 × 50-μm sampling window values every 0.5° along the horizontal and vertical meridians (fixed-interval method), the mean density of expanding 0.

Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length.

Unlabelled: Despite the introduction of direct-acting antiviral (DAA) drugs against hepatitis C virus (HCV), infection remains a major public health concern because DAA therapeutics do not prevent reinfection and patients can still progress to chronic liver disease. Chronic HCV infection is supported by a variety of viral immune evasion strategies, but, remarkably, 20% to 30% of acute infections spontaneously clear prior to development of adaptive immune responses, thus implicating innate immunity in resolving acute HCV infection. However, the virus-host interactions regulating acute infection are unknown.

Pulmonary Thromboembolism Complicating Amebic Liver Abscess: First Reported Case in the United States-Case Report and Literature Review.

Even in the absence of Amebic colitis, Amebic liver abscess (ALA) is the most common extraintestinal complication of Entamoeba histolytica infection. In the USA, it is most prevalent in middle aged immigrant males from endemic countries such as Africa, Mexico, and India. One of the complications of ALA is inferior vena cava (IVC) thrombosis, which is believed to result from the mechanical compression of the IVC and the consequent thrombogenic nidus elicited from the resultant inflammatory response.

Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light-Induced Retinopathy.

Purpose: To determine if sarpogrelate, a selective 5-HT2A receptor antagonist, is protective against light-induced retinopathy in BALB/c mice.

Methods: BALB/c mice were dosed intraperitoneally with 5, 15, 30, 40, or 50 mg/kg sarpogrelate 48, 24, and 0 hours prior to bright light exposure (10,000 lux) as well as 24 and 48 hours after exposure. Additionally, a single injection regimen was evaluated by injecting mice with 50 mg/kg sarpogrelate once immediately prior to light exposure.

INSIGHTS INTO AUTOSOMAL DOMINANT STARGARDT-LIKE MACULAR DYSTROPHY THROUGH MULTIMODALITY DIAGNOSTIC IMAGING.

Purpose: Autosomal dominant Stargardt-like macular dystrophy is a rare juvenile macular dystrophy most commonly because of mutations in ELOVL4 and PROM1 genes. In this study, we review a series of cases of Stargardt-like macular dystrophy and use advanced imaging techniques to describe pathophysiologic manifestations.

Methods: A retrospective medical record review was performed for five patients from two families with ELOVL4 mutation and one patient with PROM1 mutation including reviewing diagnostic imaging, such as fundus photography, spectral domain optical coherence tomography, fundus autofluorescence, and adaptive optics flood-illuminated photography.

Emerging complexity and new roles for the RIG-I-like receptors in innate antiviral immunity.

Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors (RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns (PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2.

Innate immunity against HIV-1 infection.

During acute HIV-1 infection, viral pathogen-associated molecular patterns are recognized by pathogen-recognition receptors (PRRs) of infected cells, which triggers a signaling cascade that initiates innate intracellular antiviral defenses aimed at restricting the replication and spread of the virus. This cell-intrinsic response propagates outward via the action of secreted factors such as cytokines and chemokines that activate innate immune cells and attract them to the site of infection and to local lymphatic tissue. Antiviral innate effector cells can subsequently contribute to the control of viremia and modulate the quality of the adaptive immune response to HIV-1.

Genetic diversity in the collaborative cross model recapitulates human West Nile virus disease outcomes.

Unlabelled: West Nile virus (WNV) is an emerging neuroinvasive flavivirus that now causes significant morbidity and mortality worldwide. The innate and adaptive immune responses to WNV infection have been well studied in C57BL/6J inbred mice, but this model lacks the variations in susceptibility, immunity, and outcome to WNV infection that are observed in humans, thus limiting its usefulness to understand the mechanisms of WNV infection and immunity dynamics. To build a model of WNV infection that captures human infection outcomes, we have used the Collaborative Cross (CC) mouse model.

Alcopops, taxation and harm: a segmented time series analysis of emergency department presentations.

Background: In Australia, a Goods and Services Tax (GST) introduced in 2000 led to a decline in the price of ready-to-drink (RTD) beverages relative to other alcohol products. The 2008 RTD ("alcopops") tax increased RTD prices. The objective of this study was to estimate the change in incidence of Emergency Department (ED) presentations for acute alcohol problems associated with each tax.

Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier.

Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced.

Hepatitis regulation by the inflammasome signaling pathway.

Hepatitis is damage and inflammation of the liver. It is triggered by both environmental and endogenous insults and is a platform for developing liver cirrhosis and cancer. Both innate and adaptive immune activation contribute to hepatic inflammation and disease.

RNase L activates the NLRP3 inflammasome during viral infections.

The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1β. Although virus infection activates the NLRP3 inflammasome, the underlying events remain incompletely understood. We report that virus activation of the NLRP3 inflammasome involves the 2',5'-oligoadenylate (2-5A) synthetase(OAS)/RNase L system, a component of the interferon-induced antiviral response that senses double-stranded RNA and activates endoribonuclease RNase L to cleave viral and cellular RNAs.

Portal vein thrombosis.

Portal vein thrombosis (PVT) is the blockage or narrowing of the portal vein by a thrombus. It is relatively rare and has been linked with the presence of an underlying liver disease or prothrombotic disorders. We present a case of a young male who presented with vague abdominal symptoms for approximately one week.

Isolated rheumatoid nodules: a diagnostic dilemma.

We present a 27-year-old male with multiple nonpainful soft tissue masses over several metacarpals, bilateral elbows, the left wrist, and both knees since the age of 4. Physical exam was significant for firm, nonmobile, nodular growths over the extensor surfaces of bilateral elbows and knees and on the 2nd and 5th metacarpal phalangeal joints. Laboratory studies revealed an unremarkable rheumatoid factor, negative ANA screening and normal joint radiographs.

RIG-I in RNA virus recognition.

Antiviral immunity is initiated upon host recognition of viral products via non-self molecular patterns known as pathogen-associated molecular patterns (PAMPs). Such recognition initiates signaling cascades that induce intracellular innate immune defenses and an inflammatory response that facilitates development of the acquired immune response. The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein family are key cytoplasmic pathogen recognition receptors that are implicated in the recognition of viruses across genera and virus families, including functioning as major sensors of RNA viruses, and promoting recognition of some DNA viruses.

Proteomic analysis of mitochondrial-associated ER membranes (MAM) during RNA virus infection reveals dynamic changes in protein and organelle trafficking.

RIG-I pathway signaling of innate immunity against RNA virus infection is organized between the ER and mitochondria on a subdomain of the ER called the mitochondrial-associated ER membrane (MAM). The RIG-I adaptor protein MAVS transmits downstream signaling of antiviral immunity, with signaling complexes assembling on the MAM in association with mitochondria and peroxisomes. To identify components that regulate MAVS signalosome assembly on the MAM, we characterized the proteome of MAM, ER, and cytosol from cells infected with either chronic (hepatitis C) or acute (Sendai) RNA virus infections, as well as mock-infected cells.

High-throughput screening to identify inhibitors of lysine demethylases.

Lysine demethylases (KDMs) are epigenetic regulators whose dysfunction is implicated in the pathology of many human diseases including various types of cancer, inflammation and X-linked intellectual disability. Particular demethylases have been identified as promising therapeutic targets, and tremendous efforts are being devoted toward developing suitable small-molecule inhibitors for clinical and research use. Several High-throughput screening strategies have been developed to screen for small-molecule inhibitors of KDMs, each with advantages and disadvantages in terms of time, cost, effort, reliability and sensitivity.