A subepidermal blistering disorder

A young woman presented with generalised tense blisters. A tentative diagnosis of linear IgA bullous dermatosis (LABD) was supported by biopsy findings. Dramatic improvement was noted after 5 days of treatment with dapsone

Revisiting an old foe: The face of psychosis in neurosyphilis

A delusional, agitated middle-aged man presented to hospital with a tenacious psychotic episode. Upon appropriate therapy for neurosyphilis, dramatic resolution of this brief episode ensued, prompting a literature review of psychosis associated with neurosyphilis

Diagnostic challenges with acellular bacterial meningitis

An immunocompetent adult presenting with acellular pneumococcal meningitis is a rare occurrence and may pose a diagnostic challenge

Revisiting an old foe: The face of psychosis in neurosyphilis

A delusional, agitated middle-aged man presented to hospital with a tenacious psychotic episode. Upon appropriate therapy for neurosyphilis, dramatic resolution of this brief episode ensued, prompting a literature review of psychosis associated with neurosyphilis

Transforming Growth Factor-β1 Suppresses Hepatitis B Virus Replication by the Reduction of Hepatocyte Nuclear Factor-4α Expression

Several studies have demonstrated that cytokine-mediated noncytopathic suppression of hepatitis B virus (HBV) replication may provide an alternative therapeutic strategy for the treatment of chronic hepatitis B infection. In our previous study, we showed that transforming growth factor-beta1 (TGF-β1) could effectively suppress HBV replication at physiological concentrations. Here, we provide more evidence that TGF-β1 specifically diminishes HBV core promoter activity, which subsequently results in a reduction in the level of viral pregenomic RNA (pgRNA), core protein (HBc), nucleocapsid, and consequently suppresses HBV replication. The hepatocyte nuclear factor 4alpha (HNF-4α) binding element(s) within the HBV core promoter region was characterized to be responsive for the inhibitory effect of TGF-β1 on HBV regulation. Furthermore, we found that TGF-β1 treatment significantly repressed HNF-4α expression at both mRNA and protein levels. We demonstrated that RNAi-mediated depletion of HNF-4α was sufficient to reduce HBc synthesis as TGF-β1 did. Prevention of HNF-4α degradation by treating with proteasome inhibitor MG132 also prevented the inhibitory effect of TGF-β1. Finally, we confirmed that HBV replication could be rescued by ectopic expression of HNF-4α in TGF-β1-treated cells. Our data clarify the mechanism by which TGF-β1 suppresses HBV replication, primarily through modulating the expression of HNF-4α gene

The G1613A Mutation in the HBV Genome Affects HBeAg Expression and Viral Replication through Altered Core Promoter Activity

Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC

'Prostate Cancer' Information on the Internet: Fact or Fiction?

BACKGROUND/AIMS: In today's information era, patients often seek information regarding health using the internet. We assessed reliability and validity of internet information regarding 'prostate cancer'. METHODS: Search term 'prostate cancer' used on Google website (June 2017). Critical analysis was performed on first 100 hits using JAMA benchmarks, DISCERN score, Health on the Net. RESULTS: 33 500 000 hits returned. Top 100 hits were critically analyzed. Ten links [duplicate links (n = 7), book reviews (n = 1), dead sites (n = 2)] were excluded, therefore 90 were analyzed. Subcategories assessed included: commercial (53.33%), university/medical center (24.44%), government (13.33%); non-governmental/ non-profit organizations (8.89%). Sub-type of information content assessed included: factual (74.44%), clinical trials (18.89%); stories (5.56%); question and answer (1.11%). Website rated as HONcode seal positive (14,44%) or seal negative (85,56%). Website content based on JAMA benchmarks: 0 benchmarks (4.44%), 1 benchmark (16.67%), 2 benchmarks (34.44%), 3 benchmarks (27.78%), 4 benchmarks (16.67%). DISCERN score rated: 'low' score (16-32) = 12 websites (13.33%), 'moderate' score (33-64 points) = 68 websites (75.56%), 'high' score (≥ 65 points) = 10 websites (11.11%). CONCLUSION: Critical assessment of 'Prostate Cancer' information on the internet, showed that overall quality was observed to be accurate, however majority of individual websites are unreliable as a source of information by itself for patients. Doctors and patients need to be aware of this 'quality vs quantity' discrepancy when sourcing PCa information on the internet

Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue

Helioxanthin is a natural product that inhibits the replication of a number of viruses. We found that a previously undescribed helioxanthin analogue, 8-1, exhibited potent anti-hepatitis B virus (HBV) activity with little cytotoxicity. 8-1 suppressed both HBV RNA and protein expression, as well as DNA replication of both wild-type and 3TC-resistant virus. Time-course analyses revealed that RNA expression was blocked first after treatment with 8-1, followed by viral proteins, and then DNA. 8-1 inhibited the activity of all HBV promoters by decreasing the binding of hepatocyte nuclear factor 4 (HNF-4), HNF-3, and fetoprotein factor to the precore/core promoter enhancer II region. The amount of HNF-4 and HNF-3 was decreased posttranscriptionally by 8-1 in HBV-producing cells, but not in HBV-negative cells. Therefore, 8-1 suppresses HBV replication by posttranscriptional down-regulation of critical transcription factors in HBV-producing cells, thus diminishing HBV promoter activity and blocking viral gene expression and replication. This mechanism is unique and different from other anti-HBV compounds previously described