Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism

A Novel Closed Method to Retrieve Broken Teflon Tube During Intramedullary Nailing in Proximal Humeral Fracture

Broken medullary tubes have been used for intramedullary (IM) nailing of femoral and tibial fractures. In these reported cases, fragments of the medullary tube were retrieved by opening the fracture sites or left in situ, which might jeopardize periosteal blood supply. We herein present the case of a 58-year-old woman who underwent IM nailing for proximal humeral fracture, which was complicated by breakage of the medullary tube intraoperatively. Different instruments including guide rods, straight forceps, and cement extract hook were used to retrieve the retained fragments from the medullary canal, but these attempts were unsuccessful. Finally, the fragments were successfully removed using an anterior cruciate ligament (ACL) ENDOBUTTON depth gauge. This case highlights that medullary tubes can break during humeral IM nailing, which could be minimized by ensuring integrity of the medullary tube prior to surgery and disposing medullary tubes with more than 100 exposures. A novel method of using ACL ENDOBUTTON depth gauge to retrieve retained tube fragments is recommended because of its long and slim design

Nanoparticle-Encapsulated Chlorhexidine against Oral Bacterial Biofilms

<div><p>Background</p><p>Chlorhexidine (CHX) is a widely used antimicrobial agent in dentistry. Herein, we report the synthesis of a novel mesoporous silica nanoparticle-encapsulated pure CHX (Nano-CHX), and its mechanical profile and antimicrobial properties against oral biofilms.</p><p>Methodology/Principal Findings</p><p>The release of CHX from the Nano-CHX was characterized by UV/visible absorption spectroscopy. The antimicrobial properties of Nano-CHX were evaluated in both planktonic and biofilm modes of representative oral pathogenic bacteria. The Nano-CHX demonstrated potent antibacterial effects on planktonic bacteria and mono-species biofilms at the concentrations of 50–200 µg/mL against <i>Streptococcus mutans</i>, <i>Streptococcus sobrinus</i>, <i>Fusobacterium nucleatum</i>, <i>Aggregatibacter actinomycetemcomitans</i> and <i>Enterococccus faecalis</i>. Moreover, Nano-CHX effectively suppressed multi-species biofilms such as <i>S. mutans, F. nucleatum</i>, <i>A. actinomycetemcomitans</i> and <i>Porphyromonas gingivalis</i> up to 72 h.</p><p>Conclusions/Significance</p><p>This pioneering study demonstrates the potent antibacterial effects of the Nano-CHX on oral biofilms, and it may be developed as a novel and promising anti-biofilm agent for clinical use.</p></div

Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction

The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated

Initial Prostate Health Index (phi) and phi density predicts future risk of clinically significant prostate cancer in men with initial negative prostate biopsy: a 6-year follow-up study

Background: Men with elevated prostate-specific antigen (PSA) and initial negative prostate biopsy may have risk of prostate cancer (PCa) in the future. The role of Prostate Health Index (phi) in determining future PCa risk has not been studied before. This study aims to investigate the role of initial phi and phi density in predicting future PCa risk in men with initial negative biopsy. Methods: Five hundred sixty nine men with PSA 4–10 ng/mL were recruited between 2008 and 2015 for prostate biopsy with prior phi. Electronic clinical record of men with initial negative biopsy was reviewed. Patients and follow-up doctors were blinded to phi. Kaplan–Meier curves were used to analyze the PCa-free survival in different baseline phi and phi density groups. Results: Four hundred sixty-one men with complete follow-up data were included. Median follow-up is 77 months. PCa and HGPCa was diagnosed in 8.2% (38/461) and 4.8% (22/461) of cohort respectively. A higher baseline phi value was associated with PCa (p = 0.003) and HGPCa (p < 0.001). HGPCa was diagnosed in 0.6% (1/163) of phi < 25, 4.6% (9/195) of phi 25–34.9, and 11.7% (12/103) of phi ≥ 35 (p < 0.001). HGPCa was diagnosed in 0% (0/109) and 21.0% (13/62) with phi density of <0.4 and ≥1.2, respectively, (p < 0.001). Kaplan–Meier curves showed phi and phi density predicted PCa and HGPCa diagnoses (log-rank test, all p ≤ 0.002). Conclusions: Initial phi or phi density predicted 6-year risk of PCa in men with initial negative prostate biopsy. Men with higher phi (≥35) or phi density (≥1.2) need closer follow-up and repeated investigation, while men with lower phi (<25) or phi density (<0.4) could have less frequent follow-up

The minimal inhibitory concentration (MIC, µg/mL) of the preventive effect of Nano-CHX on the mixed-species oral biofilms in a time-dependent assay from 24 to 72 h.

<p>The minimal inhibitory concentration (MIC, µg/mL) of the preventive effect of Nano-CHX on the mixed-species oral biofilms in a time-dependent assay from 24 to 72 h.</p