Detection of hepatitis C virus (HCV) RNA in the peripheral blood mononuclear cells of HCV-infected patients following sustained virologic response.

It is unclear whether direct-acting antiviral drugs (DAAs) result in the complete eradication of HCV infection or whether some quantities of the virus may persist after achieving a sustained virologic response (SVR). Aim The aim of this work was to study the possibility of the persistence of HCV RNA in peripheral blood mononuclear cells (PBMCs) after achieving SVR following DAA treatment. This study included 100 patients infected with HCV genotype 4, who were candidates for receiving DAAs and who achieved SVR during follow-up, as determined at 12 and/or 24 weeks following the end of treatment. All patients were subjected to demographic, biochemical and hematological assessments. Detection of HCV RNA in the serum and PBMCs and determination of the HCV genotype were performed with real-time PCR. We detected HCV RNA in the PBMCs of 20 out of 100 (20%) patients infected with HCV genotype 4, who achieved SVR. However, the persistent viral load in the PBMCs was very low (range: 400-900 U/mL; mean ± SD: 645.45 ± 153 U/mL). Multiple logistic regression analysis showed that only the higher posttreatment levels of aspartate transaminase (AST) were significantly predictive of HCV RNA persistence in the PBMCs (OR: 1.29; 95% CI: 1.08-1.55). Additionally, according to the Cox proportional hazard model, liver cirrhosis was the only significant risk factor for the persistence of HCV infection in PBMCs (HR: 5.8; 95% CI: 1.3-26.1; P < 0.02). Our results indicated the persistence of HCV RNA in some HCV patients who achieved SVR after treatment with DAAs.

Assessment of Antibacterial and Anti-biofilm Effects of Vitamin C Against Pseudomonas aeruginosa Clinical Isolates.

There is a persistent need to look for alternative therapeutic modalities to help control the pandemic of antimicrobial resistance. Assessment of antibacterial and anti-biofilm effects of vitamin C (ascorbic acid) was the aim of the current study. The micro-dilution method determined the minimal inhibitory concentration (MIC) of ascorbic acid or antibiotics alone and in combinations against Pseudomonas aeruginosa (P. aeruginosa) clinical isolates. The micro-titer plate method monitored the effect of ascorbic acid on the biofilm-producing isolates of P. aeruginosa. The effect of ascorbic acid on the differential expression of different antibiotic-resistant genes and biofilm encoding genes of P. aeruginosa isolates were also tested using real-time polymerase chain reaction (PCR). For in vivo assessment of the antibacterial effects of ascorbic acid alone or combined with an antibiotic, rats were infected with P. aeruginosa clinical isolate followed by different treatment regimens. MICs of ascorbic acid among P. aeruginosa isolates were in the range of 156.2-1,250 µg/ml, while MIC50 and MIC90 were 312.5 and 625 µg/ml, respectively. At sub-inhibitory concentrations (19.5-312.5 µg/ml), ascorbic acid had 100% biofilm inhibitory effect. Furthermore, ascorbic acid-treated bacteria showed downregulation of genes underpinning biofilm formation and antibiotic resistance. In vivo assessment of vitamin C and ceftazidime in rats showed that administration of both at a lower dose for treatment of pseudomonas infection in rats had a synergistic and more powerful effect. Vitamin C shows excellent in vitro results as an antibacterial and anti-biofilm agent. Vitamin C should be routinely prescribed with antibiotics to treat bacterial infections in the clinical setting.

Latent Toxoplasmosis is Associated with Depression and Suicidal Behavior.

OBJECTIVE: Neuroinflammation is implicated in the pathophysiology of depression. Toxoplasma gondii (T. gondii) causes chronic brain inflammatory process and may thus contribute to both depression and its most serious complication, suicidal behavior. In this study, we hypothesized that latent toxoplasmosis may underlie current depression and/or suicidal behavior. METHOD: Currently depressed individuals (N = 384) and age, sex, and residence-matched healthy controls (HC) (N = 400) were tested for latent toxoplasmosis (i.e., positive serum T. gondii IgG antibodies). Exclusions included positive IgM and negative IgG antibodies indicating acute T. gondii infection and history of cognitive problems. Depression severity and history of lifetime suicide attempts were assessed using Beck Depression Inventory (BDI) and Columbia Suicide Severity Rating Scale, respectively. RESULTS: Participants with seropositive anti-T. gondii IgG antibody had a significantly higher odds of being depressed compared with seronegative participants (OR = 2.9, 95% CI: 1.9-4.3; p < 0.001). BDI score was significantly different between depressed seropositive and depressed seronegative individuals (IgG＋: mean (SD)= 39.65 (11.83) vs. IgG-: mean (SD)= 33.44(9.80); t = 5.03, p < 0.001). Further, seropositive depressed participants were more likely to have prior history of actual suicide attempts compared with seronegative participants (OR= 6.2, 95% CI: 3.4-11.2, p < 0.001). CONCLUSIONS: Latent toxoplasmosis may represent be a risk factor for depression and suicidal behavior. Screening for, and treatment of, underlying T. gondii infection may help improve depression and curb the increasing suicide rates. Future studies should prospectively test these hypotheses to be adequately implemented.HIGHLIGHTSLatent toxoplasmosis has been linked to history of psychiatric disorders.Depressed individuals have higher positivity rate of T. gondii IgG antibody than healthy controls.Depressed T. gondii seropositive individuals have increased likelihood to have history of suicidal behavior.