Cigarette butts on Baltic Sea beaches: Monitoring, pollution and mitigation measures.

OSPAR, Rake and Flood accumulation zone methods were applied at 29 beaches of the German and Lithuanian Baltic Sea coast (2011-2018) to monitor cigarette butt pollution. Also, butt pollution prevention measure - ballot bin, was tested. The number of cigarette butts was significantly higher in Germany than in Lithuania, but the percent of butts from total litter items was similar. Rake method turned out to be suitable for cigarette butt assessment, while the OSPAR method underestimates the butt pollution. The visitor number on the beach had a significant effect on the cigarette butt number: in remote beaches, without visitors, usually, no butts were observed, while the highest number and the percent of butts were observed in beaches with the highest number of visitors. The ballot bin campaign may have increased the public awareness about pollution, but turned out to be in-efficient in reducing it.

HHV-6B reduces autophagy and induces ER stress in primary monocytes impairing their survival and differentiation into dendritic cells.

HHV-6A and HHV-6B are ubiquitous human betaherpesviruses sharing more than 80% homology. HHV-6B is the most common cause of encephalitis in transplant patients and its primary infection may cause the exanthema subitum and febrile seizures in infants. HHV-6A and HHV-6B are able to infect several immune cell types such as T cells, monocytes and dendritic cells (DCs). In this study we found that HHV-6 B derived from patients affected by exanthema subitum impaired monocyte differentiation into DCs, as the infected cells acquired less CD1a DC marker and retained more CD14 monocyte marker. In agreement with the previous finding that HHV-6B dysregulated autophagy and induced endoplasmic reticulum (ER) stress in cells in which it replicated, here we found that these effects occurred also in differentiating monocytes and that ER stress relief, by using the chemical chaperone sodium 4-phenylbutirate (PBA), partially restored DC formation. This suggests that the induction of ER stress, likely exacerbated by autophagy inhibition, could contribute to the immune suppression induced by HHV-6B derived from exanthema subitem patients.

STAT3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation.

The Tyr705 STAT3 constitutive activation, besides promoting PEL cell survival, contributes to the maintenance of viral latency. We found indeed that its de-phosphorylation by AG490 induced KSHV lytic cycle. Moreover, Tyr705 STAT3 de-phosphorylation, mediated by the activation of tyrosine phosphatases, together with the increase of Ser727 STAT3 phosphorylation contributed to KSHV lytic cycle induction by TPA. We then observed that p53-p21 axis, essential for the induction of KSHV replication, was activated by the inhibition of Tyr705 and by the increase of Ser727 STAT3 phosphorylation. As a possible link between STAT3, p53-p21 and KSHV lytic cycle, we found that TPA and AG490 reduced the expression of KAP-1, promoting p53 stability, p21 transcription and KSHV lytic cycle activation in PEL cells.

Impact of HHV-6A and HHV-6B lytic infection on autophagy and endoplasmic reticulum stress.

Herpesviruses are known to manipulate autophagy to optimize their replication, counteract immune response and probably to promote tumourigenesis. This study explored, for the first time, the impact of human herpesvirus (HHV)-6 lytic infection on autophagy and demonstrated that HHV-6A and B (viruses sharing more than 80 % homology) differently affected this cellular process. Indeed, while HHV-6A (GS) infection of HSB2 cells promoted autophagy, HHV-6B (Z29) or the virus isolated from the serum of roseola infantum-affected patient-inhibited autophagy in Molt-3 cells or in PBMCs, respectively. Interestingly, the different behaviour of HHV-6A and B on the autophagic process was accompanied by different effects on endoplasmic reticulum stress, unfolded protein response and cell survival that was more strongly reduced by HHV-6B infection. We hypothesize that the ability to inhibit autophagy displayed by HHV-6B could be due to the fact that it contains gene homologues of those encoding for TRS1; the protein responsible for the block of autophagy by human cytomegalovirus. Understanding how HHV-6A/B infection regulates autophagy could be of particular interest, as it has been recently shown that this virus may be involved in Alzheimer's disease in which a dysregulation of autophagy may also play a role.

A Perspective of Immunotherapy for Prostate Cancer.

In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa.

Diagnosis of neurological herpesvirus infections: real time PCR in cerebral spinal fluid analysis.

Human herpesviruses (HHVs) cause many serious acute and persistent central nervous system (CNS) disorders. Because these infections manifest with various, often non-specific, symptoms and signs, and because specific therapy is often available, accurate diagnosis is essential. Cerebrospinal fluid (CSF) from 146 patients with acute meningitis or meningoencephalitis and 9 with "other neurological disorders" were analyzed by using an automatic system for nucleic acid extraction and quantitative real-time polymerase chain reaction (PCR) for herpes simplex 1 and 2 (HSV-1, HSV-2), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), herpesvirus-6 (HHV-6), and varicella-zoster virus (VZV). HHVs DNA was detected in 52 of 155 (33.5%) analyzed samples. In 39 CSF samples from patients with meningoencephalitis we found: VZV in 13, HSV-1 in 12, EBV in 6, HHV-6 in 4, and HSV-2 in 4. Co-infections of EBV and HSV-2, HSV-1 and HSV-2, HSV-1 and VZV were also disclosed in four cases. In addition, two patients with Guillain-Barré syndrome had HCMV and one showed HHV6 positivity, two patients with myelitis / polymyeloradiculitis had VZV and HCMV respectively, HHV-6 DNA was found in one patient with lateral amyotrophic sclerosis. Three CSF specimens from HIV-infected patients with CNS complications had HHV-6 or EBV DNA. Moreover quantitative data were also correlated to clinical conditions to obtain more information on the virus aetiopathogenic role.

Application of real time PCR in post transplant monitoring of cytomegalovirus infection: comparison with other diagnostic approaches.

Immunosuppressive status in solid organ transplant recipients is often related to the reactivation of Human Cytomegalovirus (HCMV) infection that remains one of the major causes of morbidity and mortality. Therefore, the early detection of HCMV followed by infection monitoring is important to institute prompt and appropriate treatment. In recent years good results have been obtained by HCMV DNA amplification methods; qualitative and quantitative approaches have shown good sensitivity and specificity, but they often require post-PCR manipulation that adds time to the analysis and may lead to contamination problems. Recently, Real Time PCR (RT-PCR) has been proposed in HCMV DNA analysis as a valid method for its good sensitivity and rapidity. In the present study, twenty-five solid organ transplant recipients were analyzed for HCMV diagnosis; 60 peripheral blood leukocytes and 120 plasma samples were tested by RT-PCR and the results compared to those obtained by a qualitative Nested PCR and a quantitative DNA enzyme immunoassay.

Early evidence of lymphoproliferative disorder: post-transplant monitoring of Epstein-Barr infection in adult and pediatric patients.

Transplant patients are at high risk of post-transplant lymphoproliferative disorder (PTLD). A strong correlation between Epstein-Barr virus (EBV) and PTLD is observed in pediatric patients with primary infection after transplant. Because many patients have responded to reversal of immunosuppressive therapy, an early identification of EBV is essential for the reduction of immunosuppression and/or introduction of antiviral therapy to prevent PTLD. Polymerase chain reaction (PCR) is a specific and sensitive method to identify EBV DNA in blood. The aim of our study was to establish a protocol for monitoring EBV infection in transplanted patients for early identification those at high risk of PTLD. Viral presence in peripheral blood leukocytes (PBL) and serum samples was revealed by Nested PCR; positive specimens were quantified with Real Time PCR (RT-PCR). DNA in PBL was observed in 12 cases and 6 showed EBV in sera. Quantitative analysis showed a wide range of EBV DNA copies in leukocytes that were higher than in sera. Two patients displayed high viral load values in both PBL and sera associated with clinical evidence of PTLD. Our data suggest that the study of the EBV load represents an essential approach in the diagnosis of PTLD and the analysis of serum samples could provide useful information in the post-transplant monitoring of high-risk patients.