Infectious agents in atherosclerotic cardiovascular diseases through oxidative stress

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research

Behavioral Restriction Determines Left Attentional Bias: Preliminary Evidences From COVID-19 Lockdown

During the COVID-19 lockdown, individuals were forced to remain at home, hence severely limiting the interaction within environmental stimuli, reducing the cognitive load placed on spatial competences. The effects of the behavioral restriction on cognition have been little examined. The present study is aimed at analyzing the effects of lockdown on executive function prominently involved in adapting behavior to new environmental demands. We analyze non-verbal fluency abilities, as indirectly providing a measure of cognitive flexibility to react to spatial changes. Sixteen students (mean age 20.75; SD 1.34), evaluated before the start of the lockdown (T1) in a battery of psychological tasks exploring different cognitive domains, have been reassessed during lockdown (T2). The assessment included the modified Five-Point Test (m-FPT) to analyze non-verbal fluency abilities. At T2, the students were also administered the Toronto Alexithymia Scale (TAS-20). The restriction of behaviors following a lockdown determines increased non-verbal fluency, evidenced by the significant increase of the number of new drawings. We found worsened verbal span, while phonemic verbal fluency remained unchanged. Interestingly, we observed a significant tendency to use the left part of each box in the m-FPT correlated with TAS-20 and with the subscales that assess difficulty in describing and identifying feelings. Although our data were collected from a small sample, they evidence that the restriction of behaviors determines a leftward bias, suggesting a greater activation of the right hemisphere, intrinsically connected with the processing of non-verbal information and with the need to manage an emotional situation

Detection of SARS-COV N2 Gene: Very low amounts of viral RNA or false positive?

Background: The detection of a low amount of viral RNA is crucial to identify a SARS-CoV-2 positive individual harboring a low level of virus, especially during the convalescent period. However, the detection of one gene at high Cycle threshold (Ct) has to be interpreted with caution. In this study we address this specific issue and report our real-life experience. Study design: A total of 1639 nasopharyngeal swabs (NPS) were analyzed with Xpert® Xpress SARS-CoV-2. Positive samples showing high Ct values (Ct>35) were concentrated by centrifugation and re-tested with Cepheid or other methods (RealStar SARS-CoV2 RT-PCR, Altona Diagnostics; GeneFinder COVID-19 Plus RealAmp Kit, Elitech). Results: 1599 (97.5%) negative samples, 36 (2.3%) positive samples and 4 (0.2%) presumptive positive samples were detected. In 17 out of 36 positive patients, very low viral RNA copies were suspected since positivity was detected at high Ct. We confirmed positivity for patients who showed both E and N genes detected and for patients with only N detected but with Ct <39. On the contrary, samples with only gene N detected with Ct values >39 were found negative. NPS taken 24 hours after the first collection confirmed the negativity of the 12 samples. Clinical data sustained these results since only 2 of these 12 patients showed COVID-19-like symptoms. Conclusions: These data support our consideration that detection of the N2 gene at high Ct needs to be interpreted with caution, suggesting that collaboration between virologists and clinicians is important for better understanding of results

Analysis of viral nucleic acids in duodenal biopsies from adult patients with active celiac disease: in search for an etiological relationship

BACKGROUND AND AIM: Celiac Disease (CD) is a multisystemic chronic inflammatory autoimmune disease which develops in genetically predisposed subjects and it is triggered by the ingestion of gluten. After the interaction between HLA-DQ2/DQ8 and gluten-derived peptides, lymphocytes T CD4+ start a specific immune response which ends in a chronic inflammation and mucosal damage. CD pathogenesis is complex and not entirely understood, probably due to an alteration in the gastrointestinal immune system or to its aberrant regulation. Furthermore, many environmental and immune factors could be involved, particularly viral infections. The aim of the study was to observe possible relationships between CD and infections from HHV-6 A/B, EBV, CMV, adenovirus and rotavirus. MATERIAL AND METHODS: Thirty-nine adult patients (aged 18-65 yrs) have been enrolled: specifically, 24 duodenal biopsies from active CD patients and 15 biopsies from non-CD patients were analyzed. CD diagnosis has been performed by means of serological antibodies, histology of duodenal biopsies and duodenal biopsy organ culture. Viral nucleic acids were extracted from duodenal biopsies and then amplified using Real-Time PCR technique. RESULTS: HHV-6B was found in 62.5% of CD patients and in 73.3% of non-CD patients (p=0.13). EBV was found in 4.5% of CD patients and 6.7% of non-CD patients (p=0.35). Nucleic acids from HHV-6A, CMV, adenovirus and rotavirus were not detected in any group. HHV-6B viral load in CD patients was higher than in non-CD patients, but data were not statistically significant (p=0.54). CD patients with HHV-6B viral load >50000 copies/ml resulted to be younger and had lower anti-tTG antibody titers found at organ culture than patients with lower HHV-6B viral load (p>0.05). CONCLUSIONS: There seems to be no difference in viral load and/or in the detection of viruses between CD and non-CD patients. Thus, our data do not support the possible relationship between CD and viral infections, although a larger population is needed to confirm our study results

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

Sperm cryopreservation during the SARS-CoV-2 pandemic

Purpose: Sperm cryopreservation is fundamental in the management of patients undergoing gonadotoxic treatments. Concerns have risen in relation to SARS-CoV-2 and its potential for testicular involvement, since SARS-CoV-2-positive cryopreserved samples may have unknown effects on fertilization and embryo safety. This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. Methods: We recruited 10 cancer patients (mean age 30.5 ± 9.6 years) referred to our Sperm Bank during the Italian lockdown (from March 11th to May 4th 2020) who had not undergone a nasopharyngeal swab for SARS-CoV-2 testing. Patients were administered a questionnaire on their exposure to COVID-19, and semen samples were taken. Before cryopreservation, SARS-CoV-2 RNA was extracted from a 150 µl aliquot of seminal fluid in toto using QIAamp viral RNA kit (Qiagen) and amplified by a real time RT PCR system (RealStar SARS-CoV2 RT PCR, Altona Diagnostics) targeting the E and S genes. Results: The questionnaire and medical interview revealed that all patients were asymptomatic and had had no previous contact with COVID-19 infected patients. All semen samples were negative for SARS-CoV-2 RNA. Conclusion: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation

Antiviral activity of fecal water samples from HIV-1 infected subjects treated with a specific probiotic formulation

Objectives: The aim of the study was to investigate if the supplementation with multistrain probiotics may be able to modulate T cell response in HIV-1 infected patients and to evaluate the anti-HIV activity of probiotic by studying fecal water (FW) samples. Methods: Three HIV-1-positive patients (Pt1, Pt2 and Pt3) on long-term suppressive combined antiretroviral therapy (cART) received a specific multi-strain probiotic supplementation (Vivomixx ®), for six months (T6). Levels of T cell subsets were evaluated by flow cytometry. Anti- HIV activity of FW samples was evaluated in vitro. Results: CD4+ T cells levels increased in all HIV-1 infected patients whereas activation markers (CD38 and HLA-DR) were decreased both on CD4+ and CD8+ T cells. FW samples presented an increased inhibitory activity against HIV-1 compared to T0 (FW-Pt1: T0 =40%, T6 = 65% of reduction; FW Pt2: T0 = 26%, T6 = 46% of reduction; FW Pt3: T0 = 47%, T6 = 94% of reduction). Discussion: Our data suggest that the administration of the specific probiotic formulation improves the antiviral status of people living with HIV-1 under cART, also modulating T cell response. Conclusion: Anti-HIV activity of FW may have several public health and social implications for sexually transmitted diseases that need to be further explored

Clinical care conditions and needs of palliative care patients from five italian regions: Preliminary data of the demetra project

In order to plan the right palliative care for patients and their families, it is essential to have detailed information about patients’ needs. To gain insight into these needs, we analyzed five Italian local palliative care networks and assessed the clinical care conditions of patients facing the complexities of advanced and chronic disease. A longitudinal, observational, noninterventional study was carried out in five Italian regions from May 2017 to November 2018. Patients who accessed the palliative care networks were monitored for 12 months. Sociodemographic, clinical, and symptom information was collected with several tools, including the Necesidades Paliativas CCOMS-ICO (NECPAL) tool, the Edmonton Symptom Assessment System (ESAS), and interRAI Palliative Care (interRAI-PC). There were 1013 patients in the study. The majority (51.7%) were recruited at home palliative care units. Cancer was the most frequent diagnosis (85.4%), and most patients had at least one comorbidity (58.8%). Cancer patients reported emotional stress with severe symptoms (38.7% vs. 24.3% in noncancer patients; p = 0.001) and were less likely to have clinical frailty (13.3% vs. 43.9%; p < 0.001). Our study confirms that many patients face the last few months of life with comorbidities or extreme frailty. This study contributes to increasing the general knowledge on palliative care needs in a high-income country

Spontaneous immunogenicity of ribosomal P0 protein in patients with benign and malignant breast lesions and delay of mammary tumor growth in P0-vaccinated mice

A common carboxyl-terminal epitope (C-22 P0) of the ribosomal P proteins (P0, P1 and P2) was shown to elicit autoantibodies in systemic lupus erythematosus (SLE) and in head and neck cancer patients. In this report we provide evidence for the in vivo immunogenicity of the P0 protein in breast cancer patients. Using recombinant P proteins, we demonstrated that sera from breast carcinoma patients (8/75) displayed significant reactivity to P0 protein when compared with healthy donor sera (0/45). Four out of the eight sera showed simultaneous reactivity to all P proteins. Breast benign tumor (3/17) and mammary hyperplasia (3/17) patient sera also showed significant reactivity to P proteins, thus suggesting that the occurrence of P protein autoantibodies might reveal mammary cell cycle dysregulation. Patient sera reacting with all P proteins recognized C-22 P0. Anti-P0 autoantibodies did not correlate with prognostic parameters of breast carcinomas. High level expression of C-22 P0 was found in mammary carcinomas compared with normal adjacent epithelium and benign lesions. To determine the antitumor activity of P0 as an immunogen, BALB-neuT transgenic mice displaying age-related breast cancer progression were vaccinated using xenogeneic P0 at the stage of mammary atypical hyperplasia. P0 vaccination significantly delayed the onset of mouse mammary tumors that overexpressed C-22 P0. Sera from P0 vaccinated mice recognized C-22 P0. Evidence for immunity to the P0 protein, its overexpression in carcinomas and its peculiar surface localization on cancer cells, along with its antitumor activity as an immunogen might be relevant for the use of P0 protein in monitoring cancer progression and in planning immunotherapeutic strategies