Coinfection of blood-borne hepatitis B and hepatitis C viruses (HBV and HCV, respectively) in human immunodeficiency virus type 1 (HIV-1)-positive individuals frequently occurs in inmate population and peculiar viral strains and patterns of virological markers may be observed.Plasma from 69 HIV-1-positive inmates was obtained from 7 clinical centers connected with correctional centers in different towns in Italy. HIV, HBV, and HCV markers were tested by commercial assays. Virus genotyping was carried out by sequencing the protease and reverse transcriptase-encoding region (PR-RT region) for HIV and a region encompassing the NS5B gene for HCV and subsequent phylogenetic analysis.Twelve over 14 HIV-subtyped inmates were infected with HIV-1 subtype B strains. The 2 non-B strains belonged to subtype G and CRF02_AG, in an Italian and a Gambian patient, respectively. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). Most HIV-positive patients (92.8%) showed evidence of past or present HBV and/or HCV infection. Prevalence of HBV and HCV was 81.2% for both viruses, whereas prevalence of HBV/HCV coinfection was 69.6%. A significantly higher presence of HCV infection was found in Italians [odds ratio (OR) 11.0; interval 1.7-80.9] and in drug users (OR 27.8; interval 4.9-186.0). HCV subtypes were determined in 42 HCV or HBV/HCV-coinfected individuals. HCV subtypes 1a, 3a, 4d, and 1b were found in 42.9%, 40.5%, 14.3%, and 2.4% of inmates, respectively. Low titers of HBV DNA in HBV DNA positive subjects precluded HBV subtyping.The high prevalence of HBV and HCV coinfections in HIV-infected inmates, as well as the heterogeneity of HIV and HCV subtypes suggest the need to adopt systematic controls in prisons to monitor both the burden and the genetic forms of blood-borne viral infections, in order to apply targeted therapeutic interventions.
Macrophages are widely recognized as the second major target of HIV in the body. The cellular characteristics of such resting cells markedly affect the dynamics of virus lifecycle, that is slower but far more prolonged that in lymphocytes. In addition, the limited concentrations of endogenous nucleotide pools in macrophages downregulate the enzymatic activity of reverse transcriptase. As a consequence, both the anti-HIV activity and the development of resistance to antiviral drugs in macrophages are substantially different than those found in activated lymphocytes. These peculiar characteristics of virus replication and efficacy of antiviral drugs in macrophages have a natural in vivo counterpart in extralymphoid tissues, where macrophages account for the majority of cells infected by HIV. Furthermore, the replication of HIV in macrophages of testis and central nervous system is far less affected by antiviral drugs than in lymph nodes, because of the presence of natural barriers that markedly diminish the concentration of such drugs. For all these reasons, HIV infection of macrophages should be taken into account in therapeutic strategies aimed to achieve an optimal therapeutic effect in all tissue compartments where the virus hides and replicates.
Therapeutical strategies aimed to the maximal inhibition (if not the eradication) of infection by human immunodeficiency virus should take into account the issue of the viral reservoir in the body. Recent data clearly show that latently infected lymphocytes represent a minimal part of the viral reservoir, while the majority of these cells are macrophages (variably differentiated) scattered in the tissues and lymph nodes. Immunologically-sequestred areas, such as the central nervous system, are particularly relevant in view of the different concentrations of antiviral drugs achieved in the organs. Thus, a careful analysis of the distribution of antiviral drugs, and the assessment of their activity in cells of macrophage lineage, represent key factors in the development of therapeutical strategies aimed to the "cure" of infectious patients.
Objective. To describe an intensive and multimodal ultrasound (US) training program focused on Achilles enthesitis and to illustrate the learning curve of trainees without experience. Methods. Three medical students (trainees) and two rheumatologists experienced in musculoskeletal US (trainers) were involved in the training program, which encompassed one preliminary theoretical-practical meeting and five scanning sessions (two patients per session). The students and one expert performed the US examination of the Achilles enthesis bilaterally. The trainees acquired representative images and assessed the presence of Outcome Measures in Rheumatology (OMERACT) US abnormalities of enthesitis. The experts provided feedback addressing trainees’ misinterpretations, and the quality of the acquired images was evaluated. A dedicated questionnaire was used to evaluate the students’ confidence. After each session, five sets of static images (total=100 images of most commonly scanned entheses) were provided and scored by the students according to OMERACT US definitions. Total agreement and prevalence and bias adjusted kappa (PABAK) were used to evaluate the concordance between the trainees and the expert sonographer. Results. The total agreement and PABAK significantly improved between the first and fifth scanning sessions (76.2% versus 92.9%, p<0.01, and 0.5 versus 0.79, p<0.01) and between the first and fifth static image sets (64.5% versus 81.9%, p<0.01, and 0.29 versus 0.74, p<0.01). Image quality did not significantly improve (p=0.34). A significant increase in trainees’ confidence was registered (p<0.01). Conclusions. The described training program rapidly improved the students’ performance in the US assessment of Achilles enthesitis, appearing to be an effective starting model for the future development of pathology-oriented teaching programs for the US in rheumatology.
Abstract The possible existence of yet undiscovered human tumorigenic viruses is still under scrutiny. The development of large-scale sequencing technologies, coupled with bioinformatics techniques for the characterization of metagenomic sequences, have provided an invaluable tool for the detection of unknown, infectious, tumorigenic agents, as demonstrated by several recent studies. However, discoveries of novel viruses possibly associated with tumorigenesis are scarce at best. Here, we apply a rigorous bioinformatics workflow to investigate in depth tumor metagenomes from a small but carefully selected cohort of immunosuppressed patients. While a variegated bacterial microbiome was associated with each tumor, no evidence of the presence of putative oncoviruses was found. These results are consistent with the major findings of several recent papers and suggest that new human tumorigenic viruses are not common even in immunosuppressed populations.
Medical oxygen-ozone (O2-O3) is a successful therapeutic approach accounting on the assessed beneficial action of ozone in the range 30-45 μg/ml (expanded range 10-80 μg/ml according to different protocols), as in this dosage range ozone is able to trigger a cellular hormetic response via the modulating activity of reactive oxygen species (ROS), as signaling molecules. The ozone-dependent ROS-mediated fatty acid oxidation leads to the formation of lipid ozonization products (LOPs), which act as signal transducers by triggering ROS signaling and therefore mitohormetic processes. These processes ultimately activate survival mechanisms at a cellular level, such as the Nrf2/Keap1/ARE system activation, the AMPK/FOXO/mTOR/Sir1 pathway and the Nrf2/NF-kB cross talk. Furthermore, indirectly, via these pathways, LOPs trigger the HIF-1α pathway, the HO-1 signaling and the NO/iNOS biochemical machinery. Ozone-driven shift of cytokine activation pathways, from pro-inflammatory to anti-inflammatory immediately afterwards, also exert direct immunoregulatory effects on regulatory T lymphocytes as well as on the intestinal microbiota, which in turn can affect immune response thus influencing the progression of the disease. In this review, we will describe the biological and biochemical mechanisms of action of ozone therapy with the aim of evaluating both positive and critical aspects of ozone use as a therapeutic adjuvant in the light of emerging viral infections, such as SARS-CoV-2 and microbiome-associated disorders related to SARS-CoV-2.
The aim of this study was to evaluate the prevalence of genotypic resistance for each drug-class, and of single resistance-mutations in 1075 HIV-1 infected multi-treated patients undergoing their first genotypic resistance-test (GRT) after virological failure, over the years 1999-2003. First GRT was requested in 2003 for patients at earlier stages of failure, with less advanced disease, higher CD4-cell-count, lower HIV-RNA, and lower drug-experience with respect to 1999. Prevalence of resistance to all three drug-classes decreased from 33.3% in 1999 to 14.8% in 2003 (p < 0.001). Patients with protease-inhibitor (PI) resistant viruses decreased from 68.1% in 1999 to 34.1% in 2003 (p < 0.001); patients with nucleoside reverse transcriptase-inhibitor (NRTI) resistant viruses remained unchanged (85.4% in 1999; 86.4% in 2003); patients with non-NRTI (NNRTI) resistant viruses increased from 36.1% in 1999 to 52.3% in 2003 (p = 0.005) (corresponding to an increased NNRTI-use and decreased PI-use). From 1999 to 2003, resistance-mutations to drugs with high genetic-barrier significantly decreased (L90M/V82A/M46I/I54V/G73S/I84V/G48V for PIs; M41L/D67N/L210W/V1181 for NRTIs, p < 0.05), while mutations to drugs with low genetic-barrier increased (D30N in protease, M184V/K103N/V108I in reverse transcriptase, p < 0.05). Taken together, earlier recruitment to first GRT in patients with less severe disease, and with lower prevalence of drug-resistant viruses may further improve therapeutic strategies aimed at longer and greater control of HIV-related disease progression.
Objective: Hypertension and dyslipidemia represent two of the most relevant modifiable cardiovascular risk (CVR) factors and they often coexist. The aim of our study was to evaluate the characteristics of the lipid profile of a large unselected hypertensive population referred to our Centre, to underline the magnitude of this association and possible lacks in the management of dyslipidemia. Design and method: Retrospective study on 1440 hypertensives referred to our Hypertension Centre between 2010 and 2015. Inclusion criteria were age >=18 years, a 24-hour ambulatory blood pressure monitoring (ABPM) and a complete lipid profile: total cholesterol (TC), HDL cholesterol (HDL-c) and triglycerides (TG). Dyslipidemia was defined by the presence of at least one of these characteristics: TC >=200 mg/dl, calculated LDL cholesterol (cLDL) values higher than those recommended based on individual CVR, HDL-c<40 mg/dl in men and <50 mg/dl in women, TG >=150 mg/dl. Results: Mean age: 55.9 ± 13.4 years. Male sex: 823 (57.2%). Overweight/obese: 68%. Smokers: 18.1%. Diabetics: 10.7%. Dyslipidemia: 82.6%. Patients with peripheral arterial disease (PAD): 23,7%. Mean eGFR: 75.0 ± 15.6 ml/min/1.73m2. Mean TC: 205.9 ± 39.7 mg/dl. Mean HDL-c: 51.8 ± 13.7 mg/dl. Median TG: 111 mg/dl (82–157). Mean cLDL: 129.2 ± 34.5 mg/dl. Drug therapy: 19% (statins 87.6%, ezetimibe 6.2%, others 2.2%). At target cLDL: 39% (all patients), 42.9% (treated patients). Females were less controlled, despite the same treatment rate with lipid-lowering drugs. Diabetics were also less controlled, despite a higher rate of treatment with lipid-lowering drugs. Patients with PAD not treated with lipid-lowering drugs were 78.3%. TG>=150 mg/dl: 28% (all patients), 33% (treated patients). Low HDL-c (according to sex): 28.3%. Statins frequencies: simvastatin (34.1%), atorvastatin (27.8%), rosuvastatin (13.2%), pravastatin (10.3%), others (2.2%). High intensity statins were taken only by 2% of treated patients. The hypertensives controlled by therapy were 29.9% and patients with both controlled hypertension and cLDL were only 12%. Conclusions: Our data show the frequent association between hypertension and dyslipidemia. Patients with at least one alteration of the lipid profile were often untreated with lipid-lowering drugs, even in the presence of increased CVR. Whenever treated, they received low-medium intensity statins and they often did not reach their therapeutic goals.
