Human papillomavirus genotypes and phylogenetic analysis of HPV-16 variants in HIV-1 infected subjects in Italy

A cross-sectional study was carried out to improve the state of evidence regarding the spectrum of HPV types and HPV-16 LCR variants circulating among men and women infected with HIV-1 in Italy. This study, conducted in 518 HIV-positive subjects (346 males and 172 females), showed a high prevalence of HPV anal infections (88.7%) in men and of cervical infections (65.1%) in women.A wide spectrum of HPV genotypes has been observed, as both single and multiple infections. Low-risk HPV types 6, 11 and 61 were frequently detected. HPV-16 was the prevalent high-risk type. Fourteen different HPV-16 LCR variants were found. Ten belonged to the European lineage (78.7% were detected in Italian subjects and 21.3% in foreign-born, all homo/bisexual men), two to the Asiatic lineage and two to the African-2 lineage. This study underlines the great genotypic heterogeneity characterizing anal and cervical HPV infections and the marked polymorphism of the predominant HPV-16 in this high-risk population in Italy.     

Beneficial effects of gradual intense exercise in tissues of rats fed with a diet deficient in vitamins and minerals: A pilot study

ObjectiveThis study evaluated the preliminary effects of intense physical training (swimming) on oxidative stress in rats with nutritional deficiencies.MethodsRats were fed with a standard diet or a diet deficient in vitamins and minerals for 4 months. The deficient diet contained one-fourth of the recommended vitamin and mineral levels for rats. From the second month, half of the animals were subjected to a swimming exercise in a plastic container with water maintained at 34 ± 1°C for 1 h/d, five times per week, for 11 wk. The rats were subjected to swimming exercise with loads attached to the dorsal region, which were progressively increased according to their body weight (1% to 7%). Sedentary rats were transported to the experimental room and handled as often in a similar way as the exercise group, except that they were not put in water.ResultsIn the exercised group, blood lactate levels were significantly lower and the heart weight/body weight ratio was significantly higher than in the sedentary group (P < 0.05). Increased lipid peroxidation was observed in the liver, heart, and skeletal muscle of rats fed with the deficient diet, but it was completely reversed by exercise. Exercise also decreased lipid peroxidation levels in the heart and skeletal muscle of rats fed with the standard diet (P < 0.05).ConclusionThis pilot study leads to the continuity of the studies, because the partial results observed suggest that inadequate nutrition may enhance oxidative stress, and that intense chronic physical training may activate antioxidant defenses, possibly by hormesis.     

Virtual reality in anxiety disorders: the past and the future

One of the most effective treatments of anxiety is exposure therapy: a person is exposed to specific feared situations or objects that trigger anxiety. This exposure process may be done through actual exposure, with visualization, by imagination or using virtual reality (VR), that provides users with computer simulated environments with and within which they can interact. VR is made possible by the capability of computers to synthesize a 3D graphical environment from numerical data. Furthermore, because input devices sense the subject's reactions and motions, the computer can modify the synthetic environment accordingly, creating the illusion of interacting with, and thus being immersed within the environment. Starting from 1995, different experimental studies have been conducted in order to investigate the effect of VR exposure in the treatment of subclinical fears and anxiety disorders. This review will discuss their outcome and provide guidelines for the use of VR exposure for the treatment of anxious patients.     

A Micro-Electrode Array device coupled to a laser-based system for the local stimulation of neurons by optical release of glutamate

Optical stimulation is a promising approach to investigate the local dynamic responses of cultured neurons. In particular, flash photolysis of caged compounds offers the advantage of allowing the rapid change of concentration of either extracellular or intracellular molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. We describe here the use of an ultra-violet (UV) laser diode coupled to an optical fibre for the local activation of caged compounds combined with a Micro-Electrode Array (MEA) device. Local uncaging was achieved by UV irradiation through the optical fibre previously positioned by using a red laser diode. The size of the stimulation was determined using caged fluorescein, whereas its efficacy was tested by studying the effect of uncaging the neurotransmitter glutamate. Uncaged glutamate evoked neuronal responses that were recorded using either fluorescence measurements or electrophysiological recordings with MEAs, thus showing the ability of our system to induce local neuronal excitation. This method allows overcoming the limitations of the MEA system related to unfocused electrical stimulation and induction of electrical artefacts. In addition, the coupling of a UV laser diode to an optical fibre allows a precise local stimulation and a quick change of the stimulation point.     

Modulation of IFNAR1 mRNA expression in multiple sclerosis patients

Interferon-beta receptor (IFNAR) is composed of 2 subunits, IFNAR1 and IFNAR2, the latter of which is expressed as functional (IFNAR2.2), non-functional (IFNAR2.1) and soluble (IFNAR2.3) isoform. Real-Time PCR analysis of mRNA for all IFNAR components in multiple sclerosis patients na?ve for therapy and undergoing long-term treatment with interferon-beta shows that IFNAR1 mRNA level is lower than in healthy controls. If long-term treated patients are divided according to the production of mRNA for Myxovirus protein-A, a marker of interferon-beta bioactivity, IFNAR1 mRNA reaches the values observed in controls only in Myxovirus protein-A-induced patients. Since chronic cell stimulation by interferon-beta induces IFNAR protein down-regulation, we suggest that the increase of IFNAR1 mRNA might serve as a mechanism for counterbalancing the loss of protein receptor, enhancing, at least in this sub-group of patients, cell responsiveness to interferon-beta.     

Emerging perspectives in epidermal growth factor receptor targeting in head and neck cancer

The epidermal growth factor receptor (EGFR) has been shown to be a promising therapeutic target in head and neck cancer. Cetuximab, a monoclonal antibody against EGFR, has been approved in the United States for use with radiotherapy for head and neck squamous cell carcinoma. However, the role of EGFR targeting agents in other therapeutic modalities, such as combined chemoradiotherapy or induction chemotherapy, remains to be defined. Although results from several clinical trials have demonstrated the therapeutic potentials of EGFR targeting agents in these settings, further studies are necessary before definitive conclusions can be made. The concurrent targeting of EGFR along with other pathways important in carcinogenesis may hold significant therapeutic potential. In particular, several clinical trials are studying the effects of combining agents that target the vascular endothelial growth factor with EGFR inhibitors. Last, studies are ongoing to elucidate the predictive and correlative biomarkers in anti-EGFR therapy to allow for proper patient selection. In the case of cetuximab, these correlative biomarkers may include elements of the immune system in addition to the signal transduction proteins involved in EGFR pathway.