Detectable cerebrospinal fluid JCV DNA in late-presenting HIV-positive patients: beyond progressive multifocal leukoencephalopathy?

In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009-2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45.5% vs 21.4 in the latter one: survival was higher than previously described but no predictor of poor outcome was identified. Two patients treated with 5HT2-inhibitors survived. The contributing role of JCV replication in other CNS-affecting disorders needs to be assessed as well as the benefits of 5HT2-inhibitors in HIV-positive patients with proven PML.

Sequential therapy with entecavir and PEG-INF in patients affected by chronic hepatitis B and high levels of HBV-DNA with non-D genotypes.

Complete eradication of hepatitis B virus (HBV) is rarely achieved. Treatment options include currently available nucleos(t)ide analogues and pegylated interferon. The aim of our exploratory study was to assess the effectiveness of sequential therapy for chronic hepatitis B (CHB) vs the current standard of care. We evaluated an association with entecavir and pegylated interferon alfa-2a (PEG-IFN) in 20 patients with hepatitis B, high HBV viremia and genotypes A, B, C and E. Patients received entecavir alone for 12 weeks, then entecavir and PEG-IFN for 12 weeks, lastly PEG-IFN alone for 36 weeks. The results were compared with 20 patients (control group) treated in the past with 48 weeks of PEG-IFN monotherapy. Our results show that complete sustained virological response (SVR) and partial SVR were, respectively, 60% and 80% in the study group and 10% and 30% in the control group; anti-HBe seroconversion rate were 76.9% vs 15%, and anti-HBs seroconversion were 20% vs 0%, respectively. We found a correlation among different genotypes and virological and serological outcomes - genotype C has a better virological response, while genotype A had a better serological response, and E genotype had a poor response. These results show that a sequential approach is a promising strategy of treatment in patients with CHB and high viremia in comparison with PEG-IFN monotherapy. The E genotype seems to have the worse rate of response and requires other treatment strategies.

Origin, evolution and paleoepidemiology of brucellosis.

Brucellosis is a worldwide disease. Although it has been eradicated in some countries, it continues to be an important disease in many farming areas. Previous works have described the evolution and diffusion of brucellosis in antiquity through direct analysis of ancient human remains collected by the University Museum of Chieti, Italy, and by using paleopathological and historical data. The earliest published case was reported in a skeletal individual dated to the Middle Bronze Age. However, our research group has diagnosed vertebral brucellosis in the partial skeleton of the late Pliocene Australopithecus africanus, demonstrating that this infectious disease occasionally affected our direct ancestors 2·3-2·5 million years ago. The frequency of brucellosis increased during the Roman period, when the disease would almost certainly have been endemic in Roman society, and during the Middle Ages. Most paleopathological cases involve adult male skeletal individuals, and lumbar vertebrae and sacroiliac joints are most commonly involved.

Masseter muscle activity during vestibular stimulation in man.

Experimental data report that vestibular afferents affect trigeminal system activity. The aim of this work was to evaluate whether static vestibular stimulation affects the excitability of trigeminal motoneurons in man. In order to assess this, voluntary EMG activity of masseter muscles as well as duration and latency of the early and late components of EMG exteroceptive silent period were evaluated while keeping the subject in vertical position and during 20 degrees static tilt. The experiments were performed on ten adult subjects with no orofacial, neurologic and otologic disorders. Each subject sat on a chair, which kept the complex head-jaw-neck-trunk and the limbs securely fixed, in order to minimize any interference due to the activation of somatosensory and proprioceptive afferents from these districts. The subjects were instructed to contract masseter muscles at 25% of their maximum bite force and the isometric force monitoring was used as visual feedback. Exteroceptive silent period (ESP) of masseter EMG was elicited by electrically stimulating the inferior inter-incisal gum. Results showed that static vestibular stimulation induced asymmetrical responses on voluntary masseter muscle activity, which was reduced to 70.3 +/- 16.1% (mean +/- S.D.) of the control value during ipsilateral tilt and increased to 128.8 +/- 13.0% during contralateral tilt. The duration of the early (ESP1) and late (ESP2) silent periods was also affected: during ipsilateral tilt ESP1 and ESP2 duration increased to 130.0 +/- 3.5% and to 122.1 +/- 2.1% of control, respectively; during contralateral tilt it was reduced to 76.8 +/- 1.2% and to 83.0 +/- 1.7% of control, respectively. On the contrary, changes in latencies were not significant. These data evidenced an asymmetrical effect exerted on trigeminal motor activity by static tilt. Since the influence of all receptors which could be activated by static tilt, except that arising from the macular ones, was minimized in this study, it is likely that the observed effects, induced by static tilt on masseter muscle activity, were of macular origin.

Amino acid changes in the attachment G glycoprotein of human respiratory syncytial viruses (subgroup A) isolated in Italy over several epidemics (1997-2006).

The human respiratory syncytial virus (HRSV) is the most important cause of admission to hospital for acute lower respiratory tract infections in infants and young children worldwide. Only few studies have investigated the molecular evolution of HRSV, and none has been conduct ed in Italy. The genetic diversity of the G glycoprotein of 59 subgroup A strains obtained from two clinical centers located in Northern and Central Italy was studied, during seven nonconsecutive epidemic seasons (1997-2006). The nucleotide sequences encompassing 624 bp, at the carboxy terminus of the G glycoprotein gene, were compared to sequences representative of previously defined HRSV genotypes. Phylogenetic analysis indicated that most Italian group A isolates clustered into two different lineages (GA2 and GA5), whereas only few isolates grouped into the other known lineages. Eight positively selected sites were found and it was predicted that serine and threonine of positively selected sites 117 and 262 (respectively) are O-glycosilated. The presence of multiple identical sequences in three lineages (GA1, GA5, and BE/A1) suggests that certain strains are predominant in a given epidemic season. Although most of the sites of the G glycoprotein gene of HRSV-A strains seem invariable because of strong purifying selection, some evolutionary "hot spots" may be present. Since the G glycoprotein is a major target (together with the F glycoprotein) of the HRSV humoral immune response, it is important to provide information about its genetic heterogeneity in order to address better both therapeutic and vaccine strategy.

Jaw muscle response to stimulation of type II somatosensory afferents of limbs in the rat.

Convergence of various afferent inputs onto brainstem neurones may play an important role in the regulation of trigeminal motor activity. In particular, previous studies suggest that, besides sensory inputs arising from the orofacial region, extratrigeminal information may modulate jaw muscle function. In the present study the actions exerted on masseter and digastric muscles by the activation of somatosensory afferents coming from fore- and hind limbs were examined. The electromyographic activity (EMG) of masseter and digastric muscles was recorded in 20 anaesthetised rats, and EMG responses to single and paired electrical stimulation of common radial and sciatic nerves, at a threshold intensity for the activation of group II afferent fibres, were studied. The stimulation induced an excitatory response in both masseter and digastric muscles bilaterally. Ipsiand contralateral radial nerve stimulation evoked masseter responses at latencies of 13.8 +/- 2.4 ms and of 18.0 +/- 2.6 ms, respectively, and digastric responses 1.6 +/- 0.4 ms later. Ipsi- and contralateral sciatic nerve stimulation elicited masseter responses at latencies of 21.4 +/- 2.6 ms and of 23.3 +/- 2.0 ms, respectively, and digastric responses 2.0 +/- 0.2 ms later. The same masseter and digastric motor units were excited by both radial and sciatic nerve stimulation; this suggests a convergence of somatosensory inputs arising from fore- and hind limbs on the same pool of masseter and digastric motoneurones. Paired stimulation of the two nerves did not induce any summation of the responses; this finding suggests that the two inputs, reaching a common relay station, could give rise either to occlusion or to inhibitory interactions. Spinotrigeminal relationship evidenced in this study may be involved in the coordination of jaw and limb movements.

Interleukin-8 gene expression from human alveolar macrophages: the role of adherence.

The human alveolar macrophage (AM) is an important immune effector cell of the lung, as this cell possesses potent antimicrobial activities and has the ability to present antigen. In addition, the Am can secrete a number of regulatory and chemotactic cytokines in response to both endogenous and exogenous stimuli. In this study, we demonstrate that the adherence of AM to plastic or cellular substrates is an important activation event leading to the gene expression of novel chemotactic cytokine interleukin (IL)-8. The culturing of AM on plastic induced the time-dependent accumulation of IL-8 mRNA. In addition, adherence of these cells induced the gene expression of the proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta. This adherence phenomenon was not specific to plastic, as AM cultured on collagen- or fibronectin-coated plates also expressed IL-8 mRNA upon adherence. The adherence of Am resulted in the induction of de novo IL-8 mRNA synthesis, as this mRNA accumulation was completely abrogated by actinomycin D. Adherence-induced IL-8 mRNA expression was not altered by cycloheximide, suggesting that de novo or ongoing protein synthesis was not required for induction of IL-8 message. Adherence of AM to plastic not only upregulated IL-8 mRNA levels but also induced the production of extracellular IL-8 immunoreactive protein. Both adherent and nonadherent AM treated with lipopolysaccharide generated substantial amounts of IL-8 mRNA. Adherence and lipopolysaccharide, however, acted in a synergistic fashion to dramatically augment the production of extracellular IL-8 from these cells. Our findings would suggest that AM adherence is an important macrophage-activating event that may play a critical role in the modulation of lung inflammatory responses.