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Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny of 11,541 human immunodeficiency virus-1 subtype B pol gene sequences from a large Italian cohort. Molecular transmission chains were characterized by means of different clinical/demographic factors, such as the interaction between male homosexuals and male heterosexuals. Our method takes an advantage of a flexible notion of transmission cluster and can become a general framework to analyse other epidemics. © 2011 Macmillan Publishers Limited. All rights reserved.

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load

The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND).We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016.It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Diagnosis of HAND may benefit from both laboratory analysis and advanced specific neuroimaging techniques. As regards HAND therapy, modified HAART combinations and simplification strategies have been tested, while novel exciting frontiers seem to involve the use of nanoparticles with the ability to cross the Blood-Brain Barrier (BBB).Albeit highly active antiretroviral therapy (HAART) allowed a major decrease in morbidity and mortality for AIDS patients, CNS involvement still represents a challenge in HIV patients even today, affecting up to 50% of patients with access to combination antiretroviral therapy (cART). Future studies will have to focus on CNS compartmentalization, drugs' ability to penetrate and suppress viral replication in this compartment, and on new approaches to reduce HIV-associated neuroinflammation.

Hiatal hernias (HHs) are usually divided into two main groups: sliding and para-esophageal (torsional) ones. Sometimes patients presenting HHs experience progressive anemia, whereas rarely an acute anemia with melena or hematemesis can occur. In such cases a Cameron ulcer should be suspected and a careful esophago-gastro-duodenoscopy (EGDS) with a meticulous inspection of the mucosal folds along the neck of the hernia is the best examination in order to find out the ulcer itself. In front of massive hemorrhage due to a Cameron erosion, the first aim should be the control of the bleeding itself, in order to ree1Romastablish hemodynamic stability. The Authors report the case of a 72-year-old man presenting a severe bleeding secondary to a large Cameron ulcer in a para-esophageal hiatal hernia. Firstly, a combined medical-endoscopic therapy was tried; the patient underwent transfusions of pooled red blood cells and endovenous anti-acid therapy combined with an operative endoscopic treatment; unfortunately this initial approach failed, therefore the patient was referred to surgery. The surgeons realized a minimally invasive atypical gastric resection associated with the HH repair; the post-operative course was uneventful and no other rebleeding episodes occurred. The urgency treatment of a life-threatening bleeding for Cameron ulcers remains a very challenging problem as no univocal and standardized recommendation has been described in literature since now. In this case-report the Authors make an overview of the current literature on the treatment of Cameron ulcers, describing a novel surgical technique for massive upper gastro-intestinal bleeding secondary to these lesions.

Human T helper (Th) cells (Th1- or Th2-oriented memory T cells as well as Th1- or Th2-polarized naive T cells) were infected in vitro with an R5-tropic HIV-1 strain (BaL) and assessed for their profile of cytokine production, CCR5 receptor expression, and HIV-1 p24 antigen (p24 Ag) production. Higher p24 Ag production was found in CCR5-negative Th2-like memory T cells than in CCR5-positive Th1-like memory T cells. By contrast, p24 Ag production was higher in Th1-polarized activated naive T cells in the first 4 days after infection. However, p24 Ag production in Th1-polarized T cells became comparable or even lower than the production in Th2-polarized populations later in infection or when the cells were infected with HIV-1BaL after secondary stimulation. The higher levels of p24 Ag production by Th1-polarized naive T cells soon after infection reflected a higher virus entry, as assessed by the single round infection assay using the HIV-chloramphenicol acetyl transferase (HIV-CAT) R5-tropic virus that contains the envelope protein of HIV-1 YU2 strain. The limitation of viral spread in the Th1-polarized populations, despite the initial higher level of T-cell entry of R5-tropic strains, was due to the ability of Th1 cells to produce greater amounts of beta-chemokines than Th2 cells. In fact, an inverse correlation was observed between Th1-polarized naive T cells and Th1-like memory-activated T cells in regards to p24 Ag production and the release of the following CCR5-binding chemokines: regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Moreover, infection with the HIV-1BaL strain of Th1-polarized T cells in the presence of a mixture of anti-RANTES, anti-MIP-1alpha, and anti-MIP-1beta neutralizing antibodies resulted in a significant increase of HIV-1 expression. These findings suggest that Th1-type responses may favor CD4(+) T-cell infection by R5-tropic HIV-1 strains, but HIV-1 spread in Th1 cells is limited by their ability to produce CCR5-binding chemokines. (Blood. 2000;95:1167-1174)

The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered.We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted.Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem.In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and health-care provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions.

Expression of virulence factors of Bordetella pertussis is coordinately regulated by the products of the bvg locus, which codes for a sensory protein (BvgS) and a positive regulator of transcription (BvgA), a pair in the family of bacterial 'two-component' regulators. Transcription of the bvg-regulated promoters is repressed by modulating environmental factors such as 50 mM MgSO4, 10 mM nicotinic acid (NA) or low temperature (25 degrees C). We have isolated a spontaneous mutant (SK170) which expresses virulence genes at either 25 degrees C, or in the presence of 1-5 mM NA, or 10-50 mM MgSO4. Virulence factors in strain SK170 are still repressed by higher concentrations of NA (10 mM), or by a combination of low temperature (25 degrees C) and one of the other modulating agents. From this strain, we have isolated a second mutant (SK180) that showed constitutive synthesis of the virulence factors under any growth regime. Nucleotide (nt) and deduced amino acid (aa) sequence analysis showed that SK170 contains a substitution at aa570 of BvgS and SK180 contains an additional substitution at aa680. These substitutions are confined to a 161-aa sequence that links the transmembrane (TM) and kinase domains of BvgS. These mutations also alter the transcriptional autoregulation of the P1 and P2 promoters of the bvg locus. P1, which in the wild-type (wt) strain is repressed by modulating agents, is constitutively active in the mutant strains. On the contrary, P2, which is normally induced by all three modulating agents, is active in strain SK170 only in the presence of MgSO4 or NA, while in strain SK180 this promoter is repressed by modulating agents. The mutants exhibit elevated levels of the BvgA regulatory protein and have a virulent phenotype also in the presence of modulating agents.

The VacA cytotoxin, produced by toxigenic strains of Helicobacter pylori, induces the formation of large vacuoles highly enriched in the small GTPase rab7. To probe the role of rab7 in vacuolization, HeLa cells were transfected with a series of rab mutants and exposed to VacA. Dominant-negative mutants of rab7 effectively prevented vacuolization, whereas homologous rab5 and rab9 mutants were only partially inhibitory or ineffective, respectively. Expression of wild-type or GTPase-deficient rab mutants synergized with VacA in inducing vacuolization. In vitro fusion of late endosomes was enhanced by active rab7 and inhibited by inactive rab7, consistent with vacuole formation by merging of late endosomes in a process that requires functional rab7. Taken together, the effects of overexpressed rab proteins described here indicate that continuous membrane flow along the endocytic pathway is necessary for vacuole growth.