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OBJECTIVE: Excessive body fat and the associated dysmetabolic consequences affect both developed and emerging countries. An altered gut microbiota composition is an important environmental cause of these conditions. Clinical trials targeting gut microbiome composition or functions with pro or prebiotics to promote a healthier profile are considered a promising tool for excessive body weight treatment and prevention of dysmetabolic complications. MATERIALS AND METHODS: We searched PubMed and Cochrane Library using combinations of probiotics/prebiotics and synbiotics with obesity/ weight loss/metabolic syndrome as the search terms. Clinical studies and significant pre-clinical results showing molecular mechanisms supporting clinical results were also discussed. RESULTS: Several studies in humans and in animal models have elucidated biological mechanisms supporting the observed clinical efficacy of selected probiotic and prebiotic compounds for weight management. Efficacy appears to be species or strain-specific. Fibers such as inulin or galactomannan promote independent and synergistic beneficial effects. CONCLUSIONS: Diet supplementation with synbiotics prepared using selected strains (such as Lactobacillus gasseri strains) showed to exert weight-reduction and anti-inflammatory activity in large independent studies. Their administration, together with galactomannan and/or inulin fibers, may increase weight management effects due to synergistic effect on short chain fatty acid production and microbiota 're-configuration'. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Functional constipation (FC) is a common condition in which the gut microbiota composition plays a fundamental role. The increasing knowledge on the role of gut microbes in the regulation of gut motility and stool consistency has allowed reconsidering, with a new scientific-based approach, the possibility to target the composition of intestinal bacterial populations for FC treatment. In this review, we evaluate recent attempts that used prebiotics, natural fibers or probiotics to treat FC, with a deep microbiome-based focus. MATERIALS AND METHODS: This is a literature review of articles published in Medline, Web of Science, and the Cochrane Library. Studies on FC in adults and children were identified using the following terms: constipation AND probiotics OR prebiotics OR synbiotics PR fibers OR microbiome OR microbiota. Selected animal studies were also considered if showing mechanistic observations. RESULTS: FC is associated with alteration in microbiome composition. Motility and fecal consistency are affected with different efficacy by the type of fiber, prebiotic or probiotic strain used in patients. CONCLUSIONS: Selected bacterial strains, mainly belonging to the Bifidobacterium genus, and some poorly or non-fermented natural fibers, such as Psyllium, may significantly improve FC and may represent the basis for an effective supplementation [ABSTRACT FROM AUTHOR]

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Current guidelines recommend three drug combinations to treat antiretroviral naïve HIV‐infected patients; some data of novel strategies with NRTI‐sparing regimen in this setting are now available [1,2]. The study compares [...]

In this single-centre, retrospective study, we analyzed data of 194 patients receiving antiretroviral therapy with <50 human immunodeficiency virus (HIV) RNA copies/mL in plasma and 318 HIV RNA/DNA paired samples. By kinetic polymerase chain reaction (kPCR) molecular system analysis, 104 (54%) subjects had undetectable HIV RNA and 90 (46%) had residual viraemia. Median (interquartile range) HIV DNA load was 780 (380-1930) copies/106 peripheral blood lymphocytes (PBL), and HIV DNA loads were independently associated with residual viraemia (p 0.002). Virological rebound occurred in 29/194 (15%) patients over a median (interquartile range) follow-up of 17.5 (13.5-31.5) months. Residual viraemia (p 0.002), but not HIV DNA load, was independently associated with virological rebound. [ABSTRACT FROM AUTHOR]

Background: One-week triple therapy is currently regarded as the reference of anti-Helicobacter pylori treatment. However, antibiotic-associated gastrointestinal side effects are among the major pitfalls of such regimens. Probiotic supplementation may be regarded as a therapeutic tool to prevent or reduce these troublesome drug-related manifestations. Aim: To determine whether the addition of the probiotic Lactobacillus GG to an anti-H. pylori standard triple therapy could help to prevent or minimize the occurrence of gastrointestinal side effects. Methods: One hundred and twenty healthy asymptomatic subjects screened positive for H. pylori infection and deciding to receive eradication therapy were randomized either to 1-week pantoprazole (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), tinidazole (500 mg b.i.d.) or to the same regimen supplemented with Lactobacillus GG for 14 days. Patients filled in validated questionnaires during follow-up to determine the type and severity of side effects and to judge overall tolerability. Results: Bloating, diarrhea and taste disturbances were the most frequent side effects during the eradication week and were significantly reduced in the Lactobacillus GG-supplemented group (RR = 0.4, CI 0.2–0.8; RR = 0.3, CI 0.1–0.8; RR = 0.3, CI 0.1–0.7, respectively). The same pattern was observed throughout the follow-up period. Overall assessment of treatment tolerability showed a significant trend in favor of the Lactobacillus GG-supplemented group (p = 0.03). Conclusions:Lactobacillus GG supplementation beneficially affects H. pylori therapy-related side effects and overall treatment tolerance.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Acid suppression plus two antibiotics is considered the reference anti-Helicobacter pylori treatment. Reported eradication rates are around 65–80%. Human Lactobacillus acidophilus shows an in vitro inhibitory effect on the attachment of H. pylori to gastric epithelial cell lines. Culture supernatant of this bacillus seems to decrease the in vitro viability of H. pylori. Aim: To evaluate whether the supplementation with an inactivated preparation of L. acidophilus could improve the efficacy of a standard anti-H. pylori therapy. Methods: One-hundred and twenty H. pylori-positive patients were randomly assigned to a 7-day triple therapy based on rabeprazole (20 mg b.d.), clarithromycin (250 mg t.d.s.) and amoxicillin (500 mg t.d.s.) (RCA group: 60 subjects), or to the same regimen supplemented with a lyophilized and inactivated culture of Lactobacillus acidophilus (t.d.s.) (RCAL group: 60 subjects). Results: In the RCA group, eradication was successful in 72% (42 out of 58 patients) from a per protocol (PP) analysis, or 70% (42 out of 60 patients) using an intention-to treat (ITT) analysis. In the RCAL group a significant increase in the eradication rate was observed: 88% (52 out of 59 patients) from PP analysis (P=0.03), 87% (52 out of 60 patients) from ITT analysis (P=0.02). Conclusions: These results seem to confirm the in vitro anti-H. pylori effect of L. acidophilus, suggesting that the inactivated L. acidophilus could be effective in increasing eradication rates of a standard anti-H. pylori therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection. METHODS: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 Bg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.05 IU per milliliter) at 24 weeks after the end of treatment. Safety was also assessed. RESULTS: Among 159 participants (30,30,34,30, and 35 in groups 1 through 5, respectively), the primary end-point event occurred in 7% (95% confidence interval ICI], 1 to 22) of those in group 1, in 3% (95% CI, 0 to 17) of those in group 2, in 12% (95% CI, 3 to 28) of those in group 3, in 23% (95% CI, 10 to 42) of those in group 4, and in none (95% CI, 0 to 10) of those in group 5. In groups 1 through 5, respectively, HBsAg seroconversion occurred in 3%, none, 3%, 20°/0, and none of the participants at 24 weeks after the end of treatment. HBsAg loss with or without seroconversion occurred only in participants with a screening HBsAg level below 1000 IU per milliliter. In groups 1 through 5, respectively, grade 3 or 4 adverse events occurred in 17°/0, 10°/0, 18°6, 50%, and 6% of the participants, with the most frequent event being an elevated alanine aminotransferase level. CONCLUSIONS: Among participants with chronic HBV infection who had virologic suppression with NA therapy, treatment with xalnesiran plus an immunomodulator resulted in HBsAg loss at 24 weeks after the end of treatment in a substantial percentage of participants. Grade 3 or 4 adverse events were not uncommon. (Funded by F. Hoffmann-La Roche; Piranga ClinicalTrials.gov number, NCT04225715. [ABSTRACT FROM AUTHOR]

Abstract Acute respiratory infections are a major cause of morbidity in children both in developed and developing countries. A wide range of respiratory viruses, including respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza viruses (PIVs), adenovirus, rhinovirus (HRV), have repeatedly been detected in acute lower respiratory tract infections (LRTI) in children in the past decades. However, in the last ten years thanks to progress in molecular technologies, newly discovered viruses have been identified including human Metapneumovirus (hMPV), coronaviruses NL63 (HcoV-NL63) and HKU1 (HcoV-HKU1), human Bocavirus (HBoV), new enterovirus (HEV), parechovirus (HpeV) and rhinovirus (HRV) strains, polyomaviruses WU (WUPyV) and KI (KIPyV) and the pandemic H1N1v influenza A virus. These discoveries have heavily modified previous knowledge on respiratory infections mainly highlighting that pediatric population is exposed to a variety of viruses with similar seasonal patterns. In this context establishing a causal link between a newly identified virus and the disease as well as an association between mixed infections and an increase in disease severity can be challenging. This review will present an overview of newly recognized as well as the main emerging respiratory viruses and seek to focus on the their contribution to infection and co-infection in LRTIs in childhood.

Abstract Background A novel human enterovirus (HEV) type within the species HEV-C, named EV109, was discovered from cases of respiratory illness in Nicaragua in September 2010. The aim of this study, was to retrospectively examine the presence and the role of EV109 in respiratory samples from two patients populations; infants below the age of 2 years, hospitalized for acute respiratory diseases (ARDs) and adult hematopoietic stem cell transplantation recipients. Results A total of 1149 nasopharingeal aspirates were collected and tested for the presence of EV109 by reverse transcription-PCR (RT-PCR). In positive samples, the presence of the most common respiratory viruses was also assayed and clinical symptoms were evaluated. Samples from 2 of the 974 infants tested positive for EV109 RNA (0.2%) and belonged to patients with lower ARDs; co-infection with other viral pathogens under study was observed in both cases. In transplant recipients, one out of the 175 samples analyzed, from a patients with upper respiratory simptoms tested positive for HEV 109 in the absence of co-infecting viruses. Sequence analysis of amplified EV109 genomic regions, showed only a few nucleotide differences when compared with the Nicaraguan strains. Conclusions Overall these results indicate that HEV109 variants have circulated and differentiated in different lineages worldwide. Although more cases and larger studies are needed, HEV109 infection may be associated to ARDs both in infants and in hematopoietic stem cell transplantation recipients. If these preliminary observations will be confirmed, improved molecular methods with a wider panel of potential pathogens will be useful for monitoring these categories of patients.

Abstract The characteristics of intra-host human immunodeficiency virus type 1 (HIV-1) env evolution were evaluated in untreated HIV-1-infected subjects with different patterns of disease progression, including 2 normal progressor [NP], and 5 Long term non-progressor [LTNP] patients. High-resolution phylogenetic analysis of the C2-C5 env gene sequences of the replicating HIV-1 was performed in sequential samples collected over a 3–5 year period; overall, 301 HIV-1 genomic RNA sequences were amplified from plasma samples, cloned, sequenced and analyzed. Firstly, the evolutionary rate was calculated separately in the 3 codon positions. In all LTNPs, the 3rd codon mutation rate was equal or even lower than that observed at the 1st and 2nd positions (p = 0.016), thus suggesting strong ongoing positive selection. A Bayesian approach and a maximum-likelihood (ML) method were used to estimate the rate of virus evolution within each subject and to detect positively selected sites respectively. A great number of N-linked glycosylation sites under positive selection were identified in both NP and LTNP subjects. Viral sequences from 4 of the 5 LTNPs showed extensive positive selective pressure on the CD4-binding site (CD4bs). In addition, localized pressure in the area of the IgG-b12 epitope, a broad neutralizing human monoclonal antibody targeting the CD4bs, was documented in one LTNP subject, using a graphic colour grade 3-dimensional visualization. Overall, the data shown here documenting high selective pressure on the HIV-1 CD4bs of a group of LTNP subjects offers important insights for planning novel strategies for the immune control of HIV-1 infection.