Biomarkers of aging in HIV: inflammation and the microbiome

Purpose: HIV-infected subjects present increased levels of inflammatory cytokines and T cell activation in the peripheral blood despite suppressive combination antiretroviral therapy which renders them susceptible to premature aging. The purpose of the present work was to review existing evidence on the ways in which the anatomical and microbiological abnormalities of the gastrointestinal tract can represent a major cause of organ disease in HIV infection. Methods: We conducted a systematic review of the Pubmed database for articles published from 2014 to 2018. We included studies on inflammatory/activation biomarkers associated with cardiovascular and bone disease, neurocognitive impairment and serious non-AIDS events in HIV-infected subjects. We also included researches which linked peripheral inflammation/activation to the anatomical, immune and microbiological alterations of the gastrointestinal tract. Results: Recent literature data confirm the association between non-infectious comorbidities and inflammation in HIV infection which may be driven by gastrointestinal tract abnormalities, specifically microbial translocation and dysbiosis. Furthermore, there is mounting evidence on the possible role of metabolic functions of the microbiota in the pathogenesis of premature aging in the HIV-infected population. Conclusions: Biomarkers need to be validated for their use in the management of HIV infection. Compounds which counteract microbial translocation, inflammation and dysbiosis have been investigated as alternative therapeutic strategies in viro-suppressed HIV-infected individuals, but appear to have limited efficacy, probably due to the multifactorial pathogenesis of non-infectious comorbidities in this setting

Short-Term Repeated-Sprint Training (Straight Sprint vs. Changes of Direction) in Soccer Players

Repeated-sprint training (RST) is considered a critical training method in team sports. It is well known that RST effects may depend on several variables such as the duration of the protocol and repeated-sprint methodology. Few studies have evaluated very short-term protocols and compared different RST modalities. The aim of this study was to compare the effectiveness of 2 week RST including straight sprints or changes of direction (CODs) on physical performance in a sample of soccer players. This study used a randomised pre-post parallel group trial design. The participants were assigned to either an RST group using straight sprints (RST-SS = 18 players) or an RST group using CODs (RST-COD = 18 players). The protocols were: 3 sets of 7 x 30 m sprints for the RST-SS and 7 x 20 + 20 m (one COD of 180 degrees) for the RST-COD, with 20 s and 4 min recovery between sprints and sets, respectively. The following evaluations were performed: 10 and 20 m sprint, agility test, repeated sprint test (RSTbest and RSTmean), and Yo-Yo Recovery Level 1. After the training period, the RST-SS did not report any performance variation, while the RST-COD showed improvements in the 10 m sprint and RSTbest (effect size = 0.70 and 0.65, respectively). The between-group analysis did not report any statistical difference between the RST-SS and the RST-COD. In conclusion, this study did not support the utilisation of a very short-term RST protocol with soccer players, however, the RST-COD presented some additional benefits in sprint performance compared to the RST-SS

Light Chain Amyloidosis: Patient Experience Survey from the Amyloidosis Research Consortium

The Author(s) 2015. This article is published with open access at Springerlink.com Introduction: Information detailing the experience of patients with light chain (AL) amyloidosis is lacking. The primary aim of this study was to gather data on the patient experience to understand the challenges i

Cell cycle-dependent and independent mating blocks ensure fungal zygote survival and ploidy maintenance.

To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes. In the fission yeast Schizosaccharomyces pombe, fertilization triggers the Mei3-Pat1-Mei2 signaling cascade, which represses subsequent mating and initiates meiosis. Here, we establish a degron system to specifically degrade proteins postfusion and demonstrate that mating blocks not only safeguard zygote ploidy but also prevent lysis caused by aberrant fusion attempts. Using long-term imaging and flow-cytometry approaches, we identify previously unrecognized and independent roles for Mei3 and Mei2 in zygotes. We show that Mei3 promotes premeiotic S-phase independently of Mei2 and that cell cycle progression is both necessary and sufficient to reduce zygotic mating behaviors. Mei2 not only imposes the meiotic program and promotes the meiotic cycle, but also blocks mating behaviors independently of Mei3 and cell cycle progression. Thus, we find that fungi preserve zygote ploidy and survival by at least 2 mechanisms where the zygotic fate imposed by Mei2 and the cell cycle reentry triggered by Mei3 synergize to prevent zygotic mating

Infertility and hypergonadotropic hypogonadism as first evidence of hereditary apolipoprotein A-I amyloidosis

Purpose: We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. Materials and Methods: Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. Results: All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. Conclusions: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary

High-pressure behavior and P-induced phase transition of CaB3O4(OH)3·H2O (colemanite)

Colemanite (ideally CaB3O4(OH)3\ub7H2O, space group P21/a, unit-cell parameters: a ~ 8.74, b ~ 11.26, c ~ 6.10 \uc5, \u3b2 ~ 110.1\ub0) is one of the principal mineralogical components of borate deposits and the most important mineral commodity of boron. Its high-pressure behavior is here described, for the first time, by means of in situ single-crystal synchrotron X-ray diffraction with a diamond anvil cell up to 24 GPa (and 293 K). Colemanite is stable, in its ambient-conditions polymorph, up to 13.95 GPa. Between 13.95 and 14.91 GPa, an iso-symmetric first-order single-crystal to single-crystal phase transition (reconstructive in character) toward a denser polymorph (colemanite-II) occurs, with: aCOL-II=3\ub7aCOL, bCOL-II=bCOL, and cCOL-II=2\ub7cCOL. Up to 13.95 GPa, the bulk compression of colemanite is accommodated by the Ca-polyhedron compression and the tilting of the rigid three-membered rings of boron polyhedra. The phase transition leads to an increase in the average coordination number of both the B and Ca sites. A detailed description of the crystal structure of the high-P polymorph, compared to the ambient-conditions colemanite, is given. The elastic behaviors of colemanite and of its high-P polymorph are described by means of III- and II-order Birch-Murnaghan equations of state, respectively, yielding the following refined parameters: KV0=67(4) GPa and KV\u2032=5.5(7) [\u3b2V0=0.0149(9) GPa-1] for colemanite; KV0=50(8) GPa [\u3b2V0=0.020(3) GPa-1] for its high-P polymorph