Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms

BACKGROUND: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children. METHODS: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions". RESULTS: Premature immunosenescence phenotype of B and T cells in HIV-infected children is mediated through immune system activation and chronic inflammation. Ongoing inflammation processes have been documented by increased levels of pathogen-associated molecular patterns (PAMPS), increased mitochondrial damage, higher levels of pro-inflammatory cytokines, and a positive correlation between sCD14 levels and percentages of activated CD8+ cells. Other reported features of premature aging include cellular replicative senescence, linked to an accelerated telomeres shortening. Finally, acceleration of age-associated methylation pattern and other epigenetic modifications have been described in HIV-infected children. All these features may favor the clinical manifestations related to premature aging. Lipid and bone metabolism, cancers, cardiovascular, renal, and neurological systems should be carefully monitored, particularly in children with detectable viremia and/or with CD4/CD8 ratio inversion. CONCLUSION: Aging processes in children with HIV infection impact their quality and length of life. Further studies regarding the mechanisms involved in premature aging are needed to search for potential targets of treatment

Geometry as Matrix of Construction of Roman Stone Bridges: The Augustus Bridge at Narni

The study of ancient Roman bridges embraces various disciplines and professions: engineers, architects, historians, archaeologists, and geologists. One of the first experiments completed by this research group was conducted on the Augustus Bridge at Narni: an integrated digital survey followed by the application of 3D digital modelling. Although only one of its four arches has been preserved, it can still be seen that the bridge was conceived on a large scale of technical complexity based on a precise knowledge that guided the choice of materials and architectonic solutions. The structure is immersed in an enchanting green landscape, which has for centuries attracted numerous scholars and artists. They have left us a precious iconographic heritage whose interpretation is still debated. As far as the geometry and proportions of the construction are concerned, to compare its present state with the original one, the structural ashlars of the bridge were modelled parametrically on the basis of transforming elementary geometric elements having adopted the Roman foot as the unit of measure

Geometry as Matrix of Construction of Roman Stone Bridges: The Augustus Bridge at Narni

The study of ancient Roman bridges embraces various disciplines and professions: engineers, architects, historians, archaeologists, and geologists. One of the first experiments completed by this research group was conducted on the Augustus Bridge at Narni: an integrated digital survey followed by the application of 3D digital modelling. Although only one of its four arches has been preserved, it can still be seen that the bridge was conceived on a large scale of technical complexity based on a precise knowledge that guided the choice of materials and architectonic solutions. The structure is immersed in an enchanting green landscape, which has for centuries attracted numerous scholars and artists. They have left us a precious iconographic heritage whose interpretation is still debated. As far as the geometry and proportions of the construction are concerned, to compare its present state with the original one, the structural ashlars of the bridge were modelled parametrically on the basis of transforming elementary geometric elements having adopted the Roman foot as the unit of measure

Management of newly diagnosed patients with type 2 diabetes: What are the attitudes of physicians? A SUBITO!AMD survey on the early diabetes treatment in Italy

Early intensive therapy in type 2 diabetes can prevent complications. Nevertheless, metabolic control is often sub-optimal in newly diagnosed patients. This webbased survey aimed to evaluate opinions of physicians about treatment, priorities, and barriers in the care of patients first referred to diabetes clinics. Data on physician attitudes toward therapeutic preferences for two clinical case models (same clinical profile, except HbA1c levels of 8.6 and 7.3% at the first access, respectively) were collected. Participants were asked to rank from 1 (most important) to 6 (least important) a list of priorities and barriers associated with the care of new patients. Overall, 593 physicians participated. In both case models, metformin and education were primary options, although their combination with other classes of drugs varied substantially. Main priorities were ‘‘to teach the patient how to cope with the disease’’ and ‘‘to achieve HbA1c target’’; main barriers were ‘‘lack of time’’ and ‘‘long waiting list’’. At multivariate analyses, physicians from the South of Italy had a twofold higher likelihood to attribute a rank 1–2 to organizational barriers than those operating in the North (South vs. North: OR: 2.4; 95% CI 1.4–4.1; Center vs. North: OR: 2.4; 95% CI 0.9–3.2). In the absence of a widely accepted evidence-based therapeutic algorithm driving the therapeutic choices according to the patient characteristics, prescriptions vary according to physician preferences. Education is perceived as a key-strategy, but organizational barriers and geographic disparities are an obstacle. These findings can drive new strategies to reduce clinical inertia, attitudes variability, and geographic disparities

Quantificazione del calcio coronarico (calcium score) attraverso l'utilizzo di nuove tecniche di imaging e suo ruolo prognostico in vari sottogruppi di pazienti

Coronary artery disease is the first cause of mortality in industrialized countries notwithstanding the diagnostic and therapeutic progresses. Electron beam computed tomography and multislice computed tomography with calcium score software seem to have an important role in the early diagnosis of coronary artery disease. Coronary calcium is associated with a high probability of subclinical atherosclerosis. In particular the area of calcification has a positive correlation with the histologically analyzed area of the atheromatous burden plaque. The pathophysiological mechanism may be that the calcium adherent to the plaque makes unstable the plaque with possible rupture. Several studies have analyzed the predictive value of calcium score in various subgroups of patients (asymptomatic, with chest pain, with diabetes) and they have confirmed the presence of large calcific deposits in subjects with a high cardiovascular risk. The correlation of the other risk factors with calcium score is unclear and whether this is due to genetic predisposition requires further investigation. © 2003 CEPI Srl

Premature aging and immune senescence in HIV-infected children

Objective: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. Design: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0\u20135 years, were studied for biological aging and immune senescence. Methods: Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4+ and CD8+ cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. Results: Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8+ recent thymic emigrant cells (CD45RA+CD31+) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28-CD57+), activated (CD38+HLA-DR+), and exhausted (PD1+) CD8+ cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4+ cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. Conclusions: HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8+ cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatmen

Effects of sex hormones on bronchial reactivity during the menstrual cycle

Background: Many asthmatic women complain of symptom exacerbations in particular periods, i.e. during pregnancy and menstrual cycles (perimenstrual asthma: PMA)". The goal of this study was to study the effect of the luteal and follicular phases of the menstrual cycle on bronchial reactivity (BR) in a group of asthmatic women. Methods: For this purpose, 36 pre-menopausal women were enrolled and underwent testing for resting pulmonary function, measurement of the diffusing capacity of the lung for carbon monoxide (DLCO), and airway responsiveness to methacholine in the follicular and luteal phases of their menstrual cycles. We also measured plasma hormone levels and levels of cyclic adenosine monophosphate (cAMP; a mediator of bronchial smooth muscle contraction) and testosterone in induced sputum samples. Results: Our study showed that about 30% of the asthmatic women had decreased PC20FEV1.0 in the follicular phase of menstrual cycle with a significant correlation between PC20FEV1.0 and serum testosterone levels. Moreover, marked increases in sputum testosterone levels (mean = 2.6-fold increase) together with significant increases in sputum cAMP concentrations (mean = 3.6-fold increases) were observed during the luteal phase of asthmatic patients, suggesting that testosterone contributes to the pathophysiology of PMA. We excluded the possibility that testosterone directly inhibits phosphodiesterase (PDE) activity as incubating PDE with testosterone in vitro did not reduce PDE catalytic activity. Conclusions: In conclusion, our data show that PC20FEV1.0 was decreased in the follicular phase of the menstrual cycle in about 30% of women and was associated with lower cAMP levels in sputum samples, which may contribute to bronchoconstriction. Our results also suggest a link between PMA and testosterone levels. However, whether these findings are of clinical significance in terms of the management of asthma or asthma worsening during the menstrual cycle needs further investigation

Pediatric Human Immunodeficiency Virus infection and cancer in the Highly Active Antiretroviral Treatment (HAART) era

Abstract Highly active antiretroviral therapy (HAART) changed the natural history of pediatric HIV infection. This review focuses on trends of HIV-associated cancers in childhood in the HAART era and analyses potential pathogenetic mechanisms. HAART reduced AIDS-defined-malignancies (ADM), but incidence of several non-ADM is increasing. HIV-associated immune activation and inflammation, promoting tumorigenesis, can only partially be reduced by HAART. In addition, HIV-infected children may undergo accelerated immune senescence that favors cancer development. How HAART affects this condition is an open question. Lastly, there is no evidence that prenatal exposure to HAART increases the risk of cancer in childhood, but long-term studies are needed

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches