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1.
Acta Biomed ; 91(12-S): e2020012, 2020 11 30.
Article in English | MEDLINE | ID: mdl-33263344

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: COVID-19 is characterized by super spread events occurring in communities, e.g., hospitals. To limit virus diffusion among healthcare workers the use of personal protective equipment and screening tests are highly advised; also, isolation of virus positive professionals while monitoring their health condition is recommended. This study aims to assess, in a cohort of COVID-19 positive quarantined healthcare workers, the perceived source of infection and exposure risk as well as the clinical evolution of the disease through a surveillance interview. METHODS: A retrospective observational study accounting 896 observations on 93 healthcare professionals tested positive for COVID-19. Data were collected from the Nursing and Technical Directorate of Romagna, Ravenna, Local Health Company, Italy. RESULTS: 99.5% of the positive workers accepted phone interviews with management staff. 2.6% of workers were positive with increasing records in the specialist medical area. Nurses and social health professionals were mostly affected.  Patient exposure at a distance <1 m and a contact time > 2 hours was the first cause of positivity. In COVID-19 and territorial emergency departments, the first cause was the contact with colleagues. At the time of the infection, most of the staff wore a surgical mask. Cough, asthenia, fever, anosmia, dysgeusia, and rhinitis were common symptoms. Asymptomatic percentage was about 10%. The self-perceived physical condition was high (>7) and improved during the observation period. CONCLUSIONS: The diffusion rate of COVID-19 among healthcare workers is relatively low, probably due to the use of personal protective equipment. The distancing, also among colleagues, is a fundamental measure to reduce the possibility of infection. Symptoms are mild and can be controlled by surveillance measures. Constant contact with the organization is an essential strategy for promoting recovering of workers and reducing the spread of the virus within the healthcare organization.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Health Personnel/statistics & numerical data , Occupational Exposure/adverse effects , Quarantine , Female , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Personal Protective Equipment/statistics & numerical data , Physical Distancing , Retrospective Studies
2.
Nutrients ; 12(11)2020 Nov 22.
Article in English | MEDLINE | ID: mdl-33266447

ABSTRACT

BACKGROUND AND AIM: A state of chronic, subclinical inflammation known as inflammaging is present in elderly people and represents a risk factor for all age-related diseases. Dietary supplementation with ad hoc fortified foods seems an appealing strategy to counteract inflammaging. The purpose of this study was to test the efficacy of elderly-tailored fortified milk on inflammaging and different health parameters. METHODS: A double-blind randomized cross-over study was performed on forty-eight volunteers aged 63-80 years. The fortified milk was enriched with ω-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA), vitamins (25-hydroxyvitamin D, E, C, B6, B9, B12), and trace elements (zinc, selenium). The two intervention periods lasted for 12 weeks, with a 16-week washout intermission. RESULTS: Compared to placebo, the consumption of fortified milk increased the circulating levels of different micronutrients, including vitamins and the ω-3 index of erythrocyte membranes. Conversely, it reduced the amount of arachidonic acid, homocysteine, and ω-6/ω-3 ratio. CONCLUSION: Twelve-week daily consumption of adhoc fortified milk has an overall positive impact on different health parameters related to inflammaging in the elderly.


Subject(s)
Fatty Acids, Omega-3/administration & dosage , Food, Fortified , Inflammation/epidemiology , Milk , Vitamin B Complex/administration & dosage , Vitamin D/analogs & derivatives , Aged , Aged, 80 and over , Animals , Cross-Over Studies , Double-Blind Method , Female , Health Status , Humans , Male , Micronutrients/blood , Middle Aged , Placebos , Vitamin D/administration & dosage
3.
Geroscience ; 42(2): 687-701, 2020 04.
Article in English | MEDLINE | ID: mdl-31981007

ABSTRACT

Mediterranean diet has been proposed to promote healthy aging, but its effects on aging biomarkers have been poorly investigated. We evaluated the impact of a 1-year Mediterranean-like diet in a pilot study including 120 elderly healthy subjects from the NU-AGE study (60 Italians, 60 Poles) by measuring the changes in their epigenetic age, assessed by Horvath's clock. We observed a trend towards epigenetic rejuvenation of participants after nutritional intervention. The effect was statistically significant in the group of Polish females and in subjects who were epigenetically older at baseline. A genome-wide association study of epigenetic age changes after the intervention did not return significant (adjusted p value < 0.05) loci. However, we identified small-effect alleles (nominal p value < 10-4), mapping in genes enriched in pathways related to energy metabolism, regulation of cell cycle, and of immune functions. Together, these findings suggest that Mediterranean diet can promote epigenetic rejuvenation but with country-, sex-, and individual-specific effects, thus highlighting the need for a personalized approach to nutritional interventions.


Subject(s)
Diet, Mediterranean , Epigenesis, Genetic , Rejuvenation , Aged , Female , Genome-Wide Association Study , Humans , Male , Pilot Projects , Sex Factors
4.
Eur Radiol ; 29(9): 4968-4979, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30715588

ABSTRACT

OBJECTIVES: The aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. METHODS: A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65-79 years) women and men from five European countries of the "New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe" project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-ß1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. RESULTS: BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-ß1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2. CONCLUSIONS: The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice. KEY POINTS: • Body composition markers concordantly associated positively or negatively with adipose-related and inflammatory markers, with the exception of skeletal muscle mass index. • No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-ß1, TNF-α, IL-6Rα, gp130, TNF-α-R1, and TNF-α-R2. • Skeletal muscle mass index (SMI) shows a good correlation with inflammatory profile in age-related sarcopenia.


Subject(s)
Adiposity , Body Composition , Bone Density , Inflammation Mediators/blood , Inflammation/physiopathology , Absorptiometry, Photon , Aged , Biomarkers/blood , Cross-Sectional Studies , Europe , Female , Humans , Male , Muscle, Skeletal/diagnostic imaging , Obesity/physiopathology , Sarcopenia/physiopathology , Sex Factors
5.
FASEB J ; 33(4): 5168-5180, 2019 04.
Article in English | MEDLINE | ID: mdl-30620616

ABSTRACT

The Sarcolab pilot study of 2 crewmembers, investigated before and after a 6-mo International Space Station mission, has demonstrated the substantial muscle wasting and weakness, along with disruption of muscle's oxidative metabolism. The present work aimed at evaluating the pro/anti-inflammatory status in the same 2 crewmembers (A, B). Blood circulating (c-)microRNAs (miRs), c-proteasome, c-mitochondrial DNA, and cytokines were assessed by real-time quantitative PCR or ELISA tests. Time series analysis was performed ( i.e., before flight and after landing) at 1 and 15 d of recovery (R+1 and R+15, respectively). C-biomarkers were compared with an age-matched control population and with 2-dimensional proteomic analysis of the 2 crewmembers' muscle biopsies. Striking differences were observed between the 2 crewmembers at R+1, in terms of inflamma-miRs (c-miRs-21-5p, -126-3p, and -146a-5p), muscle specific (myo)-miR-206, c-proteasome, and IL-6/leptin, thus making the 2 astronauts dissimilar to each other. Final recovery levels of c-proteasome, c-inflamma-miRs, and c-myo-miR-206 were not reverted to the baseline values in crewmember A. In both crewmembers, myo-miR-206 changed significantly after recovery. Muscle biopsy of astronaut A showed an impressive 80% increase of α-1-antitrypsin, a target of miR-126-3p. These results point to a strong stress response induced by spaceflight involving muscle tissue and the proinflammatory setting, where inflamma-miRs and myo-miR-206 mediate the systemic recovery phase after landing.-Capri, M., Morsiani, C., Santoro, A., Moriggi, M., Conte, M., Martucci, M., Bellavista, E., Fabbri, C., Giampieri, E., Albracht, K., Flück, M., Ruoss, S., Brocca, L., Canepari, M., Longa, E., Di Giulio, I., Bottinelli, R., Cerretelli, P., Salvioli, S., Gelfi, C., Franceschi, C., Narici, M., Rittweger, J. Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.


Subject(s)
Inflammation/metabolism , Muscle Proteins/metabolism , Space Flight , Astronauts , Biomarkers/metabolism , Cytokines/metabolism , DNA, Mitochondrial/metabolism , Humans , Inflammation/immunology , Leptin/metabolism , MicroRNAs/metabolism , Muscle, Skeletal/metabolism , Pilot Projects , Proteasome Endopeptidase Complex/metabolism , Proteomics
6.
J Gerontol A Biol Sci Med Sci ; 74(5): 600-607, 2019 04 23.
Article in English | MEDLINE | ID: mdl-29955888

ABSTRACT

Mitochondrial stress elicits the production of stress response molecules indicated as mitokines, including fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), and humanin (HN). Many diseases are characterized by progressive mitochondrial dysfunction with alterations of mitokine secretion. It is still controversial whether healthy aging and extreme longevity are accompanied by an altered production of mitokines. We analyzed FGF21, HN, and GDF15 plasma levels in 693 subjects aged from 21 to 113 years, and the association of these mitokines with parameters of health status. FGF21, HN, and GDF15 resulted increased in old age, with the highest levels found in centenarians. These molecules are associated with worsened parameters (such as handgrip strength, insulin sensitivity, triglycerides), particularly in 70-year-old persons, and their levels are inversely correlated with survival in the oldest subjects. Considering the positive biological effect of these molecules, our results can be interpreted in the framework of the hormetic paradigm as an attempt of the cells/tissues to cope with a stress that can have beneficial or detrimental effects depending on its intensity. Finally, persons with Down Syndrome (characterized by accelerated aging) have higher levels of GDF15 and HN with respect to their siblings, suggesting that these molecules, especially GDF15, could be considered markers of biological age.


Subject(s)
Aging/metabolism , Fibroblast Growth Factors/metabolism , Growth Differentiation Factor 15/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Longevity , Mitochondria/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/metabolism , Down Syndrome/metabolism , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Unfolded Protein Response
7.
Front Physiol ; 9: 457, 2018.
Article in English | MEDLINE | ID: mdl-29765333

ABSTRACT

Aging is a multifactorial process characterized by the accumulation of proteins undergoing oxidative modifications, either due to enhanced levels of oxidative stress or due to their decreased clearance; both facts are related to the establishment of chronic inflammatory processes. These processes are directly associated with functional and structural modifications of a key cellular component, namely the proteasome. In this study, levels of oxidized proteins, along with proteasome and immunoproteasome composition and activity on a selected group of 120 elderly volunteers were analyzed before and after the administration of a specific dietary protocol, based on an elderly tailored Mediterranean diet (the "NU-AGE diet"). A significant negative correlation between levels of oxidized/carbonylated proteins and proteasome function was confirmed, both before and after intervention. Furthermore, it was demonstrated that subgroups of non-frail subjects and women receive a greater benefit after the intervention, concerning specifically the proteasome content and activity. These data highlight the putative beneficial effects of Mediterranean diet on the major cellular proteolytic mechanism, the proteasome, in elderly people.

8.
Front Physiol ; 9: 349, 2018.
Article in English | MEDLINE | ID: mdl-29670545

ABSTRACT

Background: Findings from animal and epidemiological research support the potential neuroprotective benefits from healthy diets. However, to establish diet-neuroprotective causal relations, evidence from dietary intervention studies is needed. NU-AGE is the first multicenter intervention assessing whether a diet targeting health in aging can counteract the age-related physiological changes in different organs, including the brain. In this study, we specifically investigated the effects of NU-AGE's dietary intervention on age-related cognitive decline. Materials and Methods: NU-AGE randomized trial (NCT01754012, clinicaltrials.gov) included 1279 relatively healthy older-adults, aged 65-79 years, from five European centers. Participants were randomly allocated into two groups: "control" (n = 638), following a habitual diet; and, "intervention" (n = 641), given individually tailored dietary advice (NU-AGE diet). Adherence to the NU-AGE diet was measured over follow-up, and categorized into tertiles (low, moderate, high). Cognitive function was ascertained at baseline and at 1-year follow-up with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Neuropsychological Battery and five additional domain-specific single cognitive tests. The raw scores from the CERAD subtests [excluding the Mini-Mental State Examination (MMSE)] and the single tests were standardized into Z-scores. Global cognition (measured with MMSE and CERAD-total score), and five cognitive domains (perceptual speed, executive function, episodic memory, verbal abilities, and constructional praxis) were created. Cognitive changes as a function of the intervention were analyzed with multivariable mixed-effects models. Results: After the 1-year follow-up, 571 (89.1%) controls and 573 (89.8%) from the intervention group participated in the post-intervention assessment. Both control and intervention groups showed improvements in global cognition and in all cognitive domains after 1 year, but differences in cognitive changes between the two groups were not statistically significant. However, participants with higher adherence to the NU-AGE diet showed statistically significant improvements in global cognition [ß 0.20 (95%CI 0.004, 0.39), p-value = 0.046] and episodic memory [ß 0.15 (95%CI 0.02, 0.28), p-value = 0.025] after 1 year, compared to those adults with lower adherence. Discussion: High adherence to the culturally adapted, individually tailored, NU-AGE diet could slow down age-related cognitive decline, helping to prevent cognitive impairment and dementia.

9.
Front Physiol ; 9: 1903, 2018.
Article in English | MEDLINE | ID: mdl-30733683

ABSTRACT

Aging is a dynamic process depending on intrinsic and extrinsic factors and its evolution is a continuum of transitions, involving multifaceted processes at multiple levels. It is recognized that frailty and sarcopenia are shared by the major age-related diseases thus contributing to elderly morbidity and mortality. Pre-frailty is still not well understood but it has been associated with global imbalance in several physiological systems, including inflammation, and in nutrition. Due to the complex phenotypes and underlying pathophysiology, the need for robust and multidimensional biomarkers is essential to move toward more personalized care. The objective of the present study was to better characterize the complexity of pre-frailty phenotype using untargeted metabolomics, in order to identify specific biomarkers, and study their stability over time. The approach was based on the NU-AGE project (clinicaltrials.gov, NCT01754012) that regrouped 1,250 free-living elderly people (65-79 y.o., men and women), free of major diseases, recruited within five European centers. Half of the volunteers were randomly assigned to an intervention group (1-year Mediterranean type diet). Presence of frailty was assessed by the criteria proposed by Fried et al. (2001). In this study, a sub-cohort consisting in 212 subjects (pre-frail and non-frail) from the Italian and Polish centers were selected for untargeted serum metabolomics at T0 (baseline) and T1 (follow-up). Univariate statistical analyses were performed to identify discriminant metabolites regarding pre-frailty status. Predictive models were then built using linear logistic regression and ROC curve analyses were used to evaluate multivariate models. Metabolomics enabled to discriminate sub-phenotypes of pre-frailty both at the gender level and depending on the pre-frailty progression and reversibility. The best resulting models included four different metabolites for each gender. They showed very good prediction capacity with AUCs of 0.93 (95% CI = 0.87-1) and 0.94 (95% CI = 0.87-1) for men and women, respectively. Additionally, early and/or predictive markers of pre-frailty were identified for both genders and the gender specific models showed also good performance (three metabolites; AUC = 0.82; 95% CI = 0.72-0.93) for men and very good for women (three metabolites; AUC = 0.92; 95% CI = 0.86-0.99). These results open the door, through multivariate strategies, to a possibility of monitoring the disease progression over time at a very early stage.

10.
Nutr Rev ; 75(6): 442-455, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28595318

ABSTRACT

A coherent set of epidemiological data shows that the Mediterranean diet has beneficial effects capable of preventing a variety of age-related diseases in which low-grade, chronic inflammation/inflammaging plays a major role, but the underpinning mechanism(s) is/are still unclear. It is suggested here that the Mediterranean diet can be conceptualized as a form of chronic hormetic stress, similar to what has been proposed regarding calorie restriction, the most thoroughly studied nutritional intervention. Data on the presence in key Mediterranean foods of a variety of compounds capable of exerting hormetic effects are summarized, and the mechanistic role of the nuclear factor erythroid 2 pathway is highlighted. Within this conceptual framework, particular attention has been devoted to the neurohormetic and neuroprotective properties of the Mediterranean diet, as well as to its ability to maintain an optimal balance between pro- and anti-inflammaging. Finally, the European Commission-funded project NU-AGE is discussed because it addresses a number of variables not commonly taken into consideration, such as age, sex, and ethnicity/genetics, that can modulate the hormetic effect of the Mediterranean diet.


Subject(s)
Aging/genetics , Diet, Mediterranean , Healthy Lifestyle , Hormesis , Inflammation/diet therapy , Aging/physiology , Dietary Carbohydrates/administration & dosage , Dietary Fiber/administration & dosage , Gastrointestinal Microbiome , Humans , Inflammation/prevention & control , NF-E2-Related Factor 2/physiology , Observational Studies as Topic , Phytochemicals/administration & dosage , Randomized Controlled Trials as Topic , Stress, Physiological , Vitamins/administration & dosage
11.
Nature ; 527(7577): 226-30, 2015 Nov 12.
Article in English | MEDLINE | ID: mdl-26560301

ABSTRACT

The pressures on honeybee (Apis mellifera) populations, resulting from threats by modern pesticides, parasites, predators and diseases, have raised awareness of the economic importance and critical role this insect plays in agricultural societies across the globe. However, the association of humans with A. mellifera predates post-industrial-revolution agriculture, as evidenced by the widespread presence of ancient Egyptian bee iconography dating to the Old Kingdom (approximately 2400 BC). There are also indications of Stone Age people harvesting bee products; for example, honey hunting is interpreted from rock art in a prehistoric Holocene context and a beeswax find in a pre-agriculturalist site. However, when and where the regular association of A. mellifera with agriculturalists emerged is unknown. One of the major products of A. mellifera is beeswax, which is composed of a complex suite of lipids including n-alkanes, n-alkanoic acids and fatty acyl wax esters. The composition is highly constant as it is determined genetically through the insect's biochemistry. Thus, the chemical 'fingerprint' of beeswax provides a reliable basis for detecting this commodity in organic residues preserved at archaeological sites, which we now use to trace the exploitation by humans of A. mellifera temporally and spatially. Here we present secure identifications of beeswax in lipid residues preserved in pottery vessels of Neolithic Old World farmers. The geographical range of bee product exploitation is traced in Neolithic Europe, the Near East and North Africa, providing the palaeoecological range of honeybees during prehistory. Temporally, we demonstrate that bee products were exploited continuously, and probably extensively in some regions, at least from the seventh millennium cal BC, likely fulfilling a variety of technological and cultural functions. The close association of A. mellifera with Neolithic farming communities dates to the early onset of agriculture and may provide evidence for the beginnings of a domestication process.


Subject(s)
Beekeeping/history , Bees , Waxes/analysis , Waxes/history , Africa, Northern , Animals , Archaeology , Ceramics/chemistry , Ceramics/history , Europe , Farmers/history , Geographic Mapping , History, Ancient , Lipids/analysis , Lipids/chemistry , Middle East , Spatio-Temporal Analysis , Waxes/chemistry
12.
Adv Skin Wound Care ; 28(10): 461-4, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26375949

ABSTRACT

OBJECTIVE: The purpose of this study was to measure the prevalence of pressure ulcers (PrUs) in an older adult population. DESIGN: A cross-sectional study. SETTING: The study included all the individuals being cared for in the units of medicine, surgery, intensive care, and medical-surgical specialties of 47 hospitals, 57 public nursing homes, and 37 home care services. PARTICIPANTS: The authors' observational study included 11,957 patients older than 70 years. MAIN OUTCOME MEASURES: Of the population, 50.75% (6067) were assessed to be at risk of developing PrUs according to the Braden Scale, and 24.66% (2949) had already developed PrUs. In addition, a significant association was found between increased risk (Braden <16) and the presence of PrUs with an odds ratio (OR) of 8.71 (confidence interval [CI], 7.52-10.10) in high-risk subjects (Braden ≤ 12) and an OR of 3.86 (CI, 3.36-4.44) in very high-risk patients (Braden 13-16). In the survey, 84.6% of the subjects with PrUs were incontinent, and incontinence increased the risk of developing PrUs in the authors' sample (OR, 1.54; CI, 1.34-1.77). CONCLUSIONS: The authors' data reported in the literature show that the prevalence of PrUs increases as an individual ages. The authors gathered data that showed a large area of intervention in managing the prevention of PrUs, such as an adequate use of protective aids, correcting malnutrition, and controlling incontinence. These results suggest that clinicians should focus more on the prevention of PrUs in older adults.


Subject(s)
Geriatric Assessment , Pressure Ulcer/epidemiology , Pressure Ulcer/therapy , Age Distribution , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Italy/epidemiology , Logistic Models , Male , Multivariate Analysis , Pressure Ulcer/diagnosis , Prevalence , Severity of Illness Index , Sex Distribution , Treatment Outcome
13.
Nutrients ; 7(4): 2589-621, 2015 Apr 09.
Article in English | MEDLINE | ID: mdl-25859884

ABSTRACT

Aging is considered the major risk factor for cancer, one of the most important mortality causes in the western world. Inflammaging, a state of chronic, low-level systemic inflammation, is a pervasive feature of human aging. Chronic inflammation increases cancer risk and affects all cancer stages, triggering the initial genetic mutation or epigenetic mechanism, promoting cancer initiation, progression and metastatic diffusion. Thus, inflammaging is a strong candidate to connect age and cancer. A corollary of this hypothesis is that interventions aiming to decrease inflammaging should protect against cancer, as well as most/all age-related diseases. Epidemiological data are concordant in suggesting that the Mediterranean Diet (MD) decreases the risk of a variety of cancers but the underpinning mechanism(s) is (are) still unclear. Here we review data indicating that the MD (as a whole diet or single bioactive nutrients typical of the MD) modulates multiple interconnected processes involved in carcinogenesis and inflammatory response such as free radical production, NF-κB activation and expression of inflammatory mediators, and the eicosanoids pathway. Particular attention is devoted to the capability of MD to affect the balance between pro- and anti-inflammaging as well as to emerging topics such as maintenance of gut microbiota (GM) homeostasis and epigenetic modulation of oncogenesis through specific microRNAs.


Subject(s)
Aging , Diet, Mediterranean , Inflammation/prevention & control , Neoplasms/prevention & control , Chronic Disease , Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Humans
14.
Mol Biol Evol ; 30(9): 2157-67, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23821607

ABSTRACT

The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.


Subject(s)
Bacterial Infections/genetics , Granulomatous Disease, Chronic/genetics , Membrane Glycoproteins/genetics , NADPH Oxidases/genetics , Amino Acid Sequence , Animals , Asian People , Bacteria/enzymology , Bacterial Infections/complications , Bacterial Infections/enzymology , Bacterial Infections/ethnology , Bacterial Proteins/metabolism , Black People , Catalase/metabolism , Evolution, Molecular , Genetic Variation , Granulomatous Disease, Chronic/complications , Granulomatous Disease, Chronic/enzymology , Granulomatous Disease, Chronic/ethnology , Haplotypes , Host-Pathogen Interactions , Humans , Membrane Glycoproteins/classification , Molecular Sequence Data , Mutation , NADPH Oxidase 2 , NADPH Oxidases/classification , Phylogeny , Selection, Genetic , White People
15.
Biogerontology ; 14(3): 261-72, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23666343

ABSTRACT

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18-30 years and 260 subjects aged 69-81 years) recruited within the framework of the European research network project "Myoage". The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.


Subject(s)
Adipokines/blood , Aging/physiology , Insulin-Like Growth Factor I/metabolism , Muscle Strength/physiology , Muscle, Skeletal/physiology , Adiponectin/blood , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Hand Strength/physiology , Humans , Leptin/blood , Male , Resistin/blood , Signal Transduction/physiology , Young Adult
16.
PLoS One ; 5(3): e9827, 2010 Mar 23.
Article in English | MEDLINE | ID: mdl-20352120

ABSTRACT

BACKGROUND: Glucose is an important source of energy for living organisms. In vertebrates it is ingested with the diet and transported into the cells by conserved mechanisms and molecules, such as the trans-membrane Glucose Transporters (GLUTs). Members of this family have tissue specific expression, biochemical properties and physiologic functions that together regulate glucose levels and distribution. GLUT4 -coded by SLC2A4 (17p13) is an insulin-sensitive transporter with a critical role in glucose homeostasis and diabetes pathogenesis, preferentially expressed in the adipose tissue, heart muscle and skeletal muscle. We tested the hypothesis that natural selection acted on SLC2A4. METHODOLOGY/PRINCIPAL FINDINGS: We re-sequenced SLC2A4 and genotyped 104 SNPs along a approximately 1 Mb region flanking this gene in 102 ethnically diverse individuals. Across the studied populations (African, European, Asian and Latin-American), all the eight common SNPs are concentrated in the N-terminal region upstream of exon 7 ( approximately 3700 bp), while the C-terminal region downstream of intron 6 ( approximately 2600 bp) harbors only 6 singletons, a pattern that is not compatible with neutrality for this part of the gene. Tests of neutrality based on comparative genomics suggest that: (1) episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity downstream of intron 6 and, (2) the target of natural selection may not be in the SLC2A4 coding sequence. CONCLUSIONS: We propose that the contrast in the pattern of genetic variation between the N-terminal and C-terminal regions are signatures of the action of natural selection and thus follow-up studies should investigate the functional importance of different regions of the SLC2A4 gene.


Subject(s)
Genetic Variation , Glucose Transporter Type 4/genetics , Adipose Tissue/metabolism , Animals , Ethnicity , Evolution, Molecular , Genotype , Humans , Insulin/metabolism , Macaca mulatta , Muscle, Skeletal/metabolism , Myocardium/metabolism , Pan troglodytes , Protein Structure, Tertiary , Sequence Analysis, DNA
17.
Med Sci Monit ; 16(3): CS33-39, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20190690

ABSTRACT

BACKGROUND: Adenoid cystic carcinoma of the breast is a rare neoplasm accounting for 0.1% of all malignant breast tumors and presenting most commonly as a painful breast mass. Compared with the more common histological forms of breast cancer, it has a more favorable prognosis and lymph node involvement or distant metastases seldom occur. CASE REPORT: A unique case of multifocal adenoid cystic carcinoma of the breast presenting as a painful and well-defined lump and treated with conservative surgery with adjuvant radiotherapy is reported. CONCLUSIONS: There is no consensus on the optimal management of this disease. A breast-conserving approach may be recommended even if mastectomy has been traditionally the treatment of choice. Chemotherapy, radiation, and hormonal therapy have been infrequently used and so far have had no defined role in this kind of neoplasm. The authors found no other reports in the literature focusing on a conservative approach to multifocal adenoid cystic carcinoma.


Subject(s)
Breast Neoplasms/therapy , Carcinoma, Adenoid Cystic/therapy , Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Carcinoma, Adenoid Cystic/diagnostic imaging , Carcinoma, Adenoid Cystic/pathology , Female , Humans , Immunohistochemistry , Mammography , Ultrasonography
18.
J Child Lang ; 37(4): 865-85, 2010 Sep.
Article in English | MEDLINE | ID: mdl-19698208

ABSTRACT

The aims of this study were to investigate whether specific linguistic difficulties in preterm children persist at eight years and to examine the interrelationships between language and literacy in this population, compared with a control group of full-term children. Sixty-eight monolingual Italian preterms and 26 chronologically matched controls were recruited. Language (grammar comprehension, lexical production and phonological awareness), literacy (reading comprehension, reading and writing) and general cognitive development were investigated. Results showed no general delay in preterms, but slight difficulties in specific linguistic abilities (grammar, lexicon, phoneme synthesis and deletion of the first syllable), more difficulties in literacy (speed in reading and accuracy in writing) and certain correlations among competencies turning out to be different from the control group. In conclusion, our study established that a partially atypical trajectory emerged in preterms, showing specific long-term effects of preterm birth on language and literacy development.


Subject(s)
Dyslexia/diagnosis , Dyslexia/psychology , Infant, Low Birth Weight , Infant, Premature, Diseases/diagnosis , Language Development Disorders/diagnosis , Language Development Disorders/psychology , Child , Child, Preschool , Comprehension , Female , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Premature, Diseases/psychology , Italy , Longitudinal Studies , Male , Phonetics , Pregnancy , Semantics , Vocabulary , Writing
19.
Early Hum Dev ; 85(10): 639-45, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19748193

ABSTRACT

BACKGROUND: Since preterm birth is associated with a constellation of pre-, peri- and post-natal risk factors, we hypothesised that prematurity may continue to impact the development of linguistic abilities even up to the end of the preschool years and beyond, giving rise to an atypical developmental trajectory. The study tested this hypothesis at six years of age, investigating whether language is affected by preterm birth and how different linguistic abilities are interrelated. METHOD: Seventy monolingual Italian preterms and 34 age-matched controls were recruited. Linguistic abilities (vocabulary, grammar, and phonological awareness) as well as general cognitive developmental levels were measured. RESULTS: No general cognitive delay emerged, but less developed abilities in vocabulary, grammar, and phonological awareness were found in preterms compared to fullterms. Moreover, the relations among the different linguistic competences differed across groups. CONCLUSIONS: Our study shows that even without brain damage, preterm birth continues to affect linguistic development up to the end of the preschool years, and probably beyond, highlighting a continuity between pre- and peri-natal life and subsequent development, and pointing to an atypical developmental trajectory in this population compared to fullterms (different rates of development, different strategies employed, and differences in the relationships among linguistic abilities).


Subject(s)
Language Development , Premature Birth , Case-Control Studies , Child , Female , Humans , Infant, Newborn , Male
20.
J Med Case Rep ; 3: 43, 2009 Jan 30.
Article in English | MEDLINE | ID: mdl-19183446

ABSTRACT

INTRODUCTION: Lactating adenoma is a benign condition, representing the most prevalent breast lesion in pregnant women and during puerperium; in this paper, a case of a woman with lactating adenoma occurring during the first trimester of pregnancy is reported. There have been no reports in the literature, according to our search, focusing on magnetic resonance imaging findings in cases of lactating adenomas. Also the early onset of the lesion during the first trimester of pregnancy is quite unusual and possibly unique. CASE PRESENTATION: We report the case of a primiparous 30-year-old Caucasian woman, who noted an asymptomatic lump within her left breast during the 9th week of gestation, slightly increasing in size over the next few weeks. Ultrasound demonstrated a hypoecoic solid mass, hypervascularized and measuring 4 cm. On magnetic resonance imaging, performed in the first month after delivery, the lesion appeared as an ovoidal homogeneous mass, with regular margins and a significant contrast enhancement indicative of a giant adenoma. CONCLUSION: Magnetic resonance imaging could play an important role in the differential diagnosis of pregnancy-related breast lumps, particularly during puerperium, thus avoiding unnecessary surgical biopsies.

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