Identification, Isolation and Expansion of Myoendothelial Cells Involved in Leech Muscle Regeneration

Adult skeletal muscle in vertebrates contains myoendothelial cells that express both myogenic and endothelial markers, and which are able to differentiate into myogenic cells to contribute to muscle regeneration. In spite of intensive research efforts, numerous questions remain regarding the role of cytokine signalling on myoendothelial cell differentiation and muscle regeneration. Here we used Hirudo medicinalis (Annelid, leech) as an emerging new model to study myoendothelial cells and muscle regeneration. Although the leech has relative anatomical simplicity, it shows a striking similarity with vertebrate responses and is a reliable model for studying a variety of basic events, such as tissue repair. Double immunohistochemical analysis were used to characterize myoendothelial cells in leeches and, by injecting in vivo the matrigel biopolymer supplemented with the cytokine Vascular Endothelial Growth Factor (VEGF), we were able to isolate this specific cell population expressing myogenic and endothelial markers. We then evaluated the effect of VEGF on these cells in vitro. Our data indicate that, similar to that proposed for vertebrates, myoendothelial cells of the leech directly participate in myogenesis both in vivo and in vitro, and that VEGF secretion is involved in the recruitment and expansion of these muscle progenitor cells

Type-1 Cannabinoid Receptors Reduce Membrane Fluidity of Capacitated Boar Sperm by Impairing Their Activation by Bicarbonate

Background Mammalian spermatozoa acquire their full fertilizing ability (so called capacitation) within the female genital tract, where they are progressively exposed to inverse gradients of inhibiting and stimulating molecules. Methodology/Principal Findings In the present research, the effect on this process of anandamide, an endocannabinoid that can either activate or inhibit cannabinoid receptors depending on its concentration, and bicarbonate, an oviductal activatory molecule, was assessed, in order to study the role exerted by the type 1 cannabinoid receptor (CB1R) in the process of lipid membrane remodeling crucial to complete capacitation. To this aim, boar sperm were incubated in vitro under capacitating conditions (stimulated by bicarbonate) in the presence or in the absence of methanandamide (Met-AEA), a non-hydrolysable analogue of anandamide. The CB1R involvement was studied by using the specific inhibitor (SR141716) or mimicking its activation by adding a permeable cAMP analogue (8Br-cAMP). By an immunocytochemistry approach it was shown that the Met-AEA inhibits the bicarbonate-dependent translocation of CB1R from the post-equatorial to equatorial region of sperm head. In addition it was found that Met-AEA is able to prevent the bicarbonate-induced increase in membrane disorder and the cholesterol extraction, both preliminary to capacitation, acting through a CB1R-cAMP mediated pathway, as indicated by MC540 and filipin staining, EPR spectroscopy and biochemical analysis on whole membranes (CB1R activity) and on membrane enriched fraction (C/P content and anisotropy). Conclusions/Significance Altogether, these data demonstrate that the endocannabinoid system strongly inhibits the process of sperm capacitation, acting as membrane stabilizing agent, thus increasing the basic knowledge on capacitation-related signaling and potentially opening new perspectives in diagnostics and therapeutics of male infertility

Association of Mild Anemia with Cognitive, Functional, Mood and Quality of Life Outcomes in the Elderly: The “Health and Anemia” Study

BACKGROUND: In the elderly persons, hemoglobin concentrations slightly below the lower limit of normal are common, but scant evidence is available on their relationship with significant health indicators. The objective of the present study was to cross-sectionally investigate the association of mild grade anemia with cognitive, functional, mood, and quality of life (QoL) variables in community-dwelling elderly persons. METHODS: Among the 4,068 eligible individuals aged 65-84 years, all persons with mild anemia (n = 170) and a randomly selected sample of non-anemic controls (n = 547) were included in the study. Anemia was defined according to World Health Organization (WHO) criteria and mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Cognition and functional status were assessed using measures of selective attention, episodic memory, cognitive flexibility and instrumental and basic activities of daily living. Mood and QoL were evaluated by means of the Geriatric Depression Scale-10, the Short-Form health survey (SF-12), and the Functional Assessment of Cancer Therapy-Anemia. RESULTS: In univariate analyses, mild anemic elderly persons had significantly worse results on almost all cognitive, functional, mood, and QoL measures. In multivariable logistic regressions, after adjustment for a large number of demographic and clinical confounders, mild anemia remained significantly associated with measures of selective attention and disease-specific QoL (all fully adjusted p<.046). When the lower limit of normal hemoglobin concentration according to WHO criteria was raised to define anemia (+0.2 g/dL), differences between mild anemic and non anemic elderly persons tended to increase on almost every variable. CONCLUSIONS: Cross-sectionally, mild grade anemia was independently associated with worse selective attention performance and disease-specific QoL ratings

Pain and Frailty in Hospitalized Older Adults

Introduction: Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. Methods: In light of this knowledge gap, 3577 acutely hospitalized patients 65&nbsp;years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. Results: The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Conclusions: Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people

The multifaceted spectrum of liver cirrhosis in older hospitalised patients: Analysis of the REPOSI registry

Background: Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce. Objectives: To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties. Methods: A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed. Results: LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&amp;M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P &lt; 0.05) compared to FIT. D&amp;M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P &lt; 0.01; post-discharge: 41% vs 12%/15%, P &lt; 0.01) and less rehospitalisation (10% vs 32%/34%, P &lt; 0.01) compared to PSS and FIT. Conclusions: LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features

What do we learn from the clinical and biological evaluation of the oral cavity in centenarians?

The number of centenarians is rapidly increasing worldwide and so are the studies on this segment of the population. A general consensus in the literature is that healthy longevity is an outcome of multiple factors, but the interrelationship between good oral health and healthy aging remains not fully understood. As part of the \u201cCaT: Centenari a Trieste\u201d study, a population-based cohort study set in Trieste, Italy, we report here the results of subjective self-reported oral health parameters and objective clinical and biological oral variables and their association with cognitive impairment in 25 centenarians enrolled in the study from September 2017 to May 2019. Oral health-related variables were recorded by means of a self-evaluation questionnaire and a compre- hensive oral examination of teeth, prostheses and mucosae conducted by a trained dentist. In addition, 6-n- propylthiouracil (PROP) taste perception and salivary oxidative stress markers, specifically the Total Oxidative Status and Ferric Reducing Ability of Saliva, were measured. Finally, the oral data obtained were compared with the presence or absence of dementia in the enrolled subjects. The centenarians included in our study were generally satisfied with their oral health. Among the causes of discomfort, the most prevalent were difficulties in chewing and biting, with few subjects describing a correlation between their oral health and psycho-social issues. We evaluated possible relations of clinical and biological variables to the likelihood of being demented and did not find significant associations. We found a higher though not statistically significant mean salivary flow and antioxidant capacity of saliva in non-demented subjects. When evaluating the PROP taste perception profile, we found a higher proportion of supertasters compared with previous studies and different taste perception profiles according to dementia. Despite the relatively small number of participants, we believe that our study contributes to a better understanding of the clinical and biological profile of the oral cavity in subjects aged over 100 years, encouraging the inclusion of a comprehensive evaluation of the oral cavity in centenarian studies performed worldwide