Effectiveness of aerobiological dispersal and microenvironmental requirements together influence spatial colonization patterns of lichen species on the stone cultural heritage.

Dispersal patterns of lichen species in monumental and archaeological sites and their relationships with spatial population structure are almost unknown, hampering predictions on colonization dynamics that are fundamental for planning conservation strategies. In this work, we tested if the local abundance and distribution pattern of some common lichen species on carbonate stones of heritage sites may be related to their patterns of propagule dispersal. We combined analyses of the spatial population structure of eight species on the calcareous balustrade of a heritage site in Torino (NW Italy) with aerobiological analyses. In situ and laboratory analyses were mainly focused on the ejection of ascospores and their air take-off and potential dispersal at short and long distance. Results indicate that the spatial distribution of lichens on the stone surfaces is influenced by both species-specific patterns of propagule dispersal and microenvironmental requirements. In particular, apotheciate species that have a higher ejection of ascospores with higher potential for long range dispersal are candidate for a much aggressive spreading on the monumental surfaces. Moreover, their occurrence on natural or artificial stone surfaces in the surroundings of the stone monumental surface may easily support recolonization dynamics after cleaning interventions, as an effective supply of propagules is expected. On the other hand, species with a lower dispersal rate have a more clustered distribution and are less effective in rapid recolonization, thus representing a minor threat for cultural heritage conservation. These results support the idea that information on the reproductive strategy and dispersal patterns of lichens should be coupled with traditional analyses on stone bioreceptivity and microclimatic conditions to plan effective restoration interventions of stone surfaces.

Phosphorescent iridium-containing nanomicelles: synthesis, characterization and preliminary applications in nanomedical imaging.

Diagnostic nanomedicine constantly requires the development of novel contrast agents with intrinsic imaging capabilities. Phosphorescent Ir(iii)-complexes represent good candidates when delivered through polymeric nanoparticles. In this work, we propose a biocompatible nanoparticle made from an intrinsically phosphorescent copolymer, synthesized directly with an imaging tag present on its backbone. Polymeric nanoparticles can be obtained with the exact amount of phosphorescent moieties needed to maximize their output signal. Complete characterization and ex vivo studies confirmed that this nanosystem is suitable as a future diagnostic tool.

Attitudes towards abortion in Italian women: socio-economic trends and epidemiological features.

PURPOSE OF INVESTIGATION: The aim of this study was to analyze trends and attitudes towards abortion in Italian women in the last decades. MATERIALS AND METHODS: The authors analyzed number, socio-economic trends, and major clinical-epidemiological features of induced abortion in Italy (1980-2009). RESULTS: Up to 1996 abortion rates were higher among married women, but from 1996 to 2009 they were higher among single women. The reduction of abortions has been observed in all age-groups, except in women from 15 to 19 years of age. Abortions were higher among younger women, women without previous abortions, nulliparous women, women with junior and senior high school diplomas (2005-2006), women with an academic degree (2007-2009), and professional women. Conclu- sion: In Italy, despite the decrease of the abortion rates, voluntary termination of pregnancy is still present and the spread of contraception is scarce. More information about contraception is necessary to help lower the incidence of both unintended pregnancy and abortion.

Mechanisms of neurodegeration in type 2 diabetes and the neuroprotective potential of dipeptidyl peptidase 4 inhibitors.

Prospective epidemiological studies suggest that type 2 diabetes is a risk factor for neurodegenerative pathologies such as Alzheimer disease, vascular dementia, and Parkinson disease. Drugs that act as incretin receptor agonists or inhibit the proteolytic degradation of incretins (dipeptidyl peptidase 4 inhibitors) have been approved since 2005 for use in diabetes treatment. Dipeptidyl peptidase 4 (DPP4) cleaves N-terminal dipeptides from polypeptides when the second residue is proline, hydroxyproline, dehydroproline or alanine. The inhibition of DPP4 hydrolytic activities extends the halflife of these peptides by preventing their degradation. Several peptides have been identified as DPP4 substrates, including neuropeptides, chemokines, and the incretin hormones; hence the pleomorphic effects of DPP4 inhibition. Recently, the neuroprotective properties of these drugs have been evaluated in cell cultures and animal models, not yet in human trials. Although mechanisms distinct from glycaemic control alone have been claimed to account for protection against neuronal degeneration, the precise cellular mechanism by which DPP4 inhibitors exert their neuroprotective effects remain unknown. The present review is focused on the candidate pathways that could be involved in mediating DPP4 inhibitors-mediated protection against neuronal degeneration.

Dietary strategies for adult type 1 diabetes in light of outcome evidence.

Individuals who have type 1 diabetes need individualised medical nutrition therapies whose goals are to improve overall health and metabolic outcomes. However, interventions in the field of nutrition are challenging, as diet-related correlations with disease remain difficult to detect and the certainty of outcome in this area is elusive. Currently, patients are not meeting recommended dietary guidelines. Several alternative approaches for teaching meal planning to people with diabetes have been proposed: basic nutrition guidelines, basic diabetes guidelines, menu approaches to meal planning, exchange lists for meal planning and carbohydrate counting. The review provides an overview of suggested strategies for achieving the proposed goals and summarises evidence of outcomes.

Celiac disease and endometriosis: an insidious and worrisome association hard to diagnose: a case report.

BACKGROUND: Primary infertility is an unusual presentation of celiac disease (CD). When non-classical symptoms are present, the diagnosis is not easy and it becomes even more difficult when CD is associated with endometriosis, representing a diagnostic challenge for medical practitioners and gynecologists. CASE REPORT: A 34-year-old patient presented to the authors' observation with primary infertility. Formerly she was treated for endometriosis and the diagnosis of CD was delayed. A favorable clinical and serological response following a gluten-free-diet (GFD) was achieved and a successful pregnancy was obtained. DISCUSSION: This case report emphasizes the role of the CD in women's infertility and the possible association between CD and endometriosis. Even if the relationship between these two diseases is still unclear and further studies to address this issue are required, more attention from gynecologists is needed, considering that the later this association is diagnosed, the greater the probability of adverse outcomes of health developing.

Combined oral contraceptives: health benefits beyond contraception.

It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.

Epidemiology of cardiovascular disease in patients with type 1 diabetes: European perspective.

The International Diabetes Federation estimated that 5.1 million people aged between 20 and 79 years died from diabetes in 2013, accounting for 8.4% of global all-cause mortality among people in this age group. Type 1 diabetes is associated with a 2- to 4-fold increased mortality risk compared with the general population. Before the onset of late complications, most of the excess mortality is from potentially preventable causes of death such as ketoacidosis, whereas the long-term excess mortality is largely due to cardiovascular disease. However, a wide geographic variation in mortality of type 1 diabetic patients has been evidenced and accurate estimates of mortality attributable to diabetes are difficult to obtain. The review provides an overview of currently available evidence and summarizes main problems in estimating early and long-term mortality by cause of death in type 1 diabetes, paying particular attention to European studies.

Fertility preservation in female cancer patients: an emerging challenge for physicians.

Fertility preservation has become an issue of great importance in female cancer patients due to increasing survival rates and delayed childbearing. It is an emerging challenge for physicians, cause of several related issues (multidisciplinary approach, doctor-patient communication, ethical, religious and legal problems) and many unresolved questions. This review aims to update the latest literature data, summarizing the effects of cancer treatments on female fertility and the various options currently available to offer cancer patients the opportunity of future pregnancies. Many strategies exist for fertility preservation in young women and they should be assessed according to the patient's age, type of cancer, partner status and time available. Some techniques are well established, others are still experimental. The established methods include embryo cryopreservation, transposition of ovaries prior to radiation therapy, radiation shielding of gonads and conservative surgical approaches. The experimental methods include oocyte cryopreservation, in vitro maturation of oocytes, ovarian tissue cryopreservation and transplantation, and ovarian suppression. Improvement of these techniques as well as better characterization of their success rates and risks, await further investigation. Oocytes donation and gestational surrogacy represent the last options. Thus, the care of these patients is challenging, complex and requires a multidisciplinary approach. A close collaboration between Oncologists, Specialists in Reproductive Medicine, Gynecologic Oncologists and Endocrinologists is crucial for always offering the best possible option.

A 29-year-old woman with complex atypical hyperplasia and polycystic ovary syndrome: a challenging issue.

BACKGROUND: The standard treatment for complex atypical hyperplasia is hysterectomy and bilateral salpingo-oophorectomy. Although radical surgery offers high survival prospects, it also eliminates any chance of further fertility, thus in young nulliparous women who wish to preserve their childbearing potential, a conservative progestin therapy is preferable. CASE REPORT: The authors report a case of complex atypical hyperplasia in a 29-year-old nulliparous woman with polycystic ovary syndrome treated with norethisterone acetate in order to preserve her childbearing potential. The specimens sampled during the follow-up demonstrated inactive endometrium with pseudodecidual changes and no ultrasonographic images exhibited abnormal endometrial thickness. CONCLUSION: According to literature and to the authors' experience, they can affirm that progestin treatment is the most reasonable option for young nulliparous women affected by complex atypical hyperplasia who desire to maintain their fertility potential, showing its efficacy also in patients with an associated polycystic ovary syndrome.

Osteolytic bone metastasis is hampered by impinging on the interplay among autophagy, anoikis and ossification.

Here we show that the fate of osteolytic bone metastasis depends on the balance among autophagy, anoikis resistance and ossification, and that the hepatocyte growth factor (HGF) signaling pathway seems to have an important role in orchestrating bone colonization. These findings are consistent with the pathophysiology of bone metastasis that is influenced by the cross-talk of supportive and neoplastic cells through molecular signaling networks. We adopted the strategy to target metastasis and stroma with the use of adenovirally expressed NK4 (AdNK4) and Dasatinib to block HGF/Met axis and Src activity. In human bone metastatic 1833 cells, HGF conferred anoikis resistance via Akt and Src activities and HIF-1α induction, leading to Bim isoforms degradation. When Src and Met activities were inhibited with Dasatinib, the Bim isoforms accumulated conferring anoikis sensitivity. The proviability effect of HGF, under low-nutrient stress condition, was related to a faster autophagy deactivation with respect to HGF plus Dasatinib. In the 1833 xenograft model, AdNK4 switched metastasis vasculature to blood lacunae, increasing HIF-1α in metastasis. The combination of AdNK4 plus Dasatinib gave the most relevant results for mice survival, and the following molecular and cellular changes were found to be responsible. In bone metastasis, we observed a hypoxic condition - marked by HIF-1α - and an autophagy failure - marked by p62 without Beclin-1. Then, osteolytic bone metastases were largely prevented, because of autophagy failure in metastasis and ossification in bone marrow, with osteocalcin deposition. The abnormal repair process was triggered by the dysfunctional autophagy/anoikis interplay. In conclusion, the concomitant blockade of HGF/Met axis and Src activity seemed to induce HIF-1α in metastasis, whereas the bone marrow hypoxic response was reduced. As a consequence, anoikis resistance might be hampered favoring, instead, autophagy failure and neoformation of woven bone trabeculae. Mice survival was, therefore, prolonged by overcoming an escape strategy adopted by metastatic cells by disruption of tumor-stroma coevolution, showing the importance of autophagy inhibition for the therapy of bone metastasis.

Spores of lichen-forming fungi in the mycoaerosol and their relationships with climate factors.

Fungal particulates are a dominant component of the bioaerosol, but aerobiological studies traditionally focused on a limited set of fungi having relevance as allergens or plant pathogens. This study first analyzes the occurrence of lichen meiospores in the mycoaerosol, quantitatively evaluating in the atmosphere of an alpine environment the occurrence of polar diblastic spores, unequivocally attributable to the lichen family Teloschistaceae. The analysis of air-samples collected one week per month for one year with a Hirst-type sampler displayed a low percentage occurrence of polar-diblastic spores (<0.1%) with respect to the whole mycoaerosol, dominated by Cladosporium. Spearman's correlation tests on aerobiological and climatic data highlighted a strong relationship between the detection of Teloschistaceae spores and rainfall events, excluding seasonal patterns or daily rhythms of dispersion. The fact that all the air-sampled spores were attributable to the species of Teloschistaceae occurring in the site, together with laboratory observations of predominant short range dispersal patterns for polar diblastic and other lichen spores, indicated that sexual reproduction is mostly involved in the local expansion of colonization, dispersal from a long distance appearing a less probable phenomenon. These findings indicated that responses of lichen communities to climate factors, usually related to physiological processes, also depend on their influence on meiospore dispersal dynamics. Spatial limitations in dispersal, however, have to be taken into account in evaluating lichen distributional shifts as indicators of environmental changes.

Statin intolerance: why and what to do - with a focus on diabetic people.

The standards of medical care in diabetes recommend that statin therapy is added to lifestyle therapy for diabetic patients with overt cardiovascular disease (LDL cholesterol goal <70 mg/dl), or without cardiovascular disease who are over the age of 40 years and who have one or more other cardiovascular disease risk factors (LDL cholesterol goal <100 mg/dl). In order to reach strict LDL targets, high doses of statins may be required. However, the frequency of statin associated adverse effects and statin intolerance in clinical practice is high (up to 10-15% of statin users) especially at muscle level. The review overviews: 1) the known or hypothesised mechanisms through which causal and contributing factors are associated with adverse effects in diabetic people, and 2) the rationale of strategies for managing statin intolerant patients.

Dipeptidyl peptidase-4 inhibition: linking chemical properties to clinical safety.

The new drug class of dipeptidyl peptidase-4 (DPP4) inhibitors has been widely accepted in the daily management of type 2 diabetes since its strategic advantages with regard to body weight, risk of hypoglycaemia, and beta cell survival. We have previously evaluated the theoretical implications of DPP4 inhibition given that the enzyme is involved in regulating biological activity of hormones, neuropeptides, and cytokines. We intend now 1) to provide a critical appraisal of safety and tolerability as they emerged from the available clinical studies, and 2) to establish, if possible, a relation between chemical properties, biological activity, and the observed side effects in vivo.

Point-of-care testing in diabetes care.

Assessing modifiable risk factors for metabolic and cardiovascular diseases prior to the onset of disease could allow effective prevention initiatives. Equally, monitoring in diabetic people glucose, haemoglobin A1c, ketones, lipid profiles, and urinary microalbumin concentrations allows the prevention, early detection, and treatment of diabetes-related acute and chronic complications and has a positive impact on the process of care in the management of patients with diabetes. The point-of-care testing (PoCT) technology offers convenient aspects: immediate results, decision-making without the need for repeated visits, use of fingerstick blood samples. More patients could be identified at early stages of their disease/complication provided that pre-analytical, analytical, and post-analytical errors are minimised. Indeed, prediction requires instruments with proved precision, accuracy, validity, and reliability. Reference laboratory services are now available to manufacturers so to confirm PoCT results. There are several PoC devices on the market that may allow for "real time" screening, diagnosis, and monitoring in diabetes care. Tight glucose control has a key role in long-term health of diabetic people and in the primary prevention of diabetic chronic complications. Diabetic patients are currently educated to control capillary glucose levels daily in order to maintain them within target limits. Blood glucose meters are widely used not only by diabetic patients to self-manage their disease but also by physicians to monitor critically ill patients. Glycated haemoglobin A1c can now be measured with fast and easy automated PoCT instruments to monitor long-term serum glucose regulation. Urinalysis dipsticks and blood betahydroxybutyrate meter allow measuring urine and blood ketones to prevent ketoacidosis. Since the routine measurement of urinary albumin has been suggested in diabetes mellitus as a predictor of overt diabetic nephropathy, semi-quantitative visual dipsticks and quantitative automated methods of urine testing became available for bedside detection of urine albumin at low concentrations and for the determination of the microalbumin creatinine ratio. While the National Cholesterol Education Program recommends that all adults aged 20 years and over have their blood cholesterol checked at least once every 5 years, adult diabetic patients should measure fasting lipid profile at least annually or every two years in case of low-risk lipid values. There are PoCT devices on the market that provide a full lipid panel (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides). The overview summarises current state-of-the-art of PoCT in diabetes care.

Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme.

Dipeptidyl peptidase-4 (DPP4) or adenosine deaminase complexing protein 2 (ADCP 2) or T-cell activation antigen CD26 (EC 3.4.14.5.) is a serine exopeptidase belonging to the S9B protein family that cleaves X-proline dipeptides from the N-terminus of polypeptides, such as chemokines, neuropeptides, and peptide hormones. The enzyme is a type II transmembrane glycoprotein, expressed on the surface of many cell types, whose physiological functions are largely unknown. Protein dimerisation should be required for catalytic activity and glycosylation of the enzyme could impact on its physiological functions. The dimeric glycoprotein ADCP has been found linked to adenosine deaminase (ADA) whose relationship with lymphocyte maturation-differentiation is well-established. Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offers a new potential therapeutic approach for type 2 diabetes mellitus, as monotherapy and adjunct therapy to other oral agents. The clinical use of presently available orally active inhibitors of DPP4, however, has been associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9. Indeed, it is noteworthy that CD26 has a key role in immune regulation as a T cell activation molecule and in immune-mediated disorder. All-cause infections were increased after sitagliptin treatment. It is noteworthy that the effects of DPP4 inhibition on the immune system have not been extensively investigated. So far, only routine laboratory safety variables have been measured in published randomised controlled trials. The review summarises present knowledge in the field and suggests some potential directions of future research.

Inhibitory effect of HGF on invasiveness of aggressive MDA-MB231 breast carcinoma cells, and role of HDACs.

Hepatocyte growth factor (HGF), through Met receptor binding, fulfils numerous functions in invasive tumour growth (survival/proliferation, motility, apoptosis), but epigenetic control of gene expression in this process is poorly understood. In HGF-treated breast cancer cells we studied (a) the chemoinvasion towards CXCL12 (ligand of the chemokine-receptor CXCR4) and (b) the mechanistic basis, that is, the transduction pathways that regulate CXCR4-mediated invasion, and the role played by histone deacetylases (HDACs) after blockade with trichostatin A (TSA). In highly invasive and metastatic MDA-MB231 cells HGF had a dual inhibitory effect, reducing spontaneous migration and specific chemoinvasion towards CXCL12, the latter by decreasing CXCR4 transactivation and protein level. After HGF the levels of phosphorylated (therefore active) c-Src and Akt persistently increased, indicating a role of these signal transducers in the HGF-dependent cellular and molecular effects. c-Src wild-type expression vector (Srcwt) increased active c-Src and mimicked the HGF-dependent inhibition of CXCR4 transactivation. Our findings indicate that HDACs participated in the HGF-inhibitory effects. In fact, blockade of HDACs hindered the HGF- and Srcwt-dependent reductions of CXCR4 transactivation and invasiveness, while inhibition of endogenous c-Src was additive with HGF, further reducing specific chemoinvasion. In conclusion, in MDA-MB231 cells HDAC blockade with TSA partly counteracted the HGF-dependent effects through molecular events that included enhancement of the expression of the genes for invasiveness Met and CXCR4 (depending on serum conditions), reduction of endogenous phospho-c-Src/c-Src and phosphoAkt/Akt ratios and triggering of apoptosis. The potential therapeutic use of TSA should take into account the variable aggressiveness of breast carcinoma cells and microenvironment signals such as HGF at the secondary growth site of the tumour. It was interesting that HGF reduced motility and CXCR4 functionality only of MDA-MB231 cells, and not of low-invasive MCF-7 cells, suggesting a mechanism implicated in metastatic cell homing.

Flow cytometry study of leukocyte function: analytical comparison of methods and their applicability to clinical research.

Perturbations in the redox-based network of cellular regulatory mechanisms have been associated with oxidative-related diseases such as diabetes mellitus. In these situations the redox state of cellular redox systems becomes persistently shifted toward oxidation that may result in a sequence of pathophysiological events. Innate and adaptive immune responses depend on the production of reactive oxygen species and ATP synthesis, which are tightly regulated by the mitochondrial transmembrane potential. Mitochondrial hyperpolarisation is a key mechanism of T-cell life, apoptosis and autoimmunity. The NADPH oxidase of the phagocytic cells of the immune system generates reactive oxygen metabolites during the respiratory burst, but activated B cells also possess NADPH oxidase and reactive oxidants could play regulatory roles in immune function. Cellular thiol levels and the thiol reduction-oxidation process modulate the oxidative metabolism in the cells, transcriptional factor activation of gene expression, lymphocyte proliferation and death. Flow cytometry allows directly characterising and analysing several parameters and functions of intact living cells in a few seconds. Fluorescent lipophilic cations have been used for the measurement of the mitochondrial transmembrane potential. Evaluation of reactive oxygen intermediates generation in neutrophils may be obtained by use of oxidation-sensitive probes. The dye resazurin has been used to quantify mitochondrial activity since considered to act as an intermediate electron acceptor in the electron transport chain between the final reduction of oxygen and cytochrome oxidase. The fluorescence emitted by 5-chloromethyl fluorescein acetate stained cells reflects the total level of free intracellular thiol. In this review we will discuss the possible importance and consequences of evaluating these redox parameters in diabetes pathophysiology. Moreover, we will provide perspectives concerning the varieties of analytical procedures that are capable of measuring them. The advantages and disadvantages of each of these methods are critically discussed particularly in view of their clinical application.