A Weight of Evidence approach to support the assessment of the quality of Manila clam farming sites in a coastal lagoon.

Aquaculture productivity in coastal lagoons is endangered by a complex interplay of anthropogenic and environmental factors, amplified by the effects of climate change in these sensitive areas. To reach a more comprehensive assessment of farming sites quality, a quantitative Weight of Evidence approach (QWoE) is applied for the first time to data collected at four Manila clam (R. philippinarum) farming sites in the Venice lagoon (Italy). This included sediment quality, chemical bioaccumulation, and biological responses. Results revealed a greater hazard for sites closer to the open sea. In these areas, the combination of sediment characteristics and a higher frequency of salinity and temperature stress could explain the alterations measured at a transcriptional and biomarker level. The findings demonstrate that a QWoE approach that integrates multiple sources of evidence should also include physicochemical conditions in order to better understand the impacts of human activities and other stressors on clam aquaculture productivity.

Identification of the safe(r) by design alternatives for nanosilver-enabled wound dressings.

The use of silver nanoparticles (NPs) in medical devices is constantly increasing due to their excellent antimicrobial properties. In wound dressings, Ag NPs are commonly added in large excess to exert a long-term and constant antimicrobial effect, provoking an instantaneous release of Ag ions during their use or the persistence of unused NPs in the wound dressing that can cause a release of Ag during the end-of-life of the product. For this reason, a Safe-by-Design procedure has been developed to reduce potential environmental risks while optimizing functionality and costs of wound dressings containing Ag NPs. The SbD procedure is based on ad-hoc criteria (e.g., mechanical strength, antibacterial effect, leaching of Ag from the product immersed in environmental media) and permits to identify the best one among five pre-market alternatives. A ranking of the SbD alternatives was obtained and the safer solution was selected based on the selected SbD criteria. The SbD framework was also applied to commercial wound dressings to compare the SbD alternatives with products already on the market. The iterative procedure permitted to exclude one of the alternatives (based on its low mechanical strength) and proved to be an effective approach that can be replicated to support the ranking, prioritisation, and selection of the most promising options early in the innovation process of nano-enabled medical devices as well as to encourage the production of medical devices safer for the environment.

Caveolinopathies: translational implications of caveolin-3 in skeletal and cardiac muscle disorders.

Caveolae are specialized lipid rafts localized on the cytoplasmic surface of the sarcolemmal membrane. Caveolae contribute to the maintenance of plasma membrane integrity, constitute specific macromolecular complexes that provide highly localized regulation of ion channels, and regulate vesicular trafficking and signal transduction. In skeletal muscle, the main structural assembly of caveolae is mediated by caveolin-3. Another family of adapter proteins, the cavins, is involved in the regulation of caveolae function and in the trafficking of caveolin-derived structures. Caveolin-3 defects lead to four distinct skeletal muscle disease phenotypes: limb-girdle muscular dystrophy, rippling muscle disease, distal myopathy, and hyperCKemia. Many patients show an overlap of these symptoms, and the same mutation can be linked to different clinical phenotypes. An ever-growing interest is also focused on the association between caveolin-3 mutations and heart disorders. Indeed, caveolin-3 mutants have been described in a patient with hypertrophic cardiomyopathy and two patients with dilated cardiomyopathy, and mutations in the caveolin-3 gene (CAV3) have been identified in patients affected by congenital long QT syndrome. Although caveolin-3 deficiency represents the primary event, multiple secondary molecular mechanisms lead to muscle tissue damage. Among these, sarcolemmal membrane alterations, disorganization of skeletal muscle T-tubule network, and disruption of distinct cell signaling pathways have been determined.

Deacetylase inhibitors modulate the myostatin/follistatin axis without improving cachexia in tumor-bearing mice.

Muscle wasting, as occurring in cancer cachexia, is primarily characterized by protein hypercatabolism and increased expression of ubiquitin ligases, such as atrogin-1/MAFbx and MuRF-1. Myostatin, a member of the TGFbeta superfamily, negatively regulates skeletal muscle mass and we showed that increased myostatin signaling occurs in experimental cancer cachexia. On the other hand, enhanced expression of follistatin, an antagonist of myostatin, by inhibitors of histone deacetylases, such as valproic acid or trichostatin-A, has been shown to increase myogenesis and myofiber size in mdx mice. For this reason, in the present study we evaluated whether valproic acid or trichostatin-A can restore muscle mass in C26 tumor-bearing mice. Tumor growth induces a marked and progressive loss of body and muscle weight, associated with increased expression of myostatin and ubiquitin ligases. Treatment with valproic acid decreases muscle myostatin levels and enhances both follistatin expression and the inactivating phosphorylation of GSK-3beta, while these parameters are not affected by trichostatin-A. Neither agent, however, counteracts muscle atrophy or ubiquitin ligase hyperexpression. Therefore, modulation of the myostatin/follistatin axis in itself does not appear sufficient to correct muscle atrophy in cancer cachexia.

Muscle myostatin signalling is enhanced in experimental cancer cachexia.

BACKGROUND/AIMS: Myostatin belongs to the transforming growth factor-beta superfamily and negatively regulates skeletal muscle mass. Its deletion induces muscle overgrowth, while, on the contrary, its overexpression or systemic administration cause muscle atrophy. The present study was aimed at investigating whether muscle depletion as occurring in an experimental model of cancer cachexia, the rat bearing the Yoshida AH-130 hepatoma, is associated with modulations of myostatin signalling and whether the cytokine tumour necrosis factor-alpha may be relevant in this regard. MATERIALS AND METHODS: Protein levels of myostatin, follistatin (myostatin endogenous inhibitor) and the activin receptor type IIB have been evaluated in the gastrocnemius of tumour-bearing rats by Western blotting. Circulating myostatin and follistatin in tumour hosts were evaluated by immunoprecipitation, while the DNA-binding activity of the SMAD transcription factors was determined by electrophoretic-mobility shift assay. RESULTS: In day 4 tumour hosts muscle myostatin levels were comparable to controls, yet follistatin was reduced, and SMAD DNA-binding activity was enhanced. At day 7, both myostatin and follistatin increased in tumour bearers, while SMAD DNA-binding activity was unchanged. To investigate whether tumour necrosis factor-alpha contributed to induce such changes, rats were administered pentoxifylline, an inhibitor of tumour necrosis factor-alpha synthesis that partially corrects muscle depletion in tumour-bearing rats. The drug reduced both myostatin expression and SMAD DNA-binding activity in day 4 tumour hosts and up-regulated follistatin at day 7. CONCLUSIONS: These observations suggest that myostatin pathway should be regarded as a potential therapeutic target in cancer cachexia.

Drug use and kidney donation: what are high-risk behaviors today?

BACKGROUND: "Social risk behaviors" are usually considered as contraindications for organ donation. The organ shortage, however, necessitates expansion of the donor pool. Reconsideration of the policy toward substance abusers may be important. Opinions of the overall population may be of use to define this cultural-sensitive issue. METHODS: A semistructured questionnaire on organ donation, including opinions on drug use (cannabis and cocaine), was administered to various groups of the general public and caregivers: high school students (liceo classico: 59 students, median age 18 years; istituto tecnico: 108, age 17); first- and fourth-year medical school (77, age 19; 46, age 22); continuing medical education (44, age 32); third-year nursing school (31, age 23); "senior citizen university" (51, age 63). RESULTS: Cannabis use was mainly accepted for kidney donation (48.6% yes, 26.6% no, 29.8% uncertain/blank), but cocaine use was not (22.1% yes, 44.2% no, 33.7% uncertain/blank). In the univariate analysis, opinions differed according to age, sex, and belonging to the health care teams upon multivariate analysis being a member of the health care team was the strongest predictor of responses (P<.01). CONCLUSION: It is difficult to define social risk behaviors. Since opinions are important for organ donation, further studies and discussion are needed to periodically analyze our policies.

Is male homosexuality still a cultural taboo for kidney donation?

BACKGROUND: Among the so-called social risk behaviors, male homosexuality is probably one of the most interesting and difficult taboos. Because of changing attitudes of the general population toward irregular sexual behaviors, often considered as markers of unhealthy life styles, there is a need to reconsider at least the most important one-homosexuality. METHODS: A semistructured questionnaire included opinions on homosexuality with respect to kidney donation: Would you consider a male homosexual as a kidney donor? If you were on dialysis, would you accept a kidney from a homosexual donor? This instrument was administered to various groups of the general public and caregivers: high school students (Liceo Classico: 59 students, median age 18 years; Istituto Tecnico: n=108, median age 17); first and fourth year of medical school (n=77, age 19; 46, age 22); continuing medical education (n=44, age 32); third year of nursing school (n=31, age 23); "senior citizen university" (n=51, age 63). RESULTS: Male homosexuality was well accepted for kidney donation (71.6% yes, 9.6% no, 18.8% uncertain/blank). However, the opinions were different among the groups with male students of a technical institute showing discrimination against male homosexuals. In the univariate analysis, opinions differed according to age, gender, and belonging to the health care team. In the multivariate analysis, the latter was the strongest predictor (P<.01). The specific threats for the health are not well known, even among the caregiver population. CONCLUSION: It is difficult to define the role of homosexuality among the so-called social risk behaviors. Negative attitudes existed in some subsets of the population.

Play-back theatre, theatre laboratory, and role-playing: new tools in investigating the patient-physician relationship in the context of continuing medical education courses.

AIM: The aim of this study was to report on the validation of a role-playing approach, using play-back and theatre laboratory in the context of a continuing medical education (CME) course on predialysis and transplantation, to discuss the patient-physician relationship. METHODS: The course was developed with the help of a theatre director. The role-playing 2-day course was designed to be highly interactive for a small group (15-20 participants), based on a core of case reports (dialysis, transplantation, and return to dialysis after graft failure). Two stages were included: play-back theatre in which experiences told by the participants were mimed by a group of actors, and theatre laboratory in which different aspects of voice and touch were explored. Opinions were gathered by an anonymous semistructured questionnaire completed by all participants. RESULTS: The course obtained a high score from The Ministry of Health (14 credits, 1 per teaching hour). The opinions of the 18 participants were highly positive; all liked the courses. Sixteen of 18 asked to repeat the experience. The strong emotional involvement was an advantage for 15 of 18, sharing emotional aspects of the profession for 10 of 18, and usefulness in clarifying opinions on "dark sides" of our profession for 10 of 18. CONCLUSION: The positive opinions recorded during this experience, the first experiment with a "psycho-theatrical approach" developed in a CME course in our country, suggest the benefit of implementing nonconventional, educational approaches in a multidisciplinary discussion of the patient-physician relationship in transplantation medicine.

Making a movie on kidney transplantation: a medical school graduation thesis to explain kidney transplantation from students to students.

The aim of this study was to report on the production and the opinions of a video movie on transplantation and organ donation. The video was developed by a medical school student with the help of the students and teachers of a high school for applied arts. For this task, the making of the video was included in the high school program of the participating class. The students were tutored by their photography teacher. The video movie lasts about 50 minutes. Each "scene" lasts no more than 5 minutes, to avoid reducing the attention level. The choice of a nonmedical frame helped to have some moments to digest the technical information and to stress the importance of the patient-physician relationship. The video was employed as a part of small-group lessons in the nephrology course. A semistructured anonymous questionnaire gathered the opinion of 65 students at the end of the lessons. Student satisfaction was high; the median score was the highest (8, range 6 to 10) for the lesson based upon the movie, as compared with the conventional ones on chronic kidney disease or dialysis (7, range 5 to 10). As far as the authors know, this is the first experiment of a multimedia approach, dedicated to medical and nonmedical targets, developed as a graduation thesis in an Italian Medical School. In conclusion, the positive opinions of the students, who highly appreciated the peer-developed message, may suggest implementing such nonconventional educational approaches to support human resources and enthusiasm for kidney transplantation among the new generations.

Continuing education in medicine: a useful tool for nurses' empowerment in renal transplantation.

BACKGROUND: Continuing Education in Medicine (CEM) underlines the importance of updates and information for the health care team. Our aim was to describe the organization and results of a CEM course "educate to organ donation" that involved the nursing team in an educational experience with high school students. The course consists of theory (4 hours; the physician-patient relationship, the educational role of the nurse, the teaching policy, checklist, and results of a school education program) and practice (10 hours; the attendants join the teaching team in the classrooms and in the plenary session). Analysis of anonymous questionnaires performed after the course contained semistructured questions and analog scales. RESULTS: The first acknowledgment came from the Cabinet of Public Health, which gave the maximum number of credits (14 for 14 education hours). PARTICIPATION: presently 40 nurses, about 40% of those working in the renal unit (over 30 CEM courses are available in the hospital). Satisfaction: Overall score was median 8.5 (6 to 10) including teaching materials = 8 (4 to 10). Among the theoretical part, the lesson on patient-physician relationship obtained the highest score. The main drawback was the shortness of the practical part. The classroom meeting achieved a median score of 9.5 (7 to 10), the general session = 9 (5 to 10). All but one nurse registered for an "advanced" course, giving more time to the practical part (20 hours). CONCLUSION: CEM may represent an important way to deliver education on transplant-related issues to patients and to the general population.

[Hypervitaminosis D in institutionalized elderly in Buenos Aires]. / Hipovitaminosis D en ancianos institucionalizados de Buenos Aires.

Several studies have shown that vitamin D (Vit. D) deficiency in elderly people enhances bone mass loss. Most of these studies have been carried out in areas of low solar irradiation. In order to establish Vit. D circulating levels in elderly people in our community (34 degrees S) and their relationship with bone metabolism, 34 men and 33 women were studied at the end of the summer. These subjects, all residents of nursing homes, had a mean age of 81.9 + 8.1 years (range 69-99). Calcemia, parathyroid hormone (PTH and 25-hydroxyvitamin D (25(HO)D) were measured in serum and bone markers in serum and urine. Bone densitometry (BMD) of cortical and trabecular bone in the forearm (distal third of the radius (R33%) and ultradistal (RUD), respectively) were performed using X-ray absorptiometry. We found: 1) Low serum 25(HO)D (14.4 + 1.7 ng/ml) at summer's end. 40.5% showed levels < 10 ng/ml. 2) Secondary hyperparathyroidism (PTH: 169.4 + 30.9 pg/ml), 3) Hypocalcemia was observed in 34.5% of elderly people, 4) increased bone turnover in the subpopulation with hypovitaminosis D. 5) The serum levels of 25(HO)D correlated with BMD R33% (r = 0.55, n = 54, P < 0.001), with BMD RUD (r = 0.50, n = 54, P < 0.001) and with PTH (r = -0.44, n = 42, P < 0.01). A deficiency of Vit.D was found in our population of elderly people, probably due to diminished epidermic production of its precursors and/or to scant exposure to sunlight in the elderly. The decrease is associated to age. The positive correlation of 25(HO)D with bone mass (cortical and trabecular bone) underscores its importance for the preservation of bone mass. Hyperparathyroidism, triggered by Vit. D deficit, enhances bone loss.

[Nuclear medicine in pneumonology in the light of 9 year's experience at the S. Luigi Gonzaga Hospital]. / Medicina nucleare in pneumologia alla luce di 9 anni di sperimentazioni all'Ospedale S. Luigi Gonzaga.

An attempt is made to draw a picture of the results obtained with nuclear medicine in the pneumological field in the light of 9 years experience. An attempt is also made to identify from among recently introduced techniques (T.A.C., echotomography) which ones might be substituted for radioisotopes and when, and on what occasion they can be used as complementary treatment. It is concluded that nuclear medicine is of absolute value for functional examinations of the respiratory apparatus (perfusors and ventilators) and for lung onconscannning with Ga67 citrate and Bleomycin-Co57 under present circumstances and that in other fields certain morphological scans (bone scans) are still useful by virtue of their cost-benefit ratio.

[Indications for radiotherapy of lung cancer in the light of its clinical reality]. / Indicazioni del trattamento radiante del carcinoma del polmone alla luce della sua realtá clinica.

Reference is made to a large series and the literature in an attempt to single out cases where radiation management is indicated in the curative, palliative and anatalogic treatment of lung cancer, an in association with other therapies. It is pointed out that each case much be examined on its merits in the light of the histological type, the extent of the process, and its possible metastasis. The conclusion is drawn that radiotherapy plays a useful part in the albeit slight increase in survival of lung cancer patients under acceptable general conditions.