Ricerca clinica e ricerca empirica

In questo articolo l'autore tende a mostrare come possa funzionare l'integrazione tra ricerca clinica e ricerca empirica secondo il modello della perturbazione reciproca tra i dati e le osservazioni prodotte da due distinti sistemi di conoscenza. Viene messa in evidenza come esista un forte influenzamento della ricerca clinica sulle ipotesi che vengono testate negli studi empirici e il potenziale effetto dei dati empirici sulla chiarificazione e messa a fuoco di questioni fondamentali per la pratica clinica e la riuscita dei trattamenti. Da qui il potenziamento di 'buone pratiche' rispetto ad errori e importanti disconoscimenti dei fattori che determinano l'esito delle terapie. Conseguentemente l'interesse si orienta sui percorsi formativi nella prospettiva di favorire un approccio in cui l'attenzione del clinico in formazione si equilibra tra 'punti di ancoraggio' osservabili, mutuati dalla ricerca, approfondimenti intuitivi e quei pattern descrittivi derivati dalla esperienza clinica che arricchiscono la letteratura psicoanalitica

Memories and Future. Storia e sviluppi di un gruppo di ricerca italiano: dagli studi di efficacia alle analisi delle resistenze al cambiamento

L'obiettivo di questo articolo è di riassumere brevemente come si sia formato e sviluppato il nostro gruppo di ricerca e quali indirizzi di ricerca abbia preso nel corso degli anni. Tale fine risponde all'esigenza condivisa di una maggiore collaborazione e integrazione tra i vari gruppi che si sviluppi anche al di fuori dei contatti stimolanti, ma purtroppo sporadici, che avvengono ai congressi, sia nazionali che internazionali, in modo da aprire eventuali nuove strade di condivisione di percorsi di ricerca comune. Siamo convinti che la conoscenza reciproca sia la "via maestra" alla costruzione di nuovi progetti e alla realizzazione di quelle conoscenze scientifiche per cui la nostra Società è nata

Processed Animal Proteins from Insect and Poultry By-Products in a Fish Meal-Free Diet for Rainbow Trout: Impact on Intestinal Microbiota and Inflammatory Markers

Sustainability of aquaculture is tied to the origin of feed ingredients. In search of sustainable fish meal-free formulations for rainbow trout, we evaluated the effect of Hermetia illucens meal (H) and poultry by-product meal (P), singly (10, 30, and 60% of either H or P) or in combination (10% H + 50% P, H10P50), as partial replacement of vegetable protein (VM) on gut microbiota (GM), inflammatory, and immune biomarkers. Fish fed the mixture H10P50 had the best growth performance. H, P, and especially the combination H10P50 partially restored \u3b1-diversity that was negatively affected by VM. Diets did not differ in the Firmicutes:Proteobacteria ratio, although the relative abundance of Gammaproteobacteria was reduced in H and was higher in P and in the fishmeal control. H had higher relative abundance of chitin-degrading Actinomyces and Bacillus, Dorea, and Enterococcus. Actinomyces was also higher in H feed, suggesting feed-chain microbiome transmission. P increased the relative abundance of protein degraders Paeniclostridium and Bacteroidales. IL-1\u3b2, IL-10, TGF-\u3b2, COX-2, and TCR-\u3b2 gene expression in the midgut and head kidney and plasma lipopolysaccharide (LPS) revealed that the diets did not compromise the gut barrier function or induce inflammation. H, P, and H10P50 therefore appear valid protein sources in fishmeal-free aquafeeds

Growth and Welfare of Rainbow Trout (Oncorhynchus mykiss) in Response to Graded Levels of Insect and Poultry By-Product Meals in Fishmeal-Free Diets

This study compared the nutrient-energy retention, digestive function, growth performance, and welfare of rainbow trout (ibw 54 g) fed isoproteic (42%), isolipidic (24%), fishmeal-free diets (CV) over 13 weeks. The diets consisted of plant-protein replacement with graded levels (10, 30, 60%) of protein from poultry by-product (PBM) and black soldier fly H. illucens pupae (BSFM) meals, either singly or in combination. A fishmeal-based diet was also tested (CF). Nitrogen retention improved with moderate or high levels of dietary PBM and BSFM relative to CV (p < 0.05). Gut brush border enzyme activity was poorly affected by the diets. Gastric chitinase was up-regulated after high BSFM feeding (p < 0.05). The gut peptide and amino acid transport genes were differently regulated by protein source and level. Serum cortisol was unaffected, and the changes in metabolites stayed within the physiological range. High PBM and high BSFM lowered the leukocyte respiratory burst activity and increased the lysozyme activity compared to CV (p < 0.05). The BSFM and PBM both significantly changed the relative percentage of lymphocytes and monocytes (p < 0.05). In conclusion, moderate to high PBM and BSFM inclusions in fishmeal-free diets, either singly or in combination, improved gut function and nutrient retention, resulting in better growth performance and the good welfare of the rainbow trout

Residual peripheral blood CD26+leukemic stem cells in chronic myeloid leukemia patients during TKI therapy and during treatment-free remission

Chronic myeloid leukemia (CML) patients in sustained “deep molecular response” may stop TKI treatment without disease recurrence; however, half of them lose molecular response shortly after TKI withdrawing. Well-defined eligibility criteria to predict a safe discontinuation up-front are still missing. Relapse is probably due to residual quiescent TKI-resistant leukemic stem cells (LSCs) supposedly transcriptionally low/silent and not easily detectable by BCR-ABL1 qRT-PCR. Bone marrow Ph+ CML CD34+/CD38− LSCs were found to specifically co-express CD26 (dipeptidylpeptidase-IV). We explored feasibility of detecting and quantifying CD26+ LSCs by flow cytometry in peripheral blood (PB). Over 400 CML patients (at diagnosis and during/after therapy) entered this cross-sectional study in which CD26 expression was evaluated by a standardized multiparametric flow cytometry analysis on PB CD45+/CD34+/CD38− stem cell population. All 120 CP-CML patients at diagnosis showed measurable PB CD26+ LSCs (median 19.20/μL, range 0.27–698.6). PB CD26+ LSCs were also detectable in 169/236 (71.6%) CP-CML patients in first-line TKI treatment (median 0.014 cells/μL; range 0.0012–0.66) and in 74/112 (66%), additional patients studied on treatment-free remission (TFR) (median 0.015/μL; range 0.006–0.76). Notably, no correlation between BCR-ABL/ABLIS ratio and number of residual LSCs was found both in patients on or off TKIs. This is the first evidence that “circulating” CML LSCs persist in the majority of CML patients in molecular response while on TKI treatment and even after TKI discontinuation. Prospective studies evaluating the dynamics of PB CD26+ LSCs during TKI treatment and the role of a “stem cell response” threshold to achieve and maintain TFR are ongoing

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

Quantitative comparison of barbiturates in essential hand and head tremor

The tremorolytic effects of primidone and phenobarbital in essential tremor of hands and head were compared in a double-blind, placebo-controlled trial. Quantitative measurements of tremor were obtained in 15 patients by means of an accelerometric method. Only primidone proved to be superior to placebo in reducing hand tremor, suggesting that its tremorolytic effectiveness is largely dependent on the parent drug rather than its metabolite phenobarbital. Head tremor tended to improve only in three out of six patients with both primidone and phenobarbital, but, likely due to the small number of affected patients, the effect failed to reach statistical significance

Primidone in the Long-Term Treatment of Essential Tremor: a prospective study with computerized quantitative analysis.

The long-term efficacy of primidone (375-750 mg/day) in essential tremor was evaluated prospectively in 11 patients who had shown a favorable response to 4-week treatment with the drug under placebo-controlled conditions. On accelerometric evaluation, the magnitude of tremor after 3, 6, and 12 months on primidone was still significantly reduced compared with the initial placebo period. After discontinuation of primidone, tremor amplitude reverted to the placebo levels. Some loss of efficacy during long-term administration, however, was suggested by the results of self-assessment, physician's assessment, and performance tests. Three patients discontinued prematurely the drug because the sedative effects outweighed the potential therapeutic benefit. Side effects (especially drowsiness and sedation) were common at 4 weeks and 3 months but tended to subside thereafter. It is concluded that primidone retains at least part of its tremorolytic effect for up to 1 year, although the overall clinical benefit is limited in most patients

Introducing children in the primary school to the concept of ecosystem services

The respect for Earth and life in all its diversity and the protection of the integrity of the environment are two of the fundamental principles declared in the Earth Charter 2000, which aims to build a right, peaceful, and sustainable global society. Due to the increasing effects of the environmental crisis, there is a need for a greater environmental sensibility and consciousness, and one path to reach this goal passes through environmental education projects with children. Here we carried out a project about the involvement of children in environmental-related issues, using as a teaching tool the ecosystem services. The project aims to develop in children a sensitivity towards the environment, good social and civic competence, and make the new generations more aware of environmental issues through the discovery of their territory. The topic of ecosystem services was introduced through a storytelling approach and some questions, as a reference point for activities. The 17 children taking part in the project were 9 years old and the considerations obtained were supported and tested by questionnaires appropriate to their age and level of comprehension. Successively, videos of urbanized and degraded environments in our territory were shown, thus had to describe and map them in their town. Thus, children were asked to make a proposal for the recovery of a degraded area in their town. After one year, a meeting with the children took place and they were asked to fill out a questionnaire regarding the project, and the consequences it brought to their lives. The results highlighted that the majority of children remember this project with a positive feeling and had an improved competence and critical sense regarding the environment and ecosystem services