La valutazione degli interventi di prossimità. Uno studio pilota

Nonostante negli ultimi anni le attività di prevenzione dell’addiction da sostanze e da comportamenti si siano moltiplicate, nella maggior parte dei casi per tali attività, e per gli interventi di prossimità in particolare, non vengono attuati adeguati processi di valutazione. Ciò anche a causa della mancanza di sistemi di valutazione e di modelli teorici di riferimento condivisi. Il presente studio costituisce il primo passo di un progetto di ricerca più ampio finalizzato alla valutazione degli effetti degli interventi di prossimità. Lo studio descrive, in particolare, i rapporti esistenti tra frequenza di assunzione della sostanza o di attuazione del comportamento problematico, stadio del cambiamento e fattori di vulnerabilità e di protezione. Lo studio dimostra, inoltre, che il sistema di valutazione adottato è in grado di rilevare le differenze esistenti tra momenti diversi del percorso di cambiamento, in cui la frequenza di attuazione del comportamento problematico assume significato in relazione a variabili psicologiche e di contesto

Human sinusoidal subendothelial cells regulate homing and invasion of circulating metastatic prostate cancer cells to bone marrow

: Subendothelial cells (pericytes) are the clonogenic, multipotent and self-renewing skeletal stem cells (SSCs) found in bone marrow (BM) stroma. They express genes maintaining hematopoietic stem cell (HMC) niche identity and, transplanted in immunocompromised mice, organize the hematopoietic microenvironment (HME) generating humanized bone/BM ossicles. To create a mouse model of hematogenous metastasis of human prostate cancer (PC) cells to human bone/BM, we injected PC cells in the blood circulatory system of Severe Combined Immunodeficiency (SCID)/beige mice bearing heterotopic ossicles. Results indicate that PC cells could efficiently home to mice-implanted extraskeletal BM ossicles, but were not able to colonize mice skeletal segments. In humanized bone/BM ossicles, early foci of PC cells occupied a perisinusoidal position, in close contact with perivascular stromal cells. These findings demonstrate the importance of the SSC compartment in recreating a suitable environment to metastatic PC cells. Our data support the hypothesis that BM SSCs committed to a pericyte fate can specify for homing niches of PC cells, suggesting an involvement of specific interactions with subendothelial stromal cells in extravasation of circulating metastatic PC cells to BM

Tear levels of neuropeptides increase after specific allergen challenge in allergic conjunctivitis

Growing evidence is showing a role of neurogenic inflammation in allergic reactions, with sensory and autonomic nerve fibers releasing neuromediators, which may actively participate in the allergic inflammatory cascade. Although the cornea is the most densely innervated tissue of the human body, little is known on the role of neuromediators at the ocular surface. In this study, we aimed at evaluating the role of substance P (SP), calcitonine gene related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) in allergic reactions of the ocular surface

Capsaicin-induced corneal sensory denervation and healing impairment are reversed by NGF treatment.

PURPOSE. We aimed to evaluate the nerve growth factor (NGF) pathway and its influence on corneal healing mechanisms in normal conditions and in an animal model of corneal denervation induced by capsaicin. METHODS. Peripheral sensory damage was induced in rat pups by subcutaneous injection of capsaicin and the effects evaluated by hot-plate test, corneal nerve count, and tear secretion. Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and immunohistochemistry. The effects of exogenous NGF administration as eye drop formulation were also tested. RESULTS. Capsaicin treatment induced a significant reduction of peripheral sensitivity, corneal innervation, tear secretion, and corneal healing rate. The ocular effects of capsaicin treatment were associated with an NGF pathway alteration. NGF eye drop treatment aided corneal healing mechanisms through a significant increase in the NGF receptors TrkA and p75, and in the stem cell marker p63. CONCLUSIONS. In this study, we show that an alteration in the NGF pathway is responsible for a delay in corneal healing in an animal model of sensory denervation. Moreover, we show that NGF eye drop administration modulates corneal innervation, epithelial cell healing, and corneal stem cells. These findings may trigger further research on the role of the NGF pathway in limbal stem cell deficiency. (Invest Ophthalmol Vis Sci. 2012; 53:8280‐8287) DOI:10.1167/iovs.12-1059

Biological activity of new bioactive steroids deriving from biotransformation of cortisone

Cortisone is a metabolite belonging to the corticosteroid class that is used pharmaceutically directly as a drug or prodrug. In addition to its large consumption, its use is linked to several side effects, so pharmaceutical research aims to develop effective drugs with low or no side effects, alternative compounds to cortisone are part of an active investment in ongoing research on drug discovery. Since biotransformation can be considered a source of new molecules with potential therapeutic use, the present work focuses on a preliminary in vitro study aimed at evaluating the mutagenic, anti-inflammatory, antioxidant and neuroprotective activity of SCA and SCB molecules obtained from the biotransformation of cortisone using Rh. Rhodnii strain DSM 43960. The results obtained are very encouraging due to the safety of biotransformed compounds with reference to genotoxicity checked by Ames test, to the very high antioxidant capacity and to the anti-inflammatory activity. In fact, thecompounds inhibited both the TNF alpha-stimulated expression and secretion of NFkB target cytokines, and COX activity, and can activate the glucocorticoid receptor. Finally SCA and SCB exhibited neuroprotective properties

Level and correlates of physical activity and sedentary behavior in patients with type 2 diabetes: a cross-sectional analysis of the italian diabetes and exercise study-2

OBJECTIVE: Patients with type 2 diabetes usually show reduced physical activity (PA) and increased sedentary (SED)-time, though to a varying extent, especially for low-intensity PA (LPA), a major determinant of daily energy expenditure that is not accurately captured by questionnaires. This study assessed the level and correlates of PA and SED-time in patients from the Italian Diabetes and Exercise Study_2 (IDES_2). METHODS: Three-hundred physically inactive and sedentary patients with type 2 diabetes were enrolled in the IDES_2 to be randomized to an intervention group, receiving theoretical and practical exercise counseling, and a control group, receiving standard care. At baseline, LPA, moderate-to-vigorous-intensity PA (MVPA), and SED-time were measured by accelerometer. Physical fitness and cardiovascular risk factors and scores were also assessed. RESULTS: LPA was 3.93±1.35 hours∙day-1, MVPA was 12.4±4.6 min∙day-1, and SED-time was 11.6±1.2 hours∙day-1, with a large range of values (0.89-7.11 hours∙day-1, 0.6-21.0 min∙day-1, and 9.14-15.28 hours∙day-1, respectively). At bivariate analysis, LPA and MVPA correlated with better cardiovascular risk profile and fitness parameters, whereas the opposite was observed for SED-time. Likewise, values of LPA, MVPA, and SED-time falling in the best tertile were associated with optimal or acceptable levels of cardiovascular risk factors and scores. At multivariate analysis, age, female gender, HbA1c, BMI or waist circumference, and high-sensitivity C reactive protein (for LPA and SED-time only) were negatively associated with LPA and MPA and positively associated with SED-time in an independent manner. CONCLUSIONS: Physically inactive and sedentary patients with type 2 diabetes from the IDES_2 show a low level of PA, though values of LPA, MVPA, and SED-time vary largely. Furthermore, there is a strong correlation of these measures with glycemic control, adiposity and inflammation, thus suggesting that even small improvements in LPA, MVPA, and SED-time might be associated with significant improvement in cardiovascular risk profile

Medial pivot vs posterior stabilized total knee arthroplasty designs: a gait analysis study

Aim To compare a medial pivot (MP) total knee arthroplasty (TKA) with posterior stabilized (PS) TKA designs from a subjective, clinical and biomechanical point of view, in a single-centre, single-surgeon, case-control non-randomized trial. Methods Sixteen patients were randomly picked up from case series into each group. Subjective outcome was assessed using the Forgotten Joint Score Questionnaire (FJSQ). Clinical evaluation included range of motion (ROM). All patients underwent gait analysis by a treadmill with force-measuring plaques and videorecording device; data were recorded for 30 seconds and included cadence, step length, stance time and walking speed. A blinded qualitative analysis of the pattern of gait was defined as biphasic or non-biphasic. Descriptive statistics for the continuous study variables and statistical significance were calculated for all parameters with independent-samples t-test and χ2 test to analyse difference in pattern of gait between groups. Results Mean FJSQ in the MP group was 91.87 (CI 95%: 88.12- 95.46) and 75.31 (CI 95%: 67.97-81.56) in the PS group (p=0.029). Mean post-operative ROM was 117° (CI 95%: 113°-122°) in the MP group and 112° (CI 95%: 108°-117°) in the PS group (p=0.14). No statistical difference was found between groups regarding all gait analysis parameters which have been recorded. Conclusion MP TKA design showed better subjective results using the FJSQ, but it did not improve significantly clinical and functional outcomes compared to PS TKA design, at a short-term follow-up

Qualitative versus automatic evaluation of CT perfusion parameters in acute posterior circulation ischaemic stroke

Purpose To compare the diagnostic accuracy (ACC) in the detection of acute posterior circulation strokes between qualitative evaluation of software-generated colour maps and automatic assessment of CT perfusion (CTP) parameters. Methods Were retrospectively collected 50 patients suspected of acute posterior circulation stroke who underwent to CTP (GE “Lightspeed”, 64 slices) within 24 h after symptom onset between January 2016 and December 2018. The Posterior circulation-Acute Stroke Prognosis Early CT Score (pc-ASPECTS) was used for quantifying the extent of ischaemic areas on non-contrast (NC)CT and colour-coded maps generated by CTP4 (GE) and RAPID (iSchemia View) software. Final pc-ASPECTS was calculated on follow-up NCCT and/or MRI (Philips Intera 3.0 T or Philips Achieva Ingenia 1.5 T). RAPID software also elaborated automatic quantitative mismatch maps. Results By qualitative evaluation of colour-coded maps, MTT-CTP4D and Tmax-RAPID showed the highest sensitivity (SE) (88.6% and 90.9%, respectively) and ACC (84% and 88%, respectively) compared with the other perfusion parameters (CBV, CBF). Baseline NCCT and CBF provided by RAPID quantitative perfusion mismatchmaps had the lowest SE (29.6%and 6.8%, respectively) and ACC (38% and 18%, respectively). CBF and Tmax assessment provided by quantitative RAPID perfusion mismatch maps showed significant lower SE and ACC than qualitative evaluation. No significant differences were found between the pc-ASPECTSs assessed on colour-coded MTT and Tmax maps neither between the scores assessed on colourcoded CBV-CTP4D and CBF-RAPID maps. Conclusion Qualitative analysis of colour-codedmaps resultedmore sensitive and accurate in the detection of ischaemic changes than automatic quantitative analysis

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

Background: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. Methods: Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. Results: The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. Conclusions: The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD