Immune cell infiltration and inflammatory landscape in primary brain tumours.

BACKGROUND: Primary malignant brain tumours are more than one-third of all brain tumours and despite the molecular investigation to identify cancer driver mutations, the current therapeutic options available are challenging due to high intratumour heterogeneity. In addition, an immunosuppressive and inflammatory tumour microenvironment strengthens cancer progression. Therefore, we defined an immune and inflammatory profiling of meningioma and glial tumours to elucidate the role of the immune infiltration in these cancer types. METHODS: Using tissue microarrays of 158 brain tumour samples, we assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1 (PD-L1), O-6-Methylguanine-DNA Methyltransferase (MGMT) and Transglutaminase 2 (TG2) expression by immunohistochemistry (IHC). IHC results were correlated using a Spearman correlation matrix. Transcript expression, correlation, and overall survival (OS) analyses were evaluated using public datasets available on GEPIA2 in Glioblastoma (GBM) and Lower Grade Glioma (LGG) cohorts. RESULTS: Seven out of ten markers showed a significantly different IHC expression in at least one of the evaluated cohorts whereas CD3, CD4 and 5-LOX were differentially expressed between GBMs and astrocytomas. Correlation matrix analysis revealed that 5-LOX and GzmB expression were associated in both meningiomas and GBMs, whereas 5-LOX expression was significantly and positively correlated to TG2 in both meningioma and astrocytoma cohorts. These findings were confirmed with the correlation analysis of TCGA-GBM and LGG datasets. Profiling of mRNA levels indicated a significant increase in CD3 (CD3D, CD3E), and CD138 (SDC1) expression in GBM compared to control tissues. CD4 and 5-LOX (ALOX5) mRNA levels were significantly more expressed in tumour samples than in normal tissues in both GBM and LGG. In GBM cohort, GzmB (GZMB), SDC1 and MGMT gene expression predicted a poor overall survival (OS). Moreover, in LGG cohort, an increased expression of CD3 (CD3D, CD3E, CD3G), CD8 (CD8A), GZMB, CD20 (MS4A1), SDC1, PD-L1, ALOX5, and TG2 (TGM2) genes was associated with worse OS. CONCLUSIONS: Our data have revealed that there is a positive and significant correlation between the expression of 5-LOX and GzmB, both at RNA and protein level. Further evaluation is needed to understand the interplay of 5-LOX and immune infiltration in glioma progression.

[Epidemiology in support of intervention priorities: the case of diabetes in Turin (Piedmont Region, Northern Italy)]. / L'epidemiologia a supporto delle priorità di intervento: il caso del diabete a Torino.

OBJECTIVES: to describe the epidemiology of diabetes within the city of Turin (Piedmont Region, Northern Italy) and to present the process initiated by the city network of diabetes care for the improvement of prevention and treatment of the disease. DESIGN: ecological study based on administrative database. SETTING AND PARTICIPANTS: residents in Turin from 2016 to 2018. MAIN OUTCOME MEASURES: incidence and prevalence of diabetes, percentage of glycosylated haemoglobin testing, and case-fatality. RESULTS: in the considered three-year period (2016-2018), the cumulative incidence of diabetes was 11.5 x1,000; as of 31.12.2018 the prevalence was 5.9%. 77% had performed at least one measurement of glycated haemoglobin during the previous year, and the case-fatality was 12.6% in the three-year period. The standardized prevalence per statistical zone varied from a minimum of 2% (95%CI 1.2-3.3) to a maximum of 10.2% (95%CI 9.1-11.4). The highest values were recorded in the most deprived city areas. The geographical distribution of incidence, varying between 5.1 x1,000 (95%CI 2.7-10.0) e 19.4 x1,000 (95%CI 15.8-24.0), reproduces the geography of prevalence, as well as the percentage of measurement of glycated haemoglobin, while the variability of the fatality rate is more modest without an obvious geographic pattern. CONCLUSIONS: diabetes occurs most frequently in the most deprived areas of the city, but the response of the health care system is adequate and equitable. Sharing of these results with the city health authorities and the diabetologists has led to identify as a priority interventions for the reduction of unhealthy behaviours, and for the improvements of patient care pathway, starting form the most disadvantaged areas of the city. A process of listening and involvement of all actors potentially interested in the prevention and treatment of diabetes has been started.

Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study.

BACKGROUND: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. METHODS: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. RESULTS: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. CONCLUSIONS: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.

Association between low lean mass and low bone mineral density in 653 women with hip fracture: does the definition of low lean mass matter?

BACKGROUND AND AIMS: Loss of both muscle and bone mass results in fragility fractures with increased risk of disability, poor quality of life, and death. Our aim was to assess the association between low appendicular lean mass (aLM) defined according to different criteria and low bone mineral density (BMD) in hip-fracture women. METHODS: Six hundred fifty-three women admitted to our rehabilitation hospital underwent dual energy X-ray absorptiometry 19.1 ± 4.1 (mean ± SD) days after hip-fracture occurrence. Low aLM was identified according to either Baumgartner's definition (aLM/height2 less than two standard deviations below the mean of the young reference group) or FNIH criteria: aLM <15.02 kg, or aLM adjusted for body mass index (BMI) <0.512. Low BMD was diagnosed with a T-score <-2.5 at the unfractured femoral neck. RESULTS: Using Baumgartner's definition, the association between low aLM/height2 and low BMD was significant: χ 2(1, n = 653) = 8.52 (p = 0.004), but it was erased by adjustments for age and fat mass. Using the FNIH definition the association between low aLM and low BMD was significant: χ 2(1, n = 653) = 42.5 (p < 0.001), and it was confirmed after adjustment for age and fat mass (p < 0.001). With the FNIH definition based on aLM/BMI ratio the association between low aLM/BMI ratio and low BMD was nonsignificant: χ 2(1, n = 653) = 0.003 (p = 0.957). CONCLUSIONS: The association between low aLM and low BMD in women with hip fracture dramatically depends on the adopted definition of low aLM. FNIH threshold for aLM (<15.02 kg) emerges as a useful tool to capture women with damage of the muscle-bone unit.

New therapeutic perspectives in CCDC6 deficient lung cancer cells.

Non-small cell lung cancer (NSCLC) is the main cause of cancer-related death worldwide and new therapeutic strategies are urgently needed. In this study, we have characterized a panel of NSC lung cancer cell lines for the expression of coiled-coil-domain containing 6 (CCDC6), a tumor suppressor gene involved in apoptosis and DNA damage response. We show that low CCDC6 protein levels are associated with a weak response to DNA damage and a low number of Rad51 positive foci. Moreover, CCDC6 deficient lung cancer cells show defects in DNA repair via homologous recombination. In accordance with its role in the DNA damage response, CCDC6 attenuation confers resistance to cisplatinum, the current treatment of choice for NSCLC, but sensitizes the cells to olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. Remarkably, the combination of the two drugs is more effective than each agent individually, as demonstrated by a combination index <1. Finally, CCDC6 is expressed at low levels in about 30% of the NSCL tumors we analyzed by TMA immunostaining. The weak CCDC6 protein staining is significatively correlated with the presence of lymph node metastasis (p ≤ 0.02) and negatively correlated to the disease free survival (p ≤ 0.01) and the overall survival (p ≤ 0.05). Collectively, the data indicate that CCDC6 levels provide valuable insight for OS. CCDC6 could represent a predictive biomarker of resistance to conventional single mode therapy and yield insight on tumor sensitivity to PARP inhibitors in NSCLC.

Expression and potential role of the peptide orexin-A in prostate cancer.

The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed. Here, we demonstrate for the first time the immunohistochemical localization of orexin-A in human PCa specimens, and the expression of prepro-orexin and OX1 receptor at both protein and mRNA levels in these tissues. Orexin-A administration to the human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor expression resulting in a decrease of cell survival. Noteworthy, nanomolar concentrations of the peptide counteract the testosterone-induced nuclear translocation of the androgen receptor in the cells: the orexin-A action is prevented by the addition of the OX1 receptor antagonist SB-408124 to the test system. These findings indicate that orexin-A/OX1 receptor interaction interferes with the activity of the androgen receptor which regulates PCa onset and progression, thus suggesting that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer.

Presarcopenia and sarcopenia in hip-fracture women: prevalence and association with ability to function in activities of daily living.

BACKGROUND AND AIMS: Sarcopenia staging systems have been proposed, but little is known on their application in hip-fracture patients. Our aim was to assess the prevalence of presarcopenia and sarcopenia and their association with ability to function in activities of daily living in hip-fracture women. METHODS: We investigated white women (N = 138 of 149) who were consecutively admitted to a rehabilitation hospital because of their first hip fracture. In each woman, we measured appendicular lean mass (aLM) by dual-energy X-ray absorptiometry, at a median of 18 days after hip fracture occurrence. On the same day, we assessed grip strength with a handheld dynamometer. Functional autonomy was assessed by the Barthel Index. We used the European Working Group on Sarcopenia in Older People (EWGSOP) definition to calculate the prevalence of presarcopenia and sarcopenia, taking into account both aLM/height(2) and handgrip strength. Gait speed was not considered, because of the recent hip fracture. RESULTS: Twenty-three (17 %) of the 138 women fulfilled the diagnostic criteria for presarcopenia whereas 80 (58 %) were sarcopenic. The women with presarcopenia were younger, healthier and with higher Barthel Index scores (median 65 vs. 55; interquartile range 60-75 and 50-60, respectively; p < 0.001) than those with sarcopenia. Significant differences in Barthel Index scores at the time of assessment (but not at the end of the rehabilitation course) persisted after multiple adjustments (p < 0.001). CONCLUSIONS: The prevalence of presarcopenia and sarcopenia was high in hip-fracture women. Presarcopenic women had higher ability to function in activities of daily living than sarcopenic women.

Parathyroid-hormone variance is only marginally explained by a panel of determinants: a cross-sectional study of 909 hip-fracture patients.

Several factors affect the levels of parathyroid hormone (PTH) in hip-fracture patients. We hypothesized that a panel of easily assessable determinants could account for both a substantial proportion of PTH variance and the occurrence of secondary hyperparathyroidism. We evaluated 909 of 981 hip-fracture inpatients admitted consecutively to our Rehabilitation division. In each patient we assessed PTH, 25-hydroxyvitamin D, albumin-adjusted total calcium, phosphate, magnesium, and creatinine on a fasting blood sample 21.3 ± 6.1 (mean ± SD) days after fracture occurrence. Glomerular filtration rate (GFR) was estimated by the 4-variable Modification of Diet in Renal Disease Study equation. Functional level was assessed using the Barthel index. On multivariate analysis, six factors (phosphate, albumin-adjusted total calcium, estimated GFR (eGFR), 25-hydroxyvitamin D, age, and magnesium) were significantly associated with PTH levels. Overall, the panel of variables accounted for 23.7 % of PTH variance. Among the 909 patients, 304 (33.4 %) had PTH levels exceeding the normal range. Six factors (phosphate, albumin-adjusted total calcium, eGFR, 25-hydroxyvitamin D, age, and Barthel index scores) were significantly associated with the category of PTH level (either normal or elevated). The model correctly classified 70.4 % of cases. For the optimal cut-off point, sensitivity was 80 % and specificity was 61 %. Data shows that six factors were significantly associated with PTH levels in hip-fracture inpatients. However, the six factors accounted for only 23.7 % of PTH variance and the presence or absence of secondary hyperparathyroidism was correctly categorized in a modest proportion of cases. We conclude that more knowledge is needed on the factors affecting PTH levels after hip fracture.

Handgrip strength but not appendicular lean mass is an independent predictor of functional outcome in hip-fracture women: a short-term prospective study.

OBJECTIVE: To investigate the contribution of muscle mass and handgrip strength in predicting the functional outcome after hip fracture in women. DESIGN: Observational study. SETTING: Rehabilitation hospital. PARTICIPANTS: White women (N=123 of 149) who were consecutively admitted to a rehabilitation hospital because of their first fracture of the hip. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We measured appendicular lean mass (aLM) by dual-energy x-ray absorptiometry (DXA) 21.1 ± 8.7 (mean ± SD) days after hip fracture occurrence in the 123 women. On the same day, we assessed grip strength at the nondominant arm with a dynamometer. At the end of acute inpatient rehabilitation we measured the ability to function in activities of daily living by using the Barthel Index, and lower limb performance by using the Timed Up and Go (TUG) test. RESULTS: We found significant correlations between handgrip strength measured before rehabilitation and Barthel Index scores after rehabilitation (ρ=.50; P<.001), Barthel Index effectiveness (ρ=.45; P<.001), and the TUG test (ρ=-.41; P<.001). Conversely, we found no significant correlations between aLM/height(2) and Barthel Index scores after rehabilitation (ρ=.075; P=.41), Barthel Index effectiveness (ρ=.06; P=.53), or the TUG test (ρ=.005; P=.96). Significant associations between grip strength and all the outcome measures persisted after adjustment for 8 potential confounders, including Barthel Index scores before rehabilitation, age, number of medications, number of comorbidities, pressure ulcers, concomitant infections, time between fracture occurrence and assessment, and aLM/height(2). CONCLUSIONS: Grip strength, but not DXA-assessed aLM, significantly predicted short-term functional outcome in women after a hip fracture.

Expression of orexin A and its receptor 1 in the human prostate.

The peptides orexin A (OXA) and orexin B, deriving from the cleavage of the precursor molecule prepro-orexin, bind two G-coupled transmembrane receptors, named as receptor 1 (OX1R) and receptor 2 for orexin, showing different affinity-binding properties. First discovered in the rat hypothalamus, orexins and their receptors have been also found in many peripheral tissues where they exert neuroendocrine, autocrine and paracrine functions. Because inconclusive data on their localization in the mammalian prostate are reported, the aim of this study was to investigate the presence of prepro-orexin, OXA and OX1R in the human normal and hyperplastic gland. Immunohistochemistry revealed the localization of both OXA and OX1R in the cytoplasm of the follicular exocrine epithelium of all tested normal and hyperplastic prostates. Positive immunostaining was mainly observed in the basal cells of the stratified epithelium, and only rarely in the apical cells. The expression of mRNAs coding for prepro-orexin and OX1R and of proteins in the tissues was also ascertained by polymerase chain reaction and Western blotting analysis, respectively. In order to gain insights into the functional activity of OXA in the prostate, we administered different concentrations of OXA to cultured prostatic epithelial cells PNT1A. We first demonstrated that PNT1A cells express OX1R. The addition of OXA did not affect PNT1A cell proliferation, while it enhanced cAMP synthesis and Ca(2+) release from intracellular storage. Overall, our results definitely demonstrate the expression of OXA and OX1R in the human prostate, and suggest an active role for them in the metabolism of the gland.

Parathyroid hormone is significantly associated with body fat compartment in men but not in women following a hip fracture.

BACKGROUND AND AIMS: Parathyroid hormone (PTH) exerts several actions beyond mineral metabolism and may affect body composition. The aim of our study was to assess the association between serum PTH and body fat compartment in hip fracture patients. METHODS: We studied 575 of 630 inpatients with hip fracture consecutively admitted to our Rehabilitation ward. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition. DXA scan was performed 18.5 ± 8.6 (mean ± SD) days after hip fracture occurrence. A blood sample was collected within 4 days after DXA scan. In each subject, we evaluated PTH, 25-hydroxyvitamin D, calcium, phosphate, albumin, magnesium, and creatinine. Glomerular filtration rate was estimated by a conventional formula. RESULTS: In the 57 men, we found a significant correlation between PTH and both body mass index (BMI) (ρ = 0.37; p = 0.020) and trunk fat percentage (ρ = 0.62; p < 0.001). After multiple adjustments, we confirmed a significant association between PTH and BMI (r = 0.38; p = 0.004) or trunk fat percentage (r = 0.51; p < 0.001). In the 518 women, we found a slightly significant correlation between PTH and BMI (ρ = 0.09; p = 0.047), but after adjustments the correlation coefficient dropped to 0.02 (p = 0.69). We found no significant relationships between PTH and trunk fat percentage at bivariate correlation (ρ = 0.04; p = 0.35) or after adjustments (r = 0.04; p = 0.38). CONCLUSIONS: PTH serum levels were robustly associated with body fat compartment in men, but not in women following a fracture of the hip. A role of PTH in affecting body composition in hip fracture men is suggested. Its potential role in male prognostic disadvantage needs further investigation.

Obsessive-compulsive-spectrum symptoms in patients with focal dystonia, hemifacial spasm, and healthy subjects.

This study is aimed at investigating obsessive-compulsive disorder (OCD) in three groups of patients matched for age and gender; namely, focal dystonia (FD), hemifacial spasm (HFS), and healthy-control subjects (HC). All subjects were investigated with the Structured Clinical Interview for DSM-I, the Hospital Anxiety and Depression Scale, the Symptom Checklist-90, the Yale-Brown Obsessive-Compulsive Scale, and the Structured Clinical Interview for Obsessive-Compulsive Spectrum Self-Report, Lifetime Version (SCI-OBS-SR-LT). The prevalence of OCD was significantly higher in both FD and HFS than in HC participants. On the SCI-OBS, HFS patients showed higher scores than FD or HC for "contamination" and "aggressiveness." Despite the different pathophysiology, OCD is highly represented in both FD and HFS, with different thematic content characterizing the two conditions.

Scenario building model to support the resilience planning of winemaking regions: The case of the Douro territory (Portugal).

Today resilience paradigm is shared by both academic and political debates, and it is gradually being implemented into plans, programmes, and project's initiatives. In this context, wine regions, particularly those designated as UNESCO sites, show their robustness and vulnerabilities as Socio-Ecological Systems. The climate change impact is increasing the exposure of their aesthetic, cultural, economic, natural values to potential losses and therefore an effective response is required To build resilient strategies, Decision Makers are increasingly considering multidimensional models in planning and assessment processes. This paper continues a research work that develops an integrated evaluation framework constituted by Multicriteria Decision Analysis to calculate a Territorial Resilience Index, a dynamical model to predict future ecological scenarios and scenario building to define a resilient strategy for the Douro territory (Portugal). This paper focuses on scenario building which uses specific tools such as Social Network Analysis to identify and investigate the relationships between real actors and stakeholders, Wilson matrix to assess the degree of uncertainty and relevance of the strategies identified by a panel of specialists, and consistency matrix to evaluate the strategies consistency in achieving the Sustainable Development Goals and UNESCO requirements. The obtained protocol of guidelines and recommendations can support Decision Makers in the design of sustainable and resilient transformation, thereby assisting in the preservation of the UNESCO site.

Appendicular lean mass does not mediate the significant association between vitamin D status and functional outcome in hip-fracture women.

OBJECTIVE: To investigate whether muscle mass mediates the significant association between vitamin D status and functional recovery after hip fracture in women. DESIGN: Observational study. SETTING: Rehabilitation hospital in Italy. PARTICIPANTS: We investigated white women (N=280) of 305 who were consecutively admitted to a rehabilitation hospital because of their first fracture of the hip. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: To assess muscle mass, we measured appendicular lean mass (aLM) by dual-energy x-ray absorptiometry (DXA), 21.2±6.2 (mean ± SD) days after hip fracture occurrence in the 280 women. On the same day, we assessed serum levels of 25-hydroxyvitamin D and parathyroid hormone (PTH). Ability to function in activities of daily living was evaluated by the Barthel Index both before and after acute inpatient rehabilitation. RESULTS: After adjustment for 8 confounders, including age, cognitive impairment, pressure ulcers, neurologic impairment, infections, fracture type, Barthel Index score at admission to rehabilitation, and aLM/height(2) (aLM/ht(2)), 25-hydroxyvitamin D levels were significantly associated both with Barthel Index scores after rehabilitation (P=.003) and their changes during rehabilitation (P=.008). Similar results were obtained when the 25-hydroxyvitamin D/PTH ratio was substituted for 25-hydroxyvitamin D levels. Conversely, aLM/ht(2) was not significantly correlated with Barthel Index scores and their changes during rehabilitation. Furthermore, we found no significant associations between either 25-hydroxyvitamin D levels or the 25-hydroxyvitamin D/PTH ratio and aLM/ht(2). CONCLUSIONS: The significant association between 25-hydroxyvitamin D levels (and 25-hydroxyvitamin D/PTH ratio) and the ability to function in women with hip fractures was not mediated by aLM assessed by DXA.

A decision support system for territorial resilience assessment and planning: An application to the Douro Valley (Portugal).

This paper aims to assess the territorial resilience of a socio-ecological system through an innovative integrated evaluation framework to aid the decision-making process in the planning of transformation scenarios. This framework employs a set of resilience indicators through a Multicriteria Decision Analysis (MCDA) coupled with a Lotka-Volterra mathematical model of cooperative type. The set of indicators aims to calculate a composite index of Territorial Resilience (TRI), whereas the mathematical model is an extension of an existing model, aimed to predict possible long-time scenarios. The proposed operational framework for rural and vineyard landscapes aims to bridge the existing gap between territorial resilience theory and practice, with an innovative Decision Support System able to assist Decision Makers and territory planners in the planning and management of resilient territorial systems. This integrated evaluation framework is applied to a famous wine region in Portugal, the Douro Valley, where Port-wine grows. Such framework, especially in a context of adaptive governance, proves to be a suitable support in the field of landscape and urban planning to evaluate the dynamics of socio-ecological systems and to envision long-term policies and actions.

The relationship between initial trunk control or postural balance and inpatient rehabilitation outcome after stroke: a prospective comparative study.

OBJECTIVE: To compare the predictive validity of trunk control in sitting position assessed by Trunk Impairment Scale and balance in lying, sitting and standing posture assessed by Postural Assessment Scale for Stroke patients on functional outcome in stroke survivors. DESIGN: Prospective observational study. SETTING: A single rehabilitation hospital in Italy. SUBJECTS: Sixty of 68 consecutive subjects admitted to a rehabilitation hospital after stroke. MAIN MEASURES: We performed Trunk Impairment Scale and Postural Assessment Scale for Stroke patients at admission to inpatient rehabilitation. Outcome measures at discharge were Functional Independence Measure score and destination (classified as either home or institution). RESULTS: After adjustment for 14 potential confounders, including Functional Independence Measure score at admission to rehabilitation, both Trunk Impairment Scale and Postural Assessment Scale for Stroke patients scores were significantly associated with the Functional Independence Measure score at discharge (P = 0.010 and P =0.04, respectively), change in the Functional Independence Measure score during rehabilitation (P = 0.003 and P<0.001, respectively), Functional Independence Measure effectiveness (P = 0.024 and P =0.017, respectively) and destination at discharge (P = 0.040 and P =0.032, respectively). The panel of prognostic variables predicted 64-65% of the variance in the final Functional Independence Measure score, 30-35% of the variance in the change of the Functional Independence Measure score during rehabilitation, and 45-46% of the variance in the Functional Independence Measure effectiveness depending on the inclusion of either Trunk Impairment Scale or Postural Assessment Scale for Stroke patients score among the predictors.

Pathological complete response induced by first-line chemotherapy with single agent docetaxel in a patient with advanced non small cell lung cancer.

BACKGROUND: Defining the optimal treatment for patients with inoperable non small cell lung cancer (NSCLC), presenting with metastatic mediastinal lymph nodes, is challenging. Nevertheless, preoperative chemotherapy or radiotherapy might offer a chance for these patients for radical surgical resection and, possibly, complete recovery. CASE PRESENTATION: A 62-year old man with IIIA-N2 inoperable NSCLC was treated with first-line single agent docetaxel. A platinum-based treatment, though considered more active, was ruled out because of renal impairment. The patient tolerated the treatment very well and, although his initial response was not impressive, after 14 cycles he obtained a complete clinical response, which was confirmed pathologically after he underwent surgical lobectomy. CONCLUSION: In non-operable NSCLC patients not eligible for a platinum-based treatment, single-agent docetaxel can provide complete pathologic responses. Failure to obtain a response after the first few cycles should not automatically discourage to continue treatment.

Promoting health equity through social capital in deprived communities: a natural policy experiment in Trieste, Italy.

The Trieste Habitat Micro-area Programme (HMP), an innovative social-health service policy, has offered a natural experiment to empirically evaluate the social mechanisms through which social capital may have an impact on health inequalities. To date, literature clarifying this causal chain is scanty. This empirical study tested the following hypotheses: H1) innovative social-health practices can activate social mechanisms intentionally and systematically so as to generate social capital; H2) such social mechanisms increase specific properties of social capital, in particular those influencing more vulnerable individuals' relationships; H3) investing in these properties can enhance capabilities and, consequently, control over the health of more vulnerable individuals. The study was carried out during 2016-2018 and used both qualitative and quantitative methods. The qualitative part investigated the field experience of the HMP through interviews, focus groups and workshops with HMP professionals. The quantitative part assessed the effect HMP might have on these properties and the capacity to face health risks of more vulnerable individuals. Three samples, each of 200 individuals, residing in the target and in control areas were interviewed using a semi-structured questionnaire. One control sample was matched to the 200 treated subjects using a Propensity Score Matching. The results of the study suggest that the HMP intervention stimulated the development of empowerment, collaboration and interdependence among vulnerable people. This produced an increase in their social capital under several aspects, including enhanced trust, network extension and participation, cooperation and reciprocal help with neighbours, as well as improving their judgement on quality, timing and efficacy of the help received from institutions, relatives or friends. These findings show that socially shared relationships can create innovative local models of a universalistic generative welfare system, which would be both inclusive and able to enhance individual capabilities. These models could be disseminated and carried over to other contexts.

Analysis of CCDC6 as a novel biomarker for the clinical use of PARP1 inhibitors in malignant pleural mesothelioma.

OBJECTIVES: CCDC6 (coiled-coil domain containing 6) is a player of the HR response to DNA damage and has been predicted to interact with BAP1, another HR-DNA repair gene highly mutated in Malignant Pleural Mesothelioma (MPM), an aggressive cancer with poor prognosis. CCDC6 levels are modulated by the deubiquitinase USP7, and CCDC6 defects have been reported in several tumors determining PARP-inhibitors sensitivity. Our aim was to investigate the functional role of CCDC6 in MPM carcinogenesis and response to PARP-inhibitors. MATERIALS AND METHODS: The interaction between CCDC6 and BAP1 was confirmed in MPM cells, by co-immunoprecipitation. Upon USP7 inhibition, that induces CCDC6 degradation, the ability to repair the DSBs and the sensitivity to PARP inhibitors, was explored by HR reporter and by cells viability assays, respectively. A TMA including 34 MPM cores was immunostained for CCDC6, USP7 and BAP1 and the results correlated by statistical analysis. RESULTS: MPM cells depleted of CCDC6 showed defects in DSBs repair and sensitivity to PARP inhibitors. The silencing of CCDC6 when combined with the overexpression of BAP1-mutant (Δ221-238) enhanced the HR-DNA repair defects and the PARP inhibitors sensitivity. In the TMA of MPM primary samples, the staining of CCDC6 and of its de-ubiquitinase USP7 showed a significant correlation in the tested primary samples (p = 0.01). CCDC6 was barely detected in 30% of the tumors that also carried BAP1 defects. CONCLUSION: The combination of CCDC6 and BAP1 staining may indicate therapeutic options for DDR targeting, acting in synergism with cisplatinum.

Type of hip fracture in patients with Parkinson disease is associated with femoral bone mineral density.

OBJECTIVE: To investigate the association between bone mineral density (BMD) and hip fracture type (cervical or trochanteric) in a sample of fallers with Parkinson disease (PD). DESIGN: Observational study. SETTING: Rehabilitation hospital in Italy. PATIENTS: We investigated 1040 of 1120 white fallers consecutively admitted to a rehabilitation hospital for hip fracture. Thirty-eight (3.65%) of the 1040 patients suffered from PD secondarily. Thirty-eight controls matched for sex, age, and hip fracture type were found among the 1002 non-PD fallers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: BMD was assessed by dual-energy x-ray absorptiometry at a mean+/-SD of 21.9+/-7.5 days after fracture occurrence in the 38 PD patients and 21.6+/-5.9 days after fracture occurrence in the 38 controls. RESULTS: BMD assessed at total femur, trochanter, and intertrochanteric region was significantly lower in the 15 PD patients with trochanteric fractures than in the 23 with cervical fractures; the mean T score differences were 0.57 (95% confidence interval [CI], 0.07-1.08; P=.028), 0.66 (95% CI, 0.04-1.28; P=.037), and 0.63 (95% CI, 0.11-1.15; P=.019), respectively. A significant association between femoral BMD and hip fracture type was found at logistic regression after adjustment for several confounders. Results in the 38 controls were similar to those obtained in the 38 PD fallers. CONCLUSIONS: In a sample of PD fallers as in a control group of non-PD fallers, BMD levels assessed at 3 femoral sites were significantly lower in the patients who sustained trochanteric fractures than in those with cervical fractures of the hip.