Hydroxytyrosol Prevents Increase of Osteoarthritis Markers in Human Chondrocytes Treated with Hydrogen Peroxide or Growth-Related Oncogene \u3b1

Hydroxytyrosol (HT), a phenolic compound mainly derived from olives, has been proposed as a nutraceutical useful in prevention or treatment of degenerative diseases. In the present study we have evaluated the ability of HT to counteract the appearance of osteoarthritis (OA) features in human chondrocytes. Pre-treatment of monolayer cultures of chondrocytes with HT was effective in preventing accumulation of reactive oxidant species (ROS), DNA damage and cell death induced by H2O2 exposure, as well as the increase in the mRNA level of pro-inflammatory, matrix-degrading and hypertrophy marker genes, such as iNOS, COX-2, MMP-13, RUNX-2 and VEGF. HT alone slightly enhanced ROS production, but did not enhance cell damage and death or the expression of OA-related genes. Moreover HT was tested in an in vitro model of OA, i.e. three-dimensional micromass cultures of chondrocytes stimulated with growth-related oncogene \u3b1 (GRO\u3b1), a chemokine involved in OA pathogenesis and known to promote hypertrophy and terminal differentiation of chondrocytes. In micromass constructs, HT pre-treatment inhibited the increases in caspase activity and the level of the messengers for iNOS, COX-2, MMP-13, RUNX-2 and VEGF elicited by GRO\u3b1. In addition, HT significantly increased the level of SIRT-1 mRNA in the presence of GRO\u3b1. In conclusion, the present study shows that HT reduces oxidative stress and damage, exerts pro-survival and anti-apoptotic actions and favourably influences the expression of critical OA-related genes in human chondrocytes treated with stressors promoting OA-like features

Antiapoptotic and Antiautophagic Effects of Eicosapentaenoic Acid in Cardiac Myoblasts Exposed to Palmitic Acid

Apoptosis is a programmed cell death that plays a critical role in cell homeostasis. In particular, apoptosis in cardiomyocytes is involved in several cardiovascular diseases including heart failure. Recently autophagy has emerged as an important modulator of programmed cell death pathway. Recent evidence indicates that saturated fatty acids induce cell death through apoptosis and this effect is specific for palmitate. On the other hand, n-3 polyunsaturated fatty acids (PUFAs) have been implicated in the protection against cardiovascular diseases, cardiac ischemic damage and myocardial dysfunction. In the present study we show that n-3 PUFA eicosapentaenoic acid (EPA) treatment to culture medium of H9c2 rat cardiomyoblasts protects cells against palmitate-induced apoptosis, as well as counteracts palmitate-mediated increase of autophagy. Further investigation is required to establish whether the antiautophagic effect of EPA may be involved in its cytoprotective outcome and to explore the underlying biochemical mechanisms through which palmitate and EPA control the fate of cardiac cells

Molecular Characterization of Cancer Associated Fibroblasts in Prostate Cancer

Background: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor–stroma interactions may yield novel therapeutic targets for prostate cancer. Methods: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity®: IPA® software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF). Results: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-β as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs. Conclusions: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells

Molecular Characterization of Cancer Associated Fibroblasts in Prostate Cancer

Background: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor-stroma interactions may yield novel therapeutic targets for prostate cancer. Methods: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity (R) : IPA (R) software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF). Results: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-beta as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs. Conclusions: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells

Quality of residential facilities in Italy: satisfaction and quality of life of residents with schizophrenia spectrum~disorders

Background Recovery and human rights promotion for people with Schizophrenia Spectrum Disorders (SSDs) is fundamental to provide good care in Residential Facilities (RFs). However, there is a concern about rehabilitation ethos in RFs. This study aimed to investigate the care quality of Italian RFs, the quality of life (QoL) and care experience of residents with SSD. Methods Fourty-eight RFs were assessed using a quality assessment tool (QuIRC-SA) and 161 residents with SSD were enrolled. Seventeen RFs provided high intensity rehabilitation (SRP1), 15 medium intensity (SRP2), and 16 medium-low level support (SRP3). Staff-rated tools measured psychiatric symptoms and psychosocial functioning; user-rated tools assessed QoL and satisfaction with services. RFs comparisons were made using ANOVA and Chi-squared. Results Over two-thirds patients (41.5 y.o., SD 9.7) were male. Seventy-six were recruited from SRP1 services, 48 from SRP2, and 27 from SRP3. The lowest QuIRC-SA scoring was Recovery Based Practice (45.8%), and the highest was promotion of Human Rights (58.4%). SRP2 had the lowest QuIRC-SA ratings and SRP3 the highest. Residents had similar psychopathology (p = 0.140) and functioning (p = 0.537). SRP3 residents were more employed (18.9%) than SRP1 (7.9%) or SRP2 (2.2%) ones, and had less severe negative symptoms (p = 0.016) and better QoL (p = 0.020) than SRP2 residents. There were no differences in the RF therapeutic milieu and their satisfaction with care. Conclusions Residents of the lowest supported RFs in Italy had less severe negative symptoms, better QoL and more employment than others. The lowest ratings for Recovery Based Practice across all RFs suggest more work is needed to improve recovery

TRANSUDATIVE PLEURAL EFFUSION DUE TO PLEUROPERITONEAL COMMUNICATION IN PERITONEAL DIALYSIS PATIENTS WITH POLYCISTIC KIDNEY DISEASE

BACKGROUND. Transudative pleural effusion due to pleuroperitoneal communication (PPC) is an uncommon complication of peritoneal dialysis (PD). PPC prevalence ranges from 1.6 to 10% in PD patients. PPC is more frequent on the right side and in females. PD is often not proposed to patients with polycistic kidney disease (PKD-pts) due to either possible complications for increased intra-abdominal pressure or infectious risk due to diverticula. This study tries to analyse the outcome of PD in PKD-pts. METHODS. between July 1979 and May 2017, 1026 patients started PD in our centre: 46 (4.5%) patients had PKD and 980 (95.8%) other nephropathy. RESULTS. Not significant difference was found between PKD-pts and and non-PKD patients (nPKD-pts) for age at PD initiation. Fifteen (1.5%) cases of PPC occurred overall (Female/Male:12/3): 6/45 (13.3%) in PKD-pts and 9/980 (0.9%) in nPKD-pts. In eight patients, the diagnosis of PPC occurred within two months of start of PD, in four patients between three and seven months of PD and in three patients between two and five years before PPC diagnosis (p = NS). In 13 patients, the interval between the placement of the catheter and start of the PD (break-in time) was less than 45 days; in a patient it was about three months and in another of about three years (Median 22 days, QI-QIII: 13-30). Break-in in PKD and nPKD-pts was not significant for the appearance of PPC. Final outcome in 46 PKD-pts: 21 patients had died, 19 received a kidney transplant and 6 shifted to HD. CONCLUSIONS. In our experience, PKD does not appear to be a contraindication for PD. PPC is more frequent in this population, but its prevalence does not preclude PD as a valid replacement therapy

En studie om sagoarbete i grundskolan

Syftet med studien och våra frågeställningar var att få fördjupade kunskaper om sagans möjlighet att öka förutsättningar till elevernas lärande och utveckling. Vi ville också se om det är relevant att öka sagoarbetet i undervisningen. Tidigare forskning användes i studien för att fördjupa förståelsen om sagoarbete i läroprocessen. Piagets och Vygotskijs teorier har använts för att belysa hur intresse och motivation kan vara en hjälp för lärandet. För att samla in empiri har vi använt oss av intervjuer med elever som kan visa oss deras förhållningssätt till sagor. Vi intervjuade även lärare för att få deras uppfattning av sagoarbete i skolan samt för att se om de tycker att sagoarbete kan främja elevers lärande. Vår förhoppning är att kunna svara på om det är betydelsefullt att öka sagornas inflytande i dagens undervisning i grundskola. Examensarbetet innehåller en historisk bakgrund som är utformad som en tidslinje, för att tydliggöra sagans möjligheter för lärande. Många sagor som vi känner till idag blev skapade för många år sedan, men de har fortfarande inte förlorat sin aktualitet. Vi tittade närmare på fyra välkända sagor. Tidslinjen börjar med sagan om Rödluvan och vargen av Bröderna Grimm som var nämnd av elever och pedagoger i studiens intervjuer. Därefter fortsätter vi med Den fula ankungen av Hans Christian Andersen. Vi tar också upp Nils Holgerssons underbara resa genom Sverige av Selma Lagerlöf och till sist berättelsen om Pippi Långstrump av Astrid Lindgren. Resultatet av studien visar att sagoarbetet som utgångspunkt för att öka intresse och motivation kan vara till hjälp för att uppnå kvalitativt lärande genom en givande undervisning som är grundad på elevernas förutsättningar. Resultatet visar också att ett ökat sagoarbete kan leda till en positiv uppmärksamhet i vardagsundervisningen för eleverna. Slutsatsen blir att sagoarbete kan vara en rik källa till inspiration och till ett lustfyllt lärande för eleverna. Lärarna såg gärna en ökning av sagornas användning i sina lektioner. Vi har också uppmärksammat att både elever och lärarna är väl bevandrade i sagornas värld

PRIMA E DOPO IL TRAPIANTO DI RENE: EMODIALISI VS. DIALISI PERITONEALE.

INTRODUZIONE. Nonostante si cerchi di avviare i pazienti CKD5 direttamente al trapianto di rene (tx), evitando la dialisi, il temporaneo transito in essa è spesso indispensabile. La dialisi deve essere quindi gestita al meglio, per ottimizzare le condizioni del paziente al momento del tx. Una meta-analisi pubblicata nel 2016 suggeriva che la scelta della dialisi peritoneale nel pre-tx era associata ad una migliore sopravvivenza a 5 anni dal trapianto ed una minore incidenza di delayed graft function (DGF). [1] SCOPO DELLO STUDIO. Valutare se la metodica dialitica influenza l’immissione in lista, le condizioni al tx e i suoi esiti a un anno. PAZIENTI E METODI. Sono stati selezionati i pazienti del nostro Centro sottoposti a primo tx di rene dal 01.01.2008 al 1.1.2017 e con almeno un anno di osservazione post tx. RISULTATI. Sono stati inclusi 131 pazienti, 69 dall’emodialisi (HD) e 67 dalla dialisi peritoneale (DP). I pazienti in DP entravano in lista attiva prima di quelli in HD: mediana di 9 mesi (IQ-IIIQ: 5-14) dall’inizio della dialisi vs. 14 (IQ-IIIQ: 8-24; p=0.01). L’attesa in lista tx era minore nel gruppo DP con una mediana di 23 mesi (IQ-IIIQ: 11.5-37) rispetto ai 35 (IQ-IIIQ: 15-51) del gruppo HD (p=0.007). Considerata la più precoce immissione in lista e il minor tempo al trapianto in DP, l’età dialitica al trapianto era significativamente inferiore in DP (4.5 IQ-IIIQ: 3.1-6 anni vs 2.6 IQ-IIIQ: 1.7-4 anni p<0.0001). Al momento del tx le due popolazioni non differivano per prevalenza di comorbidità (ipertensione arteriosa, diabete mellito, cardiopatia ischemica, vascolopatia periferica e cerebrale, neoplasia) ad eccezione di malattia sistemica, più frequente in HD (30.4% vs 14.5%; p=0.03). Al momento del tx, i valori di emoglobina (Hb) erano maggiori in HD (Hb media 11.4±0.7 g/dL in HD e 11.1±0.9 g/dL in DP; p=0.03), così come i valori di albuminemia (media 4.1±0.3 g/dL in HD e 3.7±0.4 g/dL in DP; p< 0.001). Parimenti il Body Mass Index era superiore in HD (media di 24.6 ± 4.6 in HD vs 23.1 ± 3.5 in DP p=0.04). La diuresi residua era maggiore in DP (mediana 1200ml/die, IQ-IIIQ: 700-1800 vs 200 ml/die, IQ-IIIQ: 0-1000; p < 0.001). Tutti gli indicatori durante il primo anno post tx risultavano simili, ad eccezione dell’anuria post tx che era maggiore in HD (16.7% vs 5.1%; p=0.49). L’incidenza di rigetto, l’ospedalizzazione e le complicanze infettive e cardiovascolari erano simili. La funzione renale a 3 mesi e ad 1 anno era simile nei due gruppi, in particolare a 3 mesi la creatinina sierica media era 1.5 ± 0.6 mg/dl in HD e 1.5 ± 0.5 mg/dl in DP e ad 1 anno 1.6 ± 1.0 mg/dl in HD e 1.5 ± 0.5 mg/dl in DP. Non si è verificato nessun caso di peritonite sclerosante incapsulante post Tx. A fine osservazione, la sopravvivenza del graft e la sopravvivenza della popolazione era pari al 100%. CONCLUSIONI Nella nostra casistica non si sono evidenziate differenze negli indicatori e negli esiti nel primo anno post-tx tra pazienti HD e DP. Tuttavia, la più rapida immissione in lista e i minori tempi di attesa consentono al paziente in DP di trascorrere meno tempo in dialisi

PERITONITE IN DP: CONFRONTO TRA METODICHE

INTRODUZIONE. La peritonite è una complicanza temuta in dialisi peritoneale (DP). Il rischio di peritonite potrebbe variare tra APD, CAPD e incrementale manuale (IM) in rapporto alle caratteristiche della metodica e al numero/momento delle connessioni. SCOPO. Esistono differenze nel decorso ed esito della peritonite tra pazienti APD, CAPD e IM? PAZIENTI E METODI. Pazienti trattati con DP nel nostro centro dal 01/01/09 al 31/12/17, suddivisi in funzione della metodica in uso. Analisi degli episodi di peritonite. RISULTATI. Selezionati 389 pazienti (215 APD, 61 CAPD, 113 IM), 99 dei quali con almeno un episodio di peritonite (30% APD, 23% CAPD, 18% IM; p=0,041). L’incidenza era di 0,27 episodi/paziente-anno per APD, 0,30 per CAPD, 0,16 per IM. L’analisi multivariata secondo Cox non rilevava differenze significative nella sopravvivenza dalla peritonite tra i tre gruppi, sia al primo episodio (p=0,518) che con rientro dei pazienti (p=0,129). Tuttavia dal confronto tra metodiche a dose piena vs IM emergeva una differenza significativa (p=0,014).Per gli esiti, la percentuale di pazienti guariti era 78% APD, 63% CAPD, 77% IM (p=0,374) e non vi erano differenze nella sopravvivenza della metodica (p=0,060) né del paziente (p=0,734).Per la comparsa di peritoniti successive alla prima, non vi erano differenze significative tra i tre gruppi (APD 31%; CAPD 29%; IM 10%; p=0,178).Non vi erano differenze significative nel tasso di exite-site infection (ESI) concomitanti (p=0,504) né tra gli esiti delle colture: Gram+ 40%, 42%, 41%, p=0,976; Gram- 24%, 16%, 18%, p=0,660; colture miste 6%, 21%, 5%, p=0,077; non crescita 27%, 11%, 36%, p=0,164. CONCLUSIONI. IM è associata a minor rischio di peritonite rispetto alle metodiche DP a dose piena, tuttavia il decorso di tali eventi è sovrapponibile