Evaluation of the burden of HPV-related hospitalizations as a useful tool to increase awareness: 2007–2017 data from the sicilian hospital discharge records

In light of the implementation of human papillomavirus (HPV) prevention strategies, epidemiological studies in different geographical areas are required in order to assess the impact of HPV-related diseases. The purpose of the present study was to describe the burden of HPV-related hospitalizations in Sicily. A retrospective observational study estimated 43,531 hospitalizations attributable to HPV from 2007 to 2017. During the observed period, there was a decrease for all HPV-related conditions with a higher reduction, among neoplasms, for cervical cancer (annual percent change (APC) = −9.9%, p < 0.001). The median age for cervical cancer was 45 years old, with an increasing value from 43 to 47 years (p < 0.001). The age classes with greater decreases in hospital admissions for invasive cancers were women aged 35 years or more (APC range from −5.5 to −9.86) and 25–34 years old (APC = −11.87, p < 0.001) for women with cervical carcinoma in situ. After ten years for vaccine introduction and sixteen years for cervical cancer screening availability, a relatively large decrease in hospital admissions for cervical cancer and other HPV-related diseases in Sicily was observed. Some clinical characteristics of hospitalization, such as increasing age, are suggestive clues for the impact of preventive strategies, but further research is needed to confirm this relationship

Comparison Study of MS-HRM and Pyrosequencing Techniques for Quantification of APC and CDKN2A Gene Methylation

There is increasing interest in the development of cost-effective techniques for the quantification of DNA methylation biomarkers. We analyzed 90 samples of surgically resected colorectal cancer tissues for APC and CDKN2A promoter methylation using methylation sensitive-high resolution melting (MS-HRM) and pyrosequencing. MS-HRM is a less expensive technique compared with pyrosequencing but is usually more limited because it gives a range of methylation estimates rather than a single value. Here, we developed a method for deriving single estimates, rather than a range, of methylation using MS-HRM and compared the values obtained in this way with those obtained using the gold standard quantitative method of pyrosequencing. We derived an interpolation curve using standards of known methylated/ unmethylated ratio (0%, 12.5%, 25%, 50%, 75%, and 100% of methylation) to obtain the best estimate of the extent of methylation for each of our samples. We observed similar profiles of methylation and a high correlation coefficient between the two techniques. Overall, our new approach allows MS-HRM to be used as a quantitative assay which provides results which are comparable with those obtained by pyrosequencing

Maternal Genome-Wide DNA Methylation Patterns and Congenital Heart Defects

The majority of congenital heart defects (CHDs) are thought to result from the interaction between multiple genetic, epigenetic, environmental, and lifestyle factors. Epigenetic mechanisms are attractive targets in the study of complex diseases because they may be altered by environmental factors and dietary interventions. We conducted a population based, case-control study of genome-wide maternal DNA methylation to determine if alterations in gene-specific methylation were associated with CHDs. Using the Illumina Infinium Human Methylation27 BeadChip, we assessed maternal gene-specific methylation in over 27,000 CpG sites from DNA isolated from peripheral blood lymphocytes. Our study sample included 180 mothers with non-syndromic CHD-affected pregnancies (cases) and 187 mothers with unaffected pregnancies (controls). Using a multi-factorial statistical model, we observed differential methylation between cases and controls at multiple CpG sites, although no CpG site reached the most stringent level of genome-wide statistical significance. The majority of differentially methylated CpG sites were hypermethylated in cases and located within CpG islands. Gene Set Enrichment Analysis (GSEA) revealed that the genes of interest were enriched in multiple biological processes involved in fetal development. Associations with canonical pathways previously shown to be involved in fetal organogenesis were also observed. We present preliminary evidence that alterations in maternal DNA methylation may be associated with CHDs. Our results suggest that further studies involving maternal epigenetic patterns and CHDs are warranted. Multiple candidate processes and pathways for future study have been identified

The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy

Basal-like tumours account for 15% of invasive breast carcinomas and are associated with a poorer prognosis and resistance to therapy. We hypothesised that this aggressive phenotype is because of an intrinsically elevated hypoxic response. Microarrayed tumours from 188 patients were stained for hypoxia-inducible factor (HIF)-1α, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast tumours. Tumour subtypes were correlated with standard clincopathological parameters as well as hypoxic markers. Out of 456 tumours 62 (14%) tumours were basal-like. These tumours were positively correlated with high tumour grade (P<0.001) and were associated with a significantly worse disease-free survival compared with luminal tumours (P<0.001). Fifty percent of basal-like tumours expressed HIF-1α, and more than half expressed at least one of the PHD enzymes and FIH-1. Basal-like tumours were nine times more likely to be associated with CAIX expression (P<0.001) in a multivariate analysis. Carbonic anhydrase IX expression was positively correlated with tumour size (P=0.005), tumour grade (P<0.001) and oestrogen receptor (ER) negativity (P<0.001). Patients with any CAIX-positive breast tumour phenotype and in the basal tumour group had a significantly worse prognosis than CAIX-negative tumours when treated with chemotherapy (P<0.001 and P=0.03, respectively). The association between basal phenotype and CAIX suggests that the more aggressive behaviour of these tumours is partly due to an enhanced hypoxic response. Further, the association with chemoresistance in CAIX-positive breast tumours and basal-like tumours in particular raises the possibility that targeted therapy against HIF pathway or downstream genes such as CAs may be an approach to investigate for these patients

Interventi psicosociali nel disturbo bipolare: una revisione critica della letteratura recente

Introduzione: Il disturbo bipolare (DB) e\u300 una patologia cronica che puo\u300 alterare significativa- mente il funzionamento e la qualita\u300 di vita di chi ne e\u300 affetto e di coloro che se ne prendono cura. Poiche\u301 la terapia farmacologica con stabilizzatori del tono dell\u2019umore, trattamento di prima scelta per questo disturbo, non e\u300 sempre sufficiente a garantire il raggiungimento di un completo recupero sintomatico e funzionale, negli ultimi anni sono stati proposti e validati interventi psicosociali di varia natura da associare a tale intervento terapeutico. Materiali e metodi: Il presente articolo effettua una revisione sistematica degli studi, pubblicati tra il 1984 e il 2010, relativi a modelli di intervento psicosociale che si sono dimostrati efficaci in associazione alla terapia farmacologica nel trattamento del DB. Risultati: Gli interventi psicosociali specifici per il trattamento del DB hanno mostrato una documentata efficacia nel ridurre, a lungo termine, il numero delle ricorrenze. L\u2019effetto specifico sulle ricorrenze maniacali o depressive varia a seconda del tipo di intervento: gli interventi psicoeducazionali individuali sono efficaci nel ridurre il numero di ricorrenze maniacali e non depressive; gli interventi focalizzati sulla famiglia e la terapia cognitivo-comportamentale sembrano maggiormente efficaci nel ridurre la sintomatologia depressiva; gli interventi psicoeducazionali di gruppo, infine, sembrano efficaci nel ridurre le ricorrenze di entrambe le polarita\u300

Systematic review and meta-analysis of cardiovascular risk in rheumatological disease: Symptomatic and non-symptomatic events in rheumatoid arthritis and systemic lupus erythematosus

Although each autoimmune disease is associated with specific tissue or organ damage, rheumatic diseases share a pro-inflammatory pattern that might increase cardiovascular risk. Retrospective and prospective studies on patients affected by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) highlighted the concept of “accelerated atherosclerosis”. Therefore, the purpose of this systematic review and meta-analysis is the assessment of symptomatic or asymptomatic cardiovascular events among patients with rheumatic diseases as RA and SLE. The literature research obtained all manuscripts published in the English language between 2015 and 2019 for a total of 2355 manuscripts. After selection through inclusion and exclusion criteria, four articles examined cardiovascular risk in RA patients, 8 in SLE patients, and 2 in RA and SLE patients. Patients with SLE had a RR of 1.98 (95% CI: 1.18–3.31) of symptomatic cardiovascular events compared to the unexposed cohort. The meta-regression analysis showed that younger patient (age per year increase β = −0.12 95%CI: −0.20, −0.4), belonging to studies conducted in continent different from America (β = −0.89; −95% CI: 1.67, −0.10), after 2000 (β = 0.87; 95% CI: 0.09, 1.65) and with a higher quality score 0.80 (95% CI: 0.31, 1.29) had a higher risk of cardiovascular events. In patients with RA, the RR of cardiovascular events was 1.55 (95% CI: 1.18–2.02). These data are helpful to implement cardiovascular preventive strategies among people suffering from rheumatologic diseases to decrease the incidence of cardiovascular events. However, these implementation needs to build a higher network between rheumatologists and primary care healthcare workers to furnish the same information to patients and monitor their preventive practice compliance