GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

A Comparative Study of the Spatial Distribution of Schistosomiasis in Mali in 1984–1989 and 2004–2006

Geostatistical maps are increasingly being used to plan neglected tropical disease control programmes. We investigated the spatial distribution of schistosomiasis in Mali prior to implementation of national donor-funded mass chemotherapy programmes using data from 1984–1989 and 2004–2006. The 2004–2006 dataset was collected after 10 years of schistosomiasis control followed by 12 years of no control. We found that national prevalence of Schistosoma haematobium and S. mansoni was not significantly different in 2004–2006 compared to 1984–1989 and that the spatial distribution of both infections was similar in both time periods, to the extent that models built on data from one time period could accurately predict the spatial distribution of prevalence of infection in the other time period. This has two main implications: that historic data can be used, in the first instance, to plan contemporary control programmes due to the stability of the spatial distribution of schistosomiasis; and that a decade of donor-funded mass distribution of praziquantel has had no discernable impact on the burden of schistosomiasis in subsequent generations of Malians, probably due to rapid reinfection

The effectiveness of a coordinated preventive care approach for healthy ageing (UHCE) among older persons in five European cities: A pre-post controlled trial

Background: Older persons often have multiple health and social problems and need a variety of health services. A coordinated preventive approach that integrates the provision of health and social care services could promote healthy ageing. Such an approach can be organised differently, depending on the availability and organizational structures in the local context. Therefore, it is important to evaluate the effectiveness of a coordinated preventive care approach in various European settings. Objectives: This study explored the effects of a coordinated preventive health and social care approach on the lifestyle, health and quality of life of community-dwelling older persons in five European cities. Design: International multi-center pre-post controlled trial. Setting: Community settings in cities in the United Kingdom, Greece, Croatia, the Netherlands and Spain. Participants: 1844 community-dwelling older persons (mean age = 79.5; SD = 5.6). Methods: The Urban Health Centres Europe (UHCE) approach consisted of a preventive multidimensional health assessment and, if a person was at-risk, coordinated care-pathways targeted at fall risk, appropriate medication use, loneliness and frailty. Intervention and control sites were chosen based on their location in distinct neighbourhoods in the participating cities. Persons in the catchment area of the intervention sites ‘the intervention group’ received the UHCE a

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal\u2013epithelial transition factor (MET) amplification, epithelial\u2013mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor regulation. Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises the importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes in NSCLC

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Pulsed electric fields as a green technology for the extraction of bioactive compounds from thinned peach by-products

32 Pags.- 4 Tabls.- 6 Fgs. The definitive version is available at: https://www.sciencedirect.com/science/journal/14668564Thinned fruits are agricultural by-products which nowadays have few economic or environmental benefits. However, previous studies have revealed that these immature fruits have a large amount of antioxidant compounds. The aim of this study was to evaluate whether pulsed electric fields (PEF) might be a suitable green technology for enhancing the extraction of phenols, flavonoids and antioxidant compounds from fresh thinned peaches, thus reducing the use of methanol. Moreover, response surface methodology has been used to determine the optimal PEF treatment conditions, observing that the solvent is the main factor. The highest amounts of bioactive compounds were extracted using 80% methanol and no PEF. Methanol combined with PEF produced a negative effect on the extraction yield. However, the use of water as a solvent increased the amount of total bioactive compounds and individual phenols (chlorogenic acid, coumaric acid and neochlorogenic acid). Thus, PEF-assisted extraction of bioactive compounds from thinned peach fruits using water as a solvent is an alternative to conventional extraction methods which require dried products, large amounts of organic solvents and long extraction times.This work was supported by the Department of Industry and Innovation of the Aragón Government and the European Social Fund (Project 229402/1 – Plant Food Research Group (T41)).Peer reviewe

Identification of an interstitial 18p11.32-p11.31 duplication including the EMILIN2 gene in a family with porokeratosis of Mibelli.

Porokeratosis is a rare disease of epidermal keratinization characterized by the histopathological feature of the cornoid lamella, a column of tightly fitted parakeratocytic cells, whose etiology is still unclear. Porokeratosis of Mibelli is a subtype of porokeratosis presenting a single plaque or a small number of plaques of variable size located unilaterally on limbs. It frequently appears in childhood and occurs with a higher incidence in males. Cytogenetic analyses were performed in all members of the family on lesioned and uninvolved skin. An array-CGH analysis was also performed utilizing the Human Genome CGH Microarray Kit G3 400 with 5.3 KB overall median probe spacing. Gene expression was performed on skin fibroblasts. In this study, we describe a Caucasian healthy 4-year-old child and his father showing features of porokeratosis of Mibelli. Array-CGH analysis revealed an interstitial 429.5 Kb duplication of chromosome 18p11.32-p11.3 containing four genes, namely: SMCHD1, EMILIN2, LPIN2, and MYOM1 both in patient and his father. EMILIN2 resulted overexpressed on skin fibroblasts. Also other members of this family, without evident signs of porokeratosis, carried the same duplication. Among these genes, we focused our attention on elastin microfibril interfacer 2 (EMILIN2) gene. Apoptosis plays a fundamental role in maintaining epidermal homeostasis, balancing keratinocytes proliferation, and forming the stratum corneum. EMILIN2 is known to trigger the apoptosis of different cell lines negatively affecting cell survival. It is expressed in the skin. We could speculate that the duplication and overexpression of EMILIN2 cause an abnormal apoptosis of epidermal keratinocytes and alter the process of keratinization, even if other epigenetic and genetic factors could also be involved. Our results could contribute to a better understanding of the pathogenesis of porokeratosis of Mibelli

Preparation and local anesthetic activity of benzotriazinone and benzoyltriazole derivatives.

Two sets of benzotriazinone and benzoyltriazole derivs. were prepd. and tested for local anesthetic activity in comparison with lidocaine. Several of the prepd. compds. exhibited a fairly good activity comparable or superior to that of lidocaine. The presence of a benzotriazinone or a benzoyltriazole moiety as an arom. system was quite profitable for both the intensity and duration of activity. The acute toxicity in mice of the four most potent compds. of the series was also assessed. Compd. I, which has an anesthetic activity comparable to that of lidocaine, was also characterized by a more favorable therapeutic index. All compds. were tested in vitro to evaluate their neg. chronotropic action in isolated rat right atria

Clinical images.

<p>A) Clinical image revealing a whitish-red plaque on the lower right leg of the 4-year-old proband. The affected area is made up of numerous whitish-red round papules that coalesce into irregular plaque and single papules, the area perimeter defined by a whitish border and cleaved by a central furrow. Slightly raised whitish-red portions can also be observed. B) Enlarged detail of the lesion. C) The patient's skin biopsy shows slight papillomatosis and ortokeratosis of epidermis and a cornoid lamella; the derma appears normal (H&E, 10×). D) A column of parakeratotic cells makes up the cornoid lamella (H&E, 200×). E) The examination of the skin biopsy of the father shows atrophic epidermis with two cornoid lamellae; solar elastosis and sparse perivascular lymphocytic infiltrate can be recognized (H&E, 10×). F) The cornoid lamella is very thin (H&E, 200×).</p