Immunohistochemical/histochemical double staining method in the study of columnar metaplasia of the oesophagus

Intestinal metaplasia in Barrett\u2019s oesopha- gus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotyp- ic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metapla- sia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneously assess the his- tochemical features in cells that shows an aber- rant expression of such antigens. We evidenced a cytoplasmic expression of CK7 and a nuclear expression of Aurora A and p53, both in goblet cells of BO and in non-goblet cells of CLO, some of which showing mild dysplasia. These find- ings suggest that some immunophenotypic changes are present in CLO and they can pre- cede the appearance of the goblet cells or can be present independently of them, confirming the conception of BO as the condition charac- terized by any extention of columnar epitheli- um. This is the first study in which a combined immunohistochemical/histochemical method has been applied to Barrett pathology

Progressive modular rebalancing system and visual cueing for gait rehabilitation in parkinson’s disease. A pilot, randomized, controlled trial with crossover

Introduction: The progressive modular rebalancing (PMR) system is a comprehensive rehabilitation approach derived from proprioceptive neuromuscular facilitation principles. PMR training encourages focus on trunk and proximal muscle function through direct perception, strength, and stretching exercises and emphasizes bi-articular muscle function in the improvement of gait performance. Sensory cueing, such as visual cues (VC), is one of the more established techniques for gait rehabilitation in PD. In this study, we propose PMR combined with VC for improving gait performance, balance, and trunk control during gait in patients with PD. Our assumption herein was that the effect of VC may add to improved motor performance induced by the PMR treatment. The primary aim of this study was to evaluate whether the PMR system plus VC was a more effective treatment option than standard physiotherapy in improving gait function in patients with PD. The secondary aim of the study was to evaluate the effect of this treatment on motor function severity. Design: Two-center, randomized, controlled, observer-blind, crossover study with a 4-month washout period. Participants: Forty individuals with idiopathic PD in Hoehn and Yahr stages 1–4. Intervention: Eight-week rehabilitation programs consisting of PMR plus VC (treatment A) and conventional physiotherapy (treatment B). Primary outcome measures: Spatiotemporal gait parameters, joint kinematics, and trunk kinematics. Secondary outcome measures: UPDRS-III scale scores. Results: The rehabilitation program was well-tolerated by individuals with PD and most participants showed improvements in gait variables and UPDRS-III scores with both treatments. However, patients who received PMR with VC showed better results in gait function with regard to gait performance (increased step length, gait speed, and joint kinematics), gait balance (increased step width and double support duration), and trunk control (increased trunk motion) than those receiving conventional physiotherapy. While crossover results revealed some differences in primary outcomes, only 37.5% of patients crossed over between the groups. As a result, our findings should be interpreted cautiously. Conclusions: The PMR plus VC program could be used to improve gait function and severity motor of motor deficit in individuals with PD

Nintedanib in NSCLC: Evidence to date and place in therapy

The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both preclinical and clinical phase I and II trials; however, its approval for the use in clinical practice has been possible because of the positive results of the LUME-Lung 1 trial (nintedanib + docetaxel versus docetaxel alone) in terms of progression-free survival and overall survival, and a manageable tolerability profile. Therefore, the good results seen in the clinical trials with nintedanib in the second-line setting for NSCLC patients with adenocarcinoma subtype are encouraging enough to recommend it in clinical practice

Variability of Fragments of Nuclear Brca1 Gene, Exon 11, and Mitochondrial Cox1 Gene in House Mice Mus musculus

To clarify genetic differences between subspecies of the house mouse Mus musculus, their distribution, and hybridization, we first conducted a comparative analysis of variability of nucleotide sequences of fragments of the nuclear gene Brca1, exon 11 (2331 bp), and mitochondrial gene Cox1 (1260 bp) in 40 house mice from West and East Europe, Transcaucasia, Siberia, and Central and South Asia. Brca1 genotypes were divided into five main groups, which differed in a number of fixed substitutions. Genotypes of each group are characteristic for the certain geographical region and the following subspecies: M. m. musculus, M. m. domesticus, M. m. castaneus, and M. m. wagneri together with M. m. gansuensis; a fifth group corresponds to an unidentified subspecies or a distinct genetic form of M. musculus from India (Sikkim State). Besides the homozygous specimens, we revealed mice, which were heterozygous for all diagnostic loci simultaneously; these specimens were determined as hybrid. Hybrid mice were mainly found in the zones of contact of subspecies, but in some cases, quite far from one of the parent subspecies (possibly, due to transportation). In two hybrid mice (from Bakhtiari Province of Iran and Transbaikalia of Russia), unique Brca1 haplotypes were detected. It cannot be ruled out that, at least partly, they may be characteristic of the M. m. bactrianus and M. m. gansuensis subspecies, respectively. Thus, the results of the study showed that the nuclear Brca1 gene is a promising molecular genetic marker for the analysis of variability, differentiation, and hybridization of house mice as well for subspecific identification of M. musculus specimens. Despite more rapid evolution of the Cox1 gene, it is not well suited for discrimination of M.m. musculus, M. m. wagneri, M. m. gansuensis specimens and Transcaucasian representatives of M.m. domesticus due to introgression and long-term maintenance of foreign mitochondrial DNA in populations. However, Cox1 gene analysis (along with the diagnostics of animals by nuclear DNA) may be useful for estimation of population differences in M. m. castaneus and M.m. domesticus subspecies

Has VZV epidemiology changed in Italy? Results of a seroprevalence study

The aim of the study was to evaluate if and how varicella prevalence has changed in Italy. In particular a seroprevalence study was performed, comparing it to similar surveys conducted in pre-immunization era. During 2013–2014, sera obtained from blood samples taken for diagnostic purposes or routine investigations were collected in collaboration with at least one laboratory/center for each region, following the approval of the Ethics Committee. Data were stratified by sex and age. All samples were processed in a national reference laboratory by an immunoassay with high sensitivity and specificity. Statutory notifications, national hospital discharge database and mortality data related to VZV infection were analyzed as well. A total of 3707 sera were collected and tested. In the studied period both incidence and hospitalization rates decreased and about 5 deaths per year have been registered. The seroprevalence decreased in the first year of life in subjects passively protected by their mother, followed by an increase in the following age classes. The overall antibody prevalence was 84%. The comparison with surveys conducted with the same methodology in 1996–1997 and 2003–2004 showed significant differences in age groups 1–19 y. The study confirms that in Italy VZV infection typically occurs in children. The impact of varicella on Italian population is changing. The comparison between studies performed in different periods shows a significant increase of seropositivity in age class 1–4 years, expression of vaccine interventions already adopted in some regions

[OP.5C.05] SERUM URIC ACID IS INCREASED IN NORMOTENSIVE OBESE CHILDREN WITH A PARENTAL HYSTORY OF HYPERTENSION

Objective: Increased uric acid levels are closely associated with new-onset hypertension in children, and pilot studies showed that pharmacological lowering of uric acid may reduce blood pressure (BP) in obese pediatric patients. Nevertheless, controversy remains concerning a direct causative role of serum uric acid (SUA) in the pathogenesis of essential hypertension (EH). Our study was aimed to determine if normotensive obese children and adolescent offspring of adults with EH show SUA levels different than those of pediatric subjects in whom there is non family history of EH. Design and method: Fifty-nine obese normotensive children and adolescents, attending for metabolic assessment the Pediatric Diabetes Unit, Children's Hospital "G. Di Cristina", and for cardiovascular evaluation the ESH Hypertension excellence center of the University of Palermo, were studied. All the subjects, aged between 8 and 17 years, underwent routine blood chemistry and oral glucose tolerance test with glucose and insulin determinations. All subjects had blood pressure determinations below the 90th percentile and had no previous history of elevated blood pressure. Results: There were 14 subjects whose parents were both normotensive (FH-), and the remaining 45 subjects whose one or both parents were hypertensive. FH + did not differ regarding age, sex distribution, blood pressure values, body mass index, waist circumference, serum glucose levels when compared to FH-. Among the metabolic parameters assessed, only SUA was significantly higher in FH+ than in FH - (p = 0.007; figure 1)

Mammals of Italy: An annotated checklist

Checklists represent a basic tool for conservation and management of regional faunas. However, our knowledge on species composition in a territory changes over time due to species movements across borders, extinctions, introductions, as well as to new taxonomic evidence. We aimed to provide the most updated data on native and non-native species of mammals occurring, or that used to occur until recently, on the Italian political territory and seas. The checklist only includes species whose taxonomic status was explicitly agreed in the most recent peer-reviewed literature and based on the most updated taxonomic approaches. For each species, we provided the following information: scientific and common name, global and Italian range, relevant information for management and conservation (e.g. whether it is endemic, allochthonous, or listed in international regulations and red list assessments), as well as remarks on taxonomy and distribution. This new check list of Italian mammal fauna includes nine marine and 114 terrestrial species, belonging to seven orders (Erinaceomorpha, Soricomorpha, Chiroptera, Carnivora, Cetartiodactyla, Rodentia, Lagomorpha), and 28 families. Vespertilionidae represents the richest family (n=27 species), followed by Cricetidae (n=12) and Soricidae (n=11). The list includes 15–16 allocthonous species. Considering the relative small size of the country, Italy is confirmed as a hotspot of mammal diversity in Europe, hosting the highest species richness in relation to the total area

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase (KIT) exon 11 PV were included in the study. We analyzed the type and codon location of the PV according to clinicopathological characteristics and clinical outcome; the metastatic sites in relapsed patients were also investigated. Results: Tumors harboring a KIT exon 11 deletion or deletion/insertion involving the 557 and/or 558 codons, showed a more aggressive clinical behavior compared with tumors carrying deletion/deletion/insertion in other codons, or tumors with duplication/insertion/single-nucleotide variant (SNV) (7-year RFS: 50% versus 73.1% versus 88.2%, respectively; p < 0.001). Notably, among 18 relapsed patients with 557 and/or 558 deletion or deletion/insertion, 14 patients (77.8%) harbored deletions simultaneously involving 557 and 558 codons, while only 4 patients (22.2%) harbored deletions involving only 1 of the 557/558 codons. Thus, when 557 or 558 deletions occurred separately, the tumor showed a prognostic behavior similar to the GIST carrying deletions outside the 557/558 position. Remarkably, patients with GISTs stratified as intermediate risk, but carrying the 557/558 deletion, showed a similar outcome to the high-risk patients with tumors harboring deletions in codons other than 557/558, or duplication/insertion/SNV. Conclusion: Our data support the inclusion of the PV type and codon location in routine risk prediction models, and suggest that intermediate-risk patients whose GISTs harbor 557/558 deletions may also need to be treated with adjuvant imatinib like the high-risk patients