The Via Francigena Salentina as an Opportunity for Experiential Tourism and a Territorial Enhancement Tool

The essay presents the results of a 10-year archival and on-field study, carried out by a research group (bringing together archaeologists, geographers, medieval historians and art historians) of the Department of Cultural Heritage of the Salento University, who have rebuilt the Via Francigena Salentina following ancient pilgrim routes heading to the Holy Land. The researchers have mapped and catalogued natural and cultural highlights along the route, also analysing tourism services on a local scale and the environmental impact of human activities. After presenting a short assessment of the adequacy of cultural routes in meeting the new requirements imposed by the tourism demand the research analyses the Via Francigena Salentina’s main features, also taking into account goods and services provided by the territory and the capability of local professionals and administrators to drive and boost effective relationships among stakeholders, also activating enhancement processes and organic and unitary promotional initiatives and always respecting both visitors’ needs and the environment

The Via Francigena Salentina as an Opportunity for Experiential Tourism and a Territorial Enhancement Tool

Inseriti nel paesaggio attuale e nella stratificazione culturale in esso presente, gli itinerari culturali d’interesse storico e religioso costituiscono un importante strumento di valorizzazione territoriale legato al turismo lento ed esperienziale ed indirizzato alla scoperta e al recupero di antichi luoghi e “valori”. In essi il filo conduttore resta il paesaggio geografico. E’ il caso della la Via Francigena salentina che, seguendo il tracciato dell’antica via Traiana, si svolge da Fasano a Brindisi spingendosi fino ad Otranto anche innervandosi ai numerosi “diverticula” che spesso incrociavano antichi percorsi devozionali. Dell’antico tracciato storico della Via Francigena meridionale il presente lavoro ricostruisce il tratto pugliese che si svolge da Fasano ad Ostuni ed offre, contestualmente, un’attenta lettura dell’articolato paesaggio salentino e del patrimonio culturale e naturalistico oggi messo a sistema da un’interessante progettualità locale. Sulle tracce di un antico e importante cammino di fede la Via Francigena salentina mette a disposizione di studiosi e turisti un percorso storico, puntigliosamente studiato e cartografato, che è certo un’interessante alternativa ai tradizionali circuiti di viaggio, ma è anche un’ importante occasione di sviluppo locale. In esso l’offerta di servizi e di buone strutture ricettive favorisce una fruizione sostenibile e “consapevole” del territorio, in particolare di quello rurale, perfettamente in linea con i principi della Green Economy

Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson’s disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol

Background Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson’s disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF).Methods and analysis In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat.Ethics and dissemination The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences.Trial registration numbers NCT05287503, EudraCT 2021-004565-13

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10(−8)) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41–6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10(–9)). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR