Nicotinamide and calcipotriol counteract UVB-induced photoaging on primary human dermal fibroblasts

Background: Photoaging is mainly caused by ultraviolet radiations inasmuch they can damage the DNA, trigger ROS production, and activate p53/p21 pathway, which cause cell cycle arrest and senescence. The accumulationof senescent cells within the dermis contributes to tissue deregulation and skin carcinogenesis. However, the use of photoprotector molecules could reduce UV-induced damages and prevent photoaging. Therefore, the aim of this study is to evaluate whether the active forms of vitamin B3 (nicotinamide) and the analog of vitamin D3 (calcipotriol) might protect primary human dermal fibroblasts (HDFs) from UVB-induced photoaging. Methods: HDFs were isolated from a healthy adult donor and stimulated with nicotinamide (25 μM) and calcipotriol (100 nM) for 24h before UVB exposure, and then, cultured for further 24h on vitamin-supplemented media. Then, cell viability, ROS production, DNA damages, senescence markers, protein and gene expression were evaluated. Results: HDFs treated with nicotinamide and calcipotriol showed better proliferation properties and lower DNA damages due to a reduced UVB-induced ROS production. Consequently, p53/p21 pathway was less active which enhanced cell cycle progression and reduced senescence and cell death. Conclusions: Overall, our results suggest that nicotinamide and calcipotriol can counteract UVB-induced effects responsible for the onset of skin photoaging

Multilocus microsatellite analysis of European and African Candida glabrata isolates

This study aimed to elucidate the genetic relatedness and epidemiology of 127 clinical and environmental Candida glabrata isolates from Europe and Africa using multilocus microsatellite analysis. Each isolate was first identified using phenotypic and molecular methods and subsequently, six unlinked microsatellite loci were analyzed using automated fluorescent genotyping. Genetic relationships were estimated using the minimum-spanning tree (MStree) method. Microsatellite analyses revealed the existence of 47 different genotypes. The fungal population showed an irregular distribution owing to the over-representation of genetically different infectious haplotypes. The most common genotype was MG-9, which was frequently found in both European and African isolates. In conclusion, the data reported here emphasize the role of specific C. glabrata genotypes in human infections for at least some decades and highlight the widespread distribution of some isolates, which seem to be more able to cause disease than others.This research was supported in part by the EU Mare Nostrum (EUMN-III Call) program of the European Union, grant agreement number 2011-4050/001-EMA2. Dr Sanae Rharmitt was the recipient of a scholarship (10 months) signed within the EUMN program for PhD students (F.S. 1.04.11.01 UORI) under the supervision of Prof Orazio Romeo.info:eu-repo/semantics/publishedVersio

Magnusiomyces clavatus infection in a child after allogeneic hematotopoetic stem cell transplantation: Diagnostic and therapeutic implications

Magnusiomyces clavatus is an ascomycetous fungus causing invasive disease in immuno-compromised patients. Neutropenia, contaminated venous catheters, previous antifungal treatment are risk factors for this infection. We report a case of Magnusiomyces clavatus fungemia with pulmonary, renal and skin localizations in a 6-year-old boy with prolonged neutropenia because of three allogeneic hematopoietic stem cell transplantations. The infection was controlled by aggressive and strictly monitored combination therapy with voriconazole and liposomial-ampthotericine-B along with durable recover from neutropeni

Characterisation of F. musae strains obtained from plants and humans

Fusarium musae was described for the first time as a species in 2011. It appears to have its evolutionary origin within the African clade of the F. fujikuroi species complex. Recent reports have identified F. musae strains in human patients causing various diseases such as nail and skin lesions as well as systemic infections in immunocompromised patients. A worldwide collection of Fusarium strains attributed to F. musae obtained from banana and human patients was characterised phylogenetically using four informative genes βtubulin, Translation Elongation Factor 1α, DNA-directed RNA polymerase II subunit and calmodulin; appropriate classification of the different strains was then established. The draft genomes of two representative strains colonizing banana and humans were obtained (genome size: 45Mb). Furthermore, the pathogenic behaviour of each strain on detached bananas was investigated, showing the ability of the strains of human origin to cause significant crown rot infection on banana fruit. To identify the virulence and the pathogenicity mechanisms differences of representative strains, Galleria mellonella model is currently being employed. Bioluminescent and fluorescent strains are currently being produced to study the interactions with the different host

The psychological impact of COVID-19 pandemic on patients with neuroendocrine tumors: Between resilience and vulnerability

The COVID-19 pandemic has added another layer of complexity to the fears of patients with neuroendocrine tumors (NETs). Little is known regarding the psychological impact of the COVID-19 outbreak on patients with gastroenteropancreatic or bronchopulmonary (BP) NETs. We longitudinally surveyed the mental symptoms and concerns of NET patients during the plateau phase of the first (W1) and second epidemic waves (W2) in Italy. Seven specific constructs (depression, anxiety, stress, health-related quality of life, NET-related quality of life, patient–physician relationship, psychological distress) were investigated using validated screening instruments, including DASS-21, EORTC QLQ-C30, EORTC QLQ GI.NET21, PDRQ9 and IES-R. We enrolled 197 patients (98 males) with a median age of 62 years. The majority of the patients had G1/G2 neoplasms. Some 38% of the patients were on active treatment. At W1, the prevalence of depression, anxiety and stress was 32%, 36% and 26% respectively. The frequency of depression and anxiety increased to 38% and 41% at W2, whereas no modifications were recorded in the frequency of stress. Poor educational status was associated with higher levels of anxiety at both W1 (odds ratio [OR] = 1.33 ± 0.22; p =.07) and W2 (OR = 1.45 ± 0.26; p =.03). Notably, post-traumatic stress symptoms were observed in the 58% of the patients, and both single marital status (OR = 0.16, 95% confidence interval [CI] = 0.06–0.48; p =.0009) and low levels of formal education (OR = 0.47, 95% CI = 0.23–0.99; p =.05) predicted their occurrence. No significant deteriorations of health-related quality of life domains were observed from W1 to W2. High patient care satisfaction was documented despite the changes in health systems resource allocation. NET patients have an increased risk of developing post-traumatic stress symptoms as result of the COVID-19 pandemic. Specific screening measures and psychological interventions should be implemented in NET clinics to prevent, recognize and treat mental distress in this vulnerable population

EFFETTO DI REZAFUNGINA SUL BIOFILM DI ISOLATI RESISTENTI AL FLUCONAZOLO DI CANDIDA PARAPSILOSIS

Candida parapsilosis è sempre più frequentemente causa di BSI, spesso associata a una sua ridotta sensibilità agli azoli. La sua capacità di formare biofilm su materiale inerte gioca un ruolo significativo nella patogenicità e nell'invasione delle cellule ospiti. Il presente studio ha indagato l'effetto in vitro di Rezafungina su cellule planctoniche di C. parapsilosis fluconazolo sensibili (FLZ-S), resistenti a fluconazolo (FLZ-R) o resistenti a fluconazolo con resistenza intermedia a voriconazolo (FLZ-R+VRZ-I). È stata inoltre valutata una possibile differenza dell’effetto di Rezafungina sul biofilm tra ceppi FLZ-R, FLZ-R+VRZ-I e FLZ-S. Lo studio è stato condotto su 90 ceppi di C. parapsilosis di cui: 19 ceppi FLZ-S, 35 ceppi FLZ-R e 36 ceppi FLZ-R+VRZ-I. È stato eseguito il test di sensibilità (EUCAST) per determinare la MIC di Rezafungina sulle cellule planctoniche. La formazione di biofilm è stata determinata tramite il test di riduzione XTT. È stato calcolato l'effetto di Rezafungina sulle cellule sessili FLZ-S, FLZ-R e FLZ-R+VRZ-I e sono state determinate le minime concentrazioni inibenti sulle cellule sessili (SMIC) utilizzando il test di riduzione XTT. La media geometrica complessiva (GM) per Rezafungina è risultata di 0,85 mg/L (range 0,03-2 mg/L). È stata rilevata una differenza significativa (p < 0.05) tra i ceppi FLZ-S (GM = 0,39 mg/L) e i ceppi FLZ-R (GM = 1,1 mg/L) e i ceppi FLZ-R+VRZ-I (GM = 1 mg/L). Non disponendo di breakpoint per Rezafungina per C. parapsilosis, in accordo con gli Epidemiological Cut-off di EUCAST (≤4 mg/L) tutti gli isolati risultavano wild-type. L'analisi della produzione di biofilm ha mostrato: 3 ceppi buoni produttori, 7 produttori medi e 9 produttori scarsi tra i ceppi sensibili; tutti i ceppi FLZ-R e FLZ-R+VRZ-I erano scarsi produttori. Rezafungina ha mostrato un'attività ridotta contro le cellule sessili dei ceppi di C. parapsilosis. La differenza tra MIC50 e SMIC50 era significativa per tutti i pattern di sensibilità, ma la differenza maggiore è stata osservata tra i ceppi FLZ-S. Una differenza maggiore è stata osservata tra la MIC planctonica e la MIC sessile dei ceppi buoni produttori di biofilm (tutti azolo sensibili). Nello specifico, tra i FLZ-S sono stati rilevati valori SMIC 4-5 volte superiori alla MIC planctonica per i buoni produttori e valori SMIC 2-4 volte superiori per i produttori medi, mentre è stata osservata una differenza minore nei cattivi produttori di biofilm; tra i ceppi FLZ-R e tra i ceppi FLZ-R+VRZ-I, tutti scarsi produttori di biofilm, è stato osservato un intervallo SMIC tra 0 e +2. La Rezafungina ha comunque dimostrato una certa attività contro i biofilm di C. parapsilosis, come indicato da SMIC50, sebbene la sua attività contro la forma sessile sia più limitata con ceppi buoni produttori di biofilm