Targeting of PDGF-C/NRP-1 autocrine loop as a new strategy for counteracting the invasiveness of melanoma resistant to braf inhibitors

: Melanoma resistance to BRAF inhibitors (BRAFi) is often accompanied by a switch from a proliferative to an invasive phenotype. Therefore, the identification of signaling molecules involved in the development of metastatic properties by resistant melanoma cells is of primary importance. We have previously demonstrated that activation of neuropilin-1 (NRP-1) by platelet-derived growth factor (PDGF)-C confers melanoma cells with an invasive behavior similar to that of BRAFi resistant tumors. Aims of the present study were to evaluate the role of PDGF-C/NRP-1 autocrine loop in the acquisition of an invasive and BRAFi-resistant phenotype by melanoma cells and the effect of its inhibition on drug resistance and extracellular matrix (ECM) invasion. Furthermore, we investigated whether PDGF-C serum levels were differentially modulated by drug treatment in metastatic melanoma patients responsive or refractory to BRAFi as single agents or in combination with MEK inhibitors (MEKi). The results indicated that human melanoma cells resistant to BRAFi express higher levels of PDGF-C and NRP-1 as compared to their susceptible counterparts. Overexpression occurs early during development of drug resistance and contributes to the invasive properties of resistant cells. Accordingly, silencing of NRP-1 or PDGF-C reduces tumor cell invasiveness. Analysis of PDGF-C in the serum collected from patients treated with BRAFi or BRAFi+MEKi, showed that in responders PDGF-C levels decrease after treatment and raise again at tumor progression. Conversely, in non-responders treatment does not affect PDGF-C serum levels. Thus, blockade of NRP-1 activation by PDGF-C might represent a new therapeutic approach to counteract the invasiveness of BRAFi-resistant melanoma

Giardia duodenalis in colony stray cats from Italy

Giardia duodenalis is the most common intestinal protozoan in humans and animals worldwide, including eight morphologically identical assemblages, infecting pets, livestock, wildlife and human beings. Assemblages A and B are those with the higher zoonotic potential, and they have been detected in several mammals other than humans; the others (C to H) show a higher host specificity. Cats can harbour both the specific Assemblage F and the zoonotic ones A and B. Several studies have been carried out on G. duodenalis genotypes in cats; however, the role of this species in the epidemiology of giardiasis is still poorly understood. In this scenario, the present study carried out the detection and genetic characterization at sub-assemblage level of G. duodenalis from colony stray cats in central Italy. In the period 2018-2019, 133 cat faecal samples were analysed for the presence of G. duodenalis cysts by a direct immunofluorescence assay. Positive samples were subsequently subjected to molecular analyses for assemblage/sub-assemblage identification. Forty-seven samples (35.3%) were positive for G. duodenalis cysts by immunofluorescence. G. duodenalis DNA was amplified at SSU-rDNA locus from 39 isolates: 37 were positive for zoonotic Assemblage A and 2 showed a mixed infection (A + B). Positive results for the beta-giardin gene were achieved for 25 isolates. Sequence analysis revealed 16 isolates belonging to Sub-assemblage AII and 8 to Sub-assemblage AIII. One isolate resulted as ambiguous AI/AIII. Large sequence variability at the sub-assemblage level was detected, with several double peaks and mutations, making complex a proper isolate allocation. When compared with previous studies, the 35.3% prevalence of G. duodenalis in cats reported in the present article was surprisingly high. Moreover, all positive cats resulted to be infected with zoonotic assemblages/sub-assemblages, thus indicating stray cats as a possible source of human giardiasis and highlighting the sanitary relevance of cat colonies in the study area

Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease

Degenerative Jargon Aphasia: Unusual Progression of Logopenic/Phonological Progressive Aphasia?

Primary progressive aphasia (PPA) corresponds to the gradual degeneration of language which can occur as nonfluent/agrammatic PPA, semantic variant PPA or logopenic variant PPA. We describe the clinical evolution of a patient with PPA presenting jargon aphasia as a late feature. At the onset of the disease (ten years ago) the patient showed anomia and executive deficits, followed later on by phonemic paraphasias and neologisms, deficits in verbal short-term memory, naming, verbal and semantic fluency. At recent follow-up the patient developed an unintelligible jargon with both semantic and neologistic errors, as well as with severe deficit of comprehension which precluded any further neuropsychological assessment. Compared to healthy controls, FDG-PET showed a hypometabolism in the left angular and middle temporal gyri, precuneus, caudate, posterior cingulate, middle frontal gyrus, and bilaterally in the superior temporal and inferior frontal gyri. The clinical and neuroimaging profile seems to support the hypothesis that the patient developed a late feature of logopenic variant PPA characterized by jargonaphasia and associated with superior temporal and parietal dysfunction

MYELOID MICROVESICLES ARE A MARKER AND THERAPEUTIC TARGET FOR NEUROINFLAMMATION

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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

A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes

Measurement of CP asymmetry in B-s(0) -> D-s(-/+) K--/+ decays

We report on measurements of the time-dependent CP violating observables in $B^0_s\rightarrow D^{\mp}_s K^{\pm}$ decays using a dataset corresponding to 1.0 fb$^{-1}$ of pp collisions recorded with the LHCb detector. We find the CP violating observables $C_f=0.53\pm0.25\pm0.04$, $A^{\Delta\Gamma}_f=0.37\pm0.42\pm0.20$, $A^{\Delta\Gamma}_{\bar{f}}=0.20\pm0.41\pm0.20$, $S_f=-1.09\pm0.33\pm0.08$, $S_{\bar{f}}=-0.36\pm0.34\pm0.08$, where the uncertainties are statistical and systematic, respectively. We use these observables to make the first measurement of the CKM angle $\gamma$ in $B^0_s\rightarrow D^{\mp}_s K^{\pm}$ decays, finding $\gamma$ = (115$_{-43}^{+28}$)$^\circ$ modulo 180$^\circ$ at 68% CL, where the error contains both statistical and systematic uncertainties.We report on measurements of the time-dependent CP violating observables in B$_{s}^{0}$  → D$_{s}^{∓}$ K$^{±}$ decays using a dataset corresponding to 1.0 fb$^{−1}$ of pp collisions recorded with the LHCb detector. We find the CP violating observables C$_{f}$ = 0.53±0.25±0.04, A$_{f}^{ΔΓ}$  = 0.37 ± 0.42 ± 0.20, ${A}_{\overline{f}}^{\varDelta \varGamma }=0.20\pm 0.41\pm 0.20$ , S$_{f}$ = −1.09±0.33±0.08, ${S}_{\overline{f}}=-0.36\pm 0.34\pm 0.08$ , where the uncertainties are statistical and systematic, respectively. Using these observables together with a recent measurement of the B$_{s}^{0}$ mixing phase −2β$_{s}$ leads to the first extraction of the CKM angle γ from B$_{s}^{0}$  → D$_{s}^{∓}$ K$^{±}$ decays, finding γ = (115$_{− 43}^{+ 28}$ )° modulo 180° at 68% CL, where the error contains both statistical and systematic uncertainties.We report on measurements of the time-dependent CP violating observables in $B^0_s\rightarrow D^{\mp}_s K^{\pm}$ decays using a dataset corresponding to 1.0 fb$^{-1}$ of pp collisions recorded with the LHCb detector. We find the CP violating observables $C_f=0.53\pm0.25\pm0.04$, $A^{\Delta\Gamma}_f=0.37\pm0.42\pm0.20$, $A^{\Delta\Gamma}_{\bar{f}}=0.20\pm0.41\pm0.20$, $S_f=-1.09\pm0.33\pm0.08$, $S_{\bar{f}}=-0.36\pm0.34\pm0.08$, where the uncertainties are statistical and systematic, respectively. Using these observables together with a recent measurement of the $B^0_s$ mixing phase $-2\beta_s$ leads to the first extraction of the CKM angle $\gamma$ from $B^0_s \rightarrow D^{\mp}_s K^{\pm}$ decays, finding $\gamma$ = (115$_{-43}^{+28}$)$^\circ$ modulo 180$^\circ$ at 68% CL, where the error contains both statistical and systematic uncertainties