Intracellular accumulation of tau oligomers in astrocytes and their synaptotoxic action rely on Amyloid Precursor Protein Intracellular Domain-dependent expression of Glypican-4

: Several studies including ours reported the detrimental effects of extracellular tau oligomers (ex-oTau) on glutamatergic synaptic transmission and plasticity. Astrocytes greatly internalize ex-oTau whose intracellular accumulation alters neuro/gliotransmitter handling thereby negatively affecting synaptic function. Both amyloid precursor protein (APP) and heparan sulfate proteoglycans (HSPGs) are required for oTau internalization in astrocytes but the molecular mechanisms underlying this phenomenon have not been clearly identified yet. Here we found that a specific antibody anti-glypican 4 (GPC4), a receptor belonging to the HSPG family, significantly reduced oTau uploading from astrocytes and prevented oTau-induced alterations of Ca2+-dependent gliotransmitter release. As such, anti-GPC4 spared neurons co-cultured with astrocytes from the astrocyte-mediated synaptotoxic action of ex-oTau, thus preserving synaptic vesicular release, synaptic protein expression and hippocampal LTP at CA3-CA1 synapses. Of note, the expression of GPC4 depended on APP and, in particular, on its C-terminal domain, AICD, that we found to bind Gpc4 promoter. Accordingly, GPC4 expression was significantly reduced in mice in which either APP was knocked-out or it contained the non-phosphorylatable amino acid alanine replacing threonine 688, thus becoming unable to produce AICD. Collectively, our data indicate that GPC4 expression is APP/AICD-dependent, it mediates oTau accumulation in astrocytes and the resulting synaptotoxic effects

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

Inositol supplementation and IVF outcome: preliminary data

Myo-Inositol (MI) is involved in several aspects of human reproduction. Elevated concentrations of myo-inositol in human follicular fluids, in fact, seem to play a positive role in follicular maturity, since to represent a possible marker of good oocyte quality. Nevertheless its positive role in PCOS patients is a consequence of a defect in the insulin signaling (inositol- containing phosphoglycan mediators) pathway that seems to be implicated in the pathogenesis of insulin resistance. The aim of this study was to analyze the effect of myo-inositol supplementation to “standard” therapy in PCOS women and in “poor responders”, submitted to In Vitro Fecundation (IVF) cycles. In particular, we have investigated its influence on ovarian response to hormonal stimulation and on oocytes quality. Preliminary results of our study, anyway, appear in contrast with results of previous studies; supplementation with MI, in fact, do not seem to improve the response neither in PCOS patients nor in poor responders

LA PREVENZIONE ED IL TRATTAMENTO DELLE PATOLOGIE HPV-CORRELATE: FOLLOW-UP E PERFORMANCE RIPRODUTTIVA

Relationship between HPV-infection and reproductive performance includes patients who during trial become pregnant. Main chapter indeed represents genital lesions treatments sequelae. Clinical phase 3 studies showed that spontaneous abortion rate in both groups (Gardasil and placebo respectively) was comparable (33% vs 31.6%). Moreover, there were 25 cases of congenital abnormalities among newborns and live foetuses, and congenital abnormalities global rate was similar than normal population. Therefore, there is no evidence that Gardasil adversely influences fertility, pregnancy and neonatal outcome. Cold-cut conization, laser-conization, laser-ablation, LEEP or LLETZ are conservative techniques that can treat with efficacy invasive cervical cancer. Neverthless, outcome data relative to successive pregnancies are discordant. LLETZ is associated to greater risk of early childbirth, low-weight birth and PROM. Similar results are obtained with laser-conization. Also cold-cut conization is significatively associated with incremented risk of early childbirth, low-weight and caesarean section

Ceftazidime-Avibactam as Osteomyelitis Therapy: A Miniseries and Review of the Literature

Bone and joint infections (BJIs) caused by multidrug-resistant gram-negative bacteria are becoming a concern due to limited therapeutic options. Although not approved for these indications, an ever-growing amount of evidence supports the efficacy and safety of ceftazidime–avibactam as a therapy for osteomyelitis and prosthetic joint infections. Here, we present three cases of difficult-to-treat resistant Pseudomonas aeruginosa osteomyelitis that were successfully treated with ceftazidime–avibactam alone or in combination therapy with fosfomycin and amikacin. Ceftazidime–avibactam was prescribed at a daily dose of 2.5 g every 8 h for 42 days in all cases. One potential drug-related adverse effect was observed, i.e., Clostridioides difficile infection, which occurred after fourteen days of treatment with ceftazidime–avibactam