Awareness towards Chikungunya virus infection risk by general practitioners in Rome: a questionnaire based survey before the 2017 outbreak

Autochthonous cases of Chikungunya (CHIKV) have been recently detected in Rome. A survey was conduct- ed prior to the 2017 outbreak to assess knowledge, attitude, and practices towards CHIKV infections on 103 randomly selected general practitioners (GPs), practicing in the centre of Rome. Only 24.3% were aware of CHIKV and completed the interview. Among completers, the knowledge of basic elements of CHIKV in- fection was insufficient. Only two thirds of them were able to identify possible CHIKV cases in hypothetical clinical scenarios presented by the interviewer. Our study highlights the need to improve GP knowledge to- wards CHIKV, as a necessary step to establish an efficacious epidemic surveillance

Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy : pain relief and neuroprotection share a PPAR-alpha-mediated mechanism

Peer reviewedPublisher PD

Sirtuins 1–7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia

The sirtuin family comprises seven NAD+-dependent deacetylases which control the overall health of organisms through the regulation of pleiotropic metabolic pathways. Sirtuins are important modulators of adipose tissue metabolism and their expression is higher in lean than obese subjects. At present, the role of sirtuins in adipose-derived stem cells has not been investigated yet. Therefore, in this study, we evaluated the expression of the complete panel of sirtuins in adipose-derived stem cells isolated from both subcutaneous and visceral fat of non-obese and obese subjects. We aimed at investigating the influence of obesity on sirtuins' levels, their role in obesity-associated inflammation, and the relationship with the peroxisome proliferator-activated receptor delta, which also plays functions in adipose tissue metabolism. The mRNA levels in the four types of adipose-derived stem cells were evaluated by quantitative polymerase chain reaction, in untreated cells and also after 8 h of hypoxia exposure. Correlations among sirtuins' expression and clinical and molecular parameters were also analyzed. We found that sirtuin1-6 exhibited significant higher mRNA expression in visceral adipose-derived stem cells compared to subcutaneous adipose-derived stem cells of non-obese subjects. Sirtuin1-6 levels were markedly reduced in visceral adipose-derived stem cells of obese patients. Sirtuins' expression in visceral adipose-derived stem cells correlated negatively with body mass index and C-reactive protein and positively with peroxisome proliferator-activated receptor delta. Finally, only in the visceral adipose-derived stem cells of obese patients hypoxia-induced mRNA expression of all of the sirtuins. Our results highlight that sirtuins' levels in adipose-derived stem cells are consistent with protective effects against visceral obesity and inflammation, and suggest a transcriptional mechanism through which acute hypoxia up-regulates sirtuins in the visceral adipose-derived stem cells of obese patients

Two-loop Euler-Heisenberg effective actions from charged open strings

We present the multiloop partition function of open bosonic string theory in the presence of a constant gauge field strength, and discuss its low-energy limit. The result is written in terms of twisted determinants and differentials on higher-genus Riemann surfaces, for which we provide an explicit representation in the Schottky parametrization. In the field theory limit, we recover from the string formula the two-loop Euler-Heisenberg effective action for adjoint scalars minimally coupled to the background gauge field.Comment: 32 pages, 3 eps figures, plain LaTeX. References added, minor changes to the text. Published version, affiliation correcte

The twisted open string partition function and Yukawa couplings

We use the operator formalism to derive the bosonic contribution to the twisted open string partition function in toroidal compactifications. This amplitude describes, for instance, the planar interaction between g+1 magnetized or intersecting D-branes. We write the result both in the closed and in the open string channel in terms of Prym differentials on the appropriate Riemann surface. Then we focus on the g=2 case for a 2-torus. By factorizing the twisted partition function in the open string channel we obtain an explicit expression for the 3-twist field correlator, which is the main ingredient in the computation of Yukawa couplings in D-brane phenomenological models. This provides an alternative method for computing these couplings that does not rely on the stress-energy tensor technique.Comment: 32 pages, 5 figures, Latex; v2: typos correcte

Splenomegaly impacts prognosis in essential thrombocythemia and polycythemia vera: A single center study

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019

Discovery of a Novel Small Molecule Inhibitor Targeting the Frataxin/Ubiquitin Interaction via Structure-Based Virtual Screening and Bioassays

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardiodegenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the mitochondrial protein frataxin. Here, we report findings that frataxin is degraded via the ubiquitin-proteasomal pathway and that it is ubiquitinated at residue K147 in Calu-6 cells. A theoretical model of the frataxin-K147/Ub complex, constructed by combining bioinformatics interface predictions with information-driven docking, revealed a hitherto unnoticed, potential ubiquitin-binding domain in frataxin. Through structure-based virtual screening and cell-based assays, we discovered a novel small molecule (compound (+)-11) able to prevent frataxin ubiquitination and degradation. (+)-11 was synthesized and tested for specific binding to frataxin by an UF-LC/MS based ligand-binding assay. Follow-up scaffold-based searches resulted in the identification of a lead series with micromolar activity in disrupting the frataxin/Ub interaction. This study also suggests that frataxin could be a potential target for FRDA drug development

The lncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation

Non‐coding RNAs (ncRNAs) constitute the majority of the transcriptome, as the result of pervasive transcription of the mammalian genome. Different RNA species, such as lncRNAs, miRNAs, circRNA, mRNAs, engage in regulatory networks based on their reciprocal interactions, often in a competitive manner, in a way denominated “competing endogenous RNA (ceRNA) networks” (“ceRNET”): miRNAs and other ncRNAs modulate each other, since miRNAs can regulate the expression of lncRNAs, which in turn regulate miRNAs, titrating their availability and thus competing with the binding to other RNA targets. The unbalancing of any network component can derail the entire regulatory circuit acting as a driving force for human diseases, thus assigning “new” functions to “old” molecules. This is the case of XIST, the lncRNA characterized in the early 1990s and well known as the essential molecule for X chromosome inactivation in mammalian females, thus preventing an imbalance of X‐linked gene expression between females and males. Currently, literature concerning XIST biology is becoming dominated by miRNA associations and they are also gaining prominence for other lncRNAs produced by the X‐inactivation center. This review discusses the available literature to explore possible novel functions related to ceRNA activity of lncRNAs produced by the X‐inactivation center, beyond their role in dosage compensation, with prospective implications for emerging gender‐biased functions and pathological mechanisms