Engineering of janus-like dendrimers with peptides derived from glycoproteins of herpes simplex virus type 1: Toward a versatile and novel antiviral platform

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol–ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting biocon-jugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics

Natural Formulations Based on Olea europaea L. Fruit Extract for the Topical Treatment of HSV-1 Infections

In the present study, a hydroxytyrosol-rich Olea europaea L. fruit extract (OFE) was added to three thoroughly green formulations—hydrogel, oleogel, and cream—in order to evaluate their antiviral activity against HSV-1. The extract was characterized by different analytical techniques, i.e., FT-IR, XPS, and TGA. HPLC analyses were carried out to monitor the content and release of hydroxytyrosol in the prepared formulations. The total polyphenol content and antioxidant activity were investigated through Folin–Ciocâlteu’s reagent, DPPH, and ABTS assays. The ability of the three formulations to convey active principles to the skin was evaluated using a Franz cell, showing that the number of permeated polyphenols in the hydrogel (272.1 ± 1.8 GAE/g) was significantly higher than those in the oleogel and cream (174 ± 10 and 179.6 ± 2 GAE/g, respectively), even if a negligible amount of hydroxytyrosol crossed the membrane for all the formulations. The cell viability assay indicated that the OFE and the three formulations were not toxic to cultured Vero cells. The antiviral activity tests highlighted that the OFE had a strong inhibitory effect against HSV-1 with a 50% inhibitory concentration (IC50) at 25 µg/mL, interfering directly with the viral particles. Among the three formulations, the hydrogel exhibited the highest antiviral activity also against the acyclovir-resistant strain

The impact of increasing education levels on rising life expectancy: a decomposition analysis for Italy, Denmark, and the USA

Significant reductions in mortality are reflected in strong increases in life expectancy particularly in industrialized countries. Previous analyses relate these improvements primarily to medical innovations and advances in health-related behaviors. Mostly ignored, however, is the question to what extent the gains in life expectancy are related to structural changes in the populations due to increasing education levels. We decompose changes of the total populations’ life expectancy at age 30 in Italy, Denmark, and the USA, over the 20-year period between 1990 and 2010 into the effects of education-specific mortality changes (“M effect”) and changes in the populations’ educational structure (“P effect”). We use the “replacement decomposition technique” to further subdivide the M effect into the contributions by the individual education groups. While most of the increases in life expectancy are due to the effect of changing mortality, a large proportion of improvements in longevity can indeed be attributed to the changing structure of the population by level of education in all three countries. The estimated contribution of the P effect ranges from around 15% for men in the USA to approximately 40% for women in Denmark. This study demonstrates strong associations between education and overall population health, suggesting that education policies can also be seen as indirect health policies

Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, and significantly enhanced the radiation-induced growth delay of FSaII tumors (s.c.) in the legs of C3H mice. Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. Conclusion: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR

Caratteristiche del puerperio e complicanze nel parto vaginale e nel taglio cesareo. Confronto fra la popolazione italiana e straniera nella casistica 2000-2004 del Policlinico “A. Gemelli”

Obiettivo: questo studio prende in esame le caratteristiche di 14.604 donne che hanno partorito presso il nostro Dipartimento nel periodo 2000-2004. Metodi: sono state esaminate le seguenti variabili: età materna, nazionalità, modalità di parto e complicanze nel puerperio. Risultati: sono emerse le seguenti considerazioni: un aumento della natalità (da 2.874 parti nel 2000 a 2.974 nel 2004), in parte legato alla presenza sempre più cospicua di donne straniere (dal 14% nel 2000 al 20,7% nel 2004), come riflesso del fenomeno di immigrazione, e in parte anche ad una lenta ma costante ripresa di nascite tra le donne italiane. Inoltre, abbiamo osservato un cambiamento delle caratteristiche epidemiologiche della popolazione ostetrica: età materna avanzata, una maggiore consapevolezza e coscienza della gravidanza e del parto, che ha inciso profondamente sull’incidenza del taglio cesareo. Conclusioni: alla luce di tali considerazioni si rende necessaria una rielaborazione dei protocolli di assistenza clinica e strumentale al puerperio, che hanno tentato di rispondere, da un lato, ad una richiesta di competenze super-specialistiche e, dall’altro, ad un desiderio di “umanizzazione” del percorso nascita. Dai risultati ottenuti, che denotano un “controllo” delle complicanze infettive, emorragiche e tromboemboliche, possiamo confermare la validità di tali modelli assistenziali, sostenuti anche da un elevato grado di soddisfazione espresso dalle pazienti durante la degenza