Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: The effect of different substitution patterns

New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)- glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking analysis allowed to identify several key features of the binding mode of such compounds to the protease

Feasibility and acceptability of expressive writing with postpartum women: a randomised controlled trial

Abstract Background: Pregnancy, birth and adjusting to a new baby is a potentially stressful time that can negatively affect women’s mental and physical health. Expressive writing, where people write about a stressful event for at least 15 minutes on three consecutive days, has been associated with improved health in some groups but it is not clear whether it is feasible and acceptable for use with postpartum women. This study therefore examined the feasibility and acceptability of expressive writing for postpartum women as part of a randomised controlled trial (RCT). Methods: The Health After Birth Trial (HABiT) was an RCT evaluating expressive writing for postpartum women which included measures of feasibility and acceptability. At 6 to 12 weeks after birth 854 women were randomised to expressive writing, a control writing task or normal care, and outcome measures of health were measured at baseline, one month later and six months later. Feasibility was measured by recruitment, attrition, and adherence to the intervention. Quantitative and qualitative measures of acceptability of the materials and the task were completed six months after the intervention. Results: Recruitment was low (10.7% of those invited to participate) and the recruited sample was from a restricted sociodemographic range. Attrition was high, increased as the study progressed (35.8% at baseline, 57.5% at one month, and 68.1% at six months) and was higher in the writing groups than in the normal care group. Women complied with instructions to write expressively or not, but adherence to the instruction to write for 15 minutes per day for three days was low (Expressive writing: 29.3%; Control writing: 23.5%). Acceptability measures showed that women who wrote expressively rated the materials/task both more positively and more negatively than those in the control writing group, and qualitative comments revealed that women enjoyed the writing and/or found it helpful even when it was upsetting. Conclusions: The feasibility of offering expressive writing as a universal self-help intervention to all postpartum women 6 to 12 weeks after birth in the HABiT trial was low, but the expressive writing intervention was acceptable to the majority of women who completed it

Experimental assessment on exploiting low carbon ethanol fuel in a light-duty dual-fuel compression ignition engine

Compression ignition (CI) engines are widely used in modern society, but they are also recognized as a significative source of harmful and human hazard emissions such as particulate matter (PM) and nitrogen oxides (NOx). Moreover, the combustion of fossil fuels is related to the growing amount of greenhouse gas (GHG) emissions, such as carbon dioxide (CO2). Stringent emission regulatory programs, the transition to cleaner and more advanced powertrains and the use of lower carbon fuels are driving forces for the improvement of diesel engines in terms of overall efficiency and engine-out emissions. Ethanol, a light alcohol and lower carbon fuel, is a promising alternative fuel applicable in the dual-fuel (DF) combustion mode to mitigate CO2 and also engine-out PM emissions. In this context, this work aims to assess the maximum fuel substitution ratio (FSR) and the impact on CO2 and PM emissions of different nozzle holes number injectors, 7 and 9, in the DF operating mode. The analysis was conducted within engine working constraints and considered the influence on maximum FSR of calibration parameters, such as combustion phasing, rail pressure, injection pattern and exhaust gas recirculation (EGR). The experimental tests were carried out on a single-cylinder light-duty CI engine with ethanol introduced via port fuel injection (PFI) and direct injection of diesel in two operating points, 1500 and 2000 rpm and at 5 and 8 bar of brake mean effective pressure (BMEP), respectively. Noise and the coefficient of variation in indicated mean effective pressure (COVIMEP) limits have been chosen as practical constraints. In particular, the experimental analysis assesses for each parameter or their combination the highest ethanol fraction that can be injected. To discriminate the effect on ethanol fraction and the combustion process of each parameter, a one-at-a-time-factor approach was used. The results show that, in both operating points, the EGR reduces the maximum ethanol fraction injectable; nevertheless, the ethanol addition leads to outstanding improvement in terms of engine-out PM. The adoption of a 9 hole diesel injector, for lower load, allows reaching a higher fraction of ethanol in all test conditions with an improvement in combustion noise, on average 3 dBA, while near-zero PM emissions and a reduction can be noticed, on the average of 1 g/kWh, and CO2 compared with the fewer nozzle holes case. Increasing the load insensitivity to different holes number was observed

On the asymptotic behaviour of solutions to the fractional porous medium equation with variable density

We are concerned with the long time behaviour of solutions to the fractional porous medium equation with a variable spatial density. We prove that if the density decays slowly at infinity, then the solution approaches the Barenblatt-type solution of a proper singular fractional problem. If, on the contrary, the density decays rapidly at infinity, we show that the minimal solution multiplied by a suitable power of the time variable converges to the minimal solution of a certain fractional sublinear elliptic equation.Comment: To appear in DCDS-

Quale analisi cefalometrica per la chirurgia maxillo-mandibolare in pazienti con sindrome delle apnee ostruttive notturne?

L’avanzamento maxillo-mandibolare (AMM) è un trattamento efficace per pazienti affetti da sindrome delle apnee ostruttive notturne (OSAS) di grado severo. Sebbene il miglioramento dell’OSAS sia l’obiettivo principale di tale chirurgia, è necessario evitare un avanzamento maxillo-mandibolare eccessivo per garantire un gradevole risultato in termini di estetica facciale. A tale scopo, è necessario programmare preoperatoriamente l’entità dell’AMM mediante un’analisi estetica e cefalometrica. Le analisi cefalometriche di Steiner e Delaire vengono comunemente impiegate nella programmazione della chirurgia ortognatica per deformità dentofaciali, tuttavia resta controverso il ruolo di tali analisi nei pazienti con OSAS candidati a AMM. Quarantotto pazienti con OSAS severa sono stati sottoposti a AMM. Abbiamo effettuato le analisi cefalometriche di Steiner e Delaire in tutti i soggetti. Per il tracciato di Steiner, abbiamo misurato la variazione degli angoli SNA e SNB, mentre per l’analisi di Delaire, abbiamo misurato la variazione degli angoli C3/FM-CPA e C3/ FM-Me. L’AMM medio è stato di 6,9 + 3,8 mm per il mascellare superiore e 13,6 + 5 mm per la mandibola. Dopo l’intervento abbiamo riscontrato un miglioramento dell’Indice di Apnea-Ipopnea (40,47 + 7,64 preoperatoriamente vs. 12,56 + 5,78 postoperatoriamente). In tutti i pazienti, entrambe le tecniche cefalometriche hanno dimostrato una retrusione bimascellare preoperatoria. Dopo l’intervento, l’angolo SNA medio è aumentato da 78,18° a 85,58° (p < 0,001), mentre l’angolo C3/FM-CPA medio è aumentato da 81,19° a 89,71° (p < 0,001). Il valore medio dell’angolo SNB è aumentato da 74,33° a 80,73° (p < 0,001), mentre l’angolo medio C3/FM-CPA è passato da 80,10° a 87,29° (p < 0,001). Postoperatoriamente, sia il mascellare superiore che la mandibola risultavano in una posizione più protrusa (p < 0,001) se analizzati secondo l’analisi di Steiner rispetto al tracciato di Delaire. L’utilizzo dell’analisi cefalometrica di Delaire nella programmazione dell’AMM in pazienti con OSAS comporta un avanzamento maxillo-mandibolare superiore rispetto al tracciato di Steiner. È opportuno considerare le conseguenze di tale risulto sull’estetica facciale durante la programmazione chirurgica e nel consenso informato preoperatorio in pazienti con OSAS candidati a AMM

Stochastic Reaction-diffusion Equations Driven by Jump Processes

We establish the existence of weak martingale solutions to a class of second order parabolic stochastic partial differential equations. The equations are driven by multiplicative jump type noise, with a non-Lipschitz multiplicative functional. The drift in the equations contains a dissipative nonlinearity of polynomial growth.Comment: See journal reference for teh final published versio

Using concept mapping in the development of the EU-PAD framework (EUropean-Physical Activity Determinants across the life course): a DEDIPAC-study.

BACKGROUND: A large proportion of European children, adults and older adults do not engage in sufficient physical activity (PA). Understanding individual and contextual factors associated with PA behaviours is essential for the identification and implementation of effective preventative environments, policies, and programmes that can promote an active lifestyle across life course and can potentially improve health. The current paper intends to provide 1) a multi-disciplinary, Pan-European and life course view of key determinants of PA behaviours and 2) a proposal of how these factors may cluster. METHODS: After gathering a list of 183 potential PA behaviours-associated factors and a consensus meeting to unify/consolidate terminology, a concept mapping software was used to collate European experts' views of 106 identified factors for youth (<19 years), adults (19-64 years), and older adults (≥65 years). The analysis evaluated common trends in the clustering of factors and the ratings of the distinct factors' expected modifiability and population-level impact on PA behaviours across the life course. Priority for research was also assessed for each cluster. RESULTS: The concept mapping resulted in six distinct clusters, broadly merged in two themes: 1) the 'Person', which included clusters 'Intra-Personal Context and Wellbeing' and 'Family and Social Economic Status' (42 % of all factors) and 2) the 'Society', which included the remaining four clusters 'Policy and Provision', 'Cultural Context and Media', 'Social Support and Modelling', and 'Supportive Environment' (58 % of all factors). Overall, 25 factors were rated as the most impactful on PA behaviours across the life course and being the most modifiable. They were mostly situated in the 'Intra-Personal Context and Wellbeing' cluster. Furthermore, 16 of them were rated as top priority for research. CONCLUSIONS: The current framework provides a preliminary overview of factors which may account for PA behaviour across the life course and are most relevant to the European community. These insights could potentially be a foundation for future Pan-European research on how these factors might interact with each other, and assist policy makers to identify appropriate interventions to maximize PA behaviours and thus the health of European citizens

An Italian Study

The literature provides some evidence that the use of violent video games increases the risk for young people to develop aggressive cognitions and even behaviors. We aimed to verify whether exposure to violent video games is linked to problems of aggression in a sample of Italian children. Four questionnaires were administered to 346 children between 7 and 14 years of age, attending primary and secondary schools in Northern Italy. Variables measured were externalization, quality of interpersonal relationships, aggression, quality of coping strategies, and parental stress. Participants who preferred violent games showed higher scores for externalization and aggression. The use of violent video games and age were linked to higher levels of aggression, coping strategies, and the habitual video game weekly consumption of participants. Our data confirm the role of violent video games as risk factors for problems of aggressive behavior and of externalization in childhood and early adolescence

A single case report of granular cell tumor of the tongue successfully treated through 445 nm diode laser

Oral granular cell tumor (GCT) is a relatively rare, benign lesion that can easily be misdiagnosed. Particularly, the presence of pseudoepitheliomatous hyperplasia might, in some cases, lead to the hypothesis of squamous cell carcinoma. Surgical excision is the treatment of choice. Recurrence has been reported in up to 15% of cases treated with conventional surgery. Here, we reported a case of GCT of the tongue in a young female patient, which was successfully treated through 445 nm diode laser excision. Laser surgery might reduce bleeding and postoperative pain and may be associated with more rapid healing. Particularly, the vaporization effect on remnant tissues could eliminate GCT cells on the surgical bed, thus hypothetically leading to a lower rate of recurrence. In the present case, complete healing occurred in 1 week, and no recurrence was observed after 6 months. Laser surgery also allows the possibility to obtain second intention healing. Possible laser-induced histopathological artifacts should be carefully considered

Age-dependent skewing of X chromosome inactivation appears delayed in centenarians\u2019 offspring. Is there a role for allelic imbalance in Healthy Aging and Longevity?

Recently, it has been proposed that age-related X chromosome inactivation (XCI) skewing can clinically result in late-onset X-linked disorders. This observation leads to hypothesize that age-related skewed XCI might also influence lifespan in women. To investigate this issue, we employed a new experimental model of longevity and healthy aging including 55 female centenarians, 40 of their offspring, 33 age-matched offspring of both non-long-lived parents and 41 young women. Peripheral blood DNA from 169 females was screened for heterozygosity at the HUMARA locus. We confirmed that skewing of XCI is an age-dependent phenomenon. However, skewed XCI was significantly less severe and frequent in centenarians' offspring [degree of skewing (DS) = 0.16 \ub1 0.02] compared to age-matched offspring of both non-long-lived parents (DS = 0.24 \ub1 0.02) (P &lt; 0.05). A second goal was to assess whether changes in XCI pattern could be a consequence of loss of methylation on X chromosome. Using a methylation array evaluating 1085 CpG sites across X chromosome and eleven CpG sites located at HUMARA locus, no differences in methylation levels and profiles emerged between all groups analysed, thus suggesting that age-associated epigenetic changes could not influence HUMARA results. In conclusion, the results presented herein highlight for the first time an interesting link between skewing of XCI and healthy aging and longevity. We speculate that the allelic imbalance produced by XCI skewing may compromise the cooperative and compensatory organization occurring between the two cell populations that make up the female mosaic