Chemical characterization of non-psychoactive Cannabis sativa L. extracts, in vitro antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells

In this study, extracts from non-psychoactive Cannabis sativa L. varieties were characterized by means of ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) and their antiproliferative activity was assessed in vitro. The human chronic myelogenous leukaemia cell line K562 was chosen to investigate the mechanism of cell death. The effect on the cell cycle and cell death was analysed by flow cytometry. Proteins related to apoptosis were studied by western blotting. Mechanical properties of cells were assessed using the Micropipette Aspiration Technique (MAT). The results indicated that the cannabidiol (CBD)-rich extract inhibited cell proliferation of K562 cell line in a dose-dependent manner and induced apoptosis via caspase 3 and 7 activation. A significant decrease in the mitochondrial membrane potential was detected, together with the release of cytochrome c into the cytosol. The main apoptotic markers were not involved in the mechanism of cell death. The extract was also able to modify the mechanical properties of cells. Thus, this hemp extract and its pure component CBD deserve further investigation for a possible application against myeloproliferative diseases, also in association with other anticancer drugs

Botanical sources, chemistry, analysis, and biological activity of furanocoumarins of pharmaceutical interest

The aim of this work is to provide a critical review of plant furanocoumarins from different points of view, including their chemistry and biosynthetic pathways to their extraction, analysis, and synthesis, to the main biological activities found for these active compounds, in order to highlight their potential within pharmaceutical science. The limits and the possible improvements needed for research involving these molecules are also highlighted and discussed

Late complications of robot-assisted radical cystectomy with totally intracorporeal urinary diversion

Introduction and objectives: To evaluate late complications in a large cohort of patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD). Materials and methods: We prospectively enrolled patients who underwent RARC and ICUD between August 2012 and June 2019. We excluded patients with Ejection fraction < 36%, retinal vasculopathy, ventriculoperitoneal shunts, and those treated without curative intent. All complications and their onset date have been recorded, defined, and graded according to Clavien classification adapted for radical cystectomy. Results: 210 patients were included, 76% of whom were men, with a mean age of 62 years. Urinary diversions used were Padua Ileal Bladder (PIB) in 80% of cases, and ileal conduit (IC) in 20% of patients (generally older and with more comorbidity). The mean follow-up was 30 ± 22 months. The stenosis rate of uretero-ileal anastomosis was 14%, while a reduction in eGFR (≥ 20%) was observed in about half of the cases. UTIs occurred in 37% of the patients, especially in the first 12 months. Only 2% of patients had bowel occlusion, whereas incisional hernia, lymphocele, and systemic events (metabolic acidosis and major cardiovascular events) occurred respectively in 20%, 10%, and 1% of cases. Conclusions: Our study evaluates first late complications in a cohort of patients who underwent RARC with ICUD. These data are encouraging and in line with findings from a historical series of open radical cystectomy (ORC). This study is a further step in supporting RARC as a safe and effective surgical option for the treatment of muscle-invasive bladder cancer (MIBC) in tertiary referral centers

Artificial Intelligence Can Guide Antibiotic Choice in Recurrent UTIs and Become an Important Aid to Improve Antimicrobial Stewardship

Background: A correct approach to recurrent urinary tract infections (rUTIs) is an important pillar of antimicrobial stewardship. We aim to define an Artificial Neural Network (ANN) for predicting the clinical efficacy of the empiric antimicrobial treatment in women with rUTIs. Methods: We extracted clinical and microbiological data from 1043 women. We trained an ANN on 725 patients and validated it on 318. Results: The ANN showed a sensitivity of 87.8% and specificity of 97.3% in predicting the clinical efficacy of empirical therapy. The previous use of fluoroquinolones (HR = 4.23; p = 0.008) and cephalosporins (HR = 2.81; p = 0.003) as well as the presence of Escherichia coli with resistance against cotrimoxazole (HR = 3.54; p = 0.001) have been identified as the most important variables affecting the ANN output decision predicting the fluoroquinolones-based therapy failure. A previous isolation of Escherichia coli with resistance against fosfomycin (HR = 2.67; p = 0.001) and amoxicillin-clavulanic acid (HR = 1.94; p = 0.001) seems to be the most influential variable affecting the output decision predicting the cephalosporins- and cotrimoxazole-based therapy failure. The previously mentioned Escherichia coli with resistance against cotrimoxazole (HR = 2.35; p < 0.001) and amoxicillin-clavulanic acid (HR = 3.41; p = 0.007) seems to be the most influential variable affecting the output decision predicting the fosfomycin-based therapy failure. Conclusions: ANNs seem to be an interesting tool to guide the antimicrobial choice in the management of rUTIs at the point of care

Particulate air pollution, blood mitochondrial DNA copy number, and telomere length in mothers in the first trimester of pregnancy : effects on fetal growth

Growing evidences have shown that particulate matter (PM) exposures during pregnancy are associated with impaired fetal development and adverse birth outcomes, possibly as a result of an exaggerated systemic oxidative stress and inflammation. Telomere length (TL) is strongly linked to biological age and is impacted by oxidative stress. We hypothesized that PM exposure during different time windows in the first trimester of pregnancy influences both mitochondrial DNA copy number (mtDNAcn), an established biomarker for oxidative stress, and TL. Maternal blood TL and mtDNAcn were analysed in 199 healthy pregnant women recruited at the 11th week of pregnancy by quantitative polymerase chain reaction. We also examined whether maternal mtDNAcn and TL were associated with fetal growth outcomes measured at the end of the first trimester of pregnancy (fetal heart rate, FHR; crown-rump length, CRL; and nuchal translucency, NT) and at delivery (birth weight, length, head circumference). The possible modifying effect of prepregnancy maternal body mass index was evaluated. PM10 exposure during the first pregnancy trimester was associated with an increased maternal mtDNAcn and a reduced TL. As regards ultrasound fetal outcomes, both FHR and CRL were positively associated with PM2.5, whereas the association with FHR was confirmed only when examining PM10 exposure. PM10 was also associated with a reduced birth weight. While no association was found between mtDNAcn and CRL, we found a negative relationship between mtDNAcn and fetal CRL only in overweight women, whereas normal-weight women exhibited a positive, albeit nonsignificant, association. As abnormalities of growth in utero have been associated with postnatal childhood and adulthood onset diseases and as PM is a widespread pollutant relevant to the large majority of the human population and obesity a rising risk factor, our results, if confirmed in a larger population, might represent an important contribution towards the development of more targeted public health strategies

Reverse end-diastolic flow in a fetus with a rare liver malformation: a case report

<p>Abstract</p> <p>Introduction</p> <p>We describe a case of early and persistent reverse end-diastolic flow in the middle cerebral artery in a fetus with severe ascites. These features are associated with a rare liver malformation known as ductal plate malformation.</p> <p>Case presentation</p> <p>A 28-year-old Caucasian woman was referred to our high-risk obstetric unit at 24 weeks' gestation for fetal ascites detected during a routine ultrasound examination. During her hospitalization we performed medical investigations, including a fetal paracentesis, to detect the etiology of fetal ascites. The cause of fetal ascites (then considered non-immune or idiopathic) was not evident, but a subsequent ultrasound examination at 27 weeks' gestation showed a reverse end-diastolic flow in the middle cerebral artery without any other Doppler abnormalities. A cesarean section was performed at 28 weeks' gestation because of the compromised fetal condition. An autopsy revealed a rare malformation of intrahepatic bile ducts known as ductal plate malformation.</p> <p>Conclusion</p> <p>Persistent reverse flow in the middle cerebral artery should be considered a marker of adverse pregnancy outcome. We recommend careful ultrasound monitoring in the presence of this ultrasonographic sign to exclude any other cause of increased intracranial pressure. To better understand the nature of these ultrasonographic signs, additional reports are deemed necessary. In fact in our case, as confirmed by histopathological examination, the fetal condition was extremely compromised due to failure of the fetal liver. Ductal plate malformation altered the liver structures causing hypoproteinemia and probably portal hypertension. These two conditions therefore explain the severe hydrops that compromised the fetal situation.</p

After personalism: rethinking power transfers in Turkmenistan and Uzbekistan

What happens to elites when the personalistic leader they supported for so long suddenly dies? This article tackles comparatively transitions out of first presidencies in Turkmenistan and Uzbekistan, presenting an analytical framework that seeks to explain why these transitions unfolded in relatively smooth fashion. The overall stability defining power transfer processes instigated by the non-violent death of personalistic rulers in both contexts is explained here through the intersection of three key factors: the regimes’ resort to succession practices consolidated in the Soviet era, the emergence of temporary forms of collective decision-making in both transitional contexts, and the implementation of de-personalisation strategies pursuing the obliteration of specific pockets of cadres but stopping short of wider regime re-organisation. The findings of this article contribute to broader debates on the politics of de-personalisation, while putting forward a comprehensive framework to analyse transitions out of personalism in and beyond post-Soviet Eurasia

Social Design. Design e bene comune.

Per questo primo doppio numero della rivista, Social Design. Design e "bene comune", curato da Marinella Ferrara, Francesco E. Guida, Mario Piazza, Paola Proverbio e Raimonda Riccini, quasi come una sfida, si è provato a rompere l’ortodossia di un approccio lineare alla storia. In questo orientamento, che tende a portare più vicino a noi i temi storici, il Social Design si offre in modo calzante per il suo essere questione contemporanea e complessa, ampia e ambigua financo controversa, anche solo dal punto di vista delle diverse espressioni sinonimiche con cui si presenta: design etico, design umanitario, design per la collettività, design di pubblica utilità, design per l’utenza ampliata, design per la sostenibilità, ... Il numero ha ricevuto la Menzione d'Onore alla XXVII edizione del Compasso d'Oro (giugno 2022), ed è stato segnalato nell'ADI Design Index 2021 (promosso da ADI, Associazione per il Disegno Industriale) nella sezione "Ricerca teorica, storica, critica e progetti editoriali"