Abemaciclib: A CDK4/6 inhibitor for the treatment of HR+/HEeR2- advanced breast cancer

Although early breast cancer (BC) is highly curable, advanced or metastatic disease poses numerous challenges in terms of medical management and treatment decisions and is associated with significantly worse prognosis. Among the new targeted agents, anticancer drugs exploiting the cell-cycle machinery have shown great potential in preclinical studies. CDK4/6 inhibitors target the cyclin D/CDK/retinoblastoma signaling pathway, inducing cell-cycle arrest, reduced cell viability and tumor shrinking. As the cyclin D/CDK complex is activated downstream of estrogen signaling, the combination of CDK4/6 inhibitors with standard endocrine therapies represents a rational approach to elicit synergic antitumor activity in hormone receptor-positive BC. The results of clinical trials have indeed confirmed the superiority of the combination of CDK4/6 inhibitors plus endocrine therapies over endocrine therapy alone. Currently approved are three compounds that exhibit similar structural characteristics as well as biological and clinical activities. Abemaciclib is the latest CDK4/6 inhibitor approved by the US Food and Drug Administration (FDA) in view of the results of the MONARCH 1 and 2 trials. Further trials are ongoing as other important questions await response. In this review, we focus on abemaciclib to examine preclinical and clinical results, describing current therapeutic indications, open questions and ongoing clinical trials

Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma

Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16(INK4A) tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependent kinase 4 and 6 inhibitor, that normally phosphorylates RB1, which has to be un-phosphorylated in order to block cell-cycle at G1 in normal cells. Adding CDK inhibitor molecules to MM in pre-clinical studies has been proven to restore the normal function of p16(INK4A), blocking thereby MM cell cycle at G1. Future randomised phase III studies with CDK4/6 inhibitors in MM carrying relevant CDK4/6, cyclin D1/3 or p16 aberrations will be warranted

The Outcomes of an Opioid-Free Anaesthetic Plan in Fourteen Dogs Undergoing Enucleation Using an Ultrasound-Guided Supra-Temporal Retrobulbar Block: A Retrospective Case Series

The objective of this retrospective case series is to report the outcomes of an opioid-free anesthetic plan in dogs undergoing enucleation surgery. A total of 14 dogs were admitted for enucleation between March and December 2020. A multimodal approach to perioperative analgesia was used, with a focus on retrobulbar anesthesia. A combination of an ultrasound-guided retrobulbblock with a supratemporal approach in association with ketamine, dexmedetomidine and non-steroidal anti-inflammatory drugs was used in the reported cases. Intraoperative nociception was defined as an increase of 20% from the baseline in one or more of the following parameters: heart rate, respiratory rate or mean arterial pressure. An ultrasound-guided retrobulbar block in an opioid-free anesthesia regime was effective at managing the perioperative analgesia of 13 out of 14 dogs. In only one case, a bolus of fentanyl was administered to treat intraoperative nociception. Recovery was uneventful in all the dogs, and the postoperative pain scores remained below the intervention threshold at all time points. To the authors’ knowledge, this is the first reported case series of opioid-free anesthesia for enucleation in dogs

Sexual dysfunction in subjects treated with inhibitors of 5a-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis

Sexual dysfunction in subjects treated with inhibitors of 5a-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysi

Large-scale monitoring of coppice forest clearcuts by multitemporal very high resolution satellite imagery. A case study from central Italy

Reliable assessment of forest resource stock, productivity and harvesting is a commonly agreed objective of environmental monitoring programs. Distinctively, the assessment of wood harvesting has become even more relevant to evaluate the sustainability of forest management and to quantify forest carbon budget. This paper presents the development and testing of procedures for assessing forest harvesting in coppice forests by very high resolution (VHR) satellite imagery. The study area is located in central Italy over approximately 34,000 km2. A set of SPOT5 HRG multispectral images was acquired for the study years (2002–2007). Official administrative statistics of coppice clearcutswere also acquired.More than 9500 clearcuts weremapped and dated by on-screen interpretation of the SPOT5 images. In a subset of the study area various methods for semi-automatic clearcut mapping were tested by pixel- and object-oriented approaches. The following results are presented: (i) clearcut map developed by visual interpretation of the SPOT5 images resulted in high thematic (overall accuracy of 0.99) and geometric (rootmean square error of clearcut boundary delineation of 5.3 m) reliability; (ii) object-oriented approach achieved significantly better accuracy than pixel-based methods for semi-automatic classification of the coppice clearcuts; (iii) comparison between mapped clearcut area and official forest harvesting statistics proved a significant underestimation by the latter (65% of the total mapped clearcut area). A sample-based procedure exploiting VHR satellite imagery is finally proposed to correct the official statistics of coppice clearcuts.L'articolo è disponibile sul sito dell'editore www.sciencedirect.co

Estimation of canopy attributes in beech forests using true colourdigital images from a small fixed-wing UAV

Accurate estimates of forest canopy are essential for the characterization of forest ecosystems. Remotely-sensed techniques provide a unique way to obtain estimates over spatially extensive areas, but their application is limited by the spectral and temporal resolution available from these systems, which is often not suited to meet regional or local objectives. The use of unmanned aerial vehicles (UAV) as remote sensing platforms has recently gained increasing attention, but their applications in forestry are still at an experimental stage. In this study we described a methodology to obtain rapid and reliable estimates of forest canopy from a small UAV equipped with a commercial RGB camera. The red, green and blue digital numbers were converted to the green leaf algorithm (GLA)and to the CIE L∗a∗b∗colour space to obtaine stimates of canopy cover, foliage clumping and leaf area index (L) from aerial images. Canopy attributes were compared with in situ estimates obtained from two digital canopy photographic techniques (cover and fisheye photography).The method was tested in beech forests. UAV images accurately quantified canopy cover even in very dense stand conditions, despite a tendency to not detecting small within-crown gaps in aerial images, leading to a measurement of a quantity much closer to crown cover estimated from in situ cover photography. Estimates of L from UAV images significantly agreed with that obtained from fisheye images, but the accuracy of UAV estimates is influenced by the appropriate assumption of leaf angle distribution. We concluded that true colour UAV images can be effectively used to obtain rapid, cheap and meaningful estimates of forest canopy attributes at medium-large scales. UAV can combine the advantage of high resolution imagery with quick turnaround series, being therefore suitable for routine forest stand monitoring and real-time applications.L'articolo è disponibile sul sito dell'editore www.elsevier.com/locate/ja

The SIAMS-ED Trial: A National, Independent, Multicentre Study on Cardiometabolic and Hormonal Impairment of Men with Erectile Dysfunction Treated with Vardenafil

Increased cardiovascular risk has been associated with reduced response to proerectile drugs. The Italian Society of Andrology and Sexual Medicine (SIAMS) promoted an independent, multicenter study performed in 604 men (55 ± 12 yrs) suffering from erectile dysfunction (ED) to assess multiple health outcomes and response to 6-month vardenafil challenge in a real-life setting. Overall, 30.8% men had metabolic syndrome. Cardiovascular risk stratification revealed a greater number of ED subjects with moderate risk of a major adverse cardiovascular event than the general population (P < 0.01). Age-adjusted pulse pressure was positively correlated with ED severity and negatively with androgens and waist circumference (P < 0.01). A decline in total testosterone was observed with increasing arterial pulse pressure (P < 0.05), which was not accompanied by compensatory LH rise. Follow-up on 185 men treated with vardenafil in an nonrandomized, open, single-arm trial documented a significant rise in IIEF-5 (delta = 6.1 ± 4.8) that was maintained in men with high cardiovascular risk. Mild adverse events occurred in <5%, with no differences between cardiovascular risk classes. In summary, ED is a frequent symptom in patients with an elevated, but often unknown, risk of future cardiovascular events. Androgens predict vascular resistance in ED patients. Vardenafil's response and safety profile were preserved in subjects with higher cardiovascular risk

Use of Kluyveromyces marxianus to Increase Free Monoterpenes and Aliphatic Esters in White Wines

An increasing interest in novel wine productions is focused on non-Saccharomyces yeasts due to their potential in improving sensory profiles. Although Kluyveromyces marxianus has been originally isolated from grapes and its enzymatic activities are used in oenology, rarely it has been used as co-starter. The K. marxianus Km L2009 strain has been characterized here and selected as a co-starter both at laboratory- and winery-scale fermentation. The Km L2009 strain showed growth of up to 40 (mg/L) of sulfites and 6% (v/v) of ethanol. Gas chromatographic analysis demonstrates that wines produced by mixed fermentation contain remarkably higher quantities of free monoterpenes and aliphatic esters than wines produced only by commercial strains of Saccharomyces cerevisiae. Differences in the volatile organic compound composition produced sensorially distinct wines. In light of these results, it is possible to state that even within the K. marxianus species it is possible to select strains capable of improving the aromatic quality of wines

Stand structure attributes in potential Old-Growth Forests in the Apennines, Italy

The aim of this paper is to provide early feedback on stand structure attributes in Italian Apennines forests that could be considered Old Growth Forests in the Mediterranean Eco-Region. Few data are nowadays available relating to this Region. 10 forest reserves across the Apennines were selected and a census of trees and structural parameters was conducted in permanent plots (0.16-1.0 ha), one plot for each selected forest stand. Dimensional and structural characters indicate a large variability among the investigated forest stands. The considered parameters are compared with those reported for other European countries. Old growth features and characteristics of each indicator should be revised and referred to the particular climatic and biogeographic context. The chosen forest study sites are to be considered old if related to common Apennine stands but, in some cases, their development stage is not so close to “truly” Old Growth Forest. Permanent plots allow future investigations on dynamic processes leading to real Old Growth Mediterranean Forests in Italian Apennines