Basal cell carcinoma: A comprehensive review

Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge

MiR-1227 targets SEC23A to regulate the shedding of large extracellular vesicles

Cancer cells shed a heterogenous mixture of extracellular vesicles (EVs), differing in both size and composition, which likely influence physiological processes in different manners. However, how cells differentially control the shedding of these EV populations is poorly understood. Here, we show that miR-1227, which is enriched in prostate cancer EVs, compared to the cell of origin, but not in EVs derived from prostate benign epithelial cells, induces the shedding of large EVs (such as large oncosomes), while inhibiting the shedding of small EVs (such as exosomes). RNA sequencing from cells stably expressing miR-1227, a modified RISCTRAP assay that stabilizes and purifies mRNA-miR-1227 complexes for RNA sequencing, and in silico target prediction tools were used to identify miR-1227 targets that may mediate this alteration in EV shedding. The COPII vesicle protein SEC23A emerged and was validated by qPCR, WBlot, and luciferase assays as a direct target of miR-1227. The inhibition of SEC23A was sufficient to induce the shedding of large EVs. These results identify a novel mechanism of EV shedding, by which the inhibition of SEC23A by miR-1227 induces a shift in EV shedding, favoring the shedding of large EV over small EV

Monitoring of total positive end-expiratory pressure during mechanical ventilation by artificial neural networks

Ventilation treatment of acute lung injury (ALI) requires the application of positive airway pressure at the end of expiration (PEEPapp) to avoid lung collapse. However, the total pressure exerted on the alveolar walls (PEEPtot) is the sum of PEEPapp and intrinsic PEEP (PEEPi), a hidden component. To measure PEEPtot, ventilation must be discontinued with an end-expiratory hold maneuver (EEHM). We hypothesized that artificial neural networks (ANN) could estimate the PEEPtot from flow and pressure tracings during ongoing mechanical ventilation. Ten pigs were mechanically ventilated, and the time constant of their respiratory system (τRS) was measured. We shortened their expiratory time (TE) according to multiples of τRS, obtaining different respiratory patterns (Rpat). Pressure (PAW) and flow (V′AW) at the airway opening during ongoing mechanical ventilation were simultaneously recorded, with and without the addition of external resistance. The last breath of each Rpat included an EEHM, which was used to compute the reference PEEPtot. The entire protocol was repeated after the induction of ALI with i.v. injection of oleic acid, and 382 tracings were obtained. The ANN had to extract the PEEPtot, from the tracings without an EEHM. ANN agreement with reference PEEPtot was assessed with the Bland–Altman method. Bland Altman analysis of estimation error by ANN showed −0.40 ± 2.84 (expressed as bias ± precision) and ±5.58 as limits of agreement (data expressed as cmH2O). The ANNs estimated the PEEPtot well at different levels of PEEPapp under dynamic conditions, opening up new possibilities in monitoring PEEPi in critically ill patients who require ventilator treatment

American palm ethnomedicine: A meta-analysis

<p>Abstract</p> <p>Background</p> <p>Many recent papers have documented the phytochemical and pharmacological bases for the use of palms (<it>Arecaceae</it>) in ethnomedicine. Early publications were based almost entirely on interviews that solicited local knowledge. More recently, ethnobotanically guided searches for new medicinal plants have proven more successful than random sampling for identifying plants that contain biodynamic ingredients. However, limited laboratory time and the high cost of clinical trials make it difficult to test all potential medicinal plants in the search for new drug candidates. The purpose of this study was to summarize and analyze previous studies on the medicinal uses of American palms in order to narrow down the search for new palm-derived medicines.</p> <p>Methods</p> <p>Relevant literature was surveyed and data was extracted and organized into medicinal use categories. We focused on more recent literature than that considered in a review published 25 years ago. We included phytochemical and pharmacological research that explored the importance of American palms in ethnomedicine.</p> <p>Results</p> <p>Of 730 species of American palms, we found evidence that 106 species had known medicinal uses, ranging from treatments for diabetes and leishmaniasis to prostatic hyperplasia. Thus, the number of American palm species with known uses had increased from 48 to 106 over the last quarter of a century. Furthermore, the pharmacological bases for many of the effects are now understood.</p> <p>Conclusions</p> <p>Palms are important in American ethnomedicine. Some, like <it>Serenoa repens </it>and <it>Roystonea regia</it>, are the sources of drugs that have been approved for medicinal uses. In contrast, recent ethnopharmacological studies suggested that many of the reported uses of several other palms do not appear to have a strong physiological basis. This study has provided a useful assessment of the ethnobotanical and pharmacological data available on palms.</p

Monitoraggio della meccanica respiratoria durante ventilazione artificiale in pazienti con insufficienza respiratoria acuta (il problema della PEEPi).

"La Garangola", Padov

Late, but not early, asthmatic reactions induced by toluene-diisocyanate are associated with increased airway responsiveness to methacholine.

We investigated whether airway responsiveness to methacholine differs in subjects with a history of sensitization to TDI who develop immediate, dual, late, or no asthmatic reactions after exposure to TDI, and also the effect of a TDI inhalation challenge in asthmatic subjects with hyperreactive airways with no history of sensitization to TDI. We measured FEV-1 immediately before and after exposure to TDI (0.018 ppm; 5-30 min) and then hourly for 8 h and the provocative dose (mg) of methacholine that caused a decrease in FEV-1 of 20% (PD20 FEV-1). The results of the present study suggest that the bronchoconstrictor effect of isocyanates is specifically linked to exposure to TDI and subsequent sensitization, excluding a nonspecific irritant effect on the airways. Moreover, they suggest that the increase in airway responsiveness to methacholine associated with the late asthmatic reaction is linked to factors that cause the late component of the asthmatic reaction

Attractive serial dependence in numerosity perception in dogs (Canis familiaris).

Recent literature in humans has described a perceptual phenomenon called serial dependence, by which the current stimulus appears similar to the previous one. It has been interpreted as an active stabilization process, integrating stimulus features over time for a stable and seamless conscious experience. Despite the growing number of studies investigating serial dependence across several visual domains in humans, it is not known if the phenomenon extends also to other species. In the current study we aim to fill this gap of knowledge by exploring the behavioral signature of serial dependence in numerosity perception in dogs. We enrolled 5 dogs, who were trained on quantity discrimination prior to being presented with a set of test trials. Simultaneously presented test stimuli included a variable probe (4-16 dots) and a reference (8 dots), which was preceded by a task-irrelevant inducer stimulus (4 or 16) in the identical location. We hypothesized that if dogs are susceptible to the serial dependence, the reference would be perceived either smaller or larger depending on the inducer numerosity. For each dog we fitted a psychometric curve based on the probability of choosing the reference and defined the point of subjective equality (PSE) for the reference preceded by either of the inducer, (PSE(4)=7.10; PSE(16)=10.07). To compare the perceptual effect of the two inducers, we performed an ANOVA, which revealed a significant effect of the inducer (F(2)=23.87; p<0.001), with both of theconditions being significantly different from the control condition (p(4)=0.35; p(16)=0.02, sequential Bonferroni corrections applied). This result suggests an attractive bias in consecutively presented stimuli in dogs, providing the first evidence that the phenomenon of serial dependence extends also to non-human animals. Moreover, the finding expands the similarities between humans and dogs in processing visual stimuli