Purpose/background: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. Methods/procedures: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. Findings/results: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. Implications/conclusions: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.
Iridium films grown by pulsed laser deposition (PLD) show different critical temperatures ( T<sub>c</sub> ), which can be almost twice the T<sub>c</sub> of the bulk. This difference is related to the thickness and deposition conditions. To understand this effect, we grew different films with different configuration parameters: laser focusing, distance to the Ir target, and deposition time. We then measured the T<sub>c</sub> and analyzed the film with structural measurements by X-ray diffraction (XRD), looking at a possible correlation with the grain size of the film itself. The work was performed to determine the film growth conditions at which it is possible to obtain predetermination of T<sub>c</sub> with good accuracy using XRD pattern characteristics of Ir films.
Sliced cooked ham stored in modified atmosphere packaging (MAP) can be spoiled by lactic acid bacteria (LAB) which are dominating under psychrotrophic conditions. Depending on the strains, the colonization can result in a premature spoilage characterized by off-flavors, gas and slime production, discoloration, and acidification. The purpose of this study was the isolation, identification and characterization of potential food culture with protective properties, able to prevent or delay spoilage in cooked-ham. The first step was to identify by means of microbiological analysis, the microbial consortia both in unspoiled and in spoiled lots of sliced cooked ham by the use of media for the detection lactic acid bacteria and total viable count. Counts ranged from values lower than 1 Log CFU/g to 9 Log CFU/g in spoiled and unflawed samples. The interaction between consortia was then studied in order to screen for strains able to inhibit spoilage consortia. Strains showing antimicrobial activity were identified and characterized by molecular methods and tested for their physiological features. Among a total of 140 strains isolated, nine were selected for their ability to inhibit a large number of spoilage consortia, to grow and ferment at 4 °C and to produce bacteriocins. The effectiveness of the fermentation made by food culture was evaluated, through challenge tests in situ, analysing the microbial profiles of artificially inoculated cooked-ham slices during storage by high throughput 16 S rRNA gene sequencing. The native population in situ resulted competitive against the inoculated strains and only one strain was able to significantly reduce the native populations reaching about 46.7% of the relative abundance. The results obtained in this study provide information about the selection of autochthonous LAB on the base of their action against spoilage consortia, in order to select protective potential cultures able to improve the microbial quality of sliced cooked ham.
In this paper, we propose an analysis of the automorphism group of polar codes, with the aim of designing codes tailored for automorphism ensemble (AE) decoding. Using a novel description of polar codes as monomial codes through negative monomials, we prove the equivalence between the notion of decreasing monomial codes and the universal partial order (UPO) framework for polar codes; this property is widely believed to hold true but a formal proof was missing. We further provide a rigorous mathematical connection between code word permutations and affine transformations, an important link to understand the considered automorphisms. Based on this mathematical formalisms, we analyze the algebraic properties of the affine automorphisms group of polar codes, providing a novel description of its structure. We classify automorphisms such that all automorphisms in the same class lead to the same result under permutation decoding, which gives rise to the concept of redundant automorphisms. Mathematically this is achieved by introducing equivalence classes of affine automorphisms under AE-based decoding. For practical application, we provide an algorithm to compute representatives for the equivalence classes, such that one automorphism from each equivalence class can be selected for use in AE decoding. A numerical analysis of the error correction performance of AE decoding of polar codes, based on equivalence classes, concludes the paper.
Background: According to current guidelines, a surgical biopsy is rarely required when a high-confidence radiologic interstitial lung disease (ILD) diagnosis is made on thin-section high-resolution computed tomography (HRCT). Nevertheless, disowning HRCT scans diagnosed by biopsy are more common than presumed. Our study aimed to describe the concordance rate between HRCT scans and pathological diagnoses of ILDs obtained by surgical biopsy. The current guideline suggests the use of surgical lung biopsy (SLB) in patients with newly detected ILD of unknown cause. Methods: Patients who underwent mini-invasive surgical biopsies for interstitial lung diseases from January 2018 to August 2022 were analyzed. The HRCT scans were reviewed by an observer blinded to the patient's clinical information. The concordance between histological and HRCT-scan were assessed. Results: Data from 104 patients with uncertain low confidence diagnosis of interstitial lung diseases at HRCT were analyzed. Most of the patients are male (65; 62.5%). The more frequent HRCT pattern were: alternative diagnoses (46; 44.23%), UIP probable (42; 40.38%), UIP indeterminate (7; 6.73%), and non-specific interstitial pneumonia (NSIP) (9, 8.65%). The more common histological diagnosis was UIP definite (30; 28.84%), hypersensitivity pneumonia [HP](19; 18.44%), NSIP (15; 14.42%), sarcoidosis (10; 9.60%). In 7 (20%) cases, the final pathological finding denies HRCT-scans diagnoses; indeed, a moderate agreement was observed between HRCT-scan findings and the definitive histological diagnosis (kappa index: 0.428). Conclusions: HRCT-scan has limitations if the objective is to define interstitial lung diseases accurately. Consequently, pathological assessment should be taken into account in order to provide more accurate tailored treatment strategies because the risk is to wait from 12 to 24 months to ascertain if the ILD will be treatable as progressive pulmonary fibrosis (PPF). Undeniably true, video-assisted surgical lung biopsy (VASLB) with endotracheal intubation and mechanical ventilation is associated with a risk of mortality and morbidity that is far from nil. Nevertheless, in recent years a VASLB approach performed in awake subjects under loco-regional anesthesia (awake-VASLB) has been suggested as an effective method to obtain a highly confident diagnosis in patients with diffuse pathologies of the lung parenchyma.
Background: The aim of the study was to compare the effect on perioperative outcome of intraoperative use of different devices for tissue dissection (electrocoagulation [EC] or energy devices [ED]) in patients who underwent video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer. Methods: We retrospectively reviewed 191 consecutive patients who underwent VATS lobectomy, divided into two cohorts: ED (117 patients), and EC (74 patients); after propensity score matching, 148 patients were extracted, 74 for each cohort. The primary endpoints considered were complication rate and 30-day mortality rate. The secondary endpoints considered were length of stay (LOS) and the number of lymph nodes harvested. Results: The complication rate did not differ between the two cohorts (16.22% EC group, 19.66% ED group, P=0.549), before and after propensity matching (16.22% for both EC and ED group, P=1.000). The 30-day mortality rate was 1 in the overall population. Median LOS was 5 days for both groups, before and after propensity match, with the same interquartile range, (IQR: 4-8). ED group had a significantly higher median number of lymph nodes harvested (ED median: 18, IQR: 12-24; EC median: 10, IQR: 5-19; P=0.0002). The difference was confirmed after the propensity score matching (ED median: 17, IQR: 13-23; EC median: 10, IQR: 5-19; P=0.0008). Conclusions: ED dissection during VATS lobectomy did not lead to different complication rates, mortality rates, and LOS compared to EC tissue dissection. ED use led to a significantly higher number of intraoperative lymph nodes harvested compared to EC use.
The ERBB tyrosine kinase receptors and their ligands belong to a complex family that has diverse biological effects and expression profiles in the developing mammary glands, where its members play an essential role in translating hormone signals into local effects. While our understanding of these processes stems mostly from mouse models, there is the potential for differences in how this family functions in the mammary glands of other species, particularly in light of their unique histomorphological features. Herein we review the postnatal distribution and function of ERBB receptors and their ligands in the mammary glands of rodents and humans, as well as for livestock and companion animals. Our analysis highlights the diverse biology for this family and its members across species, the regulation of their expression, and how their roles and functions might be modulated by varying stromal composition and hormone interactions. Given that ERBB receptors and their ligands have the potential to influence processes ranging from normal mammary development to diseased states such as cancer and/or mastitis, both in human and veterinary medicine, a more complete understanding of their biological functions should help to direct future research and the identification of new therapeutic targets.
A mild and efficient telescoped procedure for the stereoselective alkenylation of simple, non-activated amides using LiCH2SiMe3 and carbonyl compounds as surrogates of alkenyllithium reagents is reported. Our methodology relies on the formation of stable tetrahedral intermediates, which, upon collapse into highly reactive lithium enolates in a solvent-dependent fashion, allows for the assembly of α,β-unsaturated ketones in a single synthetic operation with high stereoselectivity.
Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine kinase and an attractive therapeutic target for Alzheimer's disease. Based on proteolysis-targeting chimera (PROTAC) technology, a small set of novel GSK-3β degraders was designed and synthesized by linking two different GSK-3β inhibitors, SB-216763 and tideglusib, to pomalidomide, as E3 recruiting element, through linkers of different lengths. Compound 1 emerged as the most effective PROTAC being nontoxic up to 20 μM to neuronal cells and already able to degrade GSK-3β starting from 0.5 μM in a dose-dependent manner. PROTAC 1 significantly reduced the neurotoxicity induced by Aβ25-35 peptide and CuSO4 in SH-SY5Y cells in a dose-dependent manner. Based on its encouraging features, PROTAC 1 may serve as a starting point to develop new GSK-3β degraders as potential therapeutic agents.
Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative condition. Despite significant advances in pre-clinical models that enhance understanding of disease pathobiology, translation of candidate drugs to effective human therapies has been disappointing. There is increasing recognition of the need for a precision medicine approach toward drug development, as many failures in translation can be attributed in part to disease heterogeneity in humans. PRECISION-ALS is an academic industry collaboration between clinicians, Computer Scientists, Information engineers, technologists, data scientists and industry partners that will address the key clinical, computational, data science and technology associated research questions to generate a sustainable precision medicine based approach toward new drug development. Using extant and prospectively collected population based clinical data across nine European sites, PRECISION-ALS provides a General Data Protection Regulation (GDPR) compliant framework that seamlessly collects , processes and analyses research-quality multimodal and multi-sourced clinical, patient and caregiver journey, digitally acquired data through remote monitoring, imaging, neuro-electric-signaling, genomic and biomarker datasets using machine learning and artificial intelligence. PRECISION-ALS represents a first-in-kind modular transferable pan-European ICT framework for ALS that can be easily adapted to other regions that face similar precision medicine related challenges in multimodal data collection and analysis.
During field surveys conducted from June to October 2020 in 13 locations belonging to five governorates in North and South Jordan, typical grapevine yellows symptoms, including leaf reddening/yellowing and rolling, were observed in wine and table grape cultivar vineyards. Percentage of symptomatic vines ranged from 10 to 55%. Nested PCR-based amplification of 16S rRNA gene detected phytoplasmas in 22% and 15.7% of the analyzed symptomatic wine and table grape cultivar plants, respectively. Amplicon nucleotide sequence analyses allowed attributing the detected phytoplasmas to ‘Candidatus Phytoplasma solani’ (taxonomic subgroup 16SrXII-A), ‘Ca. P. omanense’ (16SrXXIX-A and -B), ‘Ca. P. aurantifolia’ (16SrII-C), and ‘Ca. P. asteris’ (16SrI-R) in 72.4%, 17.2%, 6.9%, 3.4% of infected plants, respectively. Such phytoplasmas were found differentially distributed in wine and table grape cultivar vineyards in the considered locations. Further investigation allowed identifying ‘Ca. P. solani’ in the putative insect vectors Orosius cellulosus (firstly reported in Jordan), Euscelidius mundus, Laodelphax striatellus, and Circulifer sp., and in bindweed; ‘Ca. P. aurantifolia’ in the insect O. cellulosus and in bindweed; ‘Ca. P. omanense’ in the insect Psammotettix striatus; ‘Ca. P. asteris’ in the insects Arboridia adanae, Cicadulina bipunctata, Circulifer sp., L. striatellus, Hyalesthes obsoletus, and P. striatus. Based on this preliminary data, ecological cycles of such phytoplasmas are discussed. Obtained results suggest that grapevine yellows phytoplasma diversity and ecology in Jordan are more complex than previously known, leading to a potential risk of disease outbreaks.
We extensively study the Toner-Tu-Swift-Hohenberg model of motile active matter by means of direct numerical simulations in a two-dimensional confined domain. By exploring the space of parameters of the model we investigate the emergence of a new state of active turbulence which occurs when the aligning interactions and the self-propulsion of the swimmers are strong. This regime of flocking turbulence is characterized by a population of few strong vortices, each surrounded by an island of coherent flocking motion. The energy spectrum of flocking turbulence displays a power-law scaling with an exponent which depends weakly on the model parameters. By increasing the confinement we observe that the system, after a long transient characterized by power-law-distributed transition times, switches to the ordered state of a single giant vortex.
Purpose of review Personality characteristics, such as alexithymia, may lead to alterations in the autonomic nervous system functionality, predisposing individuals to an increased risk of hypertension (HTN). The present meta-analysis aimed to quantify the presence of alexithymia in people with HTN and to assess for potential sources of heterogeneity between studies. PubMed, PsycINFO and Scopus databases were systematically searched, using the following strings: (“alexithymia” OR “alexithymic”) AND (“hypertension” OR “hypertensive”). Data were meta-analyzed with random-effects models. Recent findings A total of 13 studies met the inclusion criteria. The prevalence of alexithymia in people with and without HTN were obtained from 5 studies (26.3% vs 15.0%; pooling of odd ratios, 3.15 [95% CI, 1.14;8.74]), whereas the mean level of alexithymia between people with and without HTN was obtained from 7 studies Hedges g, 1.39 [95% CI, -0.39;3.16]). There was a significant association between alexithymia prevalence and year of article publication (ĝ = -0.04; 95% CI, -0.07;-0.01), whereas no significant relationship was detected between the former and both sex and age. Summary Findings revealed a greater prevalence of alexithymia in people with HTN than in participants without HTN. These findings suggest that alexithymia may contribute to both the onset and persistence of HTN symptomatology. However, future research is needed to clarify this association.
The population experiencing high temperatures in cities is rising due to anthropogenic climate change, settlement expansion, and population growth. Yet, efficient tools to evaluate potential intervention strategies to reduce population exposure to Land Surface Temperature (LST) extremes are still lacking. Here, we implement a spatial regression model based on remote sensing data that is able to assess the population exposure to LST extremes in urban environments across 200 cities based on surface properties like vegetation cover and distance to water bodies. We define exposure as the number of days per year where LST exceeds a given threshold multiplied by the total urban population exposed, in person ⋅ day. Our findings reveal that urban vegetation plays a considerable role in decreasing the exposure of the urban population to LST extremes. We show that targeting high-exposure areas reduces vegetation needed for the same decrease in exposure compared to uniform treatment.
The efficacious delivery of therapeutic nucleic acids to cancer still remains an open issue. Through the years, several strategies have been developed for the encapsulation of genetic molecules exploiting different materials, such as viral vectors, lipidic nanoparticles and polymeric nanoparticles. Indeed, the rapid approval by regulatory authorities and the wide use of lipid nanoparticles complexing the mRNA coding for the spark protein for COVID-19 vaccination paved the way for the initiation of several clinical trials exploiting lipid nanoparticles for cancer therapy. Nevertheless, polymers still represent a valuable alternative to lipid-based formulations, due to the low cost and the chemical flexibility that allows for the conjugation of targeting ligands. This review will analyze the status of the ongoing clinical trials for cancer therapy, including vaccination and immunotherapy approaches, exploiting polymeric materials. Among those nanosized carriers, sugar-based backbones are an interesting category. A cyclodextrin-based carrier (CALAA-01) was the first polymeric material to enter a clinical trial complexed with siRNA for cancer therapy, and chitosan is one of the most characterized non-viral vectors able to complex genetic material. Finally, we will discuss the recent advances in the use of sugar-based polymers (oligo- and polysaccharides) for complexation of nucleic acids in advanced preclinical stage. This article is protected by copyright. All rights reserved.
In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, exclusions for Italy or for Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as Suppl. material 1.
In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, and exclusions to the Italian administrative regions. New combinations in the genera Pilosella and Roemeria are proposed. Furthermore, the name Papaver siculum is lectotypified. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1.
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