Engineering the Optical Properties of CsPbBr3 Nanoplatelets through Cd2+ Doping

Lead halide perovskite nanoplatelets (NPls) attract significant attention due to their exceptional and tunable optical properties. Doping is a versatile strategy for modifying and improving the optical properties of colloidal nanostructures. However, the protocols for B-site doping have been rarely reported for 2D perovskite NPls. In this work, we investigated the post-synthetic treatment of CsPbBr₃ NPls with different Cd²⁺ sources. We show that the interplay between Cd²⁺ precursor, NPl concentrations, and ligands determines the kinetics of the doping process. Optimization of the treatment allows for the boosting of linear and nonlinear optical properties of CsPbBr₃ NPls via doping or/and surface passivation. At a moderate doping level, both the photoluminescence quantum yield and two-photon absorption cross section increase dramatically. The developed protocols of post-synthetic treatment with Cd²⁺ facilitate further utilization of perovskite NPls in nonlinear optics, photonics, and lightning.     

The FlagT4G Vaccine Confers a Strong and Regulated Immunity and Early Virological Protection against Classical Swine Fever

Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination, mostly using vaccines that do not allow for differentiation of vaccinated from infected animals (DIVA). FlagT4G vaccine is a novel candidate that confers robust immunity and shows DIVA capabilities. The present study assessed the immune response elicited by FlagT4G and its capacity to protect pigs for a short time after vaccination. Five days after a single dose of FlagT4G vaccine, animals were challenged with a highly virulent CSFV strain. A strong, but regulated, interferon-α response was found after vaccination. Vaccinated animals showed clinical and virological protection against the challenge, in the absence of antibody response at 5 days post-vaccination. Upon challenge, a rapid rise in the titers of CSFV neutralizing antibodies and an increase in the IFN-γ producing cells were noticed in all vaccinated-challenged pigs. Meanwhile, unvaccinated pigs showed severe clinical signs and high viral replication, being euthanized before the end of the trial. These animals were unable to generate neutralizing antibodies and IFN-γ responses after the CSFV challenge. The results from the present study assert the fast and efficient protection by FlagT4G, a highly promising tool for CSFV control worldwide.     

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region,Italy

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson’s correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.     

Detection of New H5N1 High Pathogenicity Avian Influenza Viruses in Winter 2021–2022 in the Far East,Which Are Genetically Close to Those in Europe

Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021–2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020–2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 10^4.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs.     

High prevalence of unusual KRAS,NRAS, and BRAF mutations in POLE ‐ hypermutated colorectal cancers

Exonucleasic domain POLE (edPOLE) mutations, which are responsible for a hypermutated tumor phenotype, occur in 1–2% of colorectal cancer (CRC) cases. These alterations represent an emerging biomarker for response to immune checkpoint blockade. This study aimed to assess the molecular characteristics of edPOLE‐mutated tumors to facilitate patient screening. Based on opensource data analysis, we compared the prevalence of edPOLE mutations in a control group of unselected CRC patients (n = 222) vs a group enriched for unusual BRAF/RAS mutations (n = 198). Tumor mutational burden (TMB) and immune infiltrate of tumors harboring edPOLE mutations were then analyzed. In total, 420 CRC patients were analyzed: 11 edPOLE‐mutated tumors were identified, most frequently in microsatellite (MMR)‐proficient young (< 70 years) male patients, with left‐sided tumors harboring noncodon 12 KRAS mutation. The prevalence of edPOLE‐mutated tumors in the control vs the experimental screening group was, respectively, 0.45% (n = 1) vs 5.0% (n = 10). Among the 11 edPOLE‐mutated cases, two had a low TMB, three were hypermutated, and six were ultramutated. EdPOLE‐mutated cases had a high CD8⁺ tumor‐infiltrating lymphocyte (TIL) infiltration. These clinicopathological and molecular criteria may help to identify edPOLE mutations associated with a high TMB in CRC, and improve the selection of patients who could benefit from immunotherapy.     

Preoperative localization of lung nodules: a comparative analysis of hookwire and radio-guided procedures

BackgroundHistological diagnosis of pulmonary nodules requires surgical resection on many occasions. There are multiple localization strategies each with their own benefits and complications. The objective of this study is to compare preoperative lung nodule localization with hookwire and radiotracer injection (radioguided occult lesion localization, ROLL). To compare results, complications, and volume of the sample resected with both techniques.MethodsPatients undergoing resection of pulmonary nodules with video-assisted thoracoscopy and pre-surgical localization with hookwire or ROLL were studied. Eighty-eight pulmonary nodules were resected in 76 patients: 52 with a hook wire and 36 with a radiotracer. The localization rate, the shortest distance between the nodule and the pleura, the intrapulmonary distance of the locator, the complications, the volume of the resection piece, and the histological result were all assessed. In addition, the factors that influence the volume of the surgical piece were analyzed.ResultsAll the nodules were resected with both techniques. The intrapulmonary path of the locator is longer for the ROLL group (23.91 vs. 16.28 mm; P=0.04), with no differences in the distance from the nodule to the pleura. The rate of pneumothorax was significantly higher after the placement of a hook wire (69.2% vs. 24.2%; P<0.0001), while there were no differences in the presence of hemorrhage. The volume of the pieces resected using ROLL was more minor than with hookwire, although not statistically significant (20.19 vs. 34.26 cc; P=0.07).ConclusionsPreoperative localization with the ROLL technique is safer than the placement of hookwire. In addition, the ROLL technique shows a tendency to obtain a smaller volume of resected tissue since the marking is not affected by the intrapulmonary route used during marker placement. ROLL technique allows to locate lung nodules with fewer complications than hookwire and probably gets smaller resection samples.     

Brief Report: Dynamic calcium signals mediate the feeding response of the carnivorous sundew plant

Some of the most spectacular examples of botanical carnivory—in which predator plants catch and digest animals presumably to supplement the nutrient-poor soils in which they grow—occur within the Droseraceae family. For example, sundews of the genus Drosera have evolved leaf movements and enzyme secretion to facilitate prey digestion. The molecular underpinnings of this behavior remain largely unknown; however, evidence suggests that prey-induced electrical impulses are correlated with movement and production of the defense hormone jasmonic acid (JA), which may alter gene expression. In noncarnivorous plants, JA is linked to electrical activity via changes in cytoplasmic Ca²⁺. Here, we find that dynamic Ca²⁺ changes also occur in sundew (Drosera spatulata) leaves responding to prey-associated mechanical and chemical stimuli. Furthermore, inhibition of these Ca²⁺ changes reduced expression of JA target genes and leaf movements following chemical feeding. Our results are consistent with the presence of a conserved Ca²⁺-dependent JA signaling pathway in the sundew feeding response and provide further credence to the defensive origin of plant carnivory.     

Complex one-stop investigation of infertility: transvaginal hydrolaparoscopy

One of the intensively discussed topics recently is investigation of infertile patients. A subject of particular interest is a new technique - transvaginal hydrolaparoscopy (TVHL), which has already found its place amongst other methods of infertility exploration. Transvaginal hydrolaparoscopy allows atraumatic investigation of reproductive organs in physiologic conditions, in ambulatory settings. Significant, for clinical practice, is the possibility of a combination of transvaginal hydrolaparoscopy with other methods of investigation - sonohysterosalpinogography, hysteroscopy and salpingoscopy, which make possible integrated exploration of the reproductive system. Instillation of saline into the pelvic cavity through uterine tubes (or through puncture needle if needed) under ultrasonographic control and exposition of posterior fornix, allows better orientation in the pouch of Douglas, complex assessment of reproductive organs and determination of advisability of pelvioscopy - the relatively invasive technique as well as thorough control of the safe access to the pouch of Douglas.     

Crohn’s disease,autoimmune thyroiditis,and beta-thalassemia trait in an adolescent: an unusual combination of diseases

An adolescent with complaints of fatigue, tachycardia, abdominal discomfort, and blood-stained diarrhea is presented. Clinical and laboratory evaluation revealed a microcytemic anemia with iron deficiency, beta thalassemia, and thyrotoxicosis with thyroid antibodies. Crohn’s disease was confirmed on endoscopy. A rapid normalization of clinical and laboratory parameters was observed following the initiation of therapy and further exacerbation of her illness was prevented. Although the simultaneous occurrence of Crohn’s disease, autoimmune thyroiditis, and a beta-thalassemia trait is likely to be coincidental, the combination of an autoimmune thyroid disease and Crohn’s disease is rare in pediatrics. Several issues of importance in the treatment of these conditions are discussed. Rectal blood loss associated with Crohn’s disease may lead to severe iron deficiency, especially in patients with preexistent beta-thalassemia trait, and those with thyroiditis are prone to developing hypothyroidism following treatment, requiring that they be monitored closely.     

Fuzzy Simulation of Pharmacokinetic Models: Case Study of Whole Body Physiologically Based Model of Diazepam

The aim of the present study is to develop and implement a methodology that accounts for parameter variability and uncertainty in the presence of qualitative and semi-quantitative information (fuzzy simulations) as well as when some parameters are better quantitatively defined than others (fuzzy-probabilistic approach). The fuzzy simulations method consists of (i) representing parameter uncertainty and variability by fuzzy numbers and (ii) simulating predictions by solving the pharmacokinetic model. The fuzzy-probabilistic approach includes an additional transformation between fuzzy numbers and probability density functions. To illustrate the proposed method a diazepam WBPBPK model was used where the information for hepatic intrinsic clearance determined by in vitro-in vivo scaling was semi-quantitative. The predicted concentration time profiles were compared with those resulting from a Monte Carlo simulation. Fuzzy simulations can be used as an alternative to Monte Carlo simulation.