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Protecting cultural heritage buildings poses significant research challenges. Effective damage prevention hinges on a thorough understanding of structural behavior and the continuous monitoring of its changes over time. Advanced visualization tools are essential to provide adequate awareness of the monitoring systems installed over the years while guaranteeing a quick, basic analysis of their data. This paper addresses a crucial gap in structural health monitoring (SHM), particularly in managing complex structures and systems, by responding to the growing need for tools that not only represent 3D models enriched with heterogeneous data and metadata but also facilitate detailed analysis of sensor recordings. In response to this challenge, it proposes the integration of a 3D informational model and an interactive web-based platform for monitoring data, creating a comprehensive management tool. Piazza del Duomo UNESCO Site in Pisa serves as an ideal test case due to its historical significance, structural complexity, and the wealth of monitoring data collected over time. With their interactive architecture, the two developed integrated visualization tools that could offer an effective solution for data management and visualization in other heritage contexts, particularly in cases where the monitoring system consists of numerous sensors and has evolved substantially over the years. [ABSTRACT FROM AUTHOR]

Urban environments in Northeastern Italy, both natural and historical, are exposed to urbanization, climate change, and environmental risks that can impact perceptions of environmental quality and sustainability. However, the relationship between the perceived environmental risks, the related emotions, and the quality of urban living and well-being remains underexplored. The present study, therefore, aims to investigate the link between the perceived risk of adverse events and the emotion felt about the possibility of damage to historically and economically valuable sites, as well as the residents' restorativeness, well-being, residential satisfaction, and sense of community. Participants completed online questionnaires addressing the following variables: perceived risk of environmental events; emotions of possible damage; restorativeness; well-being; residential satisfaction; and sense of community. The results showed negative relationships between perceived risk and residential satisfaction, well-being and restorativeness, but positive relationships between negative emotions of losing places of economic value and residential satisfaction, sense of community, and restorativeness. The findings highlight the role of emotions and restorativeness with well-being and satisfaction in residents of Piazzola sul Brenta (Italy). [ABSTRACT FROM AUTHOR]

Pyroptosis is a gasdermin-mediated pro-inflammatory programmed cell death that, during microbial infections, aims to restrict the spreading of bacteria. Nevertheless, excessive pyroptosis activation leads to inflammation levels that are detrimental to the host. Pathogen-associated molecular patterns (PAMPs) present in bacteria and outer membrane vesicles (OMVs) can trigger pyroptosis pathways in different cell types with different outcomes. Moreover, some pathogens have evolved virulence factors that directly interfere with pyroptosis pathways, like Yersinia pestis YopM and Shigella flexneri IpaH7.8. Other virulence factors, such as those of Neisseria meningitidis, Neisseria gonorrhoeae, Salmonella enterica, and Helicobacter pylori affect pyroptosis pathways indirectly with important differences between pathogenic and commensal species of the same family. These pathogens deserve special attention because of the increasing antimicrobial resistance of S. flexneri and N. gonorrhoeae, the high prevalence of S. enterica and H. pylori, and the life-threatening diseases caused by N. meningitidis and Y. pestis. While inflammation due to macrophage pyroptosis has been extensively addressed, the effects of activation of pyroptosis pathways on modulation of cell cytoskeleton and cell–cell junctions in epithelia and endothelia and on the bacterial crossing of epithelial and endothelial barriers have only been partly investigated. Another important point is the diverse consequences of pyroptosis pathways on calcium influx, like activation of calcium-dependent enzymes and mitochondria dysregulation. This review will discuss the pyroptotic pathways activated by Gram-negative bacteria and their OMVs, analyzing the differences between pathogens and commensal bacteria. Particular attention will also be paid to the experimental models adopted and the main results obtained in the different models. Finally, strategies adopted by pathogens to modulate these pathways will be discussed with a perspective on the use of pyroptosis inhibitors as adjuvants in the treatment of infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study evaluated the impact of continuous positive airway pressure (C-PAP) therapy combined with a rigorous diet regimen on obese patients with obstructive sleep apnea syndrome (OSAS). Methods: Sixty obese patients (BMI ≥ 30) diagnosed with severe OSAS were recruited in order to establish the evaluation of CPAP therapy with different extents of adherence to a rigorous diet regimen. After one year, significant improvements were observed. Results: BMI reduced by 12.32%, apnea–hypopnea index (AHI) by 22.04%, oxygen desaturation index (ODI) by 15.87%, total sleep time with oxygen saturation below 90% (TST90%) by 25.2%, and Epworth Sleepiness Scale (ESS) scores by 21.74%. Patients were, then, divided into three groups, based on adherence to the restricted diet, as well as to the correct use of the nocturnal C-PAP, showing different reductions in BMI, AHI, ODI, TST90%, and ESS, according to their adherence, based on the sum of % reduction in BMI + AHI into three groups. Conclusions: These findings underscore the effectiveness of combining C-PAP therapy with a strict diet in improving OSAS symptoms and overall health in obese patients. Future studies with larger cohorts and longer follow-up periods are needed to confirm these results and explore the long-term benefits of this integrated approach. [ABSTRACT FROM AUTHOR]

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting fatty acid and amino acid oxidation with an incidence of 1 in 200,000 live births. MADD has three clinical phenotypes: severe neonatal-onset with or without congenital anomalies, and a milder late-onset form. Clinical diagnosis is supported by urinary organic acid and blood acylcarnitine analysis using tandem mass spectrometry in newborn screening programs. MADD is an autosomal recessive trait caused by biallelic mutations in the ETFA, ETFB, and ETFDH genes encoding the alpha and beta subunits of the electron transfer flavoprotein (ETF) and ETF-coenzyme Q oxidoreductase enzymes. Despite significant advancements in sequencing techniques, many patients remain undiagnosed, impacting their access to clinical care and genetic counseling. In this report, we achieved a definitive molecular diagnosis in a newborn by combining whole-genome sequencing (WGS) with RNA sequencing (RNA-seq). Whole-exome sequencing and next-generation gene panels fail to detect variants, possibly affecting splicing, in deep intronic regions. Here, we report a unique deep intronic mutation in intron 1 of the ETFDH gene, c.35-959A>G, in a patient with early-onset lethal MADD, resulting in pseudo-exon inclusion. The identified variant is the third mutation reported in this region, highlighting ETFDH intron 1 vulnerability. It cannot be excluded that these intronic sequence features may be more common in other genes than is currently believed. This study highlights the importance of incorporating RNA analysis into genome-wide testing to reveal the functional consequences of intronic mutations. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to predict the Length of hospital Stay (LoS) after laparoscopic right hemicolectomy for colon cancer using machine learning techniques. Accurately forecasting LoS is crucial for improving patient care and hospital resource management. The researchers utilized data from two large Italian studies, CoDIG 1 and CoDIG 2, to train and validate various machine learning models. The Random Forest (RF) algorithm demonstrated the best internal performance, while the Support Vector Machine (SVM) outperformed in external validation. Key factors influencing LoS included the use of fast-track protocols, type of anastomosis, and drainage. These findings could help tailor postoperative care and optimize hospital resources, ultimately enhancing patient outcomes and operational efficiency. The evolution of laparoscopic right hemicolectomy, particularly with complete mesocolic excision (CME) and central vascular ligation (CVL), represents a significant advancement in colon cancer surgery. The CoDIG 1 and CoDIG 2 studies highlighted Italy's progressive approach, providing useful findings for optimizing patient outcomes and procedural efficiency. Within this context, accurately predicting postoperative length of stay (LoS) is crucial for improving resource allocation and patient care, yet its determination through machine learning techniques (MLTs) remains underexplored. This study aimed to harness MLTs to forecast the LoS for patients undergoing right hemicolectomy for colon cancer, using data from the CoDIG 1 (1224 patients) and CoDIG 2 (788 patients) studies. Multiple MLT algorithms, including random forest (RF) and support vector machine (SVM), were trained to predict LoS, with CoDIG 1 data used for internal validation and CoDIG 2 data for external validation. The RF algorithm showed a strong internal validation performance, achieving the best performances and a 0.92 ROC in predicting long-term stays (more than 5 days). External validation using the SVM model demonstrated 75% ROC values. Factors such as fast-track protocols, anastomosis, and drainage emerged as key predictors of LoS. Integrating MLTs into predicting postoperative LOS in colon cancer surgery offers a promising avenue for personalized patient care and improved surgical management. Using intraoperative features in the algorithm enables the profiling of a patient's stay based on the planned intervention. This issue is important for tailoring postoperative care to individual patients and for hospitals to effectively plan and manage long-term stays for more critical procedures. [ABSTRACT FROM AUTHOR]

Simple Summary: The early crosstalk between the ovulated oocytes and the oviduct occurs in the fimbria, which is sensitive to the sex hormone fluctuation. Morphological and molecular changes were investigated in the oviductal fimbria epithelium of the baboon (Papio hamadryas) during the menstrual cycle. A well-differentiated epithelium consisting of ciliated and nonciliated cells was present only during the preovulatory phase when the epithelial surface displayed acidic glycans, complex fucosylated N-glycans, and oligolactosamine residues. Nonciliated cells contained small apical protrusions and thin microvilli, suggesting secretory and absorptive activities. In addition, nonciliated cells expressed HSP60 and HSP90 in the apical blebs as well as nuclear estrogen and progesterone receptors. Interestingly, ciliated cells displayed HSP70, HSP90, and progesterone receptors in the cilia. The findings, in addition to adding to knowledge of the baboon oviduct, may represent a benchmark for translational studies of the primate oviduct, including humans. The oviductal fimbria is the first extraovarian anatomical structure that the cumulus–oocyte complex (COC) encounters, and is sensitive to sex hormone changes. The morphology, glycan pattern, expression of heat shock proteins (HSPs), estradiol receptor (ER), and progesterone receptor (PR) were investigated in the oviductal fimbria epithelium of the baboon (Papio hamadryas) during the menstrual cycle. The morphology was investigated by light and scanning electron microscopy; the glycopattern was characterized using conventional and lectin histochemistry; HSPs (60, −70, −90), ER, and PR were localized immunohistochemically. Well-differentiated ciliated and nonciliated cells were present only during the preovulatory phase. The nonciliated cells contained small apical protrusions and thin microvilli. During the preovulatory phase (1) the luminal surface of the fimbria displayed acidic glycans, complex N-glycans containing fucose, and oligolactosamine residues; (2) nonciliated cells expressed HSP60 and HSP90 in the apical blebs, HSP70 in the nucleus and cytoplasm, as well as nuclear ERα and PR; (3) ciliated cells showed HSP70 in the nucleus, cytoplasm, and cilia that also expressed HSP90 and PR. These results are related to the function of the fimbria where the early COC–oviduct crosstalk occurs and may represent a benchmark for translational studies of other primates. [ABSTRACT FROM AUTHOR]

The work focuses on the characterization of the flowfield over a truncated linear aerospike by combining theoretical grounds, numerical simulations and experimental tests. The experimental investigations are carried out on a test rig designed at Politecnico di Torino for advanced nozzle testing. Fully three-dimensional CFD analyses are performed on the actual geometry of the experimental nozzle model. At low nozzle pressure ratios (nprs) the analysis combines numerical simulations and experimental testing, which are also used for validating the CFD results. At higher nprs, the flowfield characterization is performed only by three-dimensional CFD analyses. In addition to the validation of the numerical method, the edge effects at different nprs have been observed. [ABSTRACT FROM AUTHOR]

FBRSL1, together with FBRS and AUTS2 (Activator of Transcription and Developmental Regulator; OMIM 607270), constitutes a tripartite AUTS2 gene family. AUTS2 and FBRSL1 are evolutionarily more closely related to each other than to FBRS (Fibrosin 1; OMIM 608601). Despite its paralogous relation to AUTS2, FBRSL1's precise role remains unclear, though it likely shares functions in neurogenesis and transcriptional regulation. Herein, we report the clinical presentation with therapeutic approaches and the molecular etiology of a patient harboring a de novo truncating variant (c.371dupC) in FBRSL1, leading to a premature stop codon (p.Cys125Leufs*7). Our study extends previous knowledge by highlighting potential interactions and implications of this variant, alongside maternal and paternal duplications, for the patient's phenotype. Using sequence conservation data and in silico analysis of the truncated protein, we generated a predicted domain structure. Furthermore, our in silico analysis was extended by taking into account SNP array results. The extension of in silico analysis was performed due to the possibility that the coexistence of FBRSL1 truncating variant contemporary with maternal and paternal duplication could be a modifier of proband's phenotype and/or influence the novel syndrome clinical characteristics. FBRSL1 protein may be involved in neurodevelopment due to its homology with AUTS2, together with distinctive neuronal expression profiles, and thus should be considered as a potential modulation of clinical characteristics in a novel syndrome. Finally, considering that FBRSL1 is apparently involved in neurogenesis and in transcriptional regulatory networks that orchestrate gene expression, together with the observation that different genetic syndromes are associated with distinct genomic DNA methylation patterns, the specific episignature has been explored. [ABSTRACT FROM AUTHOR]

Traumatic brain injury is a significant global health issue, affecting approximately 69 million people annually. Early diagnosis is crucial for effective management, and biomarkers provide a promising approach to identifying traumatic brain injury in various settings. This study investigates the perceived usefulness of biomarker testing in two distinct contexts: emergency departments and sports settings. Comprehensive interviews were conducted among healthcare professionals in emergency departments and sports-related medical staff. The interviews assessed their perceptions of the diagnostic accuracy, practicality, and overall value of traumatic brain injury biomarker testing. The findings indicate that the perceived usefulness of biomarker testing is high among professionals in both settings. However, significant differences emerged in the perceived barriers to implementation, with emergency department staff citing logistical issues and sports professionals expressing cost concerns. Addressing identified barriers could enhance the adoption and effectiveness of these tests, ultimately improving patient outcomes. Future research should focus on optimizing testing protocols and reducing implementation challenges. This study aims to evaluate the implementation of mild traumatic brain injury biomarkers within the framework of value-based health care, focusing on diagnostic accuracy and patient outcomes. [ABSTRACT FROM AUTHOR]

Indoor microclimate conditions and air pollutant concentrations (O3, TVOC, CO, CO2, and particulate matter mass concentrations in six size bins) were measured in the Greek Archaeological Museum of Abdera, which houses priceless works of art from the birthplace of the ancient philosopher Democritus. The monitoring campaign took place during the spring and summer months, when there were the greatest number of visitors. In the exhibition rooms, daily variations in relative humidity ranged from 4% to 10%, and daily variations in air temperature ranged from 0.9 °C to 2.6 °C. These uncontrolled changes may endanger the housed antiquities. The microclimate in the storage rooms varied substantially less than in the exhibition halls due to dehumidifiers and the lack of visitors. Concerning air pollution, indoor O3 concentrations were higher than the recommended limit values for the conservation of artwork. Even more worrisome are particulate matter mass concentrations above the air quality guidelines. Despite the fact that the building is well insulated and that only artificial lighting is used in the exhibition halls, it is difficult to achieve adequate conditions for the protection of the works of art. [ABSTRACT FROM AUTHOR]

In the Pistoia Nursery-Ornamental Rural District (Italy), a leader in Europe in ornamental nurseries covering over 5200 hectares with over 2500 different species of plant, plant-parasitic nematodes represent a serious concern. The potential efficacy of a pot cultivation system using commercial substrates to control plant-parasitic nematodes was assessed. On two different plant species, two different pot cultivation managements, potted plants, and potted plants previously cultivated in natural soil were compared to plants only cultivated in natural soil. The entire soil nematode structure with and without plants was evaluated. The relationship between soil properties and soil nematode community was investigated. All the studied substrates were free from plant-parasitic nematodes. Regarding free-living nematodes, Peat–Pumice showed nematode assemblage established by colonizer and extreme colonizer bacterial feeders, whereas Peat–Perlite included both bacterial and fungal feeders, and, finally, coconut fiber also included omnivores and predators. In farming, the substrates rich in organic matter such as coconut fiber could still play an important role in suppressing plant-parasitic nematodes because of the abundance of free-living nematodes. In fact, they are of crucial importance in both the mineralization of organic matter and the antagonistic control of plant-parasitic nematodes. Potting systems equally reduce virus-vector nematodes and improve the prey/predator ratio favoring natural control. [ABSTRACT FROM AUTHOR]

Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene–phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of LMNA gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups (p value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings. [ABSTRACT FROM AUTHOR]

Vortices belong to the most important phenomena in fluid dynamics and play an essential role in many engineering applications. They can act detrimentally by harnessing the flow energy and reducing the efficiency of an aerodynamic device, whereas in other cases, their presence can be exploited to achieve targeted flow conditions. The control of the vortex parameters is desirable in both cases. In this paper, we introduce an optimization strategy for the control of vortices in the wake of a bluff body. Flow modelling is based on RANS and DES computations, validated by experimental data. The algorithm for vortex identification and characterization is based on the triple decomposition of motion. It produces a quantitative measure of vortex strength which is used to define the objective function in the optimization procedure. It is shown how the shape of an aerodynamic device can be altered to achieve the desired characteristics of vortices in its wake. The studied case is closely related to flame holders for combustion applications, but the conceptual approach has a general applicability to vortex control. [ABSTRACT FROM AUTHOR]

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3–5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of the ACTN3 rs1815739 polymorphism with match running performance and injury incidence in top-level professional football players. A total of 315 top-level professional football players from the first division of Spanish football (i.e., LaLiga) participated in this prospective and descriptive study. The ACTN3 rs1815739 genotype was identified for each player using genomic DNA samples. During LaLiga 2021–2022, players' performance was obtained through a validated camera system in all official matches. Additionally, the incidence of non-contact injuries was obtained by each team's medical staff according to the International Olympic Committee (IOC) statement. From the study sample, 116 (36.8%) players had the RR genotype, 156 (49.5%) had the RX genotype, and 43 (13.7%) had the XX genotype. The anthropometric characteristics of the players were similar across genotypes. However, the total running distance (p = 0.046), the distance at 21.0–23.9 km/h (p = 0.042), and the number of sprints (p = 0.042) were associated with the ACTN3 genotype. In all these variables, XX players had lower match performance values than RR players. Additionally, total and match injury incidences were higher in XX players than in RR players (p = 0.026 and 0.009, respectively). The rate of muscle injuries was also higher in XX players (p = 0.016). LaLiga football players with the ACTN3 XX genotype had lower match running performance and a higher incidence of non-contact injuries over the season. [ABSTRACT FROM AUTHOR]

Simple Summary: The choice between a transrectal or a transperineal approach for MRI-fusion-targeted prostate biopsy is still the subject of debate within the urologic community and across international Guidelines. Specifically, the European Association of Urology (EAU) guidelines recommend abandoning TRPB in favor of TPPB, due to lower rates of infection and sepsis. In contrast, the American Urological Association (AUA) recommends either approach, citing the absence of prospective RCTs assessing infectious risk. In this scenario, transparent reporting of the morbidity of the transrectal prostate biopsy is crucial to inform patients during shared decision-making and to evaluate the cost-effectiveness of different biopsy approaches from clinical and economic standpoints. Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien–Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway. [ABSTRACT FROM AUTHOR]

Objective: Transcatheter aortic valve implant (TAVI) is the gold standard for the high-surgical-risk group of patients with aortic valve disease and it is an alternative to surgery in patients at intermediate risk. Lethal complications can occur, and many of these are manageable only with emergent conversion to open heart surgery. We retrospectively evaluate the outcome of all patients undergoing TAVI in our departments and the impact of a complete cardiac rescue team to reduce 30-day mortality. Methods: Data from all patients undergoing TAVI between January 2020 and August 2023 in our center were analyzed. An expert complete rescue was present in catheter laboratory. Primary outcomes were in-hospital and at 30-day mortality and evaluation of all cases needed for emergent conversion to open heart surgery. Results: 825 patients were enrolled. The total mortality was 19/825 (2.3%). Eleven of the total patients (1.3%) required emergent conversion to open heart surgery. Among them, eight were alive (73%), with a theoretical decrease of 0.98% in overall mortality. Conclusions: surgical treatment is rare during TAVI. The presence of an expert complete rescue team as support means an increase in survival. Surgery must be used only to restore circulatory and to treat complication while percutaneous approaches should complete the procedure. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) resulting from chronic hypoxia (CH) occurs in patients with chronic obstructive pulmonary diseases, sleep apnea, and restrictive lung diseases, as well as in residents at high altitude. Previous studies from our group and others demonstrate a detrimental role of reactive oxygen species (ROS) in the pathogenesis of CH-induced PH, although the subcellular sources of ROS are not fully understood. We hypothesized that mitochondria-derived ROS (mtROS) contribute to enhanced vasoconstrictor reactivity and PH following CH. To test the hypothesis, we exposed rats to 4 weeks of hypobaric hypoxia (PB ≈ 380 mmHg), with control rats housed in ambient air (PB ≈ 630 mmHg). Chronic oral administration of the mitochondria-targeted antioxidant MitoQ attenuated CH-induced decreases in pulmonary artery (PA) acceleration time, increases in right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary arterial remodeling. In addition, endothelium-intact PAs from CH rats exhibited a significantly greater basal tone compared to those from control animals, as was eliminated via MitoQ. CH also augmented the basal tone in endothelium-disrupted PAs, a response associated with increased mtROS production in primary PA smooth muscle cells (PASMCs) from CH rats. However, we further uncovered an effect of NO synthase inhibition with Nω–nitro-L-arginine (L-NNA) to unmask a potent endothelial vasoconstrictor influence that accentuates mtROS-dependent vasoconstriction following CH. This basal tone augmentation in the presence of L-NNA disappeared following combined endothelin A and B receptor blockade with BQ123 and BQ788. The effects of using CH to augment vasoconstriction and PASMC mtROS production in exogenous endothelin 1 (ET-1) were similarly prevented by MitoQ. We conclude that mtROS participate in the development of CH-induced PH. Furthermore, mtROS signaling in PASMCs is centrally involved in enhanced pulmonary arterial constriction following CH, a response potentiated by endogenous ET-1. [ABSTRACT FROM AUTHOR]

PIK3CA-related disorders encompass many rare and ultra-rare conditions caused by somatic genetic variants that hyperactivate the PI3K-AKT-mTOR signaling pathway, which is essential for cell cycle control. PIK3CA-related disorders include PIK3CA-related overgrowth spectrum (PROS), PIK3CA-related vascular malformations and PIK3CA-related non-vascular lesions. Phenotypes are extremely heterogeneous and overlapping. Therefore, diagnosis and management frequently involve various health specialists. Given the rarity of these disorders and the limited number of centers offering optimal care, the Scientific Committee of the Italian Macrodactyly and PROS Association has proposed a revision of the most recent recommendations for the diagnosis, molecular testing, clinical management, follow-up, and treatment strategies. These recommendations give insight on molecular diagnosis, eligible samples, preferable sequencing, and validation methods and management of negative results. The purpose of this paper is to promote collaboration between health care centers and clinicians with a joint shared approach. Finally, we suggest the direction of present and future research studies, including new systemic target therapies, which are currently under evaluation in several clinical trials, such as specific inhibitors that can be employed to downregulate the signaling pathway. [ABSTRACT FROM AUTHOR]

Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare primary skin cancer, with an annual incidence of 1/100,000 and about 85 cases published in the literature. It is considered the cutaneous counterpart of undifferentiated nasopharyngeal carcinoma (UNC, Schmincke–Regaud tumor) but has no association with EBV. We present an interesting case with features of LELCS in a 93-year-old man, right frontal–orbital region, diagnosed histologically and with immunohistochemical features. We also emphasize contrasting morphologic features for correct nosographic classification and address current issues, suggesting potential insights. Finally, we briefly reviewed other cases described in the literature. [ABSTRACT FROM AUTHOR]

The present study aimed to analyse the performance of the Spanish men's top (LaLiga1) and second (LaLiga2) professional football division teams for eight consecutive seasons (from 2011–2012 to 2018–2019). The variables recorded were Passes, Successful Passes, Crosses, Shots, Goals, Corners, Fouls, Width, Length, Height, distance from the goalkeeper to the nearest defender (GkDef) and total distance covered (TD). The main results were that (1) LaLiga1 teams showed lower values of Length from 2013–2014, and lower values of GkDef and TD from 2014–2015; (2) LaLiga2 teams showed fewer Passes and lower values of GkDef and TD from 2014–2015, and fewer Goals and lower values of Length from 2015–2016; and (3) LaLiga1 teams showed more Passes, Successful Passes, Shots and Goals and higher values of TD compared to LaLiga2 teams during the eight-season period. This study concludes that LaLiga1 teams showed fewer final offensive actions, LaLiga2 teams showed fewer Passes and Goals and the teams of both leagues played in a space with greater density (meters by player), covering less distance as the seasons passed. The information provided in this study makes it possible to have reference values that have characterised the performance of the teams. [ABSTRACT FROM AUTHOR]

The progressive reclassification of diseases has also helped in distinguishing pathologic subtypes according to their genetic cause, better establishing patients' disease risk and assessing disease severity for personalized medicine and genotype-driven therapies [[2]]. New available genetic data allow real disease prevalence to be established while defining the diseases according to their etiology and not only their phenotypes. A genome-wide association scan identified two novel loci, one around an SNP next to the I PBX1 i gene, and another within the I PCCA i gene. Recent technical breakthroughs in genotyping and bioinformatics techniques have greatly facilitated the translation of genomics into clinical care. [Extracted from the article]

Background: (1) The aim of this article is to describe the physiopathology underlying umbilical cord diseases and their relationship with obstetric and perinatal outcomes. (2) Methods: Multicenter case series of umbilical cord diseases with illustrations from contributing institutions are presented. (3) Results: Clinical presentations of prenatal ultrasound findings, clinical prenatal features and postnatal outcomes are described. (4) Conclusions: Analysis of our series presents and discusses how umbilical cord diseases are associated with a wide variety of obstetric complications leading to a higher risk of poor perinatal outcomes in pregnancies. Knowing the physiopathology, prenatal clinical presentations and outcomes related to umbilical diseases allow for better prenatal counseling and management to potentially avoid severe obstetric and perinatal complications. [ABSTRACT FROM AUTHOR]

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare, low-grade, neuroendocrine-differentiated, cutaneous adnexal tumor, officially recognized by the World Health Organization (WHO) Skin Tumors Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between 60 and 70 years old, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-colored, and 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus, Web of Science (WoS), and Google Scholar using the following keywords: "Endocrine mucin-producing sweat gland carcinoma" and/or "EMPSGC" and/or "skin" and "cutaneous neoplasms". In addition, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 253 patients were recorded; 146 were females (57.7%) and 107 were males (42.2%). The vast majority of the lesions were in the eyelids (peri-ocular region), and only a minority of cases involved the cheeks, supra-auricular, retro-auricular, and occipital region, with very rare cases in the scalp, to which the present is also added. (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC, and much remains to be conducted in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum. [ABSTRACT FROM AUTHOR]

Background. Older patients are less likely to receive percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) compared to younger patients. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003–2018 by using the administrative Lombardy Health Database (Italy). Methods. We considered all patients aged ≥75 years hospitalized with AMI (either STEMI or NSTEMI) from 2003 to 2018 in Lombardy. Patients were grouped according to whether they were treated or not with PCI during the index hospitalization. The primary outcome was in-hospital mortality. The secondary endpoints were 1-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI. Results. 116,063 patients aged ≥75 years (mean age 83 ± 6; 48% males; 46% STEMI) were hospitalized with a primary diagnosis of AMI. Thirty-seven percent of them (n = 42,912) underwent PCI. The in-hospital mortality rate was significantly lower in PCI-treated patients (6% vs. 15%; p < 0.0001). One-year mortality and 1-year re-hospitalization for AHF/AMI were less frequent in PCI-treated patients (16% vs. 41% and 15% vs. 21%, respectively; p < 0.0001). The adjusted risks of the study endpoints were lower in PCI-treated patients: OR 0.37 (95% CI 0.36–0.39) for in-hospital mortality; HR 0.37 (95% CI 0.36–0.38) for 1-year mortality; HR 0.74 (95% CI 0.71–0.77) for 1-year re-hospitalization for AHF/AMI. Similar results were found in STEMI and NSTEMI patients considered separately. Conclusions. Our real-world data showed that in patients with AMI ≥ 75 years of age, PCI use is associated with lower in-hospital and 1-year mortality. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate AT1-R expression in normal and cancerous human kidneys, how these expressions are modified, and AT1-R functionality. AT-1R mRNA expression, determined by real-time PCR, was detected in all samples. AT-1R mRNA increased in well-differentiated cancer (G1, p < 0.01) and decreased 2.9-fold in undifferentiated cancer (G4, p < 0.001) compared with normal kidney tissues. Immunocytochemistry analysis showed that the AT-1R was expressed in the normal tubular epithelium. The glomerulus was also immunoreactive, and as expected, the smooth muscle cells of the vessel walls also expressed the receptor. A total of 35 out of 42 tumors were AT-1R positive, with the cell tumors showing varying numbers of immunoreactive cells, which were stained in a diffuse cytoplasmic and membranous pattern. Computer-assisted counting of the stained tumor cells showed that the number of AT-1R-positive cells increased in the well-differentiated cancers. The functionality of AT-1R was assessed in primary cultures of kidney epithelial cells obtained from three G3 kidney cancer tissues and corresponding histologically proven non-malignant tissue adjacent to the tumor. Indeed, Ang II stimulated, in a dose-dependent manner, the 24 h proliferation of normal kidney cells and cancer cells in the primary culture and phosphorylated extracellular regulated kinases 1 and 2. In conclusion, Ang II may be involved in the growth or function of neoplastic kidney tissue. [ABSTRACT FROM AUTHOR]

This work studies the term structure dynamics in the natural gas futures market, focusing on the Dutch Title Transfer Facility (TTF) daily futures prices. At first, using the whole dataset, we compared the in-sample fitting performance of three models: the four-factor dynamic Nelson–Siegel–Svensson (4F-DNSS) model, the five-factor dynamic De Rezende–Ferreira (5F-DRF) model, and the B-spline model. Our findings suggest that B-spline is the method that achieves the best in-line fitting results. Then, we turned our attention to forecasting, using data from 20 January 2011 to 13 May 2022 as the training set and the remaining data, from 16 May to 13 June 2022, for day-ahead predictions. In this second part of the work we combined the above mentioned models (4F-DNSS, 5F-DRF and B-spline) with a Nonlinear Autoregressive Neural Network (NAR-NN), asking the NAR-NN to provide parameter tuning. All the models provided accurate out-of-sample prediction; nevertheless, based on extensive statistical tests, we conclude that, as in the previous case, B-spline (combined with an NAR-NN) ensured the best out-of-sample prediction. [ABSTRACT FROM AUTHOR]

Background: The brain and heart are strictly linked and the electrical physiologies of these organs share common pathways and genes. Epilepsy patients have a higher prevalence of electrocardiogram (ECG) abnormalities compared to healthy people. Furthermore, the relationship between epilepsy, genetic arrhythmic diseases and sudden death is well known. The association between epilepsy and myocardial channelopathies, although already proposed, has not yet been fully demonstrated. The aim of this prospective observational study is to assess the role of the ECG after a seizure. Materials and Methods: From September 2018 to August 2019, all patients admitted to the emergency department of San Raffaele Hospital with a seizure were enrolled in the study; for each patient, neurological, cardiological and ECG data were collected. The ECG was performed at the time of the admission (post-ictal ECG) and 48 h later (basal ECG) and analyzed by two blinded expert cardiologists looking for abnormalities known to indicate channelopathies or arrhythmic cardiomyopathies. In all patients with abnormal post-ictal ECG, next generation sequencing (NGS) analysis was performed. Results: One hundred and seventeen patients were enrolled (females: 45, median age: 48 ± 12 years). There were 52 abnormal post-ictal ECGs and 28 abnormal basal ECGs. All patients with an abnormal basal ECG also had an abnormal post-ictal ECG. In abnormal post-ictal ECG, a Brugada ECG pattern (BEP) was found in eight patients (of which two had BEP type I) and confirmed in two basal ECGs (of which zero had BEP type I). An abnormal QTc interval was identified in 20 patients (17%), an early repolarization pattern was found in 4 patients (3%) and right precordial abnormalities were found in 5 patients (4%). Any kind modification of post-ictal ECG was significantly more pronounced in comparison with an ECG recorded far from the seizure (p = 0.003). A 10:1 higher prevalence of a BEP of any type (particularly in post-ictal ECG, p = 0.04) was found in our population compared to general population. In three patients with post-ictal ECG alterations diagnostic for myocardial channelopathy (BrS and ERP), not confirmed at basal ECG, a pathogenic gene variant was identified (KCNJ8, PKP2 and TRMP4). Conclusion: The 12-lead ECG after an epileptic seizure may show disease-related alterations otherwise concealed in a population at a higher incidence of sudden death and channelopathies. Post-ictal BEP incidence was higher in cases of nocturnal seizure. [ABSTRACT FROM AUTHOR]

Different approaches can be undertaken to realise a stereoselective electrochemical synthesis. Significant contributions to enantioselective electrochemical organic synthesis have been reported and largely reviewed in recent years. However, the development of general strategies for the electrochemical enantiocontrol of a transformation still presents considerable challenges; in particular, relatively few contributions of highly enantioselective catalytic electrochemical reactions have been reported to date. In this review article, the most recent examples of asymmetric electrochemical catalysis are discussed. The article is organised by the three types of enantioselective catalysis: metal-based catalysis, organocatalysis and biocatalysis; in each section, the most significant and recent advances are presented and discussed. [ABSTRACT FROM AUTHOR]

Schizophrenia is a complex mental disorder with multiple genetic and environmental factors contributing to its pathogenesis. Viral infections have been suggested to be one of the environmental factors associated with the development of this disorder. We comprehensively review all relevant published literature focusing on the relationship between schizophrenia and various viral infections, such as influenza virus, herpes virus 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), retrovirus, coronavirus, and Borna virus. These viruses may interfere with the normal maturation of the brain directly or through immune-induced mediators, such as cytokines, leading to the onset of schizophrenia. Changes in the expression of critical genes and elevated levels of inflammatory cytokines have been linked to virally-induced infections and relevant immune activities in schizophrenia. Future research is necessary to understand this relationship better and provide insight into the molecular mechanisms underlying the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

The study of the placenta is of great importance, not only in the attempt to understand the etiopathogenesis of various maternal-fetal pathologies, but also in the attempt to understand whether it is possible to find the cause of pathological neonatal outcomes. On the other hand, abnormalities of blood vessel formation, such as angiodysplasias, have been poorly characterised in the literature, and there is a need for more studies investigating the potential impact on the fetus. In this paper, we retrospectively analysed 2063 placentas received at the Department of Pathology of the University of Bari 'Aldo Moro', among which we identified 70 placentas affected by angiodysplasia. On these placentas, we carried out histochemical staining with Masson's Trichrome, orcein-alcian blue, and, subsequently, immunostaining with anti-CD31, CD34, and desmin and actin muscle smoothness antibodies. Finally, we performed a morphometric analysis on the allantochorionic and truncal vessels and correlated the results with neonatal outcomes. We studied the characteristics of the angiodysplasias in detail, dividing the patients into two classes (A and B) according to the morphology and histochemical characteristics of the affected vessels; statistical analysis reported a statistically significant association (p < 0.05) between the ratio of maximum thickness to maximum diameter (Tmax/Dmax) and neonatal outcome, with only 30% physiological outcome in the cohort of the placentas affected by angiodysplasia. These results shed light on a rather neglected aspect in the 2015 Amsterdam Classification, as well as in the literature, and provided strong evidence that placental angiodysplasia is predictive of an increased likelihood of the pathological fetal outcome, while other factors remain in the field. Studies with larger case series and guidelines with more attention to these aspects are mandated to further investigate the predictive potential of this pathology. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy. Pathogenic rare mutations in the SCN5A gene, encoding the alpha-subunit of the voltage-dependent cardiac Na+ channel protein (Nav1.5), are identified in 20% of BrS patients, affecting the correct function of the channel. To date, even though hundreds of SCN5A variants have been associated with BrS, the underlying pathogenic mechanisms are still unclear in most cases. Therefore, the functional characterization of the SCN5A BrS rare variants still represents a major hurdle and is fundamental to confirming their pathogenic effect. Human cardiomyocytes (CMs) differentiated from pluripotent stem cells (PSCs) have been extensively demonstrated to be reliable platforms for investigating cardiac diseases, being able to recapitulate specific traits of disease, including arrhythmic events and conduction abnormalities. Based on this, in this study, we performed a functional analysis of the BrS familial rare variant NM_198056.2:c.3673G>A (NP_932173.1:p.Glu1225Lys), which has been never functionally characterized before in a cardiac-relevant context, as the human cardiomyocyte. Using a specific lentiviral vector encoding a GFP-tagged SCN5A gene carrying the specific c.3673G>A variant and CMs differentiated from control PSCs (PSC-CMs), we demonstrated an impairment of the mutated Nav1.5, thus suggesting the pathogenicity of the rare BrS detected variant. More broadly, our work supports the application of PSC-CMs for the assessment of the pathogenicity of gene variants, the identification of which is increasing exponentially due to the advances in next-generation sequencing methods and their massive use in genetic testing. [ABSTRACT FROM AUTHOR]

In this work, a commercial SBS was functionalized with the 2,2,6,6-tetramethylpiperidin-N-oxyl stable radical (TEMPO) via free-radical activation initiated with benzoyl peroxide (BPO). The obtained macroinitiator was used to graft both vinylbenzyl chloride (VBC) and styrene/VBC random copolymer chains from SBS to create g-VBC-x and g-VBC-x-co-Sty-z graft copolymers, respectively. The controlled nature of the polymerization as well as the use of a solvent allowed us to reduce the extent of the formation of the unwanted, non-grafted (co)polymer, thereby facilitating the graft copolymer's purification. The obtained graft copolymers were used to prepare films via solution casting using chloroform. The –CH2Cl functional groups of the VBC grafts were then quantitatively converted to –CH2(CH3)3N+ quaternary ammonium groups via reaction with trimethylamine directly on the films, and the films, therefore, were investigated as anion exchange membranes (AEMs) for potential application in a water electrolyzer (WE). The membranes were extensively characterized to assess their thermal, mechanical, and ex situ electrochemical properties. They generally presented ionic conductivity comparable to or higher than that of a commercial benchmark as well as higher water uptake and hydrogen permeability. Interestingly, the styrene/VBC-grafted copolymer was found to be more mechanically resistant than the corresponding graft copolymer not containing the styrene component. For this reason, the copolymer g-VBC-5-co-Sty-16-Q with the best balance of mechanical, water uptake, and electrochemical properties was selected for a single-cell test in an AEM-WE. [ABSTRACT FROM AUTHOR]

Over recent years, preclinical and clinical evidence has implicated myocardial inflammation (M-Infl) in the pathophysiology and phenotypes of traditionally genetic cardiomyopathies. M-Infl resembling myocarditis on imaging and histology occurs frequently as a clinical manifestation of classically genetic cardiac diseases, including dilated and arrhythmogenic cardiomyopathy. The emerging role of M-Infl in disease pathophysiology is leading to the identification of druggable targets for molecular treatment of the inflammatory process and a new paradigm in the field of cardiomyopathies. Cardiomyopathies constitute a leading cause of heart failure and arrhythmic sudden death in the young population. The aim of this review is to present, from bedside to bench, the current state of the art about the genetic basis of M-Infl in nonischemic cardiomyopathies of the dilated and arrhythmogenic spectrum in order to prompt future research towards the identification of novel mechanisms and treatment targets, with the ultimate goal of lowering disease morbidity and mortality. [ABSTRACT FROM AUTHOR]

Traumatic brain injury affects 69 million people every year. One of the main limitations in managing TBI patients is the lack of univocal diagnostic criteria, including the absence of standardized assessment methods and guidelines. Computerized axial tomography is the first-choice examination, despite the limited prevalence of positivity; moreover, its performance is undesirable due to the risk of radiological exposure, prolonged stay in emergency departments, inefficient use of resources, high cost, and complexity. Furthermore, immediacy and accuracy in diagnosis and management of TBIs are critically unmet medical needs. Especially in the context of sports-associated TBI, there is a strong need for prognostic indicators to help diagnose and identify at-risk subjects to avoid their returning to play while the brain is still highly vulnerable. Fluid biomarkers may emerge as new prognostic indicators to develop more accurate prediction models, improving risk stratification and clinical decision making. This review describes the current understanding of the cellular sources, temporal profile, and potential utility of leading and emerging blood-based protein biomarkers of TBI; its focus is on biomarkers that could improve the management of mild TBI cases and can be measured readily and directly in the field, as in the case of sports-related contexts. [ABSTRACT FROM AUTHOR]

Sigma-2 receptor (S2R) is a S2R ligand-binding site historically associated with reportedly 21.5 kDa proteins that have been linked to several diseases, such as cancer, Alzheimer's disease, and schizophrenia. The S2R is highly expressed in various tumors, where it correlates with the proliferative status of the malignant cells. Recently, S2R was reported to be the transmembrane protein TMEM97. Prior to that, we had been investigating the translocator protein (TSPO) as a potential 21.5 kDa S2R candidate protein with reported heme and sterol associations. Here, we investigate the contributions of TMEM97 and TSPO to S2R activity in MCF7 breast adenocarcinoma and MIA PaCa-2 (MP) pancreatic carcinoma cells. Additionally, the role of the reported S2R-interacting partner PGRMC1 was also elucidated. Proximity ligation assays and co-immunoprecipitation show a functional association between S2R and TSPO. Moreover, a close physical colocalization of TMEM97 and TSPO was found in MP cells. In MCF7 cells, co-immunoprecipitation only occurred with TMEM97 but not with PGRMC1, which was further confirmed by confocal microscopy experiments. Treatment with the TMEM97 ligand 20-(S)-hydroxycholesterol reduced co-immunoprecipitation of both TMEM97 and PGRMC1 in immune pellets of immunoprecipitated TSPO in MP cells. To the best of our knowledge, this is the first suggestion of a (functional) interaction between TSPO and TMEM97 that can be affected by S2R ligands. [ABSTRACT FROM AUTHOR]

(I) This study aimed to evaluate the impact on physical demands induced by FIFA's new rule implemented based on the number of substitutions caused by COVID-19. (II) Sixty-six matches were analysed in peak periods (microcycles of three matches in a week) in the competition period before and after the pandemic. The variables collected were organised by team (22 from LaLigaTM SmartBank 2019–2020) for a total of 132 team records and 1077 player performance reports using a multi-camera tracking system and Mediacoach® software. Physical performance variables were analysed in the first half, second half and whole match, thus determining the individual and collective performances of the team. (III) This study shows how, despite the increase in substitutions allowed with the new rule, physical performance increased in some variables in the congested periods (e.g., total distance run and distance run in the first and second halves). Additionally, the players' physical performance involved in a substitution was greater than it was for players who completed the game. (IV) The new substitution rule helps to maintain and even improve physical performance. This measure could improve intensity levels in both individual and team performance. It could even safeguard the physical integrity of the players by reducing the risk of injury, as fewer players have to play the full match. [ABSTRACT FROM AUTHOR]

During the summer of 2016, severe dieback was observed on young potted Prunus lusitanica (Portugal laurel) plants in a nursery in the Pistoia province (Tuscany, Italy). Cylindrocarpon-like isolates were consistently recovered from diseased plant tissues. The combination of morphological and molecular traits, including sequence data of histone 3 and β-tubulin genes (HIS3, TUB2) and internal transcribed spacers (ITS), allowed the identification of Dactylonectria macrodidyma (Halleen, Schroers & Crous) L. Lombard & Crous (asexual form Cylindrocarpon macrodidymum) as the causal agent of the disease. Pathogenicity tests reproduced disease symptoms observed in the nursery after six months fulfilling Koch's postulates. D. macrodidyma is a soilborne plant pathogen and is to be considered of great economic importance on P. lusitanica, especially under favorable conditions such as stress and/or reduction of plant vitality. The increasingly frequent reports of the disease caused by the pathogen in various nurseries suggest that pot cultivation, together with prolonged drought periods, may play a role in favoring infections. To the best of our knowledge, this is the first report worldwide of the occurrence of dieback on Prunus lusitanica caused by D. macrodidyma. [ABSTRACT FROM AUTHOR]

The coronavirus disease no longer seems to represent an insurmountable global problem. This is thanks to the advent of coronavirus vaccines, which have alleviated the most serious symptoms associated with this disease. On the other hand, there are still many extrapulmonary symptoms of COVID-19, and among these also those of a gynecological nature. At the moment, there are several questions in this field, one above all concerns the causal link between COVID-19, vaccines and gynecological alterations. Furthermore, another important aspect is represented by the clinical impact of post-COVID-19 gynecological alterations on the female population which, to date, would seem to be mainly due to their duration, even if the extent of these symptoms is still poorly understood. Furthermore, it is not possible to foresee eventual long-term aggravations, or more serious symptoms caused by other viral variants that may arrive in the future. In this review, we focus on this theme and attempt to reorganize the different pieces of a puzzle which, to date, does not seem to have shown us its complete picture. [ABSTRACT FROM AUTHOR]

Pathogenic variants in genes are involved in histone acetylation and deacetylation resulting in congenital anomalies, with most patients displaying a neurodevelopmental disorder and dysmorphism. Arboleda-Tham syndrome caused by pathogenic variants in KAT6A (Lysine Acetyltransferase 6A; OMIM 601408) has been recently described as a new neurodevelopmental disorder. Herein, we describe a patient characterized by complex phenotype subsequently diagnosed using the clinical exome sequencing (CES) with Arboleda-Tham syndrome (ARTHS; OMIM 616268). The analysis revealed the presence of de novo pathogenic variant in KAT6A gene, a nucleotide c.3385C>T substitution that introduces a premature termination codon (p.Arg1129*). The need for straight multidisciplinary collaboration and accurate clinical description findings (bowel obstruction/megacolon/intestinal malrotation) was emphasized, together with the utility of CES in establishing an etiological basis in clinical and genetical heterogeneous conditions. Therefore, considering the phenotypic characteristics, the condition's rarity and the reviewed literature, we propose additional diagnostic criteria that could help in the development of future clinical diagnostic guidelines. This was possible thanks to objective examinations performed during the long follow-up period, which permitted scrupulous registration of phenotypic changes over time to further assess this rare disorder. Finally, given that different genetic syndromes are associated with distinct genomic DNA methylation patterns used for diagnostic testing and/or as biomarker of disease, a specific episignature for ARTHS has been identified. [ABSTRACT FROM AUTHOR]