Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect.

Bees on the run: spp. (Microsporidia) in and related products, Italy.

Introduction: The decline of the European/western honeybee () population is on account of a plethora of microorganisms, such as and , two microsporidian fungi responsible of nosemosis that affects welfare and production of the bee industry. Accordingly, this study aimed to investigate the presence of both pathogens in bees, pollen and honey from apiaries in Southwestern Italy.

Methods: From March to July 2022 and 2023, apiaries ( = 10) were selected and classified as High Impact Areas (HIAs,  = 5) and Low Impact Areas (LIAs,  = 5) according to a 5-point environmental risk index based on factors affecting bee health sand related productions.

Fragment Discovery by X-Ray Crystallographic Screening Targeting the CTP Binding Site of Pseudomonas Aeruginosa IspD.

With antimicrobial resistance (AMR) reaching alarming levels, new anti-infectives with unprecedented mechanisms of action are urgently needed. The 2-C-methylerythritol-D-erythritol-4-phosphate (MEP) pathway represents an attractive source of drug targets due to its essential role in numerous pathogenic Gram-negative bacteria and Mycobacterium tuberculosis (Mt), whilst being absent in human cells. Here, we solved the first crystal structure of Pseudomonas aeruginosa (Pa) IspD, the third enzyme in the MEP pathway and present the discovery of a fragment-based compound class identified through crystallographic screening of PaIspD.

CRISPR/Cas9 Ribonucleoprotein Nucleofection for Genome Editing in Primary Human Keratinocytes: Knockouts, Deletions, and Homology-Directed Repair Mutagenesis.

Keratinocytes are the most abundant cell type in the human epidermis, the outermost layer of the skin. For years, primary human keratinocytes (HKs) have been used as a crucial tool for studying the pathogenesis of a wide range of skin-related diseases. To mimic the physiological and pathological behavior of human skin, organotypic 3D skin models can be generated by in vitro differentiation of HKs.

3-D intrinsic attenuation tomography using ambient seismic noise applied to La Palma Island (Canary Islands).

The potential of the island of La Palma (Canary Islands) to host geothermal resources is very high, mainly due to its high volcanic activity. The primary goal of this study is to get a tridimensional image of the seismic intrinsic attenuation using ambient seismic noise and to identify anomalies that may be linked to active geothermal reservoirs on La Palma island. For this purpose, we developed a new Ambient Noise Attenuation Tomography (ANAT) technique, which uses seismic ambient noise for imaging intrinsic attenuation in 3-D at a local scale down to 5 km depth.

COVID-19-Associated Cerebellitis: A Case Report and Rehabilitation Outcome.

Introduction: The COVID-19 pandemic has brought attention to neurological complications, including cerebellitis, characterized by inflammation of the cerebellum. Despite its rare occurrence, cerebellitis has been associated with COVID-19 infection, albeit the pathogenic mechanisms remain unclear.

Case Report: We present the case of a 22-year-old male with acute onset ataxia and dysarthria during a SARS-CoV-2 infection.

Microplastic contamination in the agri-food chain: The case of honeybees and beehive products.

Microplastics, MPs, plastic fragments with a dimension lower than 5 mm, and microfibers, MFs, synthetic and natural/artificial fibrous fragments with a diameter lower than 50 μm, are ubiquitous pollutants identified in different environmental compartments. In this work the occurrence of MPs and MFs on honeybees, Apis mellifera, and beehive products was evaluated, using Fourier transform infrared microspectroscopy, confirming that MPs and MFs are widely present as air contaminants in all the apiary's areas (high and low urbanized areas) in Southern Italy. Results indicated that independently from the site, both honeybees and honey samples, are contaminated by MFs with non-natural color.

Explosive eruption style modulates volcanic electrification signals.

Volcanic lightning detection has proven useful to volcano monitoring by providing information on eruption onset, source parameters, and ash cloud directions. However, little is known about the influence of changing eruptive styles on the generation of charge and electrical discharges inside the eruption column. The 2021 Tajogaite eruption (La Palma, Canary Islands) provided the rare opportunity to monitor variations in electrical activity continuously over several weeks using an electrostatic lightning detector.

Effects of MLS Laser on pain, function, and disability in chronic non-specific low back pain: A double-blind placebo randomized-controlled trial.

Background: Among non-pharmacological interventions, Multiwave Locked System (MLS) Laser therapy has been used in patients with several musculoskeletal pathologies and in combination with other therapeutical interventions. The effects of sole MLS therapy on pain and function in patients with chronic non-specific low-back pain are unknown.

Objective: The objective of this study was to investigate the effects of MLS Laser therapy on pain, function, and disability in patients with chronic non-specific low back pain in comparison to a placebo treatment group.

The combined administration of LNC-encapsulated retinoic acid and calcitriol stimulates oligodendrocyte progenitor cell differentiation in vitro and in vivo after intranasal administration.

Intranasal administration is an efficient strategy for bypassing the BBB, favoring drug accumulation in the brain, and improving its efficiency. Lipid nanocapsules (LNC) are suitable nanocarriers for the delivery of lipophilic drugs via this route and can be used to encapsulate lipophilic molecules such as retinoic acid (RA) and calcitriol (Cal). As the hallmarks of multiple sclerosis (MS) are neuroinflammation and oligodendrocyte loss, our hypothesis was that by combining two molecules known for their pro-differentiating properties, encapsulated in LNC, and delivered by intranasal administration, we would stimulate oligodendrocyte progenitor cells (OPC) differentiation into oligodendrocytes and provide a new pro-remyelinating therapy.

Volcanic soil gas He/CO ratio: a useful geochemical tool for real-time eruption forecasting.

At many dormant volcanoes, magmatic gases are not channeled through preferential degassing routes as fumaroles and only percolate through the flanks of the volcano in a diffuse way. This type of volcanic gas emission provides valuable information, even though the soil matrix contains an important atmospheric component. This study aimed to demonstrate that chemical ratios such as He/CO in soil gases provide excellent information on the evolution of volcanic unrest episodes and help forecast the volcanic eruption onset.

Influence of a pro-inflammatory stimulus on the miRNA and lipid content of human dental stem cell-derived extracellular vesicles and their impact on microglial activation.

Neuro-inflammation occurs in numerous disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. However, anti-inflammatory drugs for the central nervous system have failed to show significant improvement when compared to a placebo in clinical trials. Our previous work demonstrated that stem cells from the apical papilla (SCAP) can decrease neuro-inflammation and stimulate oligodendrocyte progenitor cell differentiation.

Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

Purpose: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally.

Methods: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms.

Toward a near real-time magma ascent monitoring by combined fluid inclusion barometry and ongoing seismicity.

Fluid inclusion microthermometry on olivines, clinopyroxenes, and amphiboles was used during a volcanic eruption, in combination with real-time seismic data and rapid petrographic observations, for petrological monitoring purposes. By applying this approach to the study of 18 volcanic samples collected during the eruption of Tajogaite volcano on La Palma Island (Canary Islands) in 2021, changes in the magma system were identified over time and space. Magma batches with distinct petrographic and geochemical characteristics emerged from source zones whose depth progressively increased from 27 to 31 kilometers.

Correlation between inflammatory biomarkers and disease control in chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL-5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients.

Geodetic imaging of magma ascent through a bent and twisted dike during the Tajogaite eruption of 2021 (La Palma, Canary Islands).

On Sept. 19th, 2021, the largest historical eruption on the island of La Palma began, which had a significant scientific, social, and economic impact. The 2021 Tajogaite eruption was characterised by short precursors, lasting only 8 days.

Temporal trends of blood eosinophilia in severe uncontrolled CRSwNP treated with dupilumab: a real-life study.

Purpose: Induced eosinophilia is commonly related to dupilumab treatment. We analysed the temporal trends of blood eosinophilia in patients with severe uncontrolled CRSwNP during the first year of treatment with dupilumab in real-life setting to evaluate its correlation with outcomes of response and adverse events (AEs).

Methods: Seventy-four patients with severe uncontrolled CRSwNP treated with dupilumab at our institution were enrolled.

Volcanic monitoring of the 2021 La Palma eruption using long-period magnetotelluric data.

Between September and December 2021, the first subaerial volcanic eruption in the Canary Islands in 50 years took place on the island of La Palma. Since November 2021, we have been conducting a long-period magnetotelluric (MT) monitoring experiment at a site located 2.4 km east of the volcanic cone.

Effectiveness of Dupilumab in the Treatment of Adult and Older Adult Patients with Severe, Uncontrolled CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease that significantly impacts patients' quality of life. New therapeutic strategies and in particular biologic treatments are now available for these patients. It has been demonstrated that Dupilumab (an anti IL-4/IL-13 biologic drug) is effective in reducing the size of nasal polyps and in improving patients' symptoms and thus, quality of life.

Geothermal and structural features of La Palma island (Canary Islands) imaged by ambient noise tomography.

La Palma island is located in the NW of the Canary Islands and is one of the most volcanically active of the archipelago, therefore the existence of geothermal resources on the island is highly probable. The main objective of this work is to detect velocity anomalies potentially related to active geothermal reservoirs on La Palma island, by achieving a high-resolution seismic velocity model of the first few kilometres of the crust using Ambient Noise Tomography (ANT). The obtained ANT model is merged with a recent local earthquake tomography model.

Spatio-temporal velocity variations observed during the pre-eruptive episode of La Palma 2021 eruption inferred from ambient noise interferometry.

On Sept. 19th, 2021, a volcanic eruption began on the island of La Palma (Canary Islands, Spain). The pre-eruptive episode was characterized by seismicity and ground deformation that started only 9.

Hemoperfusion in Poisoning and Drug Overdose.

Hemoperfusion (HP) is an extracorporeal blood purification therapy that is used to remove poisons or drugs from the body. This chapter provides a brief overview of the technical aspects and the potential indications and limitations of HP, with the focus being on the use of HP for acute poisoning cases reported from January 1, 2000, to April 30, 2022.

Is mirror therapy associated with progressive muscle relaxation more effective than mirror therapy alone in reducing phantom limb pain in patients with lower limb amputation?

Mirror therapy is a widely used treatment for phantom limb pain (PLP) relief in patients with limb loss. Less common is progressive muscle relaxation (PMR), used mostly in other medical conditions (psychological, terminal cancer pain, etc). The purpose of this study is to evaluate the efficacy of a mirror therapy preceded by PMR intervention compared to mirror therapy preceded by unguided generic relaxation-mirror therapy in patients with lower limb amputation suffering from PLP.

Disease-related p63 DBD mutations impair DNA binding by distinct mechanisms and varying degree.

The transcription factor p63 shares a high sequence identity with the tumour suppressor p53 which manifests itself in high structural similarity and preference for DNA sequences. Mutations in the DNA binding domain (DBD) of p53 have been studied in great detail, enabling a general mechanism-based classification. In this study we provide a detailed investigation of all currently known mutations in the p63 DBD, which are associated with developmental syndromes, by measuring their impact on transcriptional activity, DNA binding affinity, zinc binding capacity and thermodynamic stability.

Elastic interaction between Mauna Loa and Kīlauea evidenced by independent component analysis.

The contrasting dynamics between Mauna Loa and Kīlauea have been studied over the last 100 years from multiple viewpoints. The fact that dynamic changes of one volcano trigger a dynamic response of the other volcano indicates a connection may exist. Petrological works show a direct relationship between the magmatic systems of these two volcanoes is not possible.