House-roof Neoumbilicoplasty: Six-step Procedure for a Natural Navel.

Background: The umbilicus significantly contributes to abdominal aesthetics, with its reconstruction often necessary after certain procedures like umbilical herniorrhaphy, laparotomies, and abdominoplasty. Neoumbilicoplasty techniques have evolved, addressing various issues through approaches like skin and cartilage grafts, and local flaps. We are reporting our technique for neoumbilicoplasty. Methods: This study describes a novel neoumbilicoplasty technique implemented in 90 patients (88 women, two men) who underwent lipoabdominoplasty between February 2021 and June 2023. Exclusion criteria included procedures unrelated to neoumbilicoplasty. Surgical steps involved precise marking, dissection, and suturing to create a natural umbilical hood. Patient satisfaction was measured using the Global Aesthetic Improvement Scale. Results: The mean age was 37.7 years, with pre- and postoperative anatomics of 24.9 kg per m² and 24.2 kg per m², respectively. The average surgery duration was 84 minutes. No major complications occurred, but minor complications included dehiscence (6%), granuloma (5%), superficial infection (2%), bruising (1%), seroma (1%), and flattening (8%). Most complications were resolved with minor interventions. Patient satisfaction was high, with 96% of patients and the surgeon expressing significant satisfaction. Conclusions: House-roof neoumbilicoplasty is an innovative technique designed to effectively restore abdominal aesthetics through straightforward steps and timing, combined with high-definition lipoabdominoplasty.

Mitochondrial membrane potential and oxidative stress interact to regulate Oma1-dependent processing of Opa1 and mitochondrial dynamics.

Mitochondrial form and function are regulated by the opposing forces of mitochondrial dynamics: fission and fusion. Mitochondrial dynamics are highly active and consequential during neuronal ischemia/reperfusion (I/R) injury. Mitochondrial fusion is executed at the mitochondrial inner membrane by Opa1. The balance of long (L-Opa1) and proteolytically cleaved short (S-Opa1) isoforms is critical for efficient fusion. Oma1 is the predominant stress-responsive protease for Opa1 processing. In neuronal cell models, we assessed Oma1 and Opa1 regulation during mitochondrial stress. In an immortalized mouse hippocampal neuron line (HT22), Oma1 was sensitive to mitochondrial membrane potential depolarization (rotenone, FCCP) and hyperpolarization (oligomycin). Further, oxidative stress was sufficient to increase Oma1 activity and necessary for depolarization-induced proteolysis. We generated Oma1 knockout (KO) HT22 cells that displayed normal mitochondrial morphology and fusion capabilities. FCCP-induced mitochondrial fragmentation was exacerbated in Oma1 KO cells. However, Oma1 KO cells were better equipped to perform restorative fusion after fragmentation, presumably due to preserved L-Opa1. We extended our investigations to a combinatorial stress of neuronal oxygen-glucose deprivation and reoxygenation (OGD/R), where we found that Opa1 processing and Oma1 activation were initiated during OGD in an ROS-dependent manner. These findings highlight a novel dependence of Oma1 on oxidative stress in response to depolarization. Further, we demonstrate contrasting fission/fusion roles for Oma1 in the acute response and recovery stages of mitochondrial stress. Collectively, our results add intersectionality and nuance to the previously proposed models of Oma1 activity.

Role of miRNA-mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy is an inherited entity characterized by irregular cell-cell adhesion, cardiomyocyte death and fibro-fatty replacement of ventricular myocytes, leading to malignant ventricular arrythmias, contractile dysfunction and sudden cardiac death. Pathogenic variants in genes that encode desmosome are the predominant cause of arrhythmogenic cardiomyopathy. Moreover, signalling pathways such as Wnt/ß-catenin and transforming growth factor-ß have been involved in the disease progression. However, still little is known about the molecular pathophysiological mechanisms that underlie arrhythmogenic cardiomyopathy pathogenesis. We used mRNA and small RNA sequencing to analyse the transcriptome of health and arrhythmogenic cardiomyopathy of autopsied human hearts. Our results showed 697 differentially expressed genes and eight differentially expressed miRNAs. Functional enrichment revealed mitochondrial respiratory-related pathways, impaired response to oxidative stress, apoptotic signalling pathways and inflammatory response-related and extracellular matrix response pathways. Furthermore, analysis of the miRNA-mRNA interactome identified eleven negatively correlated miRNA-target pairs for arrhythmogenic cardiomyopathy. Our finding revealed novel arrhythmogenic cardiomyopathy-related miRNAs with important regulatory function in disease pathogenesis, highlighting their value as potential key targets for therapeutic approaches.

Combining Orthodontic and Restorative Care with Novel Workflows.

This report describes multidisciplinary care combining orthodontics and restorative dentistry for a patient with Class II occlusion and stained mandibular and maxillary resin composite veneers. The orthodontic treatment improved severe overjet and malocclusion prior to restorative care. Occlusal assessment was provided with a novel digital device (PlaneSystem, Zirkonzahn) that is integrated with digital workflows for the evaluation of the occlusal plane and condylar path inclination. Diagnostic digital impressions and digital wax-up for intraoral mock-ups led to the patient's treatment acceptance. Minimally invasive tooth preparation, final digital impressions, and bonding under dental dam isolation fulfilled the patient's esthetic and functional demands with all-ceramic restorations.

Photoluminescence and magnetic properties of isostructural europium(III), gadolinium(III) and terbium(III) oxamate-based coordination polymers.

Developing and investigating advanced multifunctional materials with magnetic properties as candidates for assembling spin qubits for quantum computing is imperative. A new polytopic ligand based on oxamate and aniline was used to promote the synthesis of three neutral homometallic lanthanide-coordinated polymers. New complexes with the formula {Ln(phox)3(DMSO)2(H2O)}n, where Ln = Eu3+ (1), Gd3+ (2), and Tb3+ (3) [phox = N-(phenyl)oxamate and DMSO = dimethylsulfoxide], were synthesized and well characterized by spectroscopic methods as well as X-ray crystallographic analysis. All crystalline structures comprise neutral zigzag chains. The lanthanide ions are linked by three phox ligands, in which two oxygen atoms from two different ligands are responsible for connecting the trivalent lanthanide ions, and one phox ligand completes the coordination sphere in a bis-bidentate mode, together with two DMSO molecules and one water coordination molecule. The coordination sphere of lanthanide ions consisted of spherical capped square antiprism (CSAPR-9) symmetry. The magnetic properties of 1-3 were investigated in the 2-300 K temperature range. The dynamic (ac) magnetic properties of 2 reveal a frequency dependence involving the phonon bottleneck mechanism below 33 K under nonzero applied dc magnetic fields, resulting in an example of a field-induced single-molecule magnet. Solid-state photophysical measurements for Eu3+ (1) and Tb3+ (3) complexes indicate that the N-(phenyl)oxamate ligands are very efficient in sensitizing the lanthanide(III) ions in the visible region of the electromagnetic spectrum. Compounds 1 and 3 exhibited an emission in the red and green regions, respectively. Experimental results and theoretical calculations using the Sparkle/RM1 method support a quantum efficiency of ∼72% for 1, suggesting its potential as a candidate for light conversion molecular devices (LCMDs).

Unraveling the Etiology of Dilated Cardiomyopathy through Differential miRNA-mRNA Interactome.

Dilated cardiomyopathy (DCM) encompasses various acquired or genetic diseases sharing a common phenotype. The understanding of pathogenetic mechanisms and the determination of the functional effects of each etiology may allow for tailoring different therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulators in cardiovascular diseases, including DCM. However, their specific roles in different DCM etiologies remain elusive. Here, we applied mRNA-seq and miRNA-seq to identify the gene and miRNA signature from myocardial biopsies from four patients with DCM caused by volume overload (VCM) and four with ischemic DCM (ICM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for differentially expressed genes (DEGs). The miRNA-mRNA interactions were identified by Pearson correlation analysis and miRNA target-prediction programs. mRNA-seq and miRNA-seq were validated by qRT-PCR and miRNA-mRNA interactions were validated by luciferase assays. We found 112 mRNAs and five miRNAs dysregulated in VCM vs. ICM. DEGs were positively enriched for pathways related to the extracellular matrix (ECM), mitochondrial respiration, cardiac muscle contraction, and fatty acid metabolism in VCM vs. ICM and negatively enriched for immune-response-related pathways, JAK-STAT, and NF-kappa B signaling. We identified four pairs of negatively correlated miRNA-mRNA: miR-218-5p-DDX6, miR-218-5p-TTC39C, miR-218-5p-SEMA4A, and miR-494-3p-SGMS2. Our study revealed novel miRNA-mRNA interaction networks and signaling pathways for VCM and ICM, providing novel insights into the development of these DCM etiologies.

Siderophores and competition for iron govern myxobacterial predation dynamics.

Bacterial predators are decisive organisms that shape microbial ecosystems. In this study, we investigated the role of iron and siderophores during the predatory interaction between two rhizosphere bacteria: Myxococcus xanthus, an epibiotic predator, and Sinorhizobium meliloti, a bacterium that establishes nitrogen-fixing symbiosis with legumes. The results show that iron enhances the motility of the predator and facilitates its predatory capability, and that intoxication by iron is not used by the predator to prey, although oxidative stress increases in both bacteria during predation. However, competition for iron plays an important role in the outcome of predatory interactions. Using combinations of predator and prey mutants (nonproducers and overproducers of siderophores), we have investigated the importance of competition for iron in predation. The results demonstrate that the competitor that, via the production of siderophores, obtains sufficient iron for growth and depletes metal availability for the opponent will prevail in the interaction. Consequently, iron fluctuations in soils may modify the composition of microbial communities by altering the activity of myxobacterial predators. In addition, siderophore overproduction during predation can alter soil properties, affecting the productivity and sustainability of agricultural operations.

Early results of eTEP access surgery with preperitoneal repair of primary midline ventral hernias and diastasis recti. A 33 patient case series of "PeTEP".

BACKGROUND: This article aims to share the initial experience of the preperitoneal eTEP approach and its potential benefits in a selected group of patients. The eTEP Rives-Stoppa is a proven minimally invasive surgical technique for the treatment of ventral midline and off-midline hernias that has shown to be a solid, durable, and reproducible repair. The preperitoneal eTEP repair is a surgical technique that brings together the extraperitoneal access surgery with a preperitoneal repair for primary midline hernias avoiding posterior rectus sheath division and preservation of the retrorectus space while being able to treat simultaneous diastasis recti. METHODS: The analysis included 33 patients operated with the preperitoneal eTEP approach from September 2022 to September 2023 in patients with primary small to medium (< 4 cm) midline hernias, single or multiple defects with or without diastasis recti. Age, gender, hernia characteristics, operative time, and surgical site occurrences will be discussed, as well as fine details and landmarks in the operative technique. RESULTS: 33 consecutive patients were operated, 19 female (57.5%) and 14 males (42.5%) between 32 and 63 years of age, the most common comorbidity found was obesity (BMI > 30). In 70% of the cases, operative time was 90 min ± 25 min. The average hospital stay was one day, while 12 went home the same day, and so far, no reoccurrences have been reported. CONCLUSIONS: We believe the preperitoneal eTEP approach for small to medium primary midline hernias is an effective and solid repair that combines excellent features of proven surgical techniques and eliminates the need for posterior rectus sheath division while saving the retrorectus space, among other benefits that will be discussed. The reproducibility of the technique remains to be proven.

Comparing psychological versus pharmacological treatment in emotional disorders: A network analysis.

Transdiagnostic group cognitive behavioural therapy (TD-GCBT) is more effective in improving symptoms and severity of emotional disorders (EDs) than treatment as usual (TAU; usually pharmacological treatment). However, there is little research that has examined the effects of these treatments on specific symptoms. This study used Network Intervention Analysis (NIA) to investigate the direct and differential effects of TD-GCBT + TAU and TAU on specific symptoms of anxiety and depression. Data are from a multicentre randomised clinical trial (N = 1061) comparing TD-GCBT + TAU versus TAU alone for EDs. The networks included items from the PHQ-9 (depression) and GAD-7 (anxiety) questionnaire and mixed graphical models were estimated at pre-treatment, post-treatment and 3-, 6- and 12-month follow-up. Results revealed that TD-GCBT + TAU was associated with direct effects, mainly on several anxiety symptoms and depressed mood after treatment. New direct effects on other depressive symptoms emerged during the follow-up period promoted by TD-GCBT compared to TAU. Our results suggest that the improvement of anxiety symptoms after treatment might precipitate a wave of changes that favour a decrease in depressive symptomatology. NIA is a methodology that can provide fine-grained insight into the likely pathways through which treatments exert their effects.

Myxococcus xanthus predation: an updated overview.

Bacterial predators are widely distributed across a variety of natural environments. Understanding predatory interactions is of great importance since they play a defining role in shaping microbial communities in habitats such as soils. Myxococcus xanthus is a soil-dwelling bacterial predator that can prey on Gram-positive and Gram-negative bacteria and even on eukaryotic microorganisms. This model organism has been studied for many decades for its unusual lifecycle, characterized by the formation of multicellular fruiting bodies filled with myxospores. However, less is known about its predatory behavior despite being an integral part of its lifecycle. Predation in M. xanthus is a multifactorial process that involves several mechanisms working synergistically, including motility systems to efficiently track and hunt prey, and a combination of short-range and contact-dependent mechanisms to achieve prey death and feed on them. In the short-range attack, M. xanthus is best known for the collective production of secondary metabolites and hydrolytic enzymes to kill prey and degrade cellular components. On the other hand, contact-dependent killing is a cell-to-cell process that relies on Tad-like and type III secretion systems. Furthermore, recent research has revealed that metals also play an important role during predation, either by inducing oxidative stress in the prey, or by competing for essential metals. In this paper, we review the current knowledge about M. xanthus predation, focusing on the different mechanisms used to hunt, kill, and feed on its prey, considering the most recent discoveries and the transcriptomic data available.

Isolated melanoma cells in sentinel lymph node in stage IIIA melanoma correlate with a favorable prognosis similar to stage IB.

BACKGROUND: The American Joint Committee on Cancer 8th edition (AJCC v8) defines sentinel lymph nodes (SLN) containing any tumor cells as positive SLN. Consequently, even thin melanomas with isolated tumor cells (ic) in SLN are classified as stage IIIA, making them candidates for adjuvant therapy. OBJECTIVES AND ENDPOINTS: We aimed to evaluate survival outcomes of melanoma stage IIIA (ic) and compare them with stage IIIA with lymph node (LN) metastases > 0.1 mm. Primary endpoints were relapse-free survival (RFS) and distant metastases-free survival (DMFS). Secondary endpoint was melanoma specific survival (MSS). RESULTS: The discovery cohort from the Department of Dermatology, University Hospital Tuebingen, included 237 patients; confirmation cohort included 143 patients from the DeCOG trial. The Tuebingen cohort included 95 patients with stage IIIA (ic) and 142 patients with stage IIIA. The DeCOG trial included 39 patients with stage IIIA (ic) and 104 patients with stage IIIA. In the Tuebingen cohort, 10-year RFS rates for stage IIIA (ic) and IIIA were 84% (95% CI 75-94) and 49% (95% CI 39-59), respectively (p < 0.001). 10-year DMFS rates for stage IIIA (ic) and IIIA were 89% (95% CI 81-97) and 56% (95% CI 45-67), respectively; (p < 0.001). In the DeCOG cohort, 10-year RFS for stage IIIA (ic) and stage IIIA were 88% (95% CI 78-99) and 35% (95% CI 7-62), respectively; (p = 0.009). 10-year DMFS for stage IIIA (ic) and IIIA was 88% (95% CI 77-99) and 60% (95% CI 39-80), respectively (p = 0.061). CONCLUSION: Stage IIIA (ic) melanoma exhibits a prognosis similar to stage IB. Recommendation of adjuvant therapy in Stage IIIA (ic) warrants thorough discussion.

Deaths of U.S. Citizens Undergoing Cosmetic Surgery - Dominican Republic, 2009-2022.

Although infections resulting from cosmetic surgery performed outside the United States have been regularly reported, deaths have rarely been identified. During 2009-2022, 93 U.S. citizens died after receiving cosmetic surgery in the Dominican Republic. The number of deaths increased from a mean of 4.1 per year during 2009-2018 to a mean of 13.0 during 2019-2022 with a peak in of 17 in 2020. A subset of post-cosmetic surgery deaths occurring during peak years was investigated, and most deaths were found to be the result of embolic events (fat emboli or venous thromboembolism) for which a high proportion of the patients who died had risk factors, including obesity and having multiple procedures performed during the same operation. These risk factors might have been mitigated or prevented with improved surgical protocols and postoperative medical care, including prophylactic measures against venous thromboembolism. U.S. citizens interested in receiving elective cosmetic surgery outside the United States should consult with their health care professionals regarding their risk for adverse outcomes. Public health authorities can support provider education on the importance of preoperative patient evaluation and the potential danger of performing multiple cosmetic procedures in one operation.

Augmenting MEK inhibitor efficacy in BRAF wild-type melanoma: synergistic effects of disulfiram combination therapy.

BACKGROUND: MEK inhibitors (MEKi) were shown to be clinically insufficiently effective in patients suffering from BRAF wild-type (BRAF WT) melanoma, even if the MAPK pathway was constitutively activated due to mutations in NRAS or NF-1. Thus, novel combinations are needed to increase the efficacy and duration of response to MEKi in BRAF WT melanoma. Disulfiram and its metabolite diethyldithiocarbamate are known to have antitumor effects related to cellular stress, and induction of endoplasmic reticulum (ER) stress was found to synergize with MEK inhibitors in NRAS-mutated melanoma cells. Therefore, we investigated the combination of both therapeutics to test their effects on BRAF-WT melanoma cells and compared them with monotherapy using the MEKi trametinib. METHODS: The effects of combined therapy with disulfiram or its metabolite diethyldithiocarbamate and the MEKi trametinib were evaluated in a series of BRAF-WT melanoma cell lines by measuring cell viability and apoptosis induction. Cytotoxicity was additionally assessed in 3D spheroids, ex vivo melanoma slice cultures, and in vivo xenograft mouse models. The response of melanoma cells to treatment was studied at the RNA and protein levels to decipher the mode of action. Intracellular and intratumoral copper measurements were performed to investigate the role of copper ions in the antitumor cytotoxicity of disulfiram and its combination with the MEKi. RESULTS: Diethyldithiocarbamate enhanced trametinib-induced cytotoxicity and apoptosis induction in 2D and 3D melanoma culture models. Mechanistically, copper-dependent induction of oxidative stress and ER stress led to Janus kinase (JNK)-mediated apoptosis in melanoma cells. This mechanism was also detectable in patient-derived xenograft melanoma models and resulted in a significantly improved therapeutic effect compared to monotherapy with the MEKi trametinib. CONCLUSIONS: Disulfiram and its metabolite represent an attractive pharmaceutical approach to induce ER stress in melanoma cells that potentiates the antitumor effect of MEK inhibition and may be an interesting candidate for combination therapy of BRAF WT melanoma.

Evaluation of pro-regenerative and anti-inflammatory effects of isolecanoric acid in the muscle: Potential treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a devastating degenerative disease of skeletal muscles caused by loss of dystrophin, a key protein that maintains muscle integrity, which leads to progressive muscle degeneration aggravated by chronic inflammation, muscle stem cells' (MuSCs) reduced regenerative capacity and replacement of muscle with fibroadipose tissue. Previous research has shown that pharmacological GSK-3ß inhibition favors myogenic differentiation and plays an important role in modulating inflammatory processes. Isolecanoric acid (ILA) is a natural product isolated from a fungal culture displaying GSK-3ß inhibitory properties. The present study aimed to investigate the proregenerative and anti-inflammatory properties of this natural compound in the DMD context. Our results showed that ILA markedly promotes myogenic differentiation of myoblasts by increasing ß-Catenin signaling and boosting the myogenic potential of mouse and human stem cells. One important finding was that the GSK-3ß/ß-Catenin pathway is altered in dystrophic mice muscle and ILA enhances the myofiber formation of dystrophic MuSCs. Treatment with this natural compound improves muscle regeneration of dystrophic mice by, in turn, improving functional performance. Moreover, ILA ameliorates the inflammatory response in both muscle explants and the macrophages isolated from dystrophic mice to, thus, mitigate fibrosis after muscle damage. Overall, we show that ILA modulates both inflammation and muscle regeneration to, thus, contribute to improve the dystrophic phenotype.

3D-printed low-cost choke corrugated Gaussian profile horn antenna for Ka-band.

In this work, a fully 3D-printed choke corrugated Gaussian profile horn antenna (GPHA) using high-conductive filaments and a low-cost modular 3D-printing technique is implemented. The choke corrugated GPHA operates in the Ka-band, with a central frequency of 28 GHz. Although the antenna can be printed in one piece as its dimensions are within the printing limits, four pieces compose the three sections of the final 3D-printed antenna. The numerical simulations and measurements of the antenna show a good agreement, validating the possibility of cost-effective modular fabrication of this complex type of antennas.

Construção de aplicativo móvel como estratégia para adesão medicamentosa de idosos / Construction of a mobile application as a strategy for medication adherence in the elderly population

Objetivo: Descrever o processo de desenvolvimento de um aplicativo como estratégia para promover a adesão medicamentosa de idosos. Métodos: Pesquisa metodológica de produção tecnológica. Foram seguidas as etapas de levantamento de dados, montagem de banco de dados e desenvolvimento do software. Realizou-se uma revisão narrativa da literatura sobre o tema. Resultados: Para o desenvolvimento da ferramenta tecnológica realizou-se inicialmente um protótipo do aplicativo. O objetivo central foi criar um programa de aplicação para lembrar o horário de medicamentos através de avisos sonoros e informações na tela, com foco na autonomia do processo saúde-doença do público idoso, utilizando-se de uma linguagem acessível, com fontes grandes e legíveis, com cores específicas para a tela de fundo e os Ooblets adequados para o entendimento do público-alvo. Conclusão: O aplicativo contribui na adesão medicamentosa por parte dos idosos, além de auxiliar os cuidadores sobre o uso correto, horário adequado e dosagem correta. A tecnologia proposta proporciona a corresponsabilização dos longevos no seu processo saúde-doença e adesão à terapêutica prescrita. Descritores: Tecnologia; Saúde do Idoso; Polimedicação; Cuidados de Enfermagem.

Objective: To describe the process of developing an application as a strategy to promote medication adherence in the elderly population.Methods:Methodological research of technological production. The steps of data survey, database assembly and software development were followed. A narrative review of the literature on the theme was performed.Results:In order to develop the technological tool, a prototype of the application was initially made. The central objective was to create an application program to remember the medication schedule through sound warnings and on-screen information, focusing on theautonomy of the health-disease process of the elderly population, using an accessible language, with large and legible fonts, with specific colors for the background screen and Ooblets suitable for the understanding of the target audience.Conclusion: Theapplication contributes to medication adherence by the elderly patients, in addition to helping caregivers regarding the correct use, appropriate time, and correct dosage. The proposed technology provides the co-responsibility of the elderly citizens in their health-disease process and adherence to the prescribed therapy. Descriptors:Technology; Health of the Elderly; Polypharmacy; Nursing Care.

Understanding the combining ability of nutritional, agronomic and industrial traits in soybean F2 progenies.

Obtaining soybean genotypes that combine better nutrient uptake, higher oil and protein levels in the grains, and high grain yield is one of the major challenges for current breeding programs. To avoid the development of unpromising populations, selecting parents for crossbreeding is a crucial step in the breeding pipeline. Therefore, our objective was to estimate the combining ability of soybean cultivars based on the F2 generation, aiming to identify superior segregating parents and populations for agronomic, nutritional and industrial traits. Field experiments were carried out in two locations in the 2020/2021 crop season. Leaf contents of the following nutrients were evaluated: phosphorus, potassium, calcium, magnesium, sulfur, copper, iron, manganese, and zinc. Agronomic traits assessed were days to maturity (DM) and grain yield (GY), while the industrial traits protein, oil, fiber and ash contents were also measured in the populations studied. There was a significant genotype × environment (G × A) interaction for all nutritional traits, except for P content, DM and all industrial traits. The parent G3 and the segregating populations P20 and P27 can be used aiming to obtain higher nutritional efficiency in new soybean cultivars. The segregating populations P11 and P26 show higher potential for selecting soybean genotypes that combine earliness and higher grain yield. The parent G5 and segregant population P6 are promising for selection seeking improvement of industrial traits in soybean.

Hemodynamic response function description in patients with glioma.

INTRODUCTION: Functional magnetic resonance imaging is a powerful tool that has provided many insights into cognitive sciences. Yet, as its analysis is mostly based on the knowledge of an a priori canonical hemodynamic response function (HRF), its reliability in patients' applications has been questioned. There have been reports of neurovascular uncoupling in patients with glioma, but no specific description of the Hemodynamic Response Function (HRF) in glioma has been reported so far. The aim of this work is to describe the HRF in patients with glioma. METHODS: Forty patients were included. MR images were acquired on a 1.5T scanner. Activated clusters were identified using a fuzzy general linear model; HRFs were adjusted with a double-gamma function. Analyses were undertaken considering the tumor grade, age, sex, tumor location, and activated location. RESULTS: Differences are found in the occipital, limbic, insular, and sub-lobar areas, but not in the frontal, temporal, and parietal lobes. The presence of a glioma slows the time-to-peak and onset times by 5.2 and 3.8 % respectively; high-grade gliomas present 8.1 % smaller HRF widths than low-grade gliomas. DISCUSSION AND CONCLUSION: There is significant HRF variation due to the presence of glioma, but the magnitudes of the observed differences are small. Most processing pipelines should be robust enough for this magnitude of variation and little if any impact should be visible on functional maps. The differences that have been observed in the literature between functional mapping obtained with magnetic resonance vs. that obtained with direct electrostimulation during awake surgery are more probably due to the intrinsic difference in the mapping process: fMRI mapping detects all recruited areas while intra-surgical mapping indicates only the areas indispensable for the realization of a certain task. Surgical mapping might not be the gold standard to use when trying to validate the fMRI mapping process.

Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of virulence factors necessary in different steps of the infection process. This includes factors involved in bacterial motility and attachment, biofilm formation, the production and secretion of extracellular invasive enzymes and exotoxins, the production of toxic secondary metabolites, and the acquisition of iron. Expression of these virulence factors during infection is tightly regulated, which allows their production only when they are needed. This process optimizes host colonization and virulence. In this work, we review the intricate network of transcriptional regulators that control the expression of virulence factors in P. aeruginosa, including one- and two-component systems and σ factors. Because inhibition of virulence holds promise as a target for new antimicrobials, blocking the regulators that trigger the production of virulence determinants in P. aeruginosa is a promising strategy to fight this clinically relevant pathogen.

Microenvironmental Snail1-induced immunosuppression promotes melanoma growth.

Melanoma is an aggressive form of skin cancer due to its high metastatic abilities and resistance to therapies. Melanoma cells reside in a heterogeneous tumour microenvironment that acts as a crucial regulator of its progression. Snail1 is an epithelial-to-mesenchymal transition transcription factor expressed during development and reactivated in pathological situations including fibrosis and cancer. In this work, we show that Snail1 is activated in the melanoma microenvironment, particularly in fibroblasts. Analysis of mouse models that allow stromal Snail1 depletion and therapeutic Snail1 blockade indicate that targeting Snail1 in the tumour microenvironment decreases melanoma growth and lung metastatic burden, extending mice survival. Transcriptomic analysis of melanoma-associated fibroblasts and analysis of the tumours indicate that stromal Snail1 induces melanoma growth by promoting an immunosuppressive microenvironment and a decrease in anti-tumour immunity. This study unveils a novel role of Snail1 in melanoma biology and supports its potential as a therapeutic target.