Realistic morphology-preserving generative modelling of the brain.

Medical imaging research is often limited by data scarcity and availability. Governance, privacy concerns and the cost of acquisition all restrict access to medical imaging data, which, compounded by the data-hungry nature of deep learning algorithms, limits progress in the field of healthcare AI. Generative models have recently been used to synthesize photorealistic natural images, presenting a potential solution to the data scarcity problem. But are current generative models synthesizing morphologically correct samples? In this work we present a three-dimensional generative model of the human brain that is trained at the necessary scale to generate diverse, realistic-looking, high-resolution and morphologically preserving samples and conditioned on patient characteristics (for example, age and pathology). We show that the synthetic samples generated by the model preserve biological and disease phenotypes and are realistic enough to permit use downstream in well-established image analysis tools. While the proposed model has broad future applicability, such as anomaly detection and learning under limited data, its generative capabilities can be used to directly mitigate data scarcity, limited data availability and algorithmic fairness.

Generating multi-pathological and multi-modal images and labels for brain MRI.

The last few years have seen a boom in using generative models to augment real datasets, as synthetic data can effectively model real data distributions and provide privacy-preserving, shareable datasets that can be used to train deep learning models. However, most of these methods are 2D and provide synthetic datasets that come, at most, with categorical annotations. The generation of paired images and segmentation samples that can be used in downstream, supervised segmentation tasks remains fairly uncharted territory. This work proposes a two-stage generative model capable of producing 2D and 3D semantic label maps and corresponding multi-modal images. We use a latent diffusion model for label synthesis and a VAE-GAN for semantic image synthesis. Synthetic datasets provided by this model are shown to work in a wide variety of segmentation tasks, supporting small, real datasets or fully replacing them while maintaining good performance. We also demonstrate its ability to improve downstream performance on out-of-distribution data.

An ankyrin G-binding motif mediates TRAAK periodic localization at axon initial segments of hippocampal pyramidal neurons.

The axon initial segment (AIS) is a critical compartment in neurons. It converts postsynaptic input into action potentials that subsequently trigger information transfer to target neurons. This process relies on the presence of several voltage-gated sodium (NaV) and potassium (KV) channels that accumulate in high densities at the AIS. TRAAK is a mechanosensitive leak potassium channel that was recently localized to the nodes of Ranvier. Here, we uncover that TRAAK is also present in AISs of hippocampal and cortical neurons in the adult rat brain as well as in AISs of cultured rat hippocampal neurons. We show that the AIS localization is driven by a C-terminal ankyrin G-binding sequence that organizes TRAAK in a 190 nm spaced periodic pattern that codistributes with periodically organized ankyrin G. We furthermore uncover that while the identified ankyrin G-binding motif is analogous to known ankyrin G-binding motifs in NaV1 and KV7.2/KV7.3 channels, it was acquired by convergent evolution. Our findings identify TRAAK as an AIS ion channel that convergently acquired an ankyrin G-binding motif and expand the role of ankyrin G to include the nanoscale organization of ion channels at the AIS.

Clinical and serological characteristics of patients allergic to LTP.

BACKGROUND: Allergy to lipid transfer proteins (LPT) is common in Mediterranean Europe, and it causes severe reactions in patients and affects multiple foods, impairing the quality of life. OBJECTIVE: This study aimed to describe the clinical and sensitization profile of patients with LTP syndrome and to determine a clinical pattern of severity. Molecular diagnosis is shown in a broad population through microarrays. MATERIAL AND METHODS: This study was performed at the LTP Allergy Consultation of the Reina Sofia Hospital in Murcia, Spain. We analyzed the patients' characteristics, reactions, cofactors, food implicated, quality of life, skin prick test to food and aeroallergens, and serologic parameters, such as total immunoglobulin E, peach LTP (Pru p 3 IgE) and immunoglobulin G4, and microarray Immuno Solid-phase Allergen Chip (ISAC). We related the severity of the reactions with other variables. RESULTS: We presented a series of 236 patients diagnosed with LTP allergy, 54.66% suffering from anaphylaxis, 36.02% from urticaria angioedema, and 9.32% from oral allergy syndrome. The most frequently implicated food was peach, producing symptoms in 70% of patients, followed by walnut in 55%, peanut in 45%, hazelnut in 44%, and apple in 38% patients. Regarding the food that provoked anaphylaxis, walnut was the most frequent instigator, along with peach, peanut, hazelnut, almond, sunflower seed, and apple. According to the severity of LPT reaction, we did not discover significant differences in gender, age, food group involved, and serologic parameters. We found differences in the presence of cofactors, with 48.84% of cofactors in patients with anaphylaxis, compared to 27.1% in patients without anaphylaxis and in family allergy background (P < 0.0001). CONCLUSION: In our series of patients, 54% presented anaphylaxis, and the foods that most frequently produced symptoms were peaches, apples, and nuts. Cofactors and family allergy backgrounds were associated with the severity of LPT reaction.

Gene regulatory landscape of cerebral cortex folding.

Folding of the cerebral cortex is a key aspect of mammalian brain development and evolution, and defects are linked to severe neurological disorders. Primary folding occurs in highly stereotyped patterns that are predefined in the cortical germinal zones by a transcriptomic protomap. The gene regulatory landscape governing the emergence of this folding protomap remains unknown. We characterized the spatiotemporal dynamics of gene expression and active epigenetic landscape (H3K27ac) across prospective folds and fissures in ferret. Our results show that the transcriptomic protomap begins to emerge at early embryonic stages, and it involves cell-fate signaling pathways. The H3K27ac landscape reveals developmental cell-fate restriction and engages known developmental regulators, including the transcription factor Cux2. Manipulating Cux2 expression in cortical progenitors changed their proliferation and the folding pattern in ferret, caused by selective transcriptional changes as revealed by single-cell RNA sequencing analyses. Our findings highlight the key relevance of epigenetic mechanisms in defining the patterns of cerebral cortex folding.

Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.

Keep calm and make neurons: The effects of glucocorticoids on human cortical neurogenesis.

Maternal well-being is important for the development of the fetus, with a key influence on its nervous system. In this issue of Neuron, Krontira et al.1 implicate glucocorticoids, the stress hormones, in the regulation of neural stem cell identity and proliferation, with long-lasting consequences on brain architecture and educational attainment.

Multiple parallel cell lineages in the developing mammalian cerebral cortex.

Cortical neurogenesis follows a simple lineage: apical radial glia cells (RGCs) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, such as human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret and barcoded lineage tracking to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not in mouse. Neurons followed parallel differentiation trajectories in the gyrus and sulcus, with different expressions of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex.

The antimicrobial potential of adarotene derivatives against Staphylococcus aureus strains.

Multidrug-resistant (MDR) pathogens are severely impacting our ability to successfully treat common infections. Here we report the synthesis of a panel of adarotene-related retinoids showing potent antimicrobial activity on Staphylococcus aureus strains (including multidrug-resistant ones). Fluorescence and molecular dynamic studies confirmed that the adarotene analogues were able to induce conformational changes and disfunctions to the cell membrane, perturbing the permeability of the phospholipid bilayer. Since the major obstacle for developing retinoids is their potential cytotoxicity, a selected candidate was further investigated to evaluate its activity on a panel of human cell lines. The compound was found to be well tolerated, with IC50 5-15-fold higher than the MIC on S. aureus strains. Furthermore, the adarotene analogue had a good pharmacokinetic profile, reaching a plasma concentration of about 6 µM after 0.5 h after administration (150 mg/kg), at least twice the MIC observed against various bacterial strains. Moreover, it was demonstrated that the compound potentiated the growth-inhibitory effect of the poorly bioavailable rifaximin, when used in combination. Overall, the collected data pave the way for the development of synthetic retinoids as potential therapeutics for hard-to-treat infectious diseases caused by antibiotic-resistant Gram-positive pathogens.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Desempeño del analizador de orinas Laura XL-Erba Mannheim en comparación con el iRICELL-Beckman Coulter en una población general / Performance of the Laura XL urine analyzer-Erba Mannheim in comparison with IRISCell-Beckman Coulter in a general population / Desempenho do analisador de urina Laura XL-Erba Mannheim em comparação com iRICELL-Beckman Coulter em uma população geral

Resumen Los objetivos del trabajo fueron evaluar el desempeño del analizador de orinas Laura XL® Erba Mannhein, por comparación con el analizador iRICELL® Beckman Coulter y valorar la determinación de proteínas urinarias semicuantitativas como tamizaje en su estudio, con el establecimiento de un punto de corte para su cuantificación. Se emplearon 225 muestras de orina procesadas en simultáneo. Se evaluó pH, densidad, turbidez, color, hemoglobina, glucosa, cetonas, nitritos, proteínas, número de tiras reactivas positivas; células epiteliales, leucocitos, hematíes y criterio de normalidad del sedimento por microscopía. Se cuantificaron las proteínas urinarias positivas por tiras en un Modular COBAS® 8000 (Hitachi-Roche). Se empleó el coeficiente de concordancia Kappa de Cohen (k) y el índice de correlación de Spearman. Se obtuvo escasa concordancia en turbidez (k=0,334), buena concordancia en color (k=0,681), hemoglobina (k=0,620), glucosa (k=0,677), cetonas (k=0,768), nitritos (k=0,827), tiras reactivas positivas (k=0,620), células epiteliales (k=0,783), leucocitos (k=0,745) y hematíes (k=0,609); muy buena concordancia en proteínas (k=0,842) y criterio de normalidad del sedimento (k=1,000). Correlación estadísticamente significativa en pH (r=0,8064; p<0,0001), densidad (r=1,000; p<0,0001) y proteína urinaria (rs=0,9157; p<0,0001) comparada con COBAS® 8000. Se concluyó un desempeño satisfactorio de Laura XL®; se muestra un rendimiento acorde a las necesidades y normativas de este laboratorio y se avala su utilidad como test de tamizaje para la valoración de proteínas urinarias. Se estableció, además, la cuantificación de orinas que presentaron 1+ o más por tira en Laura XL®. Se consideró realizar mejoras en el software.

Abstract The objectives of this work were to evaluate the performance of the Laura XL® Erba Mannheim urine analyzer, in comparison with the iRICELL® Beckman Coulter analyzer, and to assess the determination of semiquantitative urinary protein as screening in its study, establishing a cut-off point for its quantification. A total of 225 urine samples were simultaneously processed. pH, density, turbidity, colour, hemoglobin, glucose, ketones, nitrites, proteins, and number of positive reactive strips were evaluated; and epithelial cells, leukocytes, red blood cells and criteria for normality of the sediment were evaluated by microscopy. Positive urinary proteins per strip were quantified on a Modular COBAS® 8000 (Hitachi-Roche). Cohen's Kappa concordance coefficient (k) and Spearman's correlation index were used. Little agreement was obtained in turbidity (k=0.334), good agreement in colour (k=0.681), hemoglobin (k=0.620), glucose (k=0.677), ketones (k=0.768), nitrites (k=0.827), positive test strips (k=0.620), epithelial cells (k=0.783), leukocytes (k=0.745) and red blood cells (k=0.609); very good agreement for proteins (k=0.842) and sediment normality criteria (k=1,000). Statistically significant correlation in pH (r=0.8064; p<0.0001), density (r=1.000; p<0.0001), urinary protein (rs=0.9157; p<0.0001) compared with COBAS® 8000. A satisfactory performance of Laura XL® was concluded, showing a performance consistent with the needs and regulations of this institution, and its usefulness is endorsed as a screening test for the assessment of urinary proteins, establishing the quantification of urines that present 1+ or more per strip in Laura XL®. Software improvements are considered.

Resumo Os objetivos do trabalho foram avaliar o desempenho do analisador de urina Laura XL® Erba Mannheim, em comparação com o analisador iRICELL® Beckman Coulter, e avaliar a determinação de proteínas urinárias semiquantitativa como triagem em seu estudo, estabelecendo um ponto de corte para sua quantificação. Foram utilizadas 225 amostras de urina processadas simultaneamente. Foram avaliados pH, densidade, turbidez, cor, hemoglobina, glicose, cetonas, nitritos, proteínas, número de testes reativos positivos; células epiteliais, leucócitos, hemácias e critérios de normalidade do sedimento à microscopia. As proteínas urinárias positivas por teste foram quantificadas em um Modular COBAS® 8000 (Hitachi-Roche). Foram utilizados o coeficiente de concordância Kappa de Cohen (k) e o índice de correlação de Spearman. Escassa concordância foi obtida em turbidez (k=0,334), boa concordância em cor (k=0,681), hemoglobina (k=0,620), glicose (k=0,677), cetonas (k=0,768), nitritos (k=0,827), testes reativos positivos (k=0,620), células epiteliais (k=0,783), leucócitos (k=0,745) e hemácias (k=0,609); concordância muito boa para proteínas (k=0,842) e critérios de normalidade do sedimento (k=1,000). Correlação estatisticamente significativa em pH (r=0,8064 p<0,0001), densidade (r=1,000 p<0,0001), proteína urinária (rs=0,9157 p<0,0001) em comparação com COBAS® 8000. A conclusão é um desempenho satisfatório de Laura XL®, mostrando um rendimento consistente com as necessidades e normas deste laboratorio e sua utilidade é endossada como teste de triagem para avaliação de proteínas urinárias, estabelecendo também a quantificação de urinas que apresentaram 1+ ou mais por teste em Laura XL®. Melhorias no software são consideradas.

High Levels of IL-1ß, TNF-α and MIP-1α One Month after the Onset of the Acute SARS-CoV-2 Infection, Predictors of Post COVID-19 in Hospitalized Patients.

The pandemic caused by SARS-CoV-2 infection has left behind a new symptomatology called post COVID-19, or "long COVID". The pathophysiological mechanisms still remain controversial; however, a link between persistent inflammation and these sequelae has been suggested. Herein, we longitudinally assessed up- and downstream molecules of the NLRP3 inflammasome's pathway in three study groups: healthy donors (HC, n = 14) and donors with a confirmed SARS-CoV-2 infection who had been hospitalized, the latter divided into post COVID-19 (PC, n = 27) and non-post COVID-19 patients (nPC, n = 27) based on the presence or absence of symptomatology at month 6, respectively. Plasma cytokines (IL-1ß, IL-3, IL-6, IL-8, IL-18, IP-10, MIG, TNF-α, IFN-γ, MIP-1α and MIP-1ß) and total peroxide (TPX) levels were quantified at baseline and at months 1 and 6 after the onset of the infection. Baseline values were the highest for both TPX and cytokines that progressively decreased thereafter the acute infection. IL-1ß, MIP-1α and TNF-α at month 1 were the only cytokines that showed a significant difference between nPC and PC. These findings suggest that a persistent inflammatory state one month after the onset of SARS-CoV-2 infection related to specific cytokines (IL-1ß, MIP-1α, and TNF-α) might guide to predicting post COVID-19 symptomatology.

Is the diagnostic yield of mediastinal lymph node cryobiopsy (cryoEBUS) better for diagnosing mediastinal node involvement compared to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)? A systematic review.

INTRODUCTION: New tools such as cryobiopsy of mediastinal lymph nodes (cryoEBUS) have been described to improve the diagnostic usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The literature suggests that this novel procedure could be associated with greater diagnostic usefulness than conventional EBUS-TBNA. METHODS: To develop a systematic analysis and meta-analysis on the diagnostic diagnostic yield and safety of cryobiopsy of hilar and mediastinal adenopathies compared to EBUS-TBNA. RESULTS: Seven studies that had included a total of 555 patients were considered in this review, with 365 (65.7%) of these patients having an etiology of malignant lymph node involvement. The overall diagnostic usefulness of cryoEBUS was higher compared to EBUS-TBNA (92% vs. 80%). However, when the results were analysed according to the specific aetiologies of the adenopathies, cryoEBUS was especially useful in cases of lymphomas or non-pulmonary carcinomas (83% vs. 42%) and in cases that were benign (87% vs. 60.1%), with no significant differences being found in specific cases of lung cancer. For lymphoma, cryoEBUS was diagnostic in 87% of cases compared to 12% for EBUS-TBNA and in addition, also allowed the characterisation of every lymphoma subtype. Genetic studies and immunohistochemical determination of PD-L1 was possible in almost all (97%) of the samples obtained by cryoEBUS, while this was only possible in 79% of those obtained by EBUS-TBNA. The most frequent complication was light bleeding, which was described in up to 85% of cases in some series. CONCLUSION: CryoEBUS could represent a promising technique in the diagnostic algorithm used for mediastinal and hilar involvement. Although cryoEBUS did not significantly improve the diagnosis of lung cancer compared to EBUS-TBNA, the results were significantly better in patients with benign pathologies and other tumour types, including lymphomas. In addition, it seems that the samples obtained by cryoEBUS better defined the histological subtypes of lymphoma and allowed complete molecular characterisation in cases of lung cancer. The technique has proven to be safe and no serious complications were described after the procedure.

Outcomes and clinical characteristics of the compassionate use of plitidepsin for immunocompromised adult patients with COVID-19.

OBJECTIVES: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19. DESIGN: Retrospective observational study of data -collected from January 01, 2021 to April 30, 2022- from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA. RESULTS: Thirty-three patients receiving a full course of plitidepsin (2.5 mg [n = 29] or 1.5 mg [n = 4]) were included. Most (69.7%) had a malignant hematologic disease and 27.3% had solid tumors. A total of 111 infusions were administered with lack of relevant safety events. Median time from plitidepsin initiation to SpFi ≥315 was 8 days (95% confidence interval [CI], 7-19). Median time to first negative reverse transcription-polymerase chain reaction for SARS-CoV-2 (cycle threshold >36) was 17 days (95% CI 13-25). Mortality rate was 16.3% (95% CI 3-37.3). CONCLUSION: These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.

Validation of clinical exome sequencing in the diagnostic procedure of patients with intellectual disability in clinical practice.

Intellectual disability (ID) has a prevalence of 1-3% and aproximately 30-50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren't clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.

Serum Vitamins A and E at Mid-Pregnancy and Their Relationships with Both Maternal and Cord Blood Antioxidant Status and Perinatal Conditions: The NELA Cohort.

INTRODUCTION: Most of the pregnant women do not achieve the recommended dietary intake of vitamins A and E. These vitamins may counteract oxidative stress involved in some adverse perinatal outcomes. We aimed to assess the associations between maternal vitamin A and E at mid-pregnancy with both maternal and fetal outcomes and to identify possible early biomarkers during pregnancy to predict and prevent oxidative stress in the offspring. METHODS: Data on dietary and serum levels of vitamins A and E were collected from 544 pregnant women from the Nutrition in Early Life and Asthma (NELA) study, a prospective mother-child cohort set up in Spain. RESULTS: There were large discrepancies between low dietary vitamin E intake (78% of the mothers) and low serum vitamin E levels (3%) at 24 weeks of gestation. Maternal serum vitamins A and E at mid-pregnancy were associated with higher antioxidant status not only in the mother at this time point (lower hydroperoxides and higher total antioxidant activity [TAA]) but also with the newborn at birth (higher TAA). Gestational diabetes mellitus (GDM) was negatively associated with maternal serum vitamin A (OR: 0.95 CI: 0.91-0.99, p = 0.009) at mid-pregnancy. Nevertheless, we could not detect any association between GDM and oxidative stress parameters. CONCLUSIONS: In conclusion, maternal vitamin A and E serum levels may be used as an early potential biomarker of antioxidant status of the neonate at birth. Control of these vitamins during pregnancy could help avoid morbid conditions in the newborn caused by oxidative stress in GDM pregnancies.

Stem-like signatures in human meningioma cells are under the control of CXCL11/CXCL12 chemokine activity.

BACKGROUND: Meningiomas are mainly benign brain tumors, although about 20% of histologically benign cases are clinically aggressive and recur after resection. We hypothesize that meningioma brain invasiveness and recurrence may be related to the presence of cancer stem cells and their high responsiveness to the CXCL12-CXCR4/CXCR7 chemokine axis. The aim of this study was to isolate meningioma stem cells from human samples, characterize them for biological features related to malignant behavior, and to identify the role of CXCR4/CXCR7 in these processes. METHODS: Meningioma stem cells were isolated from patient-derived primary cultures in stem cell-permissive conditions, and characterized for phenotype, self-renewal, proliferation and migration rates, vasculogenic mimicry (VM), and in vivo tumorigenesis, in comparison with differentiated meningioma cells and stem-like cells isolated from normal meninges. These cell populations were challenged with CXCL12 and CXCL11 and receptor antagonists to define the chemokine role in stem cell-related functions. RESULTS: Stem-like cells isolated from meningioma cultures display higher proliferation and migration rates, and VM, as compared to meningioma non-stem cells or cells isolated from normal meninges and were the only tumorigenic population in vivo. In meningioma cells, these stem-like functions were under the control of the CXCR4/CXCR7 chemokine axis. CONCLUSIONS: We report a role for CXCL11 and CXCL12 in the control of malignant features in stem-like cells isolated from human meningioma, providing a possible basis for the aggressive clinical behavior observed in subsets of these tumors. CXCR4/CXCR7 antagonists might represent a useful approach for meningioma at high risk of recurrence and malignant progression.

Developmental mechanisms of gyrification.

Folding of the cerebral cortex is a fundamental milestone of mammalian brain evolution associated with dramatic increases in size and complexity. Cortex folding takes place during embryonic and perinatal development and is important to optimize the functional organization and wiring of the brain, while allowing fitting a large cortex in a limited cranial volume. Cortex growth and folding are the result of complex cellular and mechanical processes that involve neural stem progenitor cells and their lineages, the migration and differentiation of neurons, and the genetic programs that regulate and fine-tune these processes. Here, we provide an updated overview of the most significant and recent advances in our understanding of developmental mechanisms regulating cortical gyrification.