Heavy-element production in a compact object merger observed by JWST.

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs)1, sources of high-frequency gravitational waves (GWs)2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process)3. Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers4-6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs. 7-12). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe.

A kilonova following a long-duration gamma-ray burst at 350 Mpc.

Gamma-ray bursts (GRBs) are divided into two populations1,2; long GRBs that derive from the core collapse of massive stars (for example, ref. 3) and short GRBs that form in the merger of two compact objects4,5. Although it is common to divide the two populations at a gamma-ray duration of 2 s, classification based on duration does not always map to the progenitor. Notably, GRBs with short (≲2 s) spikes of prompt gamma-ray emission followed by prolonged, spectrally softer extended emission (EE-SGRBs) have been suggested to arise from compact object mergers6-8. Compact object mergers are of great astrophysical importance as the only confirmed site of rapid neutron capture (r-process) nucleosynthesis, observed in the form of so-called kilonovae9-14. Here we report the discovery of a possible kilonova associated with the nearby (350 Mpc), minute-duration GRB 211211A. The kilonova implies that the progenitor is a compact object merger, suggesting that GRBs with long, complex light curves can be spawned from merger events. The kilonova of GRB 211211A has a similar luminosity, duration and colour to that which accompanied the gravitational wave (GW)-detected binary neutron star (BNS) merger GW170817 (ref. 4). Further searches for GW signals coincident with long GRBs are a promising route for future multi-messenger astronomy.

Genetic compensation triggered by mutant mRNA degradation.

Genetic robustness, or the ability of an organism to maintain fitness in the presence of harmful mutations, can be achieved via protein feedback loops. Previous work has suggested that organisms may also respond to mutations by transcriptional adaptation, a process by which related gene(s) are upregulated independently of protein feedback loops. However, the prevalence of transcriptional adaptation and its underlying molecular mechanisms are unknown. Here, by analysing several models of transcriptional adaptation in zebrafish and mouse, we uncover a requirement for mutant mRNA degradation. Alleles that fail to transcribe the mutated gene do not exhibit transcriptional adaptation, and these alleles give rise to more severe phenotypes than alleles displaying mutant mRNA decay. Transcriptome analysis in alleles displaying mutant mRNA decay reveals the upregulation of a substantial proportion of the genes that exhibit sequence similarity with the mutated gene's mRNA, suggesting a sequence-dependent mechanism. These findings have implications for our understanding of disease-causing mutations, and will help in the design of mutant alleles with minimal transcriptional adaptation-derived compensation.

Implantable loop recorders in patients with Brugada syndrome: the BruLoop study.

BACKGROUND AND AIMS: Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes. METHODS: A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years. RESULTS: During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P = .001] and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs. CONCLUSIONS: ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation.

Aquaporin-4 and transient receptor potential vanilloid 4 balance in early postnatal neurodevelopment.

In the adult brain, the water channel aquaporin-4 (AQP4) is expressed in astrocyte endfoot, in supramolecular assemblies, called "Orthogonal Arrays of Particles" (OAPs) together with the transient receptor potential vanilloid 4 (TRPV4), finely regulating the cell volume. The present study aimed at investigating the contribution of AQP4 and TRPV4 to CNS early postnatal development using WT and AQP4 KO brain and retina and neuronal stem cells (NSCs), as an in vitro model of astrocyte differentiation. Western blot analysis showed that, differently from AQP4 and the glial cell markers, TRPV4 was downregulated during CNS development and NSC differentiation. Blue native/SDS-PAGE revealed that AQP4 progressively organized into OAPs throughout the entire differentiation process. Fluorescence quenching assay indicated that the speed of cell volume changes was time-related to NSC differentiation and functional to their migratory ability. Calcium imaging showed that the amplitude of TRPV4 Ca2+ transient is lower, and the dynamics are changed during differentiation and suppressed in AQP4 KO NSCs. Overall, these findings suggest that early postnatal neurodevelopment is subjected to temporally modulated water and Ca2+ dynamics likely to be those sustaining the biochemical and physiological mechanisms responsible for astrocyte differentiation during brain and retinal development.

Electrophysiological patterns and structural substrates of Brugada syndrome: Critical appraisal and computational analyses.

Brugada syndrome (BrS) is a cardiac electrophysiological disease with unknown etiology, associated with sudden cardiac death. Symptomatic patients are treated with implanted cardiac defibrillator, but no risk stratification strategy is effective in patients that are at low to medium arrhythmic risk. Cardiac computational modeling is an emerging tool that can be used to verify the hypotheses of pathogenesis and inspire new risk stratification strategies. However, to obtain reliable results computational models must be validated with consistent experimental data. We reviewed the main electrophysiological and structural variables from BrS clinical studies to assess which data could be used to validate a computational approach. Activation delay in the epicardial right ventricular outflow tract is a consistent finding, as well as increased fibrosis and subclinical alterations of right ventricular functional and morphological parameters. The comparison between other electrophysiological variables is hindered by methodological differences between studies, which we commented. We conclude by presenting a recent theory unifying electrophysiological and structural substrate in BrS and illustrate how computational modeling could help translation to risk stratification.

Endocardial repolarization dispersion in BrS: A novel automatic algorithm for mapping activation recovery interval.

INTRODUCTION: Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients. METHODS: Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined as OType1, while those without (latent type-1 ECG and LType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps. RESULTS: 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively). CONCLUSION: ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1.

A de novo frameshift variant in MED13 gene in a patient with autism spectrum disorder and magnetic resonance imaging abnormalities mimicking tuberous sclerosis.

The mediator complex subunit 13 (MED13) gene is implicated in neurodevelopmental disorders including autism spectrum disorder (ASD), intellectual disability, and speech delay with varying severity and course. Additional, extra central nervous system, features include eye or vision problems, hypotonia, congenital heart abnormalities, and dysmorphisms. We describe a 7-year- and 4-month-old girl evaluated for ASD whose brain magnetic resonance imaging was suggestive of multiple cortical tubers. The exome sequencing (ES - trio analysis) uncovered a unique, de novo, frameshift variant in the MED13 gene (c.4880del, D1627Vfs*17), with a truncating effect on the protein. This case report thus expands the phenotypic spectrum of MED13-related disorders to include brain abnormalities.

Developmental epileptic encephalopathy in DLG4-related synaptopathy.

OBJECTIVE: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy. METHODS: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician. RESULTS: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants. SIGNIFICANCE: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG.

Fetal brain MR angiography at 1.5 T: a feasible study.

PURPOSE: The use of magnetic resonance angiography (MRA) for assessing CNS fetal vasculature has been limited. The aim of this study was to determine the feasibility and added value of 2D time-of-flight (TOF) MRA of the fetal brain vasculature with a 1.5 T scanner. METHODS: We conducted a prospective study (September 2018 to October 2022) by consecutively selecting pregnant women (≥ 18 years) with clinical indication to fetal brain MRI. On a 1.5 T scanner, a 2D TOF MRA acquisition was obtained at the end of the clinical protocol. Two neuroradiologists independently reviewed all MRIs; a qualitative scale of motion artifacts was applied to MRA images; represented vessels in MRA and T2 images were registered. RESULTS: Thirty-five fetal brain MRIs. Mean maternal age: 32 years; mean fetal gestational age (GA): 31 weeks. Artifacts were found in 74% of MRA. The number of MRAs performed without artifacts increased with GA. On MRA, the identification of the majority of vessels increased with GA; statistical significance was reached in the identification of torcular Herophili (p = 0.026), vein of Galen (p < 0.001), internal cerebral veins (p = 0.002), basilar artery (p = 0.027), vertebral arteries (p = 0.025), and middle cerebral arteries (p = 0.044). Significantly, MRA depicted the sigmoid sinuses and internal jugular veins more frequently. Vascular pathology was found in 3/35 fetal brain MRIs. CONCLUSION: Although artifacts were found in 74% of cases, MRA acquisitions were informative and of sufficient diagnostic quality in most studies. This technique may represent a valuable complimentary tool in CNS prenatal vascular studies.

Vein of Galen aneurysmal malformation: does size affect outcome?

PURPOSE: To validate a semiautomated method for segmenting vein of Galen aneurysmal malformations (VGAM) and to assess the relationship between VGAM volume and other angioarchitectural features, cardiological findings, and outcomes. METHODS: In this retrospective study, we selected all subjects with VGAM admitted to the Gaslini Children's Hospital between 2009 and 2022. Clinical data were retrieved from electronic charts. We compared 3D-Slicer segmented VGAM volumes obtained by two independent observers using phase-contrast MR venography to those obtained with manual measurements performed on T2-weighted images. The relationship between VGAM volumes and clinical and neuroimaging features was then explored. RESULTS: Forty-three subjects with VGAM (22 males, mean age 6.56 days) were included in the study. Manual and semiautomated VGAM volumes were well correlated for both readers (r = 0.86 and 0.82, respectively). Regarding reproducibility, the inter-rater interclass correlation coefficients were 0.885 for the manual method and 0.992 for the semiautomated method (p < 0.001). The standard error for repeated measures was lower for the semiautomated method (0.04 versus 0.40 of manual method). Higher VGAM volume was associated with superior sagittal sinus narrowing, jugular bulb stenosis, and aqueductal stenosis (p < 0.05). A weak correlation was found between VGAM volume and straight sinus dilatation (r = 0.331) and superior sagittal sinus index (r = - 0.325). No significant associations were found with cardiac findings, post-embolization complications, and outcome (p > 0.05). CONCLUSIONS: Semiautomated VGAM volumetry is feasible and reliable with improved reproducibility compared to the manual method. VGAM volume is not a prognostic factor for clinical outcome, but it is related to other venous findings with potential hemodynamic effects.

Brain and spine malformations and neurodevelopmental disorders in a cohort of children with CAKUT.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20-30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT. METHODS: We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.4 years) who underwent brain and/or spine MRI. Patients were grouped according to the type of CAKUT (CAKUT-K involving the kidney and CAKUT-H involving the inferior urinary tract). Group comparisons were performed using χ2 and Fisher exact tests. RESULTS: Brain/spine malformations were observed in 101/199 subjects (50.7%), 8.6% (101/1165) of our CAKUT population, including midbrain-hindbrain anomalies (40/158, 25.3%), commissural malformations (36/158, 22.7%), malformation of cortical development (23/158, 14.5%), Chiari I anomaly (12/199, 6%), cranio-cervical junction malformations (12/199, 6%), vertebral defects (46/94, 48.9%), caudal regression syndrome (29/94, 30.8%), and other spinal dysraphisms (13/94, 13.8%). Brain/spine malformations were more frequent in the CAKUT-K group (62.4%, p < 0.001). Sixty-two subjects (62/199, 31.2%) had developmental delay/intellectual disability. Neurological examination was abnormal in 40/199 (20.1%). Seizures and/or electroencephalographic anomalies were reported in 28/199 (14%) and behavior problems in 19/199 subjects (9%). Developmental delay/intellectual disability was more frequent in kidney dysplasia (65.2%) and agenesis (40.7%) (p = 0.001). CONCLUSIONS: We report a relative high frequency of brain/spine malformations and neurodevelopmental disorders in children with CAKUT who underwent MRI examinations in a tertiary referral center, widening the spectrum of anomalies associated with this condition.

Identification of genome edited cells using CRISPRnano.

Genome engineering-induced cleavage sites can be resolved by non-homologous end joining (NHEJ) or homology-directed repair (HDR). Identifying genetically modified clones at the target locus remains an intensive and laborious task. Different workflows and software that rely on deep sequencing data have been developed to detect and quantify targeted mutagenesis. Nevertheless, these pipelines require high-quality reads generated by Next Generation Sequencing (NGS) platforms. Here, we have developed a robust, versatile, and easy-to-use computational webserver named CRISPRnano (www.CRISPRnano.de) that enables the analysis of low-quality reads generated by affordable and portable sequencers including Oxford Nanopore Technologies (ONT) devices. CRISPRnano allows fast and accurate identification, quantification, and visualization of genetically modified cell lines, it is compatible with NGS and ONT sequencing reads, and it can be used without an internet connection.

Posthemorrhagic hydrocephalus management in patients with necrotizing enterocolitis: a monocentric experience.

PURPOSE: Posthemorrhagic hydrocephalus (PHH) and necrotizing enterocolitis (NEC) are two comorbidities associated with prematurity. The management of patients with both conditions is complex and it is necessary to intercept them to avoid meningitis and multilocular hydrocephalus. METHODS: In a single-center retrospective study, we analyzed 19 patients with NEC and PHH admitted from 2012 to 2022. We evaluated perinatal, imaging, and NEC-related data. We documented shunt obstruction and infection and deaths within 12 months of shunt insertion. RESULTS: We evaluated 19 patients with NEC and PHH. Six cases (31.58%) were male, the median birth weight was 880 g (650-3150), and the median gestational age was 26 weeks (23-38). Transfontanellar ultrasound was performed on 18 patients (94.74%) and Levine classification system was used: 3 cases (15.79%) had a mild Levine index, 11 cases (57.89%) had moderate, and 5 cases (26.32%) were graded as severe. Magnetic resonance showed intraventricular hemorrhage in 14 cases (73.68%) and ventricular dilatation in 15 cases (78.95%). The median age at shunt insertion was 24 days (9-122) and the median length of hospital stay was 120 days (11-316). Sepsis was present in 15 cases (78.95%). NEC-related infection involved the peritoneal shunt in 4 patients and 3 of them had subclinical NEC. At the last follow-up, 6 (31.58%) patients presented with psychomotor delay. No deaths were reported. CONCLUSIONS: Although recognition of subclinical NEC is challenging, the insertion of a ventriculoperitoneal shunt is not recommended in these cases and alternative treatments should be considered to reduce the risk of meningitis and shunt malfunction.

A case report of hemorrhagic presentation of diffuse neonatal hemangiomatosis (DNH) associated to obstructive hydrocephalus: Medical and neurosurgical considerations.

BACKGROUND: Diffuse neonatal hemangiomatosis (DNH) is a rare disorder typically recognized at birth or during the neonatal period. DNH involves three or more organ systems, including the central nervous system (CNS). In these cases, serious complications such as hemorrhages and obstructive hydrocephalus can develop. CASE REPORT: We present a case of DNH with intracranial hypertension and CNS hemorrhagic lesions on the mesencephalic aqueduct, resulting in triventricular hydrocephalus, treated with endoscopic ventriculocisternostomy (ETV) and medical therapy. DISCUSSION: DNH is a rare condition that can involve the CNS with serious complications. From a review of the literature, we highlighted only two cases of DNH with brain involvement treated surgically. We report the successful outcome of ETV, along with surgical considerations, imaging findings, and the complete resolution of cerebral and skin lesions following medical therapy. CONCLUSIONS: Medical therapy is not standardized and must be individualized. In patients who develop severe neurological symptoms such as obstructive hydrocephalus, surgery may be considered to avoid neurological sequelae.

Pathogenesis and treatment of a giant occipital bone defect with meningoencephalocele in an NF1 child: case report and review of the literature.

Autosomal dominantly inherited neurofibromatosis type I (NF1) is a systemic disorder caused by a mutation of a gene on chromosome 17q11.2 and characterized by multiple café-au-lait spots, lentiginous macules, Lisch nodules of the iris, and tumors of the nervous system. Bony manifestations such as scoliosis, dysplasia of the greater sphenoidal wing, tibial pseudoarthrosis, short stature, and macrocephaly have been reported in approximately 50% of patients. However, calvarial bone defects are rare. After screening 324 articles, 23 cases (12 adult and 11 pediatric patients) of occipital bone defects in NF1 patients were selected. All patients had a single/multiple bone defect over the lambdoid suture. Adjacent benign plexiform neurofibromas were observed in 14 patients (60.8%, 7 adults and 7 children); one adult patient was diagnosed with neurofibrosarcoma. Meningoencephalocele over the occipital defect was noted in 8 cases (34.78%, all adults). Cranioplasty was performed in only 17.39% of patients. Histologic examination was performed in 7 of the 15 patients with associated neurofibromas/neurofibrosarcomas. Biopsy of the bone margins surrounding the defect was performed in only one case. Pathologic examination of the herniated parieto-occipital or cerebellar tissue was not performed in any of the patients studied. We report the case of a 9-year-old girl with NF1 and a significant occipital bone defect and performed a systematic review of the relevant literature to highlight the challenges in treating this condition and to investigate the underlying mechanisms contributing to bone defects or dysplasia in NF1.

Navigating the complexities of encephalocraniocutaneous lipomatosis: a case series and review.

INTRODUCTION: Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome with complex skin, eye, and central nervous system (CNS) symptoms. Diagnosis and treatment are challenging due to its rarity and diverse manifestations. It often involves issues like porencephalic cysts, cortical atrophy, and low-grade gliomas in the CNS, resulting in developmental delays. The spinal cord is frequently affected, leading to problems like medullary compression and radiculopathy, causing back pain and sensory/motor deficits. Surgical interventions are reserved for symptomatic cases to address hydrocephalus or alleviate spinal lipomas. This article reviews a case series to assess surgical risks and neurological outcomes. CASE SERIES: We present a case series ECCL, focusing on the diffuse lipomatosis of the spinal cord and the intricate surgical procedures involved. A multi-stage surgical approach was adopted, with continuous neuromonitoring employed to safeguard motor pathways. We discuss clinical characteristics, imaging studies, and indications for neurosurgical interventions. DISCUSSION: ECCL is a complex syndrome. Diagnosis is challenging and includes clinical evaluation, neuroimaging, and genetic testing. Treatment targets specific symptoms, often requiring surgery for issues like lipomas or cerebral cysts. Surgery involves laminectomies, spinal fusion, and motor pathway monitoring. Thorough follow-up is crucial due to potential CNS complications like low-grade gliomas. Hydrocephalus occurs in some cases, with endoscopic third ventriculostomy (ETV) preferred over ventriculoperitoneal shunt placement. CONCLUSION: Neurosurgery for ECCL is for symptomatic cases. ETV is preferred for hydrocephalus, while the treatment for lipoma is based on the presence of symptoms; the follow-up should assess growth and prevent deformities.

Prenatal imaging of the normal and abnormal spinal cord: recommendations from the Fetal Task Force of the European Society of Paediatric Radiology (ESPR) and the European Society of Neuroradiology (ESNR) Pediatric Neuroradiology Committee.

Spinal dysraphisms are amenable to diagnosis in utero. The prognosis and the neonatal management of these conditions differ significantly depending on their types, mainly on the distinction between open and closed defects. A detailed evaluation not only of the fetal spine, but also of the brain, skull, and lower limbs is essential in allowing for the right diagnosis. In this article, recommendations from the Fetal Task Force of the European Society of Paediatric Radiology (ESPR) and the European Society of Neuroradiology (ESNR) Pediatric Neuroradiology Committee will be presented. The aim of this paper is to review the imaging features of the normal and abnormal fetal spinal cord, to clarify the prenatal classification of congenital spinal cord anomalies and to provide guidance in their reporting.

Mitochondria Transplantation Mitigates Damage in an In Vitro Model of Renal Tubular Injury and in an Ex Vivo Model of DCD Renal Transplantation.

OBJECTIVES: To test whether mitochondrial transplantation (MITO) mitigates damage in 2 models of acute kidney injury (AKI). BACKGROUND: MITO is a process where exogenous isolated mitochondria are taken up by cells. As virtually any morbid clinical condition is characterized by mitochondrial distress, MITO may find a role as a treatment modality in numerous clinical scenarios including AKI. METHODS: For the in vitro experiments, human proximal tubular cells were damaged and then treated with mitochondria or placebo. For the ex vivo experiments, we developed a non-survival ex vivo porcine model mimicking the donation after cardiac death renal transplantation scenario. One kidney was treated with mitochondria, although the mate organ received placebo, before being perfused at room temperature for 24 hours. Perfusate samples were collected at different time points and analyzed with Raman spectroscopy. Biopsies taken at baseline and 24 hours were analyzed with standard pathology, immunohistochemistry, and RNA sequencing analysis. RESULTS: In vitro, cells treated with MITO showed higher proliferative capacity and adenosine 5'-triphosphate production, preservation of physiological polarization of the organelles and lower toxicity and reactive oxygen species production. Ex vivo, kidneys treated with MITO shed fewer molecular species, indicating stability. In these kidneys, pathology showed less damage whereas RNAseq analysis showed modulation of genes and pathways most consistent with mitochondrial biogenesis and energy metabolism and downregulation of genes involved in neutrophil recruitment, including IL1A, CXCL8, and PIK3R1. CONCLUSIONS: MITO mitigates AKI both in vitro and ex vivo.

Rapid detection and online analysis of microbial changes through flow cytometry.

Short-read 16 S rRNA gene sequencing is the dominating technology to profile microbial communities in different habitats. Its uncontested taxonomic resolution paved the way for major contributions to the field. Sample measurement and analysis, that is, sequencing, is rather slow-in order of days. Alternatively, flow cytometry can be used to profile the microbiota of various sources within a few minutes per sample. To keep up with high measurement speed, we developed the open source-analyzing tool FlowSoFine. To validate the ability to distinguish microbial profiles, we examined human skin samples of three body sites (N = 3 × 54) with flow cytometry and 16 S rRNA gene amplicon sequencing. Confirmed by sequencing of the very same samples, body site was found to be significantly different by flow cytometry. For a proof-of-principle multidimensional approach, using stool samples of patients (N = 40) with/without inflammatory bowel diseases, we could discriminate the health status by their bacterial patterns. In conclusion, FlowSoFine enables the generation and comparison of cytometric fingerprints of microbial communities from different sources. The implemented interface supports the user through all analytical steps to work out the biological relevant signals from raw measurements to publication ready figures. Furthermore, we present flow cytometry as a valid method for skin microbiota analysis.