Search

Hybrid nanoparticles (hNPs), or nanoparticles composed of both organic and inorganic components, hold promise for diverse energy and environmental applications due to their ability to stabilize reactive nanomaterials against aggregation, enhancing their ability to pervade tortuous spaces and travel long distances to degrade contaminants

Objective Several risk scores have been developed and tested on coronavirus disease 2019 (COVID-19) patients to predict clinical decompensation. We aimed to compare an institutional, automated, custom-built early warning score (EWS) to the National Early Warning Score (NEWS) in COVID-19 patients. Methods A retrospective cohort analysis was performed on patients with COVID-19 infection who were admitted to an intermediate ward from March to December 2020. A machine learning–based customized EWS algorithm, which incorporates demographics, laboratory values, vital signs, and comorbidities, and the NEWS, which uses vital signs only, were calculated at 12-hour intervals. These patients were retrospectively assessed for decompensation in the subsequent 12 or 24 hours, defined as death or transfer to an intensive care unit. Results Of 709 patients, 112 (15.8%) had a decompensation event. Using the custom EWS, decompensation within 12 and 24 hours was predicted with areas under the receiver operating curve (AUC) of 0.81 and 0.79, respectively. The NEWS score applied to the same population yielded AUCs of 0.83 and 0.81, respectively. The 24-hour negative predictive values (NPV) of the NEWS and EWS in patients identified as low risk were 99.6 and 99.2%, respectively. Conclusion The NEWS score performs as well as a customized EWS in COVID-19 patients, demonstrating the significance of vital signs in predicting outcomes. The relatively high positive predictive value and NPV of both scores are indispensable for optimally allocating clinical resources. In this relatively young, healthy population, a more complex score incorporating electronic health record data beyond vital signs does not add clinical benefit.

Introduction A TCS after primary closure of meningomyeloceles is a known complication of the spina bifida disease. Data on the outcome after SSCU surgery is heterogeneous and lacking standardization. Thus we aimed to find a reliable system for assessment of the bladder function before and after SSCU surgery and document postoperative outcome. Methods A retrospective study was performed on a cohort of patients with spina bifida diagnosis. In total, 130 patients underwent 182 SSCU surgeries, 56 of those met our inclusion criteria. A classification system, including two different methods, was used. The AC system used baseline pressure and detrusor over activity to define three levels of bladder dysfunction, the second method ranked the severity of bladder dysfunction by awarding points from 0 to 2 for bladder capacity, maximal detrusor pressure during autonomous contractions, leak point pressure and vesicoureteral reflux A high score is correlated with a severe bladder dysfunction. Results Gender distribution was equally (male: n = 29; 51.8%; female: n = 27; 48.2%). The median age at SSCU was 902 years (range 0.5–22.8 years). After SSCU, the stage improved in 11 patients (19.6%), worsened in 11 (19.6%) patients and remained the same in 34 patients (60.7%) after intervention (AC score). Non-worsening was observed in a total of 45 cases (80.4%) (p n = 27, 48.2%) improved, remained unchanged (n = 12, 21.4%), 17 patients worsened (30.4%). Non-worsening in postoperative bladder functional outcome was demonstrated in 39 cases (69.6%) over all (p p n = 10; 41.7%) or improved (n = 12; 50.0%), meaning positive neuro-orthopedic outcome, only 2 (8.3%) deteriorated (p Conclusion Our study presents reliable evaluation systems for bladder function in spina bifida patients. Since indications for SSCU surgery differ, it is important to know the possible effects on bladder function after this surgical procedure. Even a mild impairment of bladder function has a risk to deteriorate after SSCU surgery. Particularly interesting becomes this with regard to the fact that the prevalence of TCS might become more frequent with the rising numbers of prenatal closures of meningomyeloceles.

Introduction Spina bifida (SB) is the most common neural tube defect in humans. Here, we analyzed systematically the neuropathological findings of the brain in SB cases. Methods 79 cases with SB aperta (SBA) and 6 cases with SB occulta (SBO) autopsied at the Charité Neuropathology from 1974 to 2000 were re-evaluated retrospectively. For this, case files and spinal cord as well as brain sections were studied. Results While no brain malformations were detected in SBO cases, 95% of SBA cases had brain malformations. Main brain anomalies identified were hydrocephalus (71%), Chiari II malformation (36%), heterotopia (34%), other cerebellar anomalies (36%), gyrification defects (33%), and ependymal denudation (29%). Hydrocephalus was observed as early as gestational week 17 and was highly associated to Chiari II and ependymal denudation. In 55% SBA was accompanied by further anomalies not primarily affecting the CNS. Conclusion We confirm using neuropathologic methods brain malformations in most SBA but none in SBO cases. In addition to our previous radiologic study, we now demonstrate the high prevalence of cerebellar malformations and cerebral heterotopias in SBA. The early detection of hydrocephalus and Chiari II malformation in fetuses raises the question whether these arise parallel rather than in strict temporal sequence.

The aim of this study is to analyze whether children with familial and sporadic neurofibromatosis type 1 (NF1) differ in psychosocial and socioeconomic aspects such as developmental delay as well as in comorbidities. Medical records of 250 children with NF1 at a median age of 10.6 years (range = 2–20 years at time of data collection) were retrospectively reviewed. Specifically, psychosocial and socioeconomic factors from 88 children with a family history for NF1 and 162 sporadic cases were compared. Comparing IQ, familial cases scored significantly lower than sporadic cases (89.8 vs. 96.5; p = 0.015). IQ scores of children with familial and sporadic NF1 differ depending on level of parental education (mean IQ for high education 101.3 [familial] and 102.8 [sporadic] vs. low education 87.5 [familial] and 90.4 [sporadic]; p

Introduction: A TCS after primary closure of meningomyeloceles is a known complication of the spina bifida disease. Data on the outcome after SSCU surgery is heterogeneous and lacking standardization. Thus we aimed to find a reliable system for assessment of the bladder function before and after SSCU surgery and document postoperative outcome.Methods: A retrospective study was performed on a cohort of 306 patients with spina bifida diagnosis. In total, 130 patients underwent 182 SSCU surgeries, 56 of those met our inclusion criteria. A classification system, including two different methods, was used. The AC system used baseline pressure and detrusor over activity to define three levels of bladder dysfunction, the second method ranked the severity of bladder dysfunction by awarding points from 0 to 2 for bladder capacity, maximal detrusor pressure during autonomous contractions, leak point pressure and vesicoureteral reflux A high score is correlated with a severe bladder dysfunction.Results: Gender distribution was equally (male: n=29; 51,8%; female: n=27; 48,2%). The median age at SSCU was 9,02 years (range 0,5 – 22,8 years).After SSCU, the stage improved in 11 patients (19.6%), worsened in 11 (19.6%) patients and remained the same in 34 patients (60.7%) after intervention (AC score). Non-worsening was observed in a total of 45 cases (80.4%) (pConclusion: Our study presents reliable evaluation systems for bladder function in spina bifida patients. Since indications for SSCU surgery differ, it is important to know the possible effects on bladder function after this surgical procedure. Even a mild impairment of bladder function has a risk to deteriorate after SSCU surgery. Particularly interesting becomes this with regard to the fact that the prevalence of TCS might become more frequent with the rising numbers of prenatal closures of meningomyeloceles.

Cerebral palsy (CP) refers to a non-progressive permanent lesion of the developing brain, which can manifest with motor function disability and various comorbidities and complications. However, there is little data on the correlation between motor and mental function in CP, as cognitive assessments are rarely the main focus of studies on children with CP.We studied a large cohort of 381 children and adolescents with CP. We analyzed the relationship between severity of CP and the presence of developmental disturbances (motor, motor-linguistic, global) including cognition, the number of aids and education.We found a strong correlation between the severity of CP according to the Gross Motor Function Classification System (GMFCS) and developmental disturbances. In line with this finding, the number of aids per individual also correlated significantly with CP severity and the extent of developmental disturbance. Going beyond the number of aids most patients already received special education in kindergarten. Later, the type of schooling correlated significantly with severity of CP and developmental disturbance. While developmental disturbance and cognition correlated, this was not the case for CP severity and cognition. The latter indicates a wide range in individual manifestation and resources.Our data underline that cognition does not necessarily correlate with CP severity. Thus, in addition to the evaluation and treatment of motor deficits, cognitive assessment should be offered early-on to improve patient-centered counselling and support with respect to appropriate education.

Molecular assemblies inside cells often undergo structural reconfiguration in response to stimuli to alter their function. Adaptive reconfiguration of cytoskeletal networks, for example, enables cellular shape change, movement, and cargo transport and plays a key role in driving complex processes such as division and differentiation. The cellular cytoskeleton is a self-assembling polymer network composed of simple filaments, so reconfiguration often occurs through the rearrangement of its component filaments' connectivities. DNA nanotubes have emerged as promising building blocks for constructing programmable synthetic analogs of cytoskeletal networks. Nucleating seeds can control when and where nanotubes grow, and capping structures can bind nanotube ends to stop growth. Such seeding and capping structures, collectively called termini, can organize nanotubes into larger architectures. However, these structures cannot be selectively activated or inactivated in response to specific stimuli to rearrange nanotube architectures, a key property of cytoskeletal networks. Here, we demonstrate how selective regulation of the binding affinity of DNA nanotube termini for DNA nanotube monomers or nanotube ends can direct the reconfiguration of nanotube architectures. Using DNA hybridization and strand displacement reactions that specifically activate or inactivate four orthogonal nanotube termini, we demonstrate that nanotube architectures can be reconfigured by selective addition or removal of distinct termini. Finally, we show how terminus activation could be a sensitive detector and amplifier of a DNA sequence signal. These results could enable the development of adaptive and multifunctional materials or diagnostic tools.

Cerebral palsy is the most common motor disability in childhood. Still, the precise definition in terms of causes and timing of the brain damage remains controversial. Several studies examine the clinical phenotype of cerebral palsy types. The aim of our study was to determine to what extent the clinical phenotype of cerebral palsy patients depends on the underlying cause. We retrospectively evaluated the clinical phenotype, abnormalities during pregnancy, and cerebral palsy cause of 384 patients, treated at Charité-Medicine University, between 2015 and 2017. The cause of cerebral palsy was identified in 79.9% of cases. Causes prior to the perinatal period were, compared to perinatal brain damage, associated significantly with different comorbidities. The term cerebral palsy does not describe a single disease but is an umbrella term covering many different diseases. Depending on the cause, a varying clinical phenotype can be found, which offers great potential in terms of individual treatment and preventing comorbidities.

PurposePerinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions.MaterialWe studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed.ResultsFrom the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%).DiscussionOur study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.

BackgroundVery long-chain fatty acids (VLCFAs) are essential for functioning of biological membranes. ELOVL fatty acid elongase 1 catalyses elongation of saturated and monounsaturated C22-C26-VLCFAs. We studied two patients with a dominantELOVL1mutation. Independently, Kutkowska-Kaźmierczaket al.had investigated the same patients and found the same mutation. We extended our study towards additional biochemical, functional, and therapeutic aspects.MethodsWe did mutation screening by whole exome sequencing. RNA-sequencing was performed in patient and control fibroblasts. Ceramide and sphingomyelin levels were measured by LC-MS/MS. ELOVL1 activity was determined by a stable isotope-labelled [13C]malonyl-CoA elongation assay. ELOVL1 expression patterns were investigated by immunofluorescence,in situhybridisation and RT-qPCR. As treatment option, we investigated VLCFA loading of fibroblasts.ResultsBoth patients carried an identical heterozygousde novo ELOVL1mutation (c.494C>T, NM_001256399; p.S165F) not deriving from a founder allele. Patients suffered from epidermal hyperproliferation and increased keratinisation (ichthyosis). Hypomyelination of the central white matter explained spastic paraplegia and central nystagmus, while optic atrophy was causative for reduction of peripheral vision and visual acuity. The mutation abrogated ELOVL1 enzymatic activity and reduced ≥C24 ceramides and sphingomyelins in patient cells. Fibroblast loading with C22:0-VLCFAs increased C24:0-ceramides and sphingomyelins. We found competitive inhibition for ceramide and sphingomyelin synthesis between saturated and monounsaturated VLCFAs. Transcriptome analysis revealed upregulation of modules involved in epidermal development and keratinisation, and downregulation of genes for neurodevelopment, myelination, and synaptogenesis. Many regulated genes carried consensus proliferator-activated receptor (PPAR)α and PPARγ binding motifs in their 5’-regions.ConclusionA dominantELOVL1mutation causes a neuro-ichthyotic disorder possibly amenable to treatment with PPAR-modulating drugs.

Diverse processes -- e.g., environmental pollution, groundwater remediation, oil recovery, filtration, and drug delivery -- involve the transport of colloidal particles in porous media. Using confocal microscopy, we directly visualize this process in situ and thereby identify the fundamental mechanisms by which particles are distributed throughout a medium. At high injection pressures, hydrodynamic stresses cause particles to be continually deposited on and eroded from the solid matrix -- notably, forcing them to be distributed throughout the entire medium. By contrast, at low injection pressures, the relative influence of erosion is suppressed, causing particles to localize near the inlet of the medium. Unexpectedly, these macroscopic distribution behaviors depend on imposed pressure in similar ways for particles of different charges, although the pore-scale distribution of deposition is sensitive to particle charge. These results reveal how the multiscale interactions between fluid, particles, and the solid matrix control how colloids are distributed in a porous medium., Comment: This article is published in Science Advances and supplementary material is available at https://advances.sciencemag.org/content/6/46/eabc2530

While drug-loaded microparticles (MPs) can serve as drug reservoirs for sustained drug release and therapeutic effects, needle clogging by MPs poses a challenge for ocular drug delivery via injection. Two polymers commonly used in ophthalmic procedures - hyaluronic acid (HA) and methylcellulose (MC) - have been tested for their applicability for ocular injections. HA and MC were physically blended with sunitinib malate (SUN)-loaded PLGA MPs for subconjunctival (SCT) injection into rat eyes. The HA and MC viscous solutions facilitated injection through fine-gauged needles due to their shear-thinning properties as shown by rheological characterizations. The diffusion barrier presented by HA and MC reduced burst drug release and extended overall release from MPs. The significant level of MP retention in the conjunctiva tissue post operation confirmed the minimal leakage of MPs following injection. The safety of HA and MC for ocular applications was demonstrated histologically.

Molecular assemblies inside cells often undergo structural reconfiguration in response to stimuli to alter their function. Adaptive reconfiguration of cytoskeletal networks, for example, enables cellular shape change, movement, and cargo transport and plays a key role in driving complex processes such as division and differentiation. The cellular cytoskeleton is a self-assembling polymer network composed of simple filaments, so reconfiguration often occurs through the rearrangement of its component filaments' connectivities. DNA nanotubes have emerged as promising building blocks for constructing programmable synthetic analogs of cytoskeletal networks. Nucleating seeds can control when and where nanotubes grow, and capping structures can bind nanotube ends to stop growth. Such seeding and capping structures, collectively called termini, can organize nanotubes into larger architectures. However, these structures cannot be selectively activated or inactivated in response to specific stimuli to rearrange nanotube architectures, a key property of cytoskeletal networks. Here, we demonstrate how selective regulation of the binding affinity of DNA nanotube termini for DNA nanotube monomers or nanotube ends can direct the reconfiguration of nanotube architectures. Using DNA hybridization and strand displacement reactions that specifically activate or inactivate four orthogonal nanotube termini, we demonstrate that nanotube architectures can be reconfigured by selective addition or removal of distinct termini. Finally, we show how terminus activation could be a sensitive detector and amplifier of a DNA sequence signal. These results could enable the development of adaptive and multifunctional materials or diagnostic tools.

Cosaviruses (CoSV) were first identified in stool samples collected from non-polio acute flaccid paralysis (AFP) cases and their healthy contacts in Pakistan in 2003. The clinical importance of CoSV remains unclear as data on epidemiology are scarce and no routine diagnostic testing is done. In this study, we characterized human CoSV (HCoSV) in a child with non-polio AFP and in sewage samples collected in Berlin, Germany. Using unbiased high-throughput sequencing and specific PCR, we characterized a HCoSV-D in stool samples of a three-year-old child hospitalized in Germany with non-polio AFP and travel history to Pakistan. The shedding pattern and absence of other relevant pathogens suggests that HCoSV-D may have been involved in the genesis of AFP. The HCoSV-RNA concentration was high, with 2.57 × 106 copies per mL fecal/suspension, decreasing in follow-up samples. To investigate the possibility of local circulation of HCoSV, we screened Berlin sewage samples collected between 2013 and 2018. Molecular testing of sewage samples has shown the presence of CoSV in several parts of the world, but until now not in Germany. Of our sewage samples, 54.3 % were positive for CoSV, with up to three viral species identified in samples. Phylogenetically, the German sequences clustered intermixed with sequences obtained globally. Together, these findings emphasize the need for further clinical, epidemiological, environmental, pathogenicity and phylogenetic studies of HCoSV.

AIM To systematically characterize radiological features of patients with spina bifida, their relationship to cognitive function, and differences between spina bifida aperta (SBA) and spina bifida occulta (SBO). METHOD In a retrospective study of 265 patients (117 females, 148 males; median age at imaging 11y, range 1-47y; SBA n=206, SBO n=59), the radiological phenotype was assessed through magnetic resonance imaging (MRI) (SBA n=171, SBO n=59). In 126 patients (SBA n=116, SBO n=10) Kaufman Assessment Battery for Children (KABC) or Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) and Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) were performed. RESULTS Patients with spina bifida show numerous brain malformations, always present for SBA but rarely for SBO. The most frequent brain malformations in SBA included abnormal corpus callosum (69%), hypoplastic pons (50%), and hypoplastic mesencephalon (20%). Cognitive total IQ scores were below average in 44% (KABC) to 49% (WISC-IV) of children with SBA, while almost all children with SBO scored at least average. Stenogyria (p=0.006), pons (p=0.003), and mesencephalon hypoplasia (p=0.01) correlated with lower total IQ score and verbal comprehension. Various brain malformations correlate significantly with several cognitive domains, while lesion level only correlates with processing speed. INTERPRETATION IQ scores were significantly lower in patients with SBA than in patients with SBO. Verbal competence, perceptual reasoning, and working memory were significantly impaired for SBA and correlated with stenogyria and abnormalities of the midbrain and corpus callosum. WHAT THIS PAPER ADDS Brain malformations occur more frequently in spina bifida aperta (SBA) than in spina bifida occulta (SBO). Cognitive impairment is less frequent in SBO. Hydrocephalus, stenogyria, midbrain, and corpus callosum abnormalities are associated with lower cognitive function. Difference in prognosis in SBO versus SBA can alter prenatal counselling.

Colloidal particles hold promise for mobilizing and removing trapped immiscible fluids from porous media, with implications for key energy and water applications. Most studies focus on accomplishing this goal using particles that can localize at the immiscible fluid interface. Therefore, researchers typically seek to optimize the surface activity of particles, as well as their ability to freely move through a pore space with minimal deposition onto the surrounding solid matrix. Here, we demonstrate that deposition can, surprisingly, promote mobilization of a trapped fluid from a porous medium without requiring any surface activity. Using confocal microscopy, we directly visualize both colloidal particles and trapped immiscible fluid within a transparent, three-dimensional (3D) porous medium. We find that as non-surface active particles deposit on the solid matrix, increasing amounts of trapped fluid become mobilized. We unravel the underlying physics by analyzing the extent of deposition, as well as the geometry of trapped fluid droplets, at the pore scale: deposition increases the viscous stresses on trapped droplets, overcoming the influence of capillarity that keeps them trapped. Given an initial distribution of trapped fluid, this analysis enables us to predict the extent of fluid mobilized through colloidal deposition. Taken together, our work reveals a new way by which colloids can be harnessed to mobilize trapped fluid from a porous medium.

Epilepsy is often associated with psychosocial comorbidity and this can be more disabling than the seizure activity. Still, these associated conditions are often underdiagnosed and therefore not sufficiently treated. We studied a large pediatric cohort of 371 patients with epilepsy to identify factors associated with negative outcome. We found that patients with early-onset epilepsy, epilepsy of known etiology, and polypharmacy were the most likely to display cognitive impairment. Behavioral problems were particularly prevalent in patients with an epilepsy duration ≥ 5 years. Similarly, early-onset epilepsy, long illness duration, epilepsy of known etiology, and polypharmacy had an adverse effect on school placement and/or social contact. With polypharmacy being the only potentially modifiable factor, it is important to balance between benefits and adverse effects of antiepileptic drugs and consider alternative therapy options in selected patients such as epilepsy surgery, vagal nerve stimulation, and ketogenic diet early-on.

The use of proteins that bind and catalyze reactions with DNA alongside DNA nanostructures has broadened the functionality of DNA devices. DNA binding proteins have been used to specifically pattern and tune structural properties of DNA nanostructures and polymerases have been employed to directly and indirectly drive structural changes in DNA structures and devices. Despite these advances, undesired and poorly understood interactions between DNA nanostructures and proteins that bind DNA continue to negatively affect the performance and stability of DNA devices used in conjunction with enzymes. A better understanding of these undesired interactions will enable the construction of robust DNA nanostructure-enzyme hybrid systems. Here, we investigate the undesired disassembly of DNA nanotubes in the presence of viral RNA polymerases (RNAPs) under conditions used for in vitro transcription. We show that nanotubes and individual nanotube monomers (tiles) are non-specifically transcribed by T7 RNAP, and that RNA transcripts produced during non-specific transcription disassemble the nanotubes. Disassembly requires a single-stranded overhang on the nanotube tiles where transcripts can bind and initiate disassembly through strand displacement, suggesting that single-stranded domains on other DNA nanostructures could cause unexpected interactions in the presence of viral RNA polymerases.

Depending on the etiology of hydrocephalus in childhood, the shunt therapy still remains challenging due to frequent shunt complications leading to possible revisions such as shunt infection or shunt malfunction. In myelomeningocele (MMC) patients who often require shunt therapy, higher revisions rates were reported. In a single-center retrospective study, experiences on shunt regimen on hydrocephalus associated with MMC are presented. Data of 160 infant hydrocephalus cases younger than 1 year of age at the time of implantation were retrospectively reviewed from the hospital database. These patients received an adjustable differential pressure valve with gravitational unit and antibiotic impregnated catheters as a primary or secondary implant during the time period of April 2007 to July 2015. The subgroup of infants cases with MMC (n = 44; age 50.6 ± 80.6 days) were compared to the remaining cohort of other hydrocephalus etiology (control group). The shunt and valve revision free survival rates were recorded until July 2017. During the mean follow-up of 48.7 ± 19.2 (7–114) months, the shunt revision free survival was 87% at 1 year and 49% at 60 months in the MMC cohort. The control group showed a shunt survival rate of 68% at 1 year and 39% at 60 months. Similarly, the valve revision free survival rate showed a significant higher rate of 92% at 1 year and 69% at 60 months in the MMC group compared to the control group (75% at 1 year and 51% at 60 months; p

Pathological fractures (PFs) are common in patients with spina bifida. However, most previous studies refer to the overall fracture rate and largely neglecting putative age-dependent aspects. The aim of this retrospective study was to characterize patterns of fracture occurrence in childhood. In a retrospective study, we identified PF, all in the lower limbs, in 13% of 210 patients with spina bifida aperta. We further identified a bimodal frequency distribution of pathological fractures, with peaks at 1-5 and 10-12 years. We could thereby distinguish two groups of patients: (i) Children with a first fracture before an age of 6 years developed frequently multiple fractures within the following years, but fracture series typically stopped by 6 years-of-age. (ii) Children with a first fracture after the age of 6 years had fewer fractures, but these occurred also in adolescence. PF occurred rarely after the age of 13 years. The age at fracture correlated with the fracture site with 85% of the fractures occurring in the femur in the first five years of life and an increased frequency of tibia and foot fractures later in life. While, overall high lesion levels and preceding immobilizing events were risk factors for PF, femur fractures in children under 6 years-of-age occurred independent of their lesion level, and the age at verticalization did not correlate with PF rates.Conclusion: Based on these findings, standardized and effective preventive physiotherapeutic and/or pharmacological interventions to tackle PF in spina bifida need to consider age-specific differences in occurrence and reoccurrence of fractures.What is Known:• Pathological fractures are common in patients with spina bifida aperta, and associated risk factors include high lesion level, immobilization and low bone density.What is New:• We first report a bimodal frequency distribution of pathological fractures in childhood (first peak 1-5 years, second peak 10-12 years) and link early-onset fracture occurrence with the risk of multiple fractures arise in a short time period but a the chance of self-limitation of fracture series within a few years.• We show that femur fractures in children under 6 years-of-age occurred independent of their lesion level, and the age at verticalization did not correlate with PF rates.• We further link the age-dependent occurrence pattern with the risk of further fractures and with the chance of self-limitation of fracture series. The earlier a first fracture occurs, the more probable multiple fractures arise in a short time period. Nevertheless, early fracture series are often self-limiting within a few years.• Femur fractures in children under 6 years-of-age occurred independent of their lesion level, and the age at verticalization did not correlate with PF rates.• Based on these findings, physiotherapeutic and/or pharmaceutical concepts need to be developed in an age-adapted manner and in consideration of the potential self-limiting nature of fracture series.

Colloidal particle transport in porous media is of practical interest in key applications including wastewater treatment, contaminant containment, enhanced oil recovery, filtration, and drug delivery. Here, we review the physicochemical principles that govern particle transport in a porous medium, both at the pore and macroscopic scales, and highlight experimental advancements in our understanding of these principles. Finally, we describe unique opportunities for the use of polymer colloids that leverage the precision of existing polymer fabrication and characterization approaches to control colloid morphology and surface properties in emerging applications.

Background Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating disease occurring several weeks after viral infection. Enteroviruses have been described as potential triggers of ADEM, but the closely related parechoviruses have not. The objective of the study is to assess the prevalence and disease presentation of ADEM after parechovirus infection in a syndromic surveillance program for pediatric infection/inflammation of the central nervous system (CNS). Methods The surveillance was conducted at the Charite Department of Pediatrics in Berlin, Germany, from November 2010 to November 2014. All hospitalized children meeting predefined case criteria underwent highly standardized prospective clinical assessments based on the published case definitions, including for ADEM. Stool samples were independently analyzed by enterovirus and parechovirus real-time polymerase chain reaction at the Robert Koch Institute. Results Of 105,557 patients screened, 774 (0.7%) fulfilled entry criteria for CNS infection/inflammation, with 114 cases ascertained as ADEM. Parechoviruses were detected in 2.5% of patients with CNS infection/inflammation, including 1 case fulfilling ADEM case criteria with the highest level of diagnostic certainty. Conclusions We report a first case of ADEM after parechovirus infection in a 5-year-old female presenting with acute hemiparesis 2 weeks after a respiratory illness. Parechovirus disease should be included in the differential diagnosis of ADEM.

Leprosy, or Hansen’s disease, is caused by infection with Mycobacterium leprae. It is a rare diagnosis within the continental United States. We present the case of a 13-year-old immigrant from the Marshall Islands who presented with recurrent nausea, vomiting, and abdominal pain which are found to be due to intermittent gastric volvulus. Gastric volvulus is also exceedingly rare, with less than 8 pediatric cases on average per year. During her second hospitalization for recurrent acute gastrointestinal issues, nonspecific skin lesions were biopsied, revealing infection with M. leprae. The patient did not exhibit classic symptoms of leprosy but did have prominent skin changes including diffuse nodules. This case explores the pathophysiology connecting leprosy to volvulus, discussing the possible role of an inflammatory response to infection in causing gastric volvulus. The finding of lepromatous leprosy may have been unrelated but was fortuitous, as early intervention will result in avoidance of debilitating peripheral neuropathy and eventual disfiguration from Hansen’s disease. This case highlights the importance of considering rare causes of gastric outlet obstruction including gastric volvulus and of considering leprosy in the differential for patients with unusual skin lesions or paresthesias who have a history of living or traveling in endemic areas.

Receptor-mediated endocytosis is an integral part of signal transduction as it mediates signal attenuation and provides spatial and temporal dimensions to signaling events. One of the best-studied leucine-rich repeat receptor-like kinases in plants, BRASSINOSTEROID INSENSITIVE 1 (BRI1), perceives its ligand, the brassinosteroid (BR) hormone, at the cell surface and is constitutively endocytosed. However, the importance of endocytosis for BR signaling remains unclear. Here we developed a bioactive, fluorescent BR analog, Alexa Fluor 647-castasterone (AFCS), and visualized the endocytosis of BRI1-AFCS complexes in living Arabidopsis thaliana cells. Impairment of endocytosis dependent on clathrin and the guanine nucleotide exchange factor for ARF GTPases (ARF-GEF) GNOM enhanced BR signaling by retaining active BRI1-ligand complexes at the plasma membrane. Increasing the trans-Golgi network/early endosome pool of BRI1-BR complexes did not affect BR signaling. Our findings provide what is to our knowledge the first visualization of receptor-ligand complexes in plants and reveal clathrin- and ARF-GEF-dependent endocytic regulation of BR signaling from the plasma membrane.