Gastrointestinal transit time of radiopaque ingested foreign bodies in children: experience of two paediatric tertiary centres.

Introduction: Foreign body (FB) ingestion is a common paediatric emergency. While guidelines exist for urgent intervention, less is known of the natural progress of FBs passing through the gastrointestinal tract (GIT). We reviewed these FB transit times in an outpatient cohort. Methods: A retrospective review was performed on all children (≤18 years) treated for radiopaque FB ingestion at two major tertiary paediatric centres from 2015 to 2016. Demographic data, FB types, outcomes and hospital visits (emergency department [ED] and outpatient) were recorded. All cases discharged from the ED with outpatient follow-up were included. We excluded those who were not given follow-up appointments and those admitted to inpatient wards. We categorised the outcomes into confirmed passage (ascertained via abdominal X-ray or reported direct stool visualisation by patients/caregivers) and assumed passage (if patients did not attend follow-up appointments). Results: Of the 2,122 ED visits for FB ingestion, 350 patients who were given outpatient follow-up appointments were reviewed (median age 4.35 years [range: 0.5-14.7], 196 [56%] male). The largest proportion (16%) was aged 1-2 years. Coins were the most common ingested FB, followed by toys. High-risk FB (magnets or batteries) formed 9% of cases (n=33). The 50th centile for FB retention was 8, 4 and 7 days for coins, batteries and other radiopaque FBs, respectively; all confirmed passages occurred at 37, 7 and 23 days, respectively. Overall, 197 (68%) patients defaulted on their last given follow-up. Conclusion: This study provides insight into the transit times of FB ingested by children, which helps medical professionals to decide on the optimal time for follow-up visits and provide appropriate counsel to caregivers.

Peripheral neuropathies associated with DNA repair disorders.

Repair of genomic DNA is a fundamental housekeeping process that quietly maintains the health of our genomes. The consequences of a genetic defect affecting a component of this delicate mechanism are quite harmful, characterized by a cascade of premature aging that injures a variety of organs, including the nervous system. One part of the nervous system that is impaired in certain DNA repair disorders is the peripheral nerve. Chronic motor, sensory, and sensorimotor polyneuropathies have all been observed in affected individuals, with specific physiologies associated with different categories of DNA repair disorders. Cockayne syndrome has classically been linked to demyelinating polyneuropathies, whereas xeroderma pigmentosum has long been associated with axonal polyneuropathies. Three additional recessive DNA repair disorders are associated with neuropathies, including trichothiodystrophy, Werner syndrome, and ataxia-telangiectasia. Although plausible biological explanations exist for why the peripheral nerves are specifically vulnerable to impairments of DNA repair, specific mechanisms such as oxidative stress remain largely unexplored in this context, and bear further study. It is also unclear why different DNA repair disorders manifest with different types of neuropathy, and why neuropathy is not universally present in those diseases. Longitudinal physiological monitoring of these neuropathies with serial electrodiagnostic studies may provide valuable noninvasive outcome data in the context of future natural history studies, and thus the responses of these neuropathies may become sentinel outcome measures for future clinical trials of treatments currently in development such as adeno-associated virus gene replacement therapies.

Application of prostatic exosomal protein in the diagnosis of histological prostatitis in patients with benign prostatic hyperplasia / 现代泌尿外科杂志

【Objective】 To investigate the feasibility of prostatic exosomal protein (PSEP) detection kit in the diagnosis of histological prostatitis (HP) in patients with benign prostatic hyperplasia (BPH), and to explore the correlation between PSEP and other clinical parameters. 【Methods】 A total of 104 patients with BPH or BPH plus HP treated during Nov.2021 and Nov.2022 were involved. The patients were instructed to fill out the International Prostate Symptom Score (IPSS) scale independently before surgery. Clinical data such as prostate volume, residual urine volume, free prostate specific antigen (fPSA), total prostate specific antigen (tPSA), and fPSA/tPSA were collected. Preoperative midstream morning urine was collected for PSEP detection. 【Results】 The sensitivity and specificity of PSEP in the diagnosis of BPH were 93.51% and 70.37%, respectively, which were highly consistent with the postoperative pathological diagnosis results (Kappa=0.663). Serum PSEP level was positively correlated with tPSA level (r=0.242, P=0.040). 【Conclusion】 PSEP has a high clinical diagnostic value in the diagnosis of HP, which can provide a reliable basis for the diagnosis of HP in BPH patients and improve the diagnosis rate.

Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells / 中国中药杂志

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

Bioprocessing of Human Mesenchymal Stem Cells: From Planar Culture to Microcarrier-Based Bioreactors.

Human mesenchymal stem cells (hMSCs) have demonstrated great potential to be used as therapies for many types of diseases. Due to their immunoprivileged status, allogeneic hMSCs therapies are particularly attractive options and methodologies to improve their scaling and manufacturing are needed. Microcarrier-based bioreactor systems provide higher volumetric hMSC production in automated closed systems than conventional planar cultures. However, more sophisticated bioprocesses are necessary to successfully convert from planar culture to microcarriers. This article summarizes key steps involved in the planar culture to microcarrier hMSC manufacturing scheme, from seed train, inoculation, expansion and harvest. Important bioreactor parameters, such as temperature, pH, dissolved oxygen (DO), mixing, feeding strategies and cell counting techniques, are also discussed.

Agitation in a Microcarrier-based Spinner Flask Bioreactor Modulates Homeostasis of Human Mesenchymal Stem Cells.

Human mesenchymal stem cells (hMSCs) are well known in cell therapy due to their secretion of trophic factors, multipotent differentiation potential, and ability for self-renewal. As a result, the number of clinical trials has been steadily increasing over the last decade highlighting the need for in vitro systems capable of producing large quantities of cells to meet growing demands. However, hMSCs are highly sensitive to microenvironment conditions, including shear stress caused by dynamic bioreactor systems, and can lead to alteration of cellular homeostasis. In this study, hMSCs were expanded on microcarriers within a 125 mL spinner flask bioreactor system. Our results demonstrate a three-fold expansion over seven days. Furthermore, our results show that culturing hMSCs in the microcarrier-based suspension bioreactor (compared to static planar culture) results in smaller cell size and higher levels of reactive oxidative species (ROS) and ROS regulator Sirtuin-3, which have implications on the nicotinamide adenine dinucleotide metabolic pathway and metabolic homeostasis. In addition, hMSCs in the bioreactor showed the increased Prostaglandin E2 secretion as well as reduced the Indoleamine-pyrrole 2,3-dioxygenase secretion upon stimulus with interferon gamma. The results of this study provide understanding of potential hMSC physiology alterations impacted by bioreactor microenvironment during scalable production of hMSCs for biomanufacturing and clinical trials.

Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects a variety of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. In addition to known host proteins, i.e. ACE2, TMPRSS2 and NRP1, we identified multiple host components, among which LDLRAD3, TMEM30A and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spikes N-terminal domain (NTD). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in a fashion independent of ACE2. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19.

Arthroscopic surgery combined with platelet-rich plasma for meniscus injury:a Meta analysis / 中国骨伤

OBJECTIVE@#To evaluate clinical efficacy of arthroscopic with platelet-rich plasma (PRP) in treating meniscus injury.@*METHODS@#From January 2015 to December 2019, clinical control study on repair meniscus injury by arthroscopic with PRP between arthroscopic were searched by PubMed, Science Direct, Cochrane library, Chinese Journal Full-text Database, Wanfang and VIP database. Literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria. Visual analogue scale(VAS) of knee joint and Lysholm score at 1, 6 and 12 months after opertaion between two groups were compared, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) at 3, 6 and 12 months after opertaion between twogroups were also compared.@*RESULTS@#Totally 9 literatures and 329 patients with meniscal injuries were screened, include 146 patients treated by arthroscopic with PRP and 183 patients treated by arthroscopic. There were no statistical differences in VAS between two groups at 1, 6 and 12 months after opertaion. There were differences in Lysholm score at 1 and 6 months after operation between two groups [@*CONCLUSION@#Arthroscopic with PRP for repair meniscus injury has short term efficacy of knee function and delay arthritis, while has similar effect in long term clinical efficacy and relieve pain.

NAD+/NADH redox alterations reconfigure metabolism and rejuvenate senescent human mesenchymal stem cells in vitro.

Human mesenchymal stem cells (hMSCs) promote endogenous tissue regeneration and have become a promising candidate for cell therapy. However, in vitro culture expansion of hMSCs induces a rapid decline of stem cell properties through replicative senescence. Here, we characterize metabolic profiles of hMSCs during expansion. We show that alterations of cellular nicotinamide adenine dinucleotide (NAD + /NADH) redox balance and activity of the Sirtuin (Sirt) family enzymes regulate cellular senescence of hMSCs. Treatment with NAD + precursor nicotinamide increases the intracellular NAD + level and re-balances the NAD + /NADH ratio, with enhanced Sirt-1 activity in hMSCs at high passage, partially restores mitochondrial fitness and rejuvenates senescent hMSCs. By contrast, human fibroblasts exhibit limited senescence as their cellular NAD + /NADH balance is comparatively stable during expansion. These results indicate a potential metabolic and redox connection to replicative senescence in adult stem cells and identify NAD + as a metabolic regulator that distinguishes stem cells from mature cells. This study also suggests potential strategies to maintain cellular homeostasis of hMSCs in clinical applications.

Influence of Microenvironment on Mesenchymal Stem Cell Therapeutic Potency: From Planar Culture to Microcarriers.

Human mesenchymal stem cells (hMSCs) are a promising candidate in cell therapy as they exhibit multilineage differentiation, homing to the site of injury, and secretion of trophic factors that facilitate tissue healing and/or modulate immune response. As a result, hMSC-derived products have attracted growing interests in preclinical and clinical studies. The development of hMSC culture platforms for large-scale biomanufacturing is necessary to meet the requirements for late-phase clinical trials and future commercialization. Microcarriers in stirred-tank bioreactors have been widely utilized in large-scale expansion of hMSCs for translational applications because of a high surface-to-volume ratio compared to conventional 2D planar culture. However, recent studies have demonstrated that microcarrier-expanded hMSCs differ from dish- or flask-expanded cells in size, morphology, proliferation, viability, surface markers, gene expression, differentiation potential, and secretome profile which may lead to altered therapeutic potency. Therefore, understanding the bioprocessing parameters that influence hMSC therapeutic efficacy is essential for the optimization of microcarrier-based bioreactor system to maximize hMSC quantity without sacrificing quality. In this review, biomanufacturing parameters encountered in planar culture and microcarrier-based bioreactor culture of hMSCs are compared and discussed with specific focus on cell-adhesion surface (e.g., discontinuous surface, underlying curvature, microcarrier stiffness, porosity, surface roughness, coating, and charge) and the dynamic microenvironment in bioreactor culture (e.g., oxygen and nutrients, shear stress, particle collision, and aggregation). The influence of dynamic culture in bioreactors on hMSC properties is also reviewed in order to establish connection between bioprocessing and stem cell function. This review addresses fundamental principles and concepts for future design of biomanufacturing systems for hMSC-based therapy.

TMT Sample Preparation for Proteomics Facility Submission and Subsequent Data Analysis.

Proteomic technologies are powerful methodologies that can aid our understanding of mechanisms of action in biological systems by providing a global view of the impact of a disease, treatment, or other condition on the proteome as a whole. This report provides a detailed protocol for the extraction, quantification, precipitation, digestion, labeling, and subsequent data analysis of protein samples. Our optimized TMT labeling protocol requires a lower tag-label concentration and achieves consistently reliable data. We have used this protocol to evaluate protein expression profiles in a variety of mouse tissues (i.e., heart, skeletal muscle, and brain) as well as cells cultured in vitro. In addition, we demonstrate how to evaluate thousands of proteins from the resulting dataset.

Intrinsic Cerebro-Cerebellar Functional Connectivity Reveals the Function of Cerebellum VI in Reading-Related Skills.

The engagement of the cerebellum VI in reading was reported in both typically developing and dyslexic readers. However, it is still not clear how the cerebellum VI contributes to reading. Here we have examined the correlation of intrinsic cerebro-cerebellar functional connectivity with two critical reading-related skills-phonological awareness (PA) and rapid automatized naming (RAN)-with fMRI technology. Specifically, we tested the hypothesis that the cerebellum may contribute to reading either by phonological skills or by automatizing skills. We chose the left and right cerebellum VI as ROIs, and we calculated the intrinsic cerebro-cerebellar functional connectivity during a resting state. We further explored whether and how cerebro-cerebellar resting state functional connectivity (RSFC) is associated with individuals' reading-related skills including PA and RAN. The results showed that the functional connectivity between the left supramarginal gyrus and bilateral cerebellum VI was related to RAN, and the connectivity between the left insula and right cerebellum VI was related to PA. However, the effect of PA did not survive after the RAN was regressed out. Control analyses further confirmed that it was the intrinsic cerebro-cerebellar functional connectivity rather than the local cerebellar functionality that associated with phonological awareness ability and rapid automatized naming ability. For the first time, the relationship between cerebro-cerebellar resting state functional connectivity and specific reading-related skills has been explored, and this has deepened our understanding of the way the cerebellum VI is involved in reading.

Parental preferences in treatment of acute uncomplicated appendicitis comparing surgery to conservative management with antibiotics and their views on research participation.

Studies show that conservative management in acute uncomplicated appendicitis (AUA) is an alternative to surgery. This study aims to determine factors affecting parental preference in management of AUA and their decision for research participation. We conducted surveys on parents whose children were admitted with suspicion of appendicitis but later confirmed not to have appendicitis. Information on appendicectomy versus conservative treatment with antibiotics was provided using a fixed script and standard information leaflet. Questionnaires covered factors influencing decisions, opinions regarding research, treatment preference and demographic data. We excluded parents not fluent in English. Of 113 respondents, 71(62.8%) chose antibiotics, 39(34.5%) chose appendicectomy, and 3(2.7%) had no preference. Reasons given for choosing antibiotics were fear of surgical risks and preferring less invasive treatment. Those choosing appendicectomy expressed preference for definitive treatment and fear of recurrence. Majority were against randomisation (n = 89, 78.8%) and blinding (n = 90, 79.7%). Over half found difficulty involving their child in research (n = 65, 57.5%). Most thought that research is important (66.4%) and beneficial to others (59.3%). Parents who perceived their child as healthy found research riskier (p = 0.039). Educated parents were more likely to find research beneficial to others (p = 0.012) but less accepting of randomisation (p = 0.001).Conclusion: More parents appear to prefer conservative treatment for acute uncomplicated appendicitis. Researchers must consider parental concerns regarding randomisation and blinding.What is Known:• Conservative management of acute uncomplicated appendicitis in paediatric patients is safe and effective, sparing the child the need for an operation; however, neither conservative nor surgical management is proven to be superior.• Randomised controlled trials provide the highest level of evidence, but it is challenging to recruit paediatric patients as participants in such clinical trials.What is New:• More parents prefer conservative management of uncomplicated appendicitis over surgical management for their children due to fear of surgical risks and complications• Randomisation in trial design is significantly associated with a parent's decision to reject their child's participation in a clinical trial.

A case-control study on the effect of food allergies on childhood asthma / 公共卫生与预防医学

Objective To analyze the effects of food allergies on asthma in children over 6 years old in Zhongshan. Methods A case-control study was designed. 279 children over 6 years old with asthma diagnosed in Boai Hospital of Zhongshan were enrolled as the case group, and 980 children without asthma from primary school were enrolled as the control group. The food allergy exposure, other related risk factors, and food allergy characteristics of the two groups were retrospectively analyzed. Logistic regression was used to analyze the OR values ​​of each factor. Results The asthma children's food allergy, family asthma history, family medicine and food allergy history, artificial feeding, adding beef and mutton or seafood before the age of one year, and frequent consumption of puffed foods such as shrimp chips were significantly higher than those of non-asthmatic children. Using multivariate logistic regression analysis, food allergy (OR=3.143, P<0.001), artificial feeding (OR=3.045, P<0.001), family history of asthma (OR=2.250, P<0.001) remained significantly in the multivariate model. For food allergies, children with asthma had more types of food allergies than children without asthma (P<0.001), and had a higher proportion of allergies to milk and eggs (P<0.001). There were higher proportion of introduction of beef and mutton and seafood before 1 year old (P<0.001), and higher proportion of frequently consuming puffed foods (P<0.001) in children with asthma than children without asthma, while the rate of desensitization treatment was lower (P<0.001). Conclusion Food allergy may be an independent risk factor for asthma. Children with asthma had a variety of allergies associated with food allergies. Desensitization treatment for food allergies may reduce the risk of asthma.

Effects of Drug Particle Size and Lipid Additives on Drug Release from Paraffin Wax Formulations Prepared by Spray Congealing Technique.

Paraffin wax is a hydrophobic meltable material that can be suitably used in spray congealing to develop drug-loaded microparticles for sustained release, taste-masking or stability enhancement of drugs. However, these functional properties may be impaired if the drug particles are not completely embedded. Moreover, highly viscous melts are unsuitable for spray dispersion. In this study, the effects of drug particle size and lipid additives, namely stearic acid (SA), cetyl alcohol (CA) and cetyl esters (CE), on melt viscosity and extent of drug particles embedment were investigated. Spray congealing was conducted on the formulations, and the resultant microparticles were analysed for their size, drug content, extent of drug particles embedment and drug release. The melt viscosity increased with smaller solid inclusions while lipid additives decreased the viscosity to varying extents. The spray-congealed microparticle size was largely dependent on the viscosity. The addition of lipid additives to paraffin wax enabled more complete embedment of the drug particles. CA produced microparticles with the lowest drug release, followed by SA and CE. The addition of CA and CE enhanced the drug release and showed potential for taste-masking. Judicious choice of drug particle size and matrix materials is important for successful spray congealing to produce microparticles with the desired characteristics.

Development of a microdevice-based human mesenchymal stem cell-mediated drug delivery system.

Cell-mediated drug delivery systems utilize living cells as vehicles to achieve controlled delivery of drugs. One of the systems features integrating cells with disk-shaped microparticles termed microdevices into cell-microdevice complexes that possess some unique advantages over their counterparts. Human mesenchymal stem cells (hMSCs) have been extensively studied as therapeutic cells and used as carrier cells for drug-loaded nanoparticles or other functional nanoparticles. This article presents the development of a microdevice-based hMSC-mediated drug delivery system for the first time. This study revealed that the microdevices could be attached to the hMSCs in a controlled and versatile manner; the produced hMSC-microdevice complexes were stable over cultivation and trypsinization, and the microdevice attachment did not affect the viability and proliferation of the hMSCs. Moreover, cultured microdevice-bound hMSCs retained their abilities to migrate on a flat surface, form a spheroid, and actively dissociate from the spheroid. These results indicate that this microdevice-based hMSC-mediated system promises to be further developed into a clinically viable drug delivery system.

Public health practitioners' views of the 'Making Every Contact Count' initiative and standards for its evaluation.

BACKGROUND: National Health Service England encourages staff to use everyday interactions with patients to discuss healthy lifestyle changes as part of the 'Making Every Contact Count' (MECC) approach. Although healthcare, government and public health organisations are now expected to adopt this approach, evidence is lacking about how MECC is currently implemented in practice. This study explored the views and experiences of those involved in designing, delivering and evaluating MECC. METHODS: We conducted a qualitative study using semi-structured interviews with 13 public health practitioners with a range of roles in implementing MECC across England. Interviews were conducted via telephone, transcribed verbatim and analysed using an inductive thematic approach. RESULTS: Four key themes emerged identifying factors accounting for variations in MECC implementation: (i) 'design, quality and breadth of training', (ii) 'outcomes attended to and measured', (iii) 'engagement levels of trainees and trainers' and (iv) 'system-level influences'. CONCLUSIONS: MECC is considered a valuable public health approach but because organisations interpret MECC differently, staff training varies in nature. Practitioners believe that implementation can be improved, and an evidence-base underpinning MECC developed, by sharing experiences more widely, introducing standardization to staff training and finding better methods for assessing meaningful outcomes.

Behavior problems and influencing factors of school-age children in Zhongshan / 预防医学

Objective @#To investigate the behavior problems and influencing factors of school-age students from the third to the sixth grade in Zhongshan,and to provide evidence for early intervention of behavior problems in children.@*Methods @#According to the proportion of population in urban area and township in Zhongshan,students of Grade Three to Six from eight primary schools（three in urban area and five in township）were recruited by stratified sampling method. The behavior problems in children were assessed by the Conners Parent Symptom Questionnaire（PSQ）. Sociodemographic information,family discipline and so on was investigated by a general questionnaire. The influencing factors for behavior problems were analyzed by a logistic regression model. @*Results @#A total of 2 292 questionnaires were issued,and 2 236 valid questionnaires were recycled,with an effective rate of 97.56%. The positive rate of behavioral problems was 11.72%. The results of multivariate logistic regression analysis showed that the risk factors for behavior problems were females（OR=1.594,95%CI：1.170-2.171）,birth asphyxia（OR=2.372,95%CI：1.320-4.261）,main family discipline（laissez-faire：OR=3.326,95%CI：1.450-7.630;doting：OR=3.244,95%CI：1.867-5.638;autocratic：OR=2.609,95%CI：1.584-4.296,mixed：OR=2.313,95%CI：1.669- 3.207）,less than four hours per week for father-child communication（OR=1.551,95%CI：1.052-2.286）,negative life events（OR=2.188,95%CI：1.448-3.308）,living in township（OR=2.031,95%CI：1.330-3.102）,academic performance （average：OR=2.786,95%CI：1.868-4.156;poor：OR=6.665,95%CI：3.236-13.727;very poor：OR=25.068,95%CI：5.786-108.617）;the protective factors were occupation of mother as civil servants or professional personnel（OR=0.449,95%CI：0.238-0.844）and higher grades（Grade Five：OR=0.496,95%CI：0.339-0.727;Grade Six：OR=0.468,95%CI：0.309-0.710）.@*Conclusion @#Females,birth asphyxia,main family discipline,less communication between father and child,occupation of mother,negative life events,place of residence,academic performance and grade were the influencing factors for behavior problems.

Structural correlates of literacy difficulties in the second language: Evidence from Mandarin-speaking children learning English.

Several neuroimaging studies have explored the neural basis of literacy difficulties in the second language (L2). However, it remains unclear whether the associated neural alterations are related to literacy abilities in the first language (L1). Using magnetic resonance imaging, we explore this issue with two experiments in Mandarin-speaking children learning English as second language. In the first experiment, we investigated children with literacy difficulties in L2 and L1 (poor in both, PB) and children with literacy difficulties only in L2 (poor in English, PE). We compared the brain structure in these two groups to a control literacy (CL) group. The results showed that the CL group had significantly less gray matter volume in the left supramarginal gyrus compared to the PB group and moderately less gray matter volume compared to the PE group. In addition, the PB group had significant greater gray matter volume in the left medial fusiform gyrus compared to the PE group and had marginally greater gray matter volume compared to the CL group. In the second experiment, we explored the relationship between the two atypical regions and literacy abilities in the two languages in an independent sample consisting of children with typical literacy. Correlation analyses revealed that the left supramarginal gyrus was significantly associated with literacy performance only in the second language, English, whereas the left medial fusiform gyrus did not correlate with the performances in either L1 or L2. Taken together, these findings suggest that literacy difficulties in an alphabetic L2 are associated with a structural abnormality in the left supramarginal gyrus, a region implicated in phonological processing, which is independent of literacy abilities in the native language.

Aggregation of Culture Expanded Human Mesenchymal Stem Cells in Microcarrier-based Bioreactor.

Three-dimensional aggregation of human mesenchymal stem cells (hMSCs) has been used to enhance their therapeutic properties but current fabrication protocols depend on laboratory methods and are not scalable. In this study, we developed thermal responsive poly(N-isopropylacrylamide) grafted microcarriers (PNIPAM-MCs), which supported expansion and thermal detachment of hMSCs at reduced temperature (23.0 °C). hMSCs were cultured on the PNIPAM-MCs in both spinner flask (SF) and PBS Vertical-Wheel (PBS-VW) bioreactors for expansion. At room temperature, hMSCs were detached as small cell sheets, which subsequently self-assembled into 3D hMSC aggregates in PBS-VW bioreactor and remain as single cells in SF bioreactor owing to different hydrodynamic conditions. hMSC aggregates generated from the bioreactor maintained comparable immunomodulation and cytokine secretion properties compared to the ones made from the AggreWell®. The results of the current study demonstrate the feasibility of scale-up production of hMSC aggregates in the suspension bioreactor using thermal responsive microcarriers for integrated cell expansion and 3D aggregation in a close bioreactor system and highlight the critical role of hydrodynamics in self-assembly of detached hMSC in suspension.