Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults.

OBJECTIVES: Mutations in the X-linked endosomal Na+/H+ exchanger 6 (NHE6) cause Christianson syndrome (CS). Here, in the largest study to date, we examine genetic diversity and clinical progression in CS into adulthood. METHOD: Data were collected as part of the International Christianson Syndrome and NHE6 (SLC9A6) Gene Network Study. 44 individuals with 31 unique NHE6 mutations, age 2-32 years, were followed prospectively, herein reporting baseline, 1 year follow-up and retrospective natural history. RESULTS: We present data on the CS phenotype with regard to physical growth and adaptive and motor regression across the lifespan including information on mortality. Longitudinal data on body weight and height were examined using a linear mixed model. The rate of growth across development was slow and resulted in prominently decreased age-normed height and weight by adulthood. Adaptive functioning was longitudinally examined; a majority of adult participants (18+ years) lost gross and fine motor skills over a 1 year follow-up. Previously defined core diagnostic criteria for CS (present in>85%)-namely non-verbal status, intellectual disability, epilepsy, postnatal microcephaly, ataxia, hyperkinesia-were universally present in age 6-16; however, an additional core feature of high pain tolerance was added (present in 91%). While neurologic examinations were consistent with cerebellar dysfunction, importantly, a majority of individuals (>50% older than 10) also had corticospinal tract abnormalities. Three participants died during the period of the study. CONCLUSIONS: In this large and longitudinal study of CS, we begin to define the trajectory of symptoms and the adult phenotype thereby identifying critical targets for treatment.

Room-Temperature Self-Healing and Recyclable Self-Crosslinked Isosorbide-Based Adhesive Bioelastomer.

Recently, renewable bio-based materials have received more and more attention due to environmental issues such as global warming and ecosystem destruction. In the present work, a series of isosorbide-based bioelastomers poly(isosorbide carbonate-co-butanediol aliphatic esters)s (PICBAs) are synthesized by a facile and economical two-step melt polycondensation. Due to the slightly self-crosslinking reaction of isosorbide, PICBAs exhibit excellent tensile strength and self-healing ability, the mechanical properties of PICBAs can recover over 95% after 48 h under room temperature. In addition, PICBAs can stick different substances, such as glass, rubber, plastic, and stones, and show better adhesive performance than 3M commercially available double-sided tape. Consequently, isosorbide-based bioelastomers PICBAs are of great potential to be used as environmentally friendly pressure-sensitive adhesives (PSA) in the future.

Improving normothermic machine perfusion and blood transfusion through biocompatible blood silicification.

The growing world population and increasing life expectancy are driving the need to improve the quality of blood transfusion, organ transplantation, and preservation. Here, to improve the ability of red blood cells (RBCs) for normothermic machine perfusion, a biocompatible blood silicification approach termed "shielding-augmenting RBC-in-nanoscale amorphous silica (SARNAS)" has been developed. The key to RBC surface engineering and structure augmentation is the precise control of the hydrolysis form of silicic acid to realize stabilization of RBC within conformal nanoscale silica-based exoskeletons. The formed silicified RBCs (Si-RBCs) maintain membrane/structural integrity, normal cellular functions (e.g., metabolism, oxygen-carrying capability), and enhance resistance to external stressors as well as tunable mechanical properties, resulting in nearly 100% RBC cryoprotection. In vivo experiments confirm their excellent biocompatibility. By shielding RBC surface antigens, the Si-RBCs provide universal blood compatibility, the ability for allogeneic mechanical perfusion, and more importantly, the possibility for cross-species transfusion. Being simple, reliable, and easily scalable, the SARNAS strategy holds great promise to revolutionize the use of engineered blood for future clinical applications.

GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.

Mutations in the endosomal Na+/H+ exchanger 6 (NHE6) cause Christianson syndrome, an X-linked neurological disorder. NHE6 functions in regulation of endosome acidification and maturation in neurons. Using yeast two-hybrid screening with the NHE6 carboxyl terminus as bait, we identify Golgi-associated, gamma adaptin ear-containing, ADP-ribosylation factor (ARF) binding protein 1 (GGA1) as an interacting partner for NHE6. We corroborated the NHE6-GGA1 interaction using: coimmunoprecipitation; overexpressed constructs in mammalian cells; and coimmunoprecipitation of endogenously expressed GGA1 and NHE6 from neuroblastoma cells, as well as from the mouse brain. We demonstrate that GGA1 interacts with organellar NHEs (NHE6, NHE7, and NHE9) and that there is significantly less interaction with cell-surface localized NHEs (NHE1 and NHE5). By constructing hybrid NHE1/NHE6 exchangers, we demonstrate the cytoplasmic tail of NHE6 interacts most strongly with GGA1. We demonstrate the colocalization of NHE6 and GGA1 in cultured, primary hippocampal neurons, using super-resolution microscopy. We test the hypothesis that the interaction of NHE6 and GGA1 functions in the localization of NHE6 to the endosome compartment. Using subcellular fractionation experiments, we show that NHE6 is mislocalized in GGA1 KO cells, wherein we find less NHE6 in endosomes, but more NHE6 transport to lysosomes, and more Golgi retention of NHE6, with increased exocytosis to the surface plasma membrane. Consistent with NHE6 mislocalization, and Golgi retention, we find the intraluminal pH in Golgi to be alkalinized in GGA1-null cells. Our study demonstrates a new interaction between NHE6 and GGA1 which functions in the localization of this intracellular NHE to the endosome compartment.

DNA methylation and whole-genome transcription analysis in CD4+ T cells from systemic lupus erythematosus patients with or without renal damage.

BACKGROUND: Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. METHODS: Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. RESULTS: We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. CONCLUSION: Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Preservation of Porcine Donation after Circulatory Death (DCD) Liver by Perfusion and Orthotopic Liver Transplantation.

Conventional static cold storage (SCS) exacerbates ischemic injury in the DCD liver, leading to severe complications for transplant recipients. To address this issue, clinical application of MP technology for donor liver preservation is underway. Simultaneously, efforts are focused on the development of various MP instruments, validated through relevant animal model experiments. Effective large animal trials play a pivotal role in clinical applications. However, challenges persist in the ex vivo preservation of DCD livers and the transplantation procedure in pigs. These hurdles encompass addressing the prolonged preservation of donor livers, conducting viability tests, alleviating ischemic injuries, and shortening the anhepatic phase. The use of a variable temperature-controlled MP device facilitates the prolonged preservation of DCD livers through sequential Dual Hypothermic Oxygenated Machine Perfusion (DHOPE) and Normothermic Machine Perfusion (NMP) modes. This protocol enhances the porcine OLTx model by improving the quality of DCD livers, optimizing the anastomosis technique, and reducing the duration of the anhepatic phase.

Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis.

Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased kidneys. Renal fibrosis involves an immune response dominated by macrophages, which activates myofibroblasts in fibrotic niches. However, macrophages exhibit high heterogeneity, hindering their potential as therapeutic cell targets. Herein, we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and spatially. We identified the major profibrotic macrophage subset (Fn1+Spp1+Arg1+) in the kidney and then constructed a 12-mer glycopeptide that was designated as bioactivated in vivo assembly PK (BIVA-PK) to deplete these cells. BIVA-PK specifically binds to and is internalized by profibrotic macrophages. By inducing macrophage cell death, BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune responses. The robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.

Effects of a special continuous quality improvement in nursing on the management of adverse care events: a retrospective study.

OBJECTIVE: To explore the application effect of the direct reporting system of adverse nursing events and special continuous nursing quality improvement measures in the management of these adverse events. METHODS: The implementation time of continuous nursing improvement based on the direct reporting system was the demarcation point. We retrospectively collected and analyzed nursing adverse event reports and hospitalization data from Xiangtan Central Hospital before implementation (2015-2018) and after implementation (2019-2022). The active reporting rate of adverse events, the composition of these events and the processing time were compared between the two groups. RESULTS: The rate of active reporting of adverse events before the implementation was lower than that after the implementation (6.7% vs. 8.1%, X2 = 25.561, P < 0.001). After the implementation of the direct reporting system for nursing events and the continuous improvement of nursing quality, the reporting proportion of first-level and second-level events decreased significantly. Moreover, the reporting proportion of third-level events increased significantly. The proportion of falls and medication errors decreased, and the proportion of unplanned extubation, infusion xerostomia and improper operation increased. The processing time of the reported nursing adverse events was significantly reduced (31.87 ± 7.83 vs. 56.87 ± 8.21, t = 18.73, P < 0.001). CONCLUSION: The direct reporting system of adverse nursing events and the continuous improvement measures for nursing quality can effectively improve the active reporting rate of adverse events, change their composition and reduce their processing time, as well as help create a safe psychological environment for both patients and nursing staff.

Diagnosis and management of intraspinal tuberculoma with osseous involvement: a case report.

Introduction and importance: Intraspinal tuberculoma is rare and challenging situation, which results in serious neurological dysfunctions. Case presentation: This case report shows an intraspinal tuberculoma with osseous involvement in a 31-year-old male patient with subacute progressing neurologic deficit. His medical history included tuberculosis of pulmonary and intestinal 8 years previously, at which time he had been treated with intestinal obstruction operation and antituberculosis treatment. A quadruple antituberculosis treatment was carried out after admission; however, his neurological condition was steadily worsening. He underwent debulking of mass for decompression and pathological analysis revealed intraspinal tuberculoma. The patient was prescribed a 12-month course of antituberculosis therapy, and a good clinical outcome was obtained subsequently. Clinical discussion: This case was treated by microsurgical resection and antituberculosis therapy, and the outcome was favourable. Conclusion: Intraspinal tuberculoma should be considered when an intraspinal mass is found with a history of tuberculosis, it can be effectively diagnosed by MRI and treated by the combination of medical and surgical treatments.

Determination and prediction of amino acid digestibility in brown rice for growing-finishing pigs.

OBJECTIVE: The experiment aimed to determine the standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in 10 brown rice samples fed to pigs, and to construct predictive models for SID of CP and AA based on the physical characteristics and chemical composition of brown rice. METHODS: Twenty-two cannulated pigs (initial body weight: 42.0±1.2 kg) were assigned to a replicated 11×3 incomplete Latin square design, including an N-free diet and 10 brown rice diets. Each period included 5 d adaptation and 2 d ileal digesta collection. Chromic oxide was added at 0.3% to all the diets as an indigestible marker for calculating the ileal CP and AA digestibility. RESULTS: The coefficients of variation of all detected indices for physical characteristics and chemical composition, except for bulk weight, dry matter (DM) and gross energy, in 10 brown rice samples were greater than 10%. The SID of CP, lysine (Lys), methionine, threonine (Thr), and tryptophan (Trp) in brown rice was 77.2% (62.6% to 85.5%), 87.5% (80.3% to 94.3%), 89.2% (78.9% to 98.9%), 55.4% (46.1% to 67.6%) and 92.5% (86.3% to 96.3%), respectively. The best prediction equations for the SID of CP, Lys, Thr, and Trp were as following, SIDCP = -664.181+8.484×DM (R2 = 0.40), SIDLys = 53.126+6.031×ether extract (EE)+0.893×thousand-kernel volume (R2 = 0.66), SIDThr = 39.916+7.843×EE (R2 = 0.41), and SIDTrp = -361.588+4.891×DM+0.387×total starch (R2 = 0.85). CONCLUSION: Overall, a great variation exists among 10 sources of brown rice, and the thousand-grain volume, DM, EE, and total starch can be used as the key predictors for SID of CP and AA.

Design and Control of Upper Limb Rehabilitation Training Robot Based on a Magnetorheological Joint Damper.

In recent years, rehabilitation robots have been developed and used in rehabilitation training for patients with hemiplegia. In this paper, a rehabilitation training robot with variable damping is designed to train patients with hemiplegia to recover upper limb function. Firstly, a magnetorheological joint damper (MR joint damper) is designed for the rehabilitation training robot, and its structural design and dynamic model are tested theoretically and experimentally. Secondly, the rehabilitation robot is simplified into a spring-damping system, and the rehabilitation training controller for human movement is designed. The rehabilitation robot dynamically adjusts the excitation current according to the feedback speed and human-machine interaction torque, so that the rehabilitation robot always outputs a stable torque. The magnetorheological joint damper acts as a clutch to transmit torque safely and stably to the robot joint. Finally, the upper limb rehabilitation device is tested. The expected torque is set to 20 N, and the average value of the output expected torque during operation is 20.02 N, and the standard deviation is 0.635 N. The output torque has good stability. A fast (0.5 s) response can be achieved in response to a sudden motor speed change, and the average expected output torque is 20.38 N and the standard deviation is 0.645 N, which can still maintain the stability of the output torque.

Is cranioplasty the optimal treatment for contralateral subdural effusion after decompressive craniectomy?: a case report.

Introduction and importance: Contralateral subdural effusion (CSDE) is a rare complication secondary to decompressive craniectomy (DC), which can lead to encephalocele and neurologic deterioration. The authors report a case that confirm the existence of unidirectional membrane valve, and cranioplasty is an effective treatment for CSDE. Case presentation: The authors reported a case of 43-year-old female was diagnosed with ruptured intracranial aneurysm and treated with interventional embolization. She underwent DC because of postoperative cerebral infarction subsequently. Her conscious state deteriorated accompanied by encephalocele in postoperative 2 week. A craniocerebral computed tomography (CT) confirmed the diagnosis of CSDE with cerebral hernia. A compression bandaging of the skull defect was applicated, whereas, her conscious state progressive deteriorated. She was transferred to the author's hospital where she underwent burr-hole drainage and clinical symptom has been improved. However, a relapse of CSDE was observed after the removal of drainage tube. Continuous lumbar drainage was employed, and which was ineffective for CSDE in this case. Finally, she underwent cranioplasty, with the help of drainage of subdural effusion, CSDE was completely resolved. Clinical discussion: CSDE is occasionally observed in patients after DC. Intracranial pressure (ICP) gradient and unidirectional membrane valve are the possible mechanisms of CSDE. At present, there is no optimal therapy for CSDE. For symptomatic CSDE patients, one or more treatment measures should be applicated. Conclusion: Cranioplasty is one of the curative and optimal method to treat symptomatic CSDE patients, early cranioplasty combined with burr-hole drainage should be performed for conservative treatment failed and intractable cases.

Experimental Study on the Skyhook Control of a Magnetorheological Torsional Vibration Damper.

This study proposes a dual-coil magnetorheological torsional vibration damper (MRTVD) and verifies the effectiveness of semi-active damping control to suppress the shaft system's torsional vibration via experimental research. Firstly, the mechanical model of the designed MRTVD and its coupling mechanical model with the rotating shaft system are established. Secondly, the torsional response of the shaft system is obtained via resonance experiments, and the influence of the current on the torsional characteristics of the magnetorheological torsional damper is analyzed. Finally, the MRTVD is controlled using the skyhook control approach. The experimental results demonstrate that when the main shaft passes through the critical speed range at various accelerations, the amplitude of the shaft's torsional vibration decreases by more than 15%, and the amplitude of the shaft's torsional angular acceleration decreases by more than 22%. These conclusions validate the inhibitory effect of MRTVD on the main shaft's torsional vibrations under skyhook control.

Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease.

We aimed to investigate the role of renal pericyte pyruvate kinase M2 (PKM2) in the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). The role of PKM2 in renal pericyte-myofibroblast transdifferentiation was investigated in an AKI-CKD mouse model. Platelet growth factor receptor beta (PDGFRß)-iCreERT2; tdTomato mice were used for renal pericyte tracing. Western blotting and immunofluorescence staining were used to examine protein expression. An 5-ethynyl-2'-deoxyuridine assay was used to measure renal pericyte proliferation. A scratch cell migration assay was used to analyse cell migration. Seahorse experiments were used to examine glycolytic rates. Enzyme-linked immunoassay was used to measure pyruvate kinase enzymatic activity and lactate concentrations. The PKM2 nuclear translocation inhibitors Shikonin and TEPP-46 were used to alter pericyte transdifferentiation. In AKI-CKD, renal pericytes proliferated and transdifferentiated into myofibroblasts and PKM2 is highly expressed in renal pericytes. Shikonin and TEPP-46 inhibited pericyte proliferation, migration, and pericyte-myofibroblast transdifferentiation by reducing nuclear PKM2 entry. In the nucleus, PKM2 promoted downstream lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) transcription, which are critical for glycolysis. Therefore, PKM2 regulates pericyte glycolytic and lactate production, which regulates renal pericyte-myofibroblast transdifferentiation. PKM2-regulated renal pericyte-myofibroblast transdifferentiation by regulating downstream LDHA and GLUT1 transcription and lactate production. Reducing nuclear PKM2 import can reduce renal pericytes-myofibroblasts transdifferentiation, providing new ideas for AKI-CKD treatment.

Physiological and Pathological Roles of NTSR2 in Several Organs and Diseases (Review).

Neurotensin (NTS) and its receptors (NTSRs) have long been the subject of study and have shown to have a vital function in a variety of systems. They are specifically implicated in the development of tumors and have both oncogenic and anti-apoptotic effects. Neurotensin receptor 2 (NTSR2), like NTSR1, belongs to the G protein-coupled receptor family and has been linked to analgesia, mental disorders, and hematological cancers. However, several research reports have revealed that it exists in numerous different systems. As a result, it seems to be an extremely promising therapeutic target for a variety of diseases. As NTSR2 is particularly prevalent in the brain and has different distribution and developmental characteristics from NTSR1, it may play a specific role in the nervous system. The present review summarizes the expression and function of NTSR2 in different systems, to highlight its potential as a diagnostic tool or therapeutic target.

Impact of Visceral Fat Area on Intraoperative Complexity and Surgical Approach Decision for Robot-Assisted Partial Nephrectomy: A Comparative Analysis with BMI.

BACKGROUND Optimizing surgical approaches for robot-assisted partial nephrectomy (RAPN) is vital for better patient outcomes. This retrospective study aimed to examine how visceral fat area (VFA) and body mass index (BMI) correlate with intraoperative complexities, thereby guiding the selection of surgical techniques for RAPN. MATERIAL AND METHODS The study analyzed the medical records of 213 Chinese patients diagnosed with a range of benign and malignant renal neoplasms and treated with RAPN in 2020. Visceral fat area was quantified using computed tomography (CT) scans taken at the umbilical level. Various perioperative indicators, such as demographic details, clinicopathological parameters, operation time, estimated blood loss (EBL), warm ischemic time (WIT), and intraoperative complications, were assessed. RESULTS For the retroperitoneal approach, patients with either visceral obesity or general obesity had longer operation times (P<0.001 and P=0.004) and had a tendency for higher EBL (P=0.003 and P=0.001) compared to non-obese patients. In the transperitoneal approach, those with visceral obesity had significantly longer operation times (P=0.008) than their non-viscerally obese counterparts; however, general obesity showed no impact on operation time (P=0.251). Estimated blood loss was higher for patients with visceral obesity (P=0.004), but no significant difference was noted among those with general obesity (P=0.980). CONCLUSIONS VFA appears to offer predictive advantages over BMI in assessing intraoperative complexities for transperitoneal RAPN. When used in conjunction with BMI, it could serve as a valuable tool in selecting the most appropriate surgical approach for RAPN.

GGA1 interacts with the endosomal Na+/H+ Exchanger NHE6 governing localization to the endosome compartment.

Mutations in the endosomal Na+/H+ exchanger (NHE6) cause Christianson syndrome (CS), an X-linked neurological disorder. Previous studies have shown that NHE6 functions in regulation of endosome acidification and maturation in neurons. Using yeast two-hybrid screening with the NHE6 carboxyl-terminus as bait, we identify Golgi-associated, Gamma adaptin ear containing, ARF binding protein 1 (GGA1) as an interacting partner for NHE6. We corroborated the NHE6-GGA1 interaction using co-immunoprecipitation (co-IP): using over-expressed constructs in mammalian cells; and co-IP of endogenously-expressed GGA1 and NHE6 from neuroblastoma cells, as well as from mouse brain. We demonstrate that GGA1 interacts with organellar NHEs (NHE6, NHE7 and NHE9) but not with cell-surface localized NHEs (NHE1 and NHE5). By constructing hybrid NHE1/NHE6 exchangers, we demonstrate that the cytoplasmic tail of NHE6 is necessary and sufficient for interactions with GGA1. We demonstrate the co-localization of NHE6 and GGA1 in cultured, primary hippocampal neurons, using super-resolution microscopy. We test the hypothesis that the interaction of NHE6 and GGA1 functions in the localization of NHE6 to the endosome compartment. Using subcellular fractionation experiments, we show that NHE6 is mis-localized in GGA1 knockout cells wherein we find less NHE6 in endosomes but more NHE6 transport to lysosomes, and more Golgi retention of NHE6 with increased exocytosis to the surface plasma membrane. Consistent with NHE6 mis-localization, and Golgi retention, we find the intra-luminal pH in Golgi to be alkalinized. Our study demonstrates a new interaction between NHE6 and GGA1 which functions in the localization of this intra-cellular NHE to the endosome compartment.

Christianson Syndrome across the Lifespan: An International Longitudinal Study in Children, Adolescents, and Adults.

Mutations in the X-linked endosomal Na+/H+ Exchanger 6 (NHE6) causes Christianson Syndrome (CS). In the largest study to date, we examine genetic diversity and clinical progression, including cerebellar degeneration, in CS into adulthood. Data were collected as part of the International Christianson Syndrome and NHE6 (SLC9A6) Gene Network Study. Forty-four individuals with 31 unique NHE6 mutations, age 2 to 32 years, were followed prospectively, herein reporting baseline, 1-year follow-up, and retrospective natural history. We present data on the CS phenotype with regard to physical growth, adaptive and motor regression, and across the lifespan, including information on mortality. Longitudinal data on body weight and height were examined using a linear mixed model: the rate of growth across development was slow and resulted in prominently decreased age-normed height and weight by adulthood. Adaptive functioning was longitudinally examined: a majority of adult (18+ years) participants lost gross and fine motor skills over a 1-year follow-up. Previously defined core diagnostic criteria for CS (present in >85%) - namely nonverbal status, intellectual disability, epilepsy, postnatal microcephaly, ataxia, hyperkinesia - were universally present in age 6 to 16; however, an additional core feature of high pain tolerance was added (present in 91%), and furthermore, evolution of symptoms were noted across the lifespan, such that postnatal microcephaly, ataxia and high pain threshold were often not apparent prior to age 6, and hyperkinesis decreased after age 16. While neurologic exams were consistent with cerebellar dysfunction, importantly, a majority of individuals (>50% older than 10) also had corticospinal tract abnormalities. Three participants died during the period of the study. In this large and longitudinal study of CS, we begin to define the trajectory of symptoms and the adult phenotype, thereby identifying critical targets for treatment.

Elevated serum uric acid is associated with cognitive impairment in acute minor ischemic stroke patients.

Background: Acute minor ischemic stroke (AMIS) has been proven to be strongly associated with post-stroke cognitive impairment (PSCI). Few studies have reported that uric acid (UA) levels are linked to PSCI in patients with AMIS, and those results are debatable. We investigated the relationship between serum UA levels and cognitive impairment in patients with AMIS. Methods: A total of 318 patients who were diagnosed with AMIS were recruited from Suining Central Hospital. Fasting serum samples were collected the day after admission for UA measurement. Cognitive function was evaluated at admission and 3 months after stroke using the Montreal Cognitive Assessment (MoCA). The relationship between UA and PSCI was examined using a multivariate binary logistic regression model. The optimal cut-off point for UA levels to predict PSCI was determined using the receiver operating characteristic (ROC) curve. Results: A total of 197 (61.9 %) of the 318 participants in this study exhibited cognitive impairment at 3 months. Serum UA was strongly linked with PSCI after adjusting for confounding factors (OR = 1.82, 95 % CI: 1.56 to 2.11, P < 0.0001). The ROC curve revealed a cut-off of 363.58 µmol/L serum UA, and the predicted sensitivity and specificity for PSCI were 67.5 % and 83.5 %, respectively. Subgroup analysis showed that confounding factors had no impact on the association between serum UA and PSCI risk. Conclusions: Higher baseline serum UA levels might be an independent risk factor for cognitive impairment in AMIS patients. Serum UA levels above 363.58 µmol/L may have clinical implications in predicting PSCI.