Nesfatin-1 ameliorates pathological abnormalities in Drosophila hTau model of Alzheimer's disease.

In human Alzheimer's disease (AD), the aggregation of tau protein is considered a significant hallmark, along with amyloid-beta. The formation of neurofibrillary tangles due to aberrant phosphorylation of tau disrupts microtubule stability, leading to neuronal toxicity, dysfunction, and subsequent cell death. Nesfatin-1 is a neuropeptide primarily known for regulating appetite and energy homeostasis. However, the function of Nesfatin-1 in a neuroprotective role has not been investigated. In this study, we aimed to elucidate the effect of Nesfatin-1 on tau pathology using the Drosophila model system. Our findings demonstrate that Nesfatin-1 effectively mitigates the pathological phenotypes observed in Drosophila human Tau overexpression models. Nesfatin-1 overexpression rescued the neurodegenerative phenotypes in the adult fly's eye and bristle. Additionally, Nesfatin-1 improved locomotive behavior, neuromuscular junction formation, and lifespan in the hTau AD model. Moreover, Nesfatin-1 controls tauopathy by reducing the protein level of hTau. Overall, this research highlights the potential therapeutic applications of Nesfatin-1 in ameliorating the pathological features associated with Alzheimer's disease.

Interventional Radiology for Bleeding Ectopic Varices: Individualized Approach Based on Vascular Anatomy.

Ectopic varices are rare but potentially life-threatening conditions usually resulting from a combination of global portal hypertension and local occlusive components. As imaging, innovative devices, and interventional radiologic techniques evolve and are more widely adopted, interventional radiology is becoming essential in the management of ectopic varices. The interventional radiologist starts by diagnosing the underlying causes of portal hypertension and evaluating the afferent and efferent veins of ectopic varices with CT. If decompensated portal hypertension is causing ectopic varices, placement of a transjugular intrahepatic portosystemic shunt is considered the first-line treatment, although this treatment alone may not be effective in managing ectopic variceal bleeding because it may not sufficiently resolve focal mesenteric venous obstruction causing ectopic varices. Therefore, additional variceal embolization should be considered after placement of a transjugular intrahepatic portosystemic shunt. Retrograde transvenous obliteration can serve as a definitive treatment when the efferent vein connected to the systemic vein is accessible. Antegrade transvenous obliteration is a vital component of interventional radiologic management of ectopic varices because ectopic varices often exhibit complex anatomy and commonly lack catheterizable portosystemic shunts. Superficial veins of the portal venous system such as recanalized umbilical veins may provide safe access for antegrade transvenous obliteration. Given the absence of consensus and guidelines, a multidisciplinary team approach is essential for the individualized management of ectopic varices. Interventional radiologists must be knowledgeable about the anatomy and hemodynamic characteristics of ectopic varices based on CT images and be prepared to consider appropriate options for each specific situation. ©RSNA, 2024 Supplemental material is available for this article.

Impact of perioperative COVID-19 infection on postoperative complication in cesarean section using Korean National Health insurance data.

The vulnerability during pregnancy has raised concerns about the potential impact of COVID-19 on obstetric anesthesia, an essential aspect of maternal care during cesarean section procedures. To evaluate the influence of COVID-19 infection on obstetric anesthesia during cesarean section, we analyzed the data from Korean National Health Insurance System (NHIS). This retrospective study utilized data from Korean NHIS. We included patients admitted with operation codes specific to cesarean section between January 1, 2020, and December 31, 2021. We classified patients into a COVID (+) group with a diagnosis code (U071) 30 days around surgery and a COVID (-) group without the code in the same period. The primary outcome was 30-day mortality that was defined as death within 30 days of admission due to any causes. Secondary outcomes were pulmonary complications (pneumonia, acute respiratory distress syndrome [ARDS], pulmonary thromboembolism [PTE], or unexpected postoperative mechanical ventilation), ICU admission, cardiac arrest, myocardial infarction [MI], other thromboembolic events, surgical site infection, sepsis, acute renal failure [ARF], and hepatic failure. Among 75,268 patients who underwent cesarean section, 107 had a COVID-19 diagnosis code, while 75,161 did not. After 1:4 propensity score matching (PSM), 535 patients were included in each group. 30-day mortality showed no significant differences between the two groups both before and after PSM. The COVID (+) group demonstrated significantly elevated rates of pneumonia, ARDS, PTE, and surgical site infection both before and after PSM. Hospital length of stay and admission costs were also significantly longer and higher, respectively, in the COVID (+) group before and after PSM. In subgroup analysis, no differences were observed in mortality and postoperative complications based on the anesthesia method after matching. COVID-19 infection is associated with increased rates of postoperative complications, including pneumonia, ARDS, PTE, surgical site infection, longer hospital stays, and increased admission costs, in patients who underwent cesarean section.

The overexpression of DSP1 in neurons induces neuronal dysfunction and neurodegeneration phenotypes in Drosophila.

Dorsal switch protein 1(DSP1), a mammalian homolog of HMGB1, is firstly identified as a dorsal co-repressor in 1994. DSP1 contains HMG-box domain and functions as a transcriptional regulator in Drosophila melanogaster. It plays a crucial role in embryonic development, particularly in dorsal-ventral patterning during early embryogenesis, through the regulation of gene expression. Moreover, DSP1 is implicated in various cellular processes, including cell fate determination and tissue differentiation, which are essential for embryonic development. While the function of DSP1 in embryonic development has been relatively well-studied, its role in the adult Drosophila brain remains less understood. In this study, we investigated the role of DSP1 in the brain by using neuronal-specific DSP1 overexpression flies. We observed that climbing ability and life span are decreased in DSP1-overexpressed flies. Furthermore, these flies demonstrated neuromuscular junction (NMJ) defect, reduced eye size and a decrease in tyrosine hydroxylase (TH)-positive neurons, indicating neuronal toxicity induced by DSP1 overexpression. Our data suggest that DSP1 overexpression leads to neuronal dysfunction and toxicity, positioning DSP1 as a potential therapeutic target for neurodegenerative diseases.

An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer.

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.

Etiology of Borderline Intellectual Functioning.

Borderline intellectual functioning (BIF), characterized by intelligence quotient scores between 70 and 85, can lead to challenges in daily life. This review explored the multifaceted nature of BIF by examining the interplay between genetic predisposition, prenatal/perinatal factors, environmental influences, and underlying medical conditions.

Impact of Complete Revascularization for Acute Myocardial Infarction In Multivessel Coronary Artery Disease Patients With Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: The clinical benefits of complete revascularization (CR) in acute myocardial infarction (AMI) patients are unclear. Moreover, the benefit of CR is unknown in AMI with diabetes mellitus (DM) patients. We sought to compare the prognosis of CR and incomplete revascularization (IR) in patients with AMI and multivessel disease, according to the presence of DM. METHODS: A total of 2,150 AMI patients with multivessel coronary artery disease were analyzed. CR was defined based on the angiographic image. The primary endpoint of this study was the patient-oriented composite outcome (POCO) defined as a composite of all-cause death, any myocardial infarction, and any revascularization within 3 years. RESULTS: Overall, 3-year POCO was significantly lower in patients receiving angiographic CR (985 patients, 45.8%) compared with IR (1,165 patients, 54.2%). When divided into subgroups according to the presence of DM, CR reduced 3-year clinical outcomes in the non-DM group but not in the DM group (POCO: 11.7% vs. 23.2%, p<0.001, any revascularization: 7.2% vs. 10.8%, p=0.024 in the non-DM group, POCO: 24.3% vs. 27.8%, p=0.295, any revascularization: 13.3% vs. 11.3%, p=0.448 in the DM group, for CR vs. IR). Multivariate analysis showed that CR significantly reduced 3-year POCO (hazard ratio, 0.52; 95% confidence interval, 0.36-0.75) only in the non-DM group. CONCLUSIONS: In AMI patients with multivessel disease, CR may have less clinical benefit in DM patients than in non-DM patients.

Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

Surgical outcomes of external double needle puncture epiglottopexy in severe laryngomalacia patients with high-risk comorbidities.

OBJECTIVES: Patients with severe laryngomalacia (LM) and high-risk comorbidities require surgical interventions such as supraglottoplasty. However, evidence supporting epiglottopexy for these patients is scarce. This study aims to report the surgical outcomes of external double needle puncture using a single thread for epiglottopexy in severe LM patients with high-risk comorbidities. METHODS: This retrospective study was conducted at a single tertiary hospital. We enrolled 32 patients under 12 months with severe LM who underwent external double needle puncture epiglottopexy. We compared clinical factors between the successful and failed groups and identified risk factors for the failure of epiglottopexy. RESULTS: Of the airway surgical outcomes, 22 (68.7 %) patients were in the successful group. In the failed group (n = 10, 32.3 %), patients received tracheostomies due to uncontrolled saliva (n = 3), the need for mechanical ventilation (n = 3), and uncontrolled LM (n = 4). There was a statistically significant difference in body weight at the time of surgery and the proportion of associated comorbidities between the two groups. Gestational age was the only factor significantly associated with successful surgical outcomes in both univariate and multivariate logistic regression analyses (odds ratio = 2.263; 95 % confidence interval, 1.042-4.918; P = 0.039). CONCLUSION: External double needle puncture epiglottopexy is an effective surgical method for patients with LM who present with a retroflexed floppy epiglottis and high-risk comorbidities. Low gestational age is a major risk factor for surgical failure. Consideration of factors such as the need for mechanical ventilation and uncontrolled saliva should be prioritized before and after surgery to enhance surgical success.

Integrative analysis of single-cell RNA-seq and gut microbiome metabarcoding data elucidates macrophage dysfunction in mice with DSS-induced ulcerative colitis.

Ulcerative colitis (UC) is a significant inflammatory bowel disease caused by an abnormal immune response to gut microbes. However, there are still gaps in our understanding of how immune and metabolic changes specifically contribute to this disease. Our research aims to address this gap by examining mouse colons after inducing ulcerative colitis-like symptoms. Employing single-cell RNA-seq and 16 s rRNA amplicon sequencing to analyze distinct cell clusters and microbiomes in the mouse colon at different time points after induction with dextran sodium sulfate. We observe a significant reduction in epithelial populations during acute colitis, indicating tissue damage, with a partial recovery observed in chronic inflammation. Analyses of cell-cell interactions demonstrate shifts in networking patterns among different cell types during disease progression. Notably, macrophage phenotypes exhibit diversity, with a pronounced polarization towards the pro-inflammatory M1 phenotype in chronic conditions, suggesting the role of macrophage heterogeneity in disease severity. Increased expression of Nampt and NOX2 complex subunits in chronic UC macrophages contributes to the inflammatory processes. The chronic UC microbiome exhibits reduced taxonomic diversity compared to healthy conditions and acute UC. The study also highlights the role of T cell differentiation in the context of dysbiosis and its implications in colitis progression, emphasizing the need for targeted interventions to modulate the inflammatory response and immune balance in colitis.

High Prevalence and Risk Factors of Functional Gastrointestinal Disorders Among University Students in South Korea.

Functional gastrointestinal disorders are common and have high prevalence in young adults. This study aimed to identify the prevalence and risk factors of functional gastrointestinal disorders in university students. A cross-sectional study was conducted in January 2021 at two universities in a South Korean city and included 493 participants. The Rome IV criteria (for functional dyspepsia and irritable bowel syndrome) and the Korean gastroesophageal reflux disease questionnaire (for gastroesophageal reflux disease) were used to define each disease. Data were analyzed using descriptive statistics and multivariate logistic regression. Gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome prevalence was 18.5%, 7.5%, and 6.5%, respectively, in university students. In multivariate analysis, school year (fourth) (odds ratio [95% confidence interval] = 2.27 [0.25, 0.78]), underlying disease (odds ratio [95% confidence interval] = 2.92 [1.42, 6.04]), physical activity less than once weekly (odds ratio [95% confidence interval] = 4.84 [1.04, 22.45]), very irregular meals (odds ratio [95% confidence interval] = 4.02 [1.54, 10.49]), overeating more than 5 times weekly (odds ratio [95% confidence interval] = 3.37 [1.19, 9.56]), and academic stress (odds ratio [95% confidence interval] = 1.02 [1.01, 1.03]) were risk factors for functional gastrointestinal disorders. Our findings indicate that a comprehensive management program focusing on eating habits and psychological factors is needed to reduce the prevalence of functional gastrointestinal disorders in university students.

Anti­inflammatory effects of methanol extract from Peperomia dindygulensis Miq. mediated by HO­1 in LPS­induced RAW 264.7 cells.

Inflammation serves as a multifaceted defense mechanism activated by pathogens, cellular damage and irritants, aiming to eliminate primary causes of injury and promote tissue repair. Peperomia dindygulensis Miq. (P. dindygulensis), prevalent in Vietnam and southern China, has a history of traditional use for treating cough, fever and asthma. Previous studies on its phytochemicals have shown their potential as anti-inflammatory agents, yet underlying mechanisms remain to be elucidated. The present study investigated the regulatory effects of P. dindygulensis on the anti-inflammatory pathways. The methanol extracts of P. dindygulensis (PDME) were found to inhibit nitric oxide (NO) production and induce heme oxygenase-1 (HO-1) expression in murine macrophages. While MAPKs inhibitors, such as SP600125, SB203580 and U0126 did not regulate HO-1 expression, the treatment of cycloheximide, a translation inhibitor, reduced HO-1. Furthermore, PDME inhibited lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and TNF-α expression at both the mRNA and protein levels. The activity of NOS and the expression of TNF-α, iNOS and COX-2 decreased in LPS-stimulated Raw 264.7 cells treated with PDME and this effect was regulated by inhibition of HO-1 activity. These findings suggested that PDME functions as an HO-1 inducer and serves as an effective natural anti-inflammatory agent in LPS-induced inflammation.

The functional and biological effects of systemic dexamethasone on mice with facial nerve crushing injury.

BACKGROUND: Corticosteroid therapy is commonly recommended for acute facial nerve weakness; however, its effectiveness in treating traumatic nerve injuries remains controversial. This study investigated the functional recovery and cellular effects of systemic dexamethasone administration after facial nerve injury. METHODS: C57BL/6 mice were assigned to two groups by intraperitoneal injection: the phosphate-buffered saline group and the dexamethasone group. Facial nerve crush injury was induced, followed by the functional grading of recovery. Cellular effects were investigated using transmission electron microscopy, flow cytometry, immunofluorescence, and intravital imaging. RESULTS: Macrophage infiltration into the facial nerves was significantly inhibited by systemic dexamethasone administration. However, dexamethasone group slightly delayed the functional recovery of the facial nerve compared to the PBS group. In addition, the morphological changes in the nerve were not significantly different between the two groups at 14 days post-injury. Macrophage migration analysis in the intravital imaging also showed no difference between groups. CONCLUSIONS: In summary, systemic dexamethasone successfully inhibited leukocyte infiltration; however, functional recovery was delayed compared to the PBS control group. Clinically, these findings indicate that more evidence and research are required to use steroid pulse therapy for the treatment of traumatic facial nerve injuries.

Differences in the incidence, characteristics, and outcomes of patients with acute kidney injury in the medical and surgical intensive care units.

BACKGROUND: Though acute kidney injury (AKI) is a prevalent complication in critically ill patients, knowledge on the epidemiological differences and clinical characteristics of patients with AKI admitted to medical and surgical intensive care units (ICUs) remains limited. METHODS: Electronic medical records of patients in ICUs in Pusan National University Hospital and Pusan National University Hospital Yangsan, from January 2011 to December 2020, were retrospectively analyzed. Different characteristics of AKI between patients were analyzed. The contribution of AKI to the in-hospital mortality rate was assessed using a Cox proportional hazards model. RESULTS: A total of 7,150 patients were included in this study. AKI was more frequent in medical (48.7%) than in surgical patients (19.7%), with the severity of AKI higher in medical patients. In surgical patients, hospital-acquired AKI was more frequent (51.0% vs. 49.0%), whereas community-acquired AKI was more common in medical patients (58.5% vs. 41.5%). 16.9% and 5.9% of medical and surgical patients died in the hospital, respectively. AKI affected patient groups to different degrees. In surgical patients, AKI patients had 4.778 folds higher risk of mortality (95% confidence interval [CI], 3.577-6.382; p < 0.001) than non-AKI patients; whereas in medical AKI patients, it was 1.239 (95% CI, 1.051-1.461; p = 0.01). CONCLUSION: While the prevalence of AKI itself is higher in medical patients, the impact of AKI on mortality was stronger in surgical patients compared to medical patients. This suggests that more attention is needed for perioperative patients to prevent and manage AKI.

The role of nafamostat mesylate anticoagulation in continuous kidney replacement therapy for critically ill patients with bleeding tendencies: a retrospective study on patient outcomes and safety.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation strategy for patients with bleeding tendencies remains debated. This study aimed to evaluate patient outcomes and safety of nafamostat mesylate (NM) compared with no anticoagulation (NA) in critically ill patients with bleeding tendencies who were undergoing CKRT. METHODS: This retrospective study enrolled 2,313 patients who underwent CKRT between March 2013 and December 2022 at the third affiliated hospital in South Korea. After applying the exclusion criteria, 490 patients were included in the final analysis, with 245 patients in the NM and NA groups each, following 1:1 propensity score matching. Subsequently, in-hospital mortality, incidence of bleeding complications, agranulocytosis, hyperkalemia, and length of hospital stay were assessed. RESULTS: No significant differences were observed between the groups regarding the lengths of hospital and ICU stays or the incidence of agranulocytosis and hyperkalemia. The NM group showed a smaller decrease in hemoglobin levels during CKRT (-1.90 g/dL vs. -2.39 g/dL) and less need for blood product transfusions than the NA group. Furthermore, the NM group exhibited a survival benefit in patients who required transfusion of all three blood products. CONCLUSION: NM is an effective and safe anticoagulant for CKRT in critically ill patients, especially those requiring transfusion of all three blood products. Although these findings are promising, further multicenter studies are needed to validate them and explore the mechanisms underlying the observed benefits.

Combination of induced pluripotent stem cell-derived motor neuron progenitor cells with irradiated brain-derived neurotrophic factor over-expressing engineered mesenchymal stem cells enhanced restoration of axonal regeneration in a chronic spinal cord injury rat model.

BACKGROUND: Spinal cord injury (SCI) is a disease that causes permanent impairment of motor, sensory, and autonomic nervous system functions. Stem cell transplantation for neuron regeneration is a promising strategic treatment for SCI. However, selecting stem cell sources and cell transplantation based on experimental evidence is required. Therefore, this study aimed to investigate the efficacy of combination cell transplantation using the brain-derived neurotrophic factor (BDNF) over-expressing engineered mesenchymal stem cell (BDNF-eMSC) and induced pluripotent stem cell-derived motor neuron progenitor cell (iMNP) in a chronic SCI rat model. METHOD: A contusive chronic SCI was induced in Sprague-Dawley rats. At 6 weeks post-injury, BDNF-eMSC and iMNP were transplanted into the lesion site via the intralesional route. At 12 weeks post-injury, differentiation and growth factors were evaluated through immunofluorescence staining and western blot analysis. Motor neuron differentiation and neurite outgrowth were evaluated by co-culturing BDNF-eMSC and iMNP in vitro in 2-dimensional and 3-dimensional. RESULTS: Combination cell transplantation in the chronic SCI model improved behavioral recovery more than single-cell transplantation. Additionally, combination cell transplantation enhanced mature motor neuron differentiation and axonal regeneration at the injured spinal cord. Both BDNF-eMSC and iMNP played a critical role in neurite outgrowth and motor neuron maturation via BDNF expression. CONCLUSIONS: Our results suggest that the combined transplantation of BDNF- eMSC and iMNP in chronic SCI results in a significant clinical recovery. The transplanted iMNP cells predominantly differentiated into mature motor neurons. Additionally, BDNF-eMSC exerts a paracrine effect on neuron regeneration through BDNF expression in the injured spinal cord.

Effect of bowel preparation completion time on bowel cleansing efficacy: Prospective randomized controlled trial of different bowel preparation completion times precolonoscopy.

OBJECTIVES: The elapse time between the completion of bowel cleansing and colonoscopy is one of the important factors for proper bowel cleansing. Although several studies have reported that a short time interval resulted in a favorable bowel cleansing, no randomized controlled trial (RCT) has been conducted to determine the effect of the elapse time. Consequently, we performed an RCT to investigate the efficacy of bowel preparation of participants who underwent colonoscopy according to the different time intervals between the completion of bowel preparation and colonoscopy. METHODS: In this single-center RCT, study participants were randomized to complete bowel preparation either 2-4 h or 4-8 h before colonoscopy. The primary end-point was successful bowel preparation, rated using the Boston Bowel Preparation Scale (BBPS). RESULTS: A total of 504 individuals were included (2-4 h, 255; 4-8 h, 249). The rate of successful bowel preparation in the 2-4 h group showed noninferiority compared with that of the 4-8 h group (97.6% vs. 95.2%; rate difference, 2.5% [-0.8% to 5.7%]; Pfor noninferiority < 0.001, Pfor superiority = 0.136). The rate for perfect cleansing (a BBPS score of 9) was higher in the 2-4 h group (56.5% vs. 39.8%, P < 0.001). CONCLUSION: When bowel cleansing was finished 2-4 h before the start of colonoscopy, the overall bowel cleansing was noninferior, and perfect cleansing was superior, compared to that when cleansing was finished 4-8 h before colonoscopy.