Analysis of four hereditary protein C deficiencies associated with vascular thromboembolism.

OBJECTIVE: To analyze the clinical features and gene mutations in four families with hereditary protein C (PC) deficiency and explore their association with vascular thromboembolism. METHODS: The clinical data of four patients with PC deficiency were retrospectively analyzed. Venous blood samples were collected from the four affected patients and their family members, and relevant coagulation indexes and thrombin production and inhibition tests were performed. PCR was used to amplify and directly sequence the PROC gene of the probands. Software analysis was conducted to assess the conservativeness and pathogenicity of the mutated loci. Protein models were constructed to analyze the spatial structure before and after the mutation. RESULTS: Thrombin generation and inhibition assays demonstrated impaired anticoagulation in all four probands. Proband 1 and 4 presented clinically with pulmonary embolism and lower extremity deep vein thrombosis (DVT), Proband 2 with cerebral infarction, and Proband 3 with DVT. Genetic analysis revealed the presence of the following mutations: c.541T > G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation, c.247-248insCT heterozygous insertion mutation, c.659G > A heterozygous missense mutation, and a new variant locus c.1146_1146delT heterozygous deletion mutation in the four probands, respectively. In particular, c.1146_1146delT heterozygous deletion mutations not reported previously. Conservativeness and pathogenicity analyses confirmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Analysis of protein modeling revealed that these mutations induced structural alterations in the protein or led to the formation of truncated proteins. According to the American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants, c.1146_1146delT was rated as pathogenic (PVS1 + M2 + PM4 + PP1 + PP3 + PP4). CONCLUSION: The identified mutations are likely associated with decreased PC levels in each of the four families. The clinical manifestations of hereditary PC deficiency exhibit considerable diversity.

The gut microbial signatures of patients with lacunar cerebral infarction.

BACKGROUND: Emerging evidence revealed that gut microbial dysbiosis is involved in the pathogenesis of multiple neurological diseases, but there is little available data on the relationship between gut microbiota and lacunar cerebral infarction (LCI). METHODS: Fecal samples from acute LCI patients (n = 65) and matched healthy controls (n = 65) were collected. The compositions and potential functions of the gut microbiota were estimated. RESULTS: The results showed that there were significant gut microbial differences between LCI and control groups. Patients with LCI had higher abundances of genus Lactobacillus, Streptococcus, Veillonella, Acidaminococcus, Bacillus, Peptoclostridium, Intestinibacter, Alloscardovia and Cloacibacillus but lower proportions of genus Agathobacter and Lachnospiraceae_UCG-004. Investigating further these microbes such as Lactobacillus and Veillonella were correlated with clinical signs. Moreover, we found that 9 gene functions of gut microbiota were different between LCI patients and controls, which were associated with amino acid metabolism and inflammatory signal transduction. Notably, four optimal microbial markers were determined, and the combination of Streptococcus, Lactobacillus, Agathobacter, Lachnospiraceae_UCG-004 and the three risk factors achieved an area under the curve (AUC) value of 0.854 to distinguish LCI from controls. CONCLUSION: These findings revealed the characterizing of gut microbiota in LCI patients and provided potential microbial biomarkers for clinical diagnosis of LCI.

Association between malnutrition risk and hemorrhagic transformation in patients with acute ischemic stroke.

Background and aims: Malnutrition is a prevalent problem occurring in different diseases. Hemorrhagic transformation (HT) is a severe complication of acute ischemic stroke (AIS). Few studies have evaluated the association between malnutrition risk and hemorrhagic transformation in patients with acute stroke. We aim to investigate the influence of malnutrition risk on the risk of hemorrhagic transformation in patients with AIS. Methods: A total of 182 consecutive adults with HT and 182 age- and sex-matched patients with stroke were enrolled in this study. The controlling nutritional status (CONUT) score was calculated to evaluate the malnutrition risk. HT was detected by follow-up imaging assessment and was radiologically classified as hemorrhagic infarction type 1 or 2 or parenchymal hematoma type 1 or 2. Logistic regression models were conducted when participants were divided into different malnutrition risk groups according to the objective nutritional score to assess the risk for HT. Results: The prevalence of moderate to severe malnutrition risk in patients with AIS was 12.5%, according to the CONUT score. Univariate analysis showed that the CONUT score is significantly higher in patients with HT than those without HT. After adjusting for potential covariables, the patients with mild risk and moderate to severe malnutrition risk were associated with a higher risk of HT compared to the patients in the normal nutritional status group [odds ratio, 3.180 (95% CI, 1.139-8.874), P = 0.027; odds ratio, 3.960 (95% CI, 1.015-15.453), P = 0.048, respectively]. Conclusion: Malnutrition risk, measured by CONUT score, was significantly associated with an increased risk of hemorrhagic transformation in patients with AIS.

Two-stage isolated AC/DC converter and its compound control strategy.

With the continued development of the new energy vehicle industry, two-stage isolated AC/DC converters are widely used because of their simple topology and easy control characteristics. In this study, we investigate the front-stage Buck power factor correction (PFC) converter and rear-stage full-bridge converter. The main circuit design and component selection were completed through a detailed analysis of the circuit characteristics. In terms of the control strategy, the front-stage adopting PI control and parameter adaptive terminal sliding mode control strategy were proposed for the rear-stage full-bridge converter. This new compound control strategy ensures an optimal regulation of the system under different operating conditions. Simulation analysis verified the correctness of the system topology and control strategy. Based on an analysis of the main parameters of the system, a low-power experimental prototype was trial-produced. The experimental results show that under the same load switching conditions, the parameter-adaptive terminal sliding mode control enhanced faster dynamic regulation and stronger robustness than the conventional PI control. The study is also a good reference in terms of engineering work.

Association Between Obesity and Post-stroke Anxiety in Patients With Acute Ischemic Stroke.

Post-stroke anxiety (PSA) is serious psychosomatic comorbidity among patients with stroke, but whether obesity could be positively associated with PSA is currently unknown. The purpose of this study was to investigate the potential association between obesity and subsequent anxiety risk in patients with stroke. A total of 441 patients with acute ischemic stroke (AIS) onset were consecutively recruited within 7 days, and PSA and post-stroke depression (PSD) were evaluated by using a 14-item Hamilton anxiety scale (HAMA) and 17-item Hamilton depression scale (HAMD) at the end of 1-month follow-up. The odds ratio (OR) with 95% CI was estimated for the incidental PSA by using logistic regression analysis. The incidence of PSA was 25.85% at the end of 1-month follow-up, with a significant difference between patients with and without abdominal obesity. Relative fat mass (RFM) and abdominal obesity were significantly associated with an elevated risk of PSA, and the crude ORs were 1.04 (95% CI: 1.01-1.08) and 1.93 (95% CI: 1.11-3.34), respectively. Even after adjustment for obesity-related risk factors and PSA-related clinical measurements, the association remained to be pronounced with abdominal obesity. However, RFM (OR = 1.03, 95% CI: 0.99-1.06, P = 0.053) and abdominal obesity (OR = 1.31, 95% CI: 0.80-2.15, P = 0.280) were not significantly associated with an elevated risk of PSD. Abdominal obesity was independently associated with the PSA instead of PSD, which may help predict PSA risk in clinical practice. Further prospective clinical studies with a long follow-up duration are warranted to verify this finding.

Low vitamin D levels and the long-term functional outcome of stroke up to 5 years.

BACKGROUND AND PURPOSE: Previous studies have established that vitamin D was associated with stroke. The purpose of this study was to investigate the relationship between vitamin D and 5-year outcome of patients with stroke including acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) stroke. METHODS: Serum 25-hydroxyvitamin D levels were prospectively analyzed in patients admitted to the First Affiliated Hospital of Wenzhou Medical University from 2013 to 2015. Modified Rankin scale (mRS) was used to evaluate their 5-year functional outcome, and univariate and multivariate logistic regressions were applied to evaluate the effects of vitamin D on stroke outcome. RESULTS: In total, 668 patients diagnosed with stroke were recruited, and 420 completed the 5-year follow-up. Ninety-five patients experienced poor outcome in the 5 years since stroke onset. Vitamin D levels in patients with poor outcome showed significant differences compared to good outcome patients (p < .001). In multivariable logistic regression analysis, after adjusting the potential confounders, the 5-year functional outcome was significantly associated with vitamin D levels. Stroke patients with vitamin D levels less than 38.4 nmol/L had a higher risk for poor outcome compared with those with vitamin D level over 71.4 nmol/L at 5-year (odds ratio [OR] = 3.66, 95% confidence interval [CI] = 1.42-9.45, p = .007), which was consistent with AIS patients (OR = 6.36, 95% CI = 1.89-21.44, p = .003). CONCLUSION: Vitamin D level less than 38.4 nmol/L at admission is a potential risk biomarker for poor functional outcome at 5-year prognosis in AIS patients, which might provide new ideas for the prognostic assessment of stroke.

The Association Between Systemic Inflammatory Markers and Post-Stroke Depression: A Prospective Stroke Cohort.

OBJECTIVE: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the post-stroke depression (PSD) have been reported. In this study, we aimed to compare the level of systemic inflammation markers between PSD and non-PSD patients and explore the association of these inflammatory markers with PSD. METHODS: Totally, 432 ischemic stroke patients were consecutively enrolled in the study and received 1 month follow-up. We used the 17-Hamilton Rating Scale to measure depressive symptoms at 1 month after stroke. With the Hamilton Depression Scale score of >7, patients were diagnosed with PSD. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and derived neutrophil-to-lymphocyte ratio (dNLR) were calculated from the admission blood work. RESULTS: Finally, 129 patients (30.5%) were diagnosed with PSD at 1 month. PSD patients showed significantly higher levels of SII (501.27 (345.43-782.58) vs 429.60 (315.64-570.98), P=0.001), NLR (2.36 (1.77-3.82) vs 2.17 (1.56-2.80), P=0.010), dNLR (1.67 (1.30-2.51) vs 1.54 (1.16-1.99), P=0.009), PLR (124.65 (95.25-155.15) vs 109.22 (92.38-142.03), P=0.015), especially SII at admission as compared to non-PSD patients. In the logistic analysis, SII value (>547.30) was independently associated with the occurrence of PSD (OR=2.181, 95% CI=1.274-3.732, p =0.004), better than dNLR (OR=1.833, 95% CI=1.071-3.137, p =0.027), PLR (OR= 1.822, 95% CI=1.063-3.122, p =0.029) and NLR (OR =1.728, 95% CI=1.009-2.958, p =0.046). CONCLUSION: Increased SII, PLR, dNLR, NLR, particularly SII at admission, are significantly correlated with PSD and may add some prognostic clues to find early discovery of PSD.

The Stress Hyperglycemia Ratio is Associated with Hemorrhagic Transformation in Patients with Acute Ischemic Stroke.

BACKGROUND: Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. Stress hyperglycemia is frequent in patients with acute illness such as stroke. We aimed to explore the association between stress hyperglycemia and HT in AIS patients. METHODS: A total of 287 consecutive participants with HT and 285 age- and sex-matched stroke patients without HT were enrolled in this study. Baseline glucose and glycated hemoglobin (HbA1c) levels were collected to measure stress hyperglycemia. The stress hyperglycemia ratio (SHR) was calculated by dividing the fasting plasma glucose at admission with HbA1c. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction type (HI) 1 or 2 or parenchymal hematoma type (PH) 1 or 2. RESULTS: Univariate analysis showed that SHR is significantly higher among patients with HT than those without HT. Compared to the patients in the lower three quartiles of SHR, the incidence of HT was significantly higher among patients with the highest quartile of SHR in total population, diabetic and non-diabetic population. We also observed that patients with the highest SHR quartile were associated with an increased risk of hemorrhagic transformation after adjusted for potential covariates (68.4% versus 39.1%; adjusted odds ratio, 2.320; 95% confidence interval, 1.207-4.459; P=0.012). CONCLUSION: The stress hyperglycemia ratio, representing the state of stress hyperglycemia, was significantly associated with an increased risk of hemorrhagic transformation in patients with acute ischemic stroke.

Parameter adaptive terminal sliding mode control for Full-Bridge DC-DC converter.

The poor dynamic performance problem of a Full-Bridge converter under a traditional control strategy is investigated in this study. A new parameter adaptive terminal sliding mode control policy is developed for a Full-Bridge DC-DC converter, by combining the integral part with the power function and differential function in the design of the sliding surface. In theory, the steady-state error of the system can approach zero within a short time. To manage the un-ideal situation after using a fixed value of power γ, an improved γ adaptive algorithm is proposed. The system output is tracked and γ is adjusted in real time. The effect of the system can be guaranteed always in an optimal state. Finally, simulation results are provided to verify the performance of the proposed design method under different conditions.

Hemostasis functions are associated with hemorrhagic transformation in non-atrial fibrillation patients: a case-control study.

BACKGROUND: Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. METHODS: We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. RESULTS: In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients. CONCLUSIONS: Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.

High fibrinogen-to-albumin ratio is associated with hemorrhagic transformation in acute ischemic stroke patients.

INTRODUCTION: Hemorrhagic transformation (HT) is a complex and multifactorial complication among patients with acute ischemic stroke (AIS), and the inflammatory response has been considered as a risk factor for HT. We aimed to evaluate the stratification of FAR (fibrinogen-to-albumin ratio), an inflammatory biomarker, in HT patients. METHODS: A total of 256 consecutive stroke patients with HT and 256 age- and gender-matched stroke patients without HT were included in this study. HT during hospitalization was diagnosed by follow-up imaging assessment and was classified into hemorrhagic infarction (HI) and parenchymal hematoma (PH) according to the recommendations of European Cooperative Acute Stroke Study II classification. Blood samples were obtained at admission. RESULTS: Higher levels of FAR were observed in patients with HT compared with the non-HT group [10.29 (8.39-12.95) vs. 8.60 (7.25-10.8), p < .001], but no significant difference was found between the PH and HI [10.88 (8.72-13.40) vs. 10.13 (8.14-12.60), p > .05]. Patients were assigned to groups of high FAR (≥9.51) and low FAR (<9.51) based on the optimal cut-off value. After adjustment for potential confounders, the high FAR remained independently associated with the increased risk of HT (OR = 5.027, 95% CI = 5.027 (2.309-10.942), p < .001). CONCLUSIONS: High FAR was independently associated with the increased risk of HT after AIS.

Liver Fibrosis Is Associated With Hemorrhagic Transformation in Patients With Acute Ischemic Stroke.

Background: Hemorrhagic transformation (HT) is a frequent, often asymptomatic event that occurs after acute ischemic stroke (AIS). Liver fibrosis, usually subclinical, is common and crucial in the development of liver disease. We aimed to investigate the association between liver fibrosis and HT in patients with AIS. Methods: We performed a single-center and retrospective study. A total of 185 consecutive participants with HT and 199 age- and sex-matched stroke patients without HT were enrolled in this study. We calculated one validated fibrosis index-Fibrosis-4 (FIB-4) score-to assess the extent of liver fibrosis. HT was detected by routine CT or MRI and was radiologically classified as hemorrhagic infarction type 1 or 2 or parenchymal hematoma type 1 or 2. HT was also classified into asymptomatic or symptomatic. We used logistic regression models adjusted for previously established risk factors to assess the risks for HT. Results: The median FIB-4 score was significantly higher among patients who developed HT than among those without HT, whereas standard hepatic assays were largely normal. Patients were assigned to groups of high FIB-4 score and low FIB-4 score based on the optimal cutoff value. Compared with the subjects in the low-FIB-4-score group, incidence of HT for the high-FIB-4-score group was significantly higher. After adjustment for potential confounders, the patients with high FIB-4 score had 3.461-fold risk of HT in AIS compared to the patients with low FIB-4 score [odds ratio, 3.461 (95% CI, 1.404-8.531)]. Conclusion: Liver fibrosis, measured by FIB-4 score, was independently associated with the risk of HT in AIS patients.

Reduced thiamine is a predictor for cognitive impairment of cerebral infarction.

OBJECTIVE: Reduced thiamine (vitamin B1 ) had been reported to be associated with cognitive impairment caused by Alzheimer disease. Our study is to explore the association between thiamine and cognitive impairment after acute ischemic stroke. MATERIALS AND METHODS: One hundred and eighty two patients with acute cerebral infarction were recruited within the first 24 hr after admission. Thiamine and other vitamin Bs of peripheral blood samples were measured. Patients were divided into with poststroke cognitive impairment (PSCI) and non-PSCI according to the score of MMSE and the degree of education. RESULTS: Reduced thiamine (<1.0 ng/ml) was independently associated with PSCI (OR: 2.033, 95% CI: 1.017-4.067, p = .045) after adjusting for potential confounding factors. Advanced age, lower education, diabetes mellitus, left hemisphere infarction, and higher National Institute of Health Stroke Scale (NIHSS) were also independent risk factors for PSCI. CONCLUSIONS: Reduced thiamine is one of the predictors for early cognitive impairment in patients with acute cerebral infarction.

The association between interleukin-8 levels and the development of withdrawal symptoms during methamphetamine abstinence.

OBJECTIVE: Withdrawal symptoms are common during methamphetamine (METH) abstinence. This study aimed to explore the association between serum interleukins and withdrawal symptoms during METH abstinence. METHODS: This study recruited 120 METH users, and 94 of them completed the 2-week follow-up. Serum interleukin-1ß, 6,8,10 were tested at admission. Withdrawal symptoms were assessed by the Methamphetamine Withdrawal Questionnaire (MAWQ). RESULTS: Serum IL-8 levels were positively correlated with MAWQ scores at the 2-week endpoint (r = .257, p = .013). The variation of the MAWQ scores during the 2-week follow-up was negatively correlated with serum IL-8 levels at admission (r = -.249, p = .026). Serum IL-8 levels remained associated with the severity of METH withdrawal symptoms (ß = .363, p = .023), after adjusting for potential confounders. LIMITATIONS: This study did not include normal controls. Most patients were male and cigarette smokers. Patients were only followed up for 2 weeks, and their toxicology data were not collected. Interleukins were only measured at admission, and were tested in serum, not in the cerebrospinal fluid. CONCLUSIONS: Our study demonstrated that higher serum IL-8 levels may predict more severe withdrawal symptoms at 2 weeks after METH abstinence.

Post-Stroke Depression and Estimated Glomerular Filtration Rate: A Prospective Stroke Cohort.

PURPOSE: Post-stroke depression (PSD) is a frequent comorbidity in patients presenting with acute ischemic stroke. Impaired kidney function has been associated with depression in non-stroke subjects. We would like to evaluate whether the estimated glomerular filtration rate (eGFR) on admission is associated with the development of PSD. PATIENTS AND METHODS: Total of 268 patients with acute ischemic stroke were recruited and completed 1-month follow-up visit. eGFR was calculated from the serum creatinine value, race, age, and sex by using the chronic kidney disease epidemiology collaboration equation (CKD-EPI creatinine equation). The 17-item Hamilton Depression Scale was used to evaluate depression symptoms. Patients with a depression score of ≥7 were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosing post-stroke depression at 1 month. Meanwhile, 114 normal control subjects were also recruited. RESULTS: Ninety-three (34.7%) patients were diagnosed as having PSD at 1 month. There was a significant intergroup difference in eGFR levels within 24 hrs after admission (F=13.608, p<0.001). The levels of eGFR within 24 hrs after admission were significantly lower in both non-PSD patients and PSD patients than in normal controls. In logistic regression, the level of eGFR (<82mL/min/1.73m2) was independently associated with increased risk of PSD even after adjusting for confounders (OR=2.328, 95% CI:1.092-4.965, p=0.029). CONCLUSION: Reduced eGFR was found to be correlated with the development of PSD and it suggests the need for greater attentions and potential interventions for depression in patients with stroke and with reduced eGFR.

Hemoglobin, anemia, and poststroke cognitive impairment: A cohort study.

OBJECTIVES: Several studies have demonstrated that anemia was associated with cognitive impairment. The aim of this study was to explore the relationship between hemoglobin and cognitive impairment in patient with acute ischemic stroke. METHODS: In total, 326 patients with acute ischemic stroke were followed up for 1 month. The main outcome was the incidence and severity of poststroke cognitive impairment (PSCI) assessed by Mini-Mental State Examination (MMSE). The impact of hemoglobin levels and anemia on PSCI was assessed by multiple regression models controlling for potential confounders. RESULTS: During the 1-month follow-up, 193 (59.2%) patients developed PSCI. Anemia was independently associated with PSCI (OR = 3.637; 95% CI, 1.216-10.881; P = .021) after adjusting for demographics, vascular risk factors, stroke severity, and functional outcome. When the hemoglobin levels stratified into tertiles, higher hemoglobin levels were associated with better cognitive function. This result was however not significant after adjusting for the same confounders above. CONCLUSIONS: Low hemoglobin levels are associated with an increased risk of PSCI. Targeted interventions in this population may reduce the incidence of PSCI and require further evaluation.

Low triiodothyronine syndrome is associated with hemorrhagic transformation in patients with acute ischaemic stroke.

Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. We explored the association between low triiodothyronine (T3) syndrome and HT in AIS patients. A total of 208 consecutive participants with HT and 208 age- and sex-matched stroke patients without HT were enrolled in this study. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction (HI) type 1 or 2 or parenchymal hematoma (PH) type 1 or 2. HT was also classified into asymptomatic or symptomatic. The incidence of low T3 syndrome was significantly higher among patients who developed HT than among those without HT. Moreover, the more severe the HT, the lower the detected T3 levels. Multivariate-adjusted binary logistic regression showed that low T3 syndrome was an independent risk factor for HT and symptomatic HT in AIS patients. Low T3 syndrome was also significantly associated with a higher risk of PH, but not with the risk of HI. Thus, low T3 syndrome was independently associated with the risk of HT, symptomatic HT, and severe HT (PH) in AIS patients, which suggests monitoring T3 could be a useful means of preventing HT in patients with ischemic stroke.

Oxidative stress mediates depot-specific functional differences of human adipose-derived stem cells.

BACKGROUND: Visceral (VS) fat depot is known to have defective adipogenic functions compared to subcutaneous (SC) fat, but its mechanism of origin is unclear. OBJECTIVE: We tested our hypothesis that the degree of oxidative stress in adipose-derived stem cells (ASCs) from these depots may account for this difference. METHODS: ASCs were isolated from VS (omental region) and SC (abdominal region) fat depots of human subjects undergoing bariatric surgery. ASCs from VS and SC fat were investigated for their cellular characteristics in reactive oxygen species (ROS), metabolism, gene expression, proliferation, senescence, migration, and adipocyte differentiation. ASCs were also treated with antioxidant ascorbic acid (vitamin C). RESULTS: We found that human VS-derived ASCs exhibit excessive oxidative stress characterized by high reactive oxygen species (ROS), compared to SC-derived ASCs. Gene expression analyses indicate that the VS-ASCs exhibit higher levels of genes involved in pro-oxidant and pro-inflammatory pathways and lower levels of genes in antioxidant and anti-inflammatory pathways. VS-ASCs have impaired cellular functions compared to SC-ASCs, such as slower proliferation, early senescence, less migratory activity, and poor adipogenic capability in vitro. Treatment with ascorbic acid decreased ROS levels drastically in VS-ASCs. Ascorbic acid treatment substantially improved proliferation, senescence, migration, and adipogenic capacities of compromised ASCs caused by high ROS. CONCLUSIONS: This finding suggests the fat depot-specific differences of cellular defects originating from stem cell population. Considering clinical potentials of human ASCs for cell therapies, this also offers a possible strategy for improving their therapeutic qualities through antioxidants.

Fast Adipogenesis Tracking System (FATS)-a robust, high-throughput, automation-ready adipogenesis quantification technique.

Adipogenesis is essential in in vitro experimentation to assess differentiation capability of stem cells, and therefore, its accurate measurement is important. Quantitative analysis of adipogenic levels, however, is challenging and often susceptible to errors due to non-specific reading or manual estimation by observers. To this end, we developed a novel adipocyte quantification algorithm, named Fast Adipogenesis Tracking System (FATS), based on computer vision libraries. The FATS algorithm is versatile and capable of accurately detecting and quantifying percentage of cells undergoing adipogenic and browning differentiation even under difficult conditions such as the presence of large cell clumps or high cell densities. The algorithm was tested on various cell lines including 3T3-L1 cells, adipose-derived mesenchymal stem cells (ASCs), and induced pluripotent stem cell (iPSC)-derived cells. The FATS algorithm is particularly useful for adipogenic measurement of embryoid bodies derived from pluripotent stem cells and was capable of accurately distinguishing adipogenic cells from false-positive stains. We then demonstrate the effectiveness of the FATS algorithm for screening of nuclear receptor ligands that affect adipogenesis in the high-throughput manner. Together, the FATS offer a universal and automated image-based method to quantify adipocyte differentiation of different cell lines in both standard and high-throughput workflows.

High Neutrophil-to-Platelet Ratio Is Associated With Hemorrhagic Transformation in Patients With Acute Ischemic Stroke.

Background: Hemorrhagic transformation (HT) is a complication that may cause neurological deterioration in patients with acute ischemic stroke. Both neutrophil and platelet have been associated with the stroke progression. The aim of this study was to explore the relationship between neutrophil-to-platelet ratio (NPR) and HT after acute ischemic stroke. Methods: A total of 279 stroke patients with HT were consecutively recruited. HT was diagnosed using magnetic resonance imaging (MRI) or computed tomography (CT) and classified into hemorrhagic infarction (HI) and parenchymal hematoma (PH). Blood samples for neutrophil and platelet counts were obtained at admission. Meanwhile, 270 age- and gender-matched controls without HT were included for comparison. Results: Among the patients with HT, 131 patients had PH and 148 patients had HI. NPR was higher in patients with PH than those with HI or non-HT [36.8 (23.7-49.2) vs. 26.6 (17.9-38.3) vs. 19.1 (14.8-24.8), P < 0.001]. After adjustment for potential confounders, high NPR remained independently associated with the increased risk of HT (OR = 2.000, 95% CI: 1.041-3.843, P = 0.037). NPR (>39.9) was independently associated with PH (OR = 2.641, 95% CI: 1.308-5.342, P = 0.007). Conclusions: High NPR was associated with the increased risk of HT especially PH in patients with acute ischemic stroke.