Integrated 3D-PrintedMicrofluidic Device for Immunocaptureand Electrochemical Assessment of Transferrin Saturation in Point-of-Care Stroke Diagnostics

ZIP14 is a transmembrane metal ion transporter that is abundantly expressed in the liver, heart, and pancreas. Previous studies of HEK 293 cells and the hepatocyte cell lines AML12 and HepG2 established that ZIP14 mediates the uptake of non-transferrin-bound iron, a form of iron that appears in the plasma during pathologic iron overload. In this study we investigated the role of ZIP14 in the cellular assimilation of iron from transferrin, the circulating plasma protein that normally delivers iron to cells by receptor-mediated endocytosis. We also determined the subcellular localization of ZIP14 in HepG2 cells. We found that overexpression of ZIP14 in HEK 293T cells increased the assimilation of iron from transferrin without increasing levels of transferrin receptor 1 or the uptake of transferrin. To allow for highly specific and sensitive detection of endogenous ZIP14 in HepG2 cells, we used a targeted knock-in approach to generate a cell line expressing a FLAG-tagged ZIP14 allele. Confocal microscopic analysis of these cells detected ZIP14 at the plasma membrane and in endosomes containing internalized transferrin. HepG2 cells in which endogenous ZIP14 was suppressed by siRNA assimilated 50% less iron from transferrin compared with controls. The uptake of transferrin, however, was unaffected. We also found that ZIP14 can mediate the transport of iron at pH 6.5, the pH at which iron dissociates from transferrin within the endosome. These results suggest that endosomal ZIP14 participates in the cellular assimilation of iron from transferrin, thus identifying a potentially new role for ZIP14 in iron metabolism.

Risk factors for stroke-related pneumonia in patients with ischaemic stroke: A systematic evaluation and meta-analysis

Objective: This paper aimed to investigate the predictive values of left atrial appendage (LAA) function and carotid atherosclerotic plaques (CAPs) for ischemic stroke (IS) in patients with nonvalvular atrial fibrillation (NVAF). Methods: Data were retrospectively collected from 40 patients with NVAF complicated by IS (stroke group) and 160 patients with NVAF not complicated by IS (non-stroke group) during the same period. The basic data of the two groups were collected, CHA2DS2-VASc scoring was performed, and the diameter, depth, morphology, and function of the LAA (LAA peak) emptying velocity (LAA-PEV) and LAA peak filling velocity (LAA-PFV) were examined in the two groups using transesophageal echocardiography. The presence of CAPs was examined using transcranial Doppler ultrasonography. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for IS in patients with NVAF. Spearman's correlation analysis was performed to investigate the relationship between LAA-PEV, LAA-PFV, and CAPs and the occurrence of IS in patients with NVAF. Finally, receiver operating characteristic (ROC) curves and the Delong test were used to analyze the predictive value of LAA function (LAA-PEV, LAA-PFV) and CAPs alone or in combination for the occurrence of IS in patients with NVAF. Results: Univariate analysis revealed that age, CHA2DS2-VASc score, and CAP incidence were higher in the stroke group than in the non-stroke group, while a history of anticoagulant drug use, LAA-PEV, and LAA-PFV were lower in the stroke group than in the non-stroke group (p < 0.05). Logistic regression analysis revealed that a higher CHA2DS2-VASc score and the presence of CAPs were independent risk factors for the occurrence of IS in patients with NVAF (odds ratio (OR) >1, p < 0.05) and history of anticoagulant drug use as well as higher LAA-PEV and LAA-PFV were protective factors against IS in patients with NVAF (OR <1, p < 0.05). Correlation analysis revealed that LAA-PEV and LAA-PFV were negatively linked (r = –0.373, –0.361, p < 0.05). In contrast, CAPs were positively related to IS in patients with NVAF (r = 0.310, p < 0.05). The area under the ROC (AUC-ROC) curve of LAA-PEV, LAA-PFV, CAPs, and combined examination to predict the occurrence of IS in patients with NVAF were 0.769, 0.761, 0.694, and 0.890, respectively. The area under curve (AUC) of the combined assessment was greater than that of the individual examinations of LAA-PEV, LAA-PFV, and CAPs (p < 0.05). Conclusion: LAA function and CAPs are closely associated with the occurrence of IS in patients with NVAF, and their combined examination has good predictive value for the occurrence of IS in patients with NVAF.

Polymorphism of IL6 receptor gene is associated with ischaemic stroke in patients with metabolic syndrome

To determine the vascular ultrasound and contrast-enhanced ultrasound characteristics of ischaemic stroke in patients with Takayasu's arteritis (TAK) and explore the diagnostic value of ultrasound characteristics for diagnosing ischaemic stroke in such patients. We retrospectively analysed 80 patients with TAK who underwent vascular ultrasound and contrast-enhanced ultrasound on admission. We analysed the ultrasound characteristics of ischaemic stroke in these patients and performed multiple logistic regression analyses to determine the independent risk factors for ischaemic stroke in the patient cohort. The value of ultrasound characteristics in patients with TAK and ischaemic stroke was evaluated using the net reclassification and integrated discrimination improvement indices. Among 80 patients, 22 (27.5%) had ischaemic stroke. Fourteen patients had anterior circulation infarction, two had posterior circulation infarction, and six had both. Multivariate analysis showed that the number of occluded arteries (odds ratio (OR), 2.01; p=0.005), high-grade enhancement (grade ≥2, OR, 6.52; p=0.016), and revascularisation (OR, 0.05; p=0.002) were independent influencing factors for ischaemic stroke in patients with TAK. The area under the curve indicated that the number of occluded arteries (≥3) and high-grade enhancement (grade ≥2) can be used to identify patients with TAK at high risk for ischaemic stroke. A higher number of cervical artery occlusions and high-grade enhancement (grade ≥2) are independent risk factors for ischaemic stroke in patients with TAK. The combination of these factors can facilitate the diagnosis of ischaemic stroke in these patients.

Objective: Stroke is a major cause of morbidity and mortality worldwide resulting from either an ischemic insult or rupture of a blood vessel in the brain. It not only leads to significant physical disability but also imposes emotional and economic burdens on patients and their families. Assessing the lipid profile in stroke patients is crucial, especially in ischemic stroke, where dyslipidemia plays a key role in atherosclerosis development. Elevated low-density lipoprotein (LDL) and triglycerides (TG) are important modifiable risk factors, and managing these can reduce the incidence and recurrence of strokes. Comprehensive lipid management should be a core component of stroke prevention and treatment strategies. Methods: This was a cross-sectional study in which 80 adult stroke patients (40 ischemic and 40 hemorrhagic strokes) were included on the basis of a predefined inclusion and exclusion criteria. The diagnosis of stroke was made on the basis of imaging and neurological examination. A comprehensive medical history, physical measurements (including body mass index), and lipid profiles (total cholesterol [TC], LDL, High-density lipoprotein [HDL], and TG) were recorded for all participants. Blood samples were taken after overnight fasting to ensure accuracy. Statistical analysis using SPSS version 21.0 compared lipid levels between the groups. An unpaired t-test and Chi-square test were used, with significance defined as a p<0.05. Results: There was a significant difference in lipid profiles between ischemic and hemorrhagic stroke patients. Ischemic stroke patients had markedly higher levels of LDL with a mean of 129.84±36.54 mg/dL compared to 106.32±26.68 mg/dL in hemorrhagic stroke patients (p=0.0015). TC levels were also significantly elevated in ischemic stroke patients, averaging 236.22±56.26 mg/dL versus 196.48±46.24 mg/dL in hemorrhagic stroke patients (p=0.0009). Total TG were higher in ischemic stroke patients (158.54±44.68 mg/dL) compared to hemorrhagic stroke patients (128.62±39.16 mg/dL, p=0.0021). HDL levels were slightly lower in ischemic stroke patients (34.54±8.26 mg/dL) compared to hemorrhagic stroke patients (38.12±9.12 mg/dL), although this difference was not statistically significant (p=0.0696). Conclusion: There were significant differences in lipid profiles between ischemic and hemorrhagic stroke patients. Ischemic stroke patients had higher levels of LDL, TC, and TG, indicating a stronger association with dyslipidemia and atherosclerosis. These findings highlight the importance of aggressive lipid management in ischemic stroke patients to reduce recurrence risk and improve outcomes.

Objectives : To compare and see the differences between systolic (SBP) and diastolic (DBP) blood pressure in ischemic and hemorrhagic patients. Methods : We conducted research using case control method in ischemic and hemorrhagic stroke patients confirmed by brain ct scan and measured the blood pressure at the onset within 72 hours. Results : Systolic and diastolic blood pressure had been measured in 36 stroke patients, which is 25 patients diagnosed ischemic stroke (69.4%), whereas 11 patients diagnosed hemorrhagic stroke (30,6%). Mean SBP in ischemic stroke patients was 179.6 ± 26.22 mmHg with median was 180 (min-max: 130–240) mmHg compare with hemorrhagic stroke mean SBP was 201.81 ± 25.62 mmHg with median was 210 (160–240) mmHg (p value 0.029). Mean DBP in ischemic stroke patients was 116.8 ± 15.74 mmHg with median was 120 (90–160) mmHg versus mean DBP in hemorrhagic stroke 135.45 ± 28.06 mmHg with median was 130 (100–180) mmHg (p value 0.069). Conclusion : There is different statistically value systolic blood pressure between ischemic stroke and hemorrhagic patients. Whereas there is no statistically significant diastolic blood pressure between two groups.

Stroke is the third leading non-communicable cause of death worldwide, with a prevalence in Indonesia reaching 10.9% of cases per year. One of the causes of stroke is dyslipidemia, a condition characterized by abnormal lipid levels in the bloodstream, which poses a significant risk factor for cardiovascular diseases. This study aims to compare total cholesterol, triglycerides, LDL, and HDL levels in patients with hemorrhagic and ischemic stroke at Sultan Imanuddin Regional General Hospital, Pangkalan Bun, using a quantitative analytical research design with a cross-sectional approach. Data were collected using purposive sampling from secondary data in the form of medical records of hemorrhagic and ischemic stroke patients at Sultan Imanuddin Regional General Hospital, Kotawaringin Barat, Pangkalan Bun, for the period of January–December 2023. Homogeneity testing was conducted using the Levene test, while data normality was assessed using the Kolmogorov-Smirnov method. Data analysis was performed using a non-parametric statistical test, specifically the Mann-Whitney test. The study results showed that the mean levels of total cholesterol, triglycerides, LDL, and HDL were 198±48, 130±69, 129±45, and 41±15 mg/dL in ischemic stroke patients, and 189±60, 105±55, 119±54, and 47±13 mg/dL in hemorrhagic stroke patients. The results of the Mann-Whitney test showed a significant difference in lipid profile levels in patients with ischemic stroke and hemorrhagic stroke. The results of the binary logistic regression test showed that in LDL and HDL levels there was a significant difference in ischemic and hemorrhagic stroke patients, while there was no difference between total cholesterol and triglyceride levels in ischemic and hemorrhagic stroke patients. In conclusion, lipid profile levels play an important role in distinguishing between hemorrhagic and ischemic stroke and can serve as an indicator for stroke risk assessment

Lipoprotein(a) [Lp(a)] is a well-established risk factor for ischaemic stroke (IS). It is unclear whether Lp(a) is associated with IS in patients with atrial fibrillation (AF). The aim of this study is to explore the association between the concentration of Lp(a) and the risk of IS in AF patients, hope to find the potential risk factor for the IS in AF patients. This study is a retrospective cohort study. The screened AF patients between January 2017 and July 2021 were matched at 1:1 by the propensity score matching (PSM) method in the Second Affiliated Hospital of Nanchang University. Associations between Lp(a) and ischaemic stroke were analysed using logistic regression models, stratified analysis and sensitivity analysis. Statistical analyses were conducted using IBM SPSS software. The number of enrolled participates is 2258, which contains 1129 non-AF patients and 1129 AF patients. Among IS patients, the median Lp(a) concentration was higher than that of controls (17.03 vs. 15.36 mg/dL, P = 0.032). The Spearman rank-order correlation coefficients revealed significant positive relationships between IS and Lp(a) (P = 0.032). In addition, a significant increase in IS risk was associated with Lp(a) levels >30.00 mg/dL in unadjusted model [OR:1.263, 95% CI(1.046-1.523), P = 0.015], model 1 [OR:1.284, 95% CI(1.062,1.552), P = 0.010], model 2 [OR: 1.297, 95% CI(1.07,1.573). P = 0.008], and model 3 [OR: 1.290, 95% CI (1.064, 1.562). P = 0.009]. The stratified analysis indicated that this correlation was not affected by female sex [1.484 (1.117, 1.972), P = 0.006], age ≤ 60 [1.864 (1.067-3.254), P=0.029], hypertension [1.359 (1.074, 1.721), P = 0.011], or non-coronary heart disease (CHD) [1.388 (1.108, 1.738), P = 0.004]. High levels of Lp(a) were significantly related to IS in AF patients and may be a potential risk factor in the onset of an IS in AF patients.

Introduction: Serum cystatin C has emerged as a risk factor of cardiovascular disease and death. Cystatin C is promoted a better marker of renal function compared to estimated glomerular filtration rate (GFR). However, the impact of cystatin C on the functional outcome after ischemic stroke in patients with CKD remains unclear. Hypothesis: We assessed the prognostic value of cystatin C for functional outcome after ischemic stroke in CKD patients. Methods: A consecutive 239 patients with CKD who were admitted within 7 days after ischemic stroke onset between January 2010 and February 2014 were included for analysis. An estimated GFR < 60mL/min/1.73 m 2 defined CKD. We compared the demographic information, clinical characteristics and laboratory findings including serum cystatin C level. We evaluated the short-term outcomes using a modified Rankin Scale (mRS) at three-months after onset of ischemic stroke. We divided patients into two groups with favorable outcome (mRS score ≤2) and unfavorable outcome (mRS score ≥3). Results: Among the total patients, 36.0% (n=86) patients had unfavorable outcome. These patients were mostly male (52.9%), with a mean age of 73.5 years. Older age, atrial fibrillation and history of previous stroke were significantly higher in the unfavorable outcome group. Participants with unfavorable outcome tended to have lower body mass index, higher initial NIHSS, lower estimated GFR, and higher C-reactive protein concentration. Compared to the favorable outcome group, cystatin C level was significantly higher (1.25±0.41 vs. 1.54±0.64 mg/dL, P = 0.001) in the unfavorable outcome group. After controlling for confounding factors, higher cystatin C levels were independently related to the unfavorable outcome at three-months (Odds ratio, 3.19; 95% Confidence interval, 1.02-9.96). In contrast, estimated GFR did not show any significant association with the unfavorable outcome (Odds ratio, 1.01; 95% Confidence interval, 0.96-1.06). Conclusions: In conclusion, our study showed that elevated cystatin C levels were independently associated with the unfavorable functional outcome after ischemic stroke in patients with CKD. Cystatin C may be a potent predictor of short-term functional outcome after ischemic stroke in CKD patients.

Risk of ischemic stroke after new-onset atrial fibrillation in patients with hyperthyroidism

Introduction: Guidelines recommend against use of Intravenous tissue Plasminogen Activator (IV tPA) in acute ischemic stroke (IS) patients with prior IS within past 3 months. However, there are limited data on the safety of IV tPA in this population. Methods: Using American Heart Association Get With the Guideline-Stroke between February 2009 and December 2015 we identified 1399 acute IS patients otherwise eligible for IV tPA but with IS within prior 3 months. Of these, 293 were treated with IV tPA. We compared them with 30,655 acute IS patients treated with IV tPA but with no prior IS history. Multivariable logistic regression models were used to evaluate association between recent prior IS (within 90 days, 1-14 days, 15-30 days, 31-90 days) with symptomatic intracranial hemorrhage (sICH) and discharge outcomes after IV tPA. Results: Age (median 80, IQR 74-87) and stroke severity as measured by NIHSS (median 11, IQR 6-18) were similar for acute IS patients treated with IV tPA with or without recent IS. However, patients with recent IS were more likely to have higher prevalence of cardiovascular risk factors. In unadjusted analysis, patients with recent IS within prior 90 days were more likely to experience sICH and in-hospital mortality and less likely to have good functional outcomes (modified Rankin Scale score, 0-1) than those with no history of IS (Table 1). On multivariate analysis, risk for sICH and in-hospital mortality was not significantly different but good functional outcomes at discharge occurred less often among patients with history of IS within prior 90 days. In a prespecified subgroup analysis, the increased risk for sICH appeared to concentrate in those with recent IS within 14 days of the acute index IS but not in later time window. Conclusions: Recent IS within 90 days is associated with increased risk of worse outcomes in acute IS patients treated with tPA. In our study, the risk of sICH after tPA was highest among those with a history of prior IS within the past 14 days.

Patients with hyperhomocysteinemia (HHcy) have a higher risk of developing ischemic stroke (IS). The association between MTRR A66G polymorphism and promoter methylation with IS in patients with HHcy is also uncertain. The present study aimed to investigate the association between the MTRR polymorphism and methylation with IS in HHcy patients. This case-control study included a total of 304 HHcy patients (95 with IS and 209 without IS). Multivariate logistic regression analyses were applied to explore the association between MTRR polymorphism and classical atherothrombotic risk factors with the risk of IS. The log-additive and dominant models were markedly different in participants with IS compared to the control group (p = 0.031 and 0.016, respectively). The log-additive and dominant showed a significant association with IS in the low level plasma homocysteine groups (p = 0.024 and 0.014, respectively). No significant difference of methylation between IS and without IS group (p > 0.05). Patients with high plasma homocysteine had a 4.041-4.941 fold higher risk of IS (p = 0.01, 0.016 and 0.041, respectively) compared to the low plasma homocysteine group. Age, diabetes, hypertension and plasma homocysteine were the risk factors for IS in patients with HHcy (p = 0.033, 0.000, 0.001 and 0.038, respectively). MTRR A66G polymorphism and an elevated plasma plasma homocysteine level were significantly associated with an increased risk of IS in patients with HHcy. Age, diabetes, hypertension and Hcy were all found to be associated with IS.

Evaluation of MTHFR C677T polymorphism in ischemic and hemorrhagic stroke patients. A case–control study in a Northern Indian population

Can cerebral microbleeds predict stroke recurrence?