1.Thrombectomy in Stroke Patients With Low Alberta Stroke Program Early Computed Tomography Score: Is Modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3 Superior to mTICI 2b?
Sameh Samir ELAWADY ; Brian Fabian SAWAY ; Hidetoshi MATSUKAWA ; Kazutaka UCHIDA ; Steven LIN ; Ilko MAIER ; Pascal JABBOUR ; Joon-Tae KIM ; Stacey Quintero WOLFE ; Ansaar RAI ; Robert M. STARKE ; Marios-Nikos PSYCHOGIOS ; Edgar A SAMANIEGO ; Adam ARTHUR ; Shinichi YOSHIMURA ; Hugo CUELLAR ; Jonathan A. GROSSBERG ; Ali ALAWIEH ; Daniele G. ROMANO ; Omar TANWEER ; Justin MASCITELLI ; Isabel FRAGATA ; Adam POLIFKA ; Joshua OSBUN ; Roberto CROSA ; Charles MATOUK ; Min S. PARK ; Michael R. LEVITT ; Waleed BRINJIKJI ; Mark MOSS ; Travis DUMONT ; Richard WILLIAMSON JR. ; Pedro NAVIA ; Peter KAN ; Reade De LEACY ; Shakeel CHOWDHRY ; Mohamad EZZELDIN ; Alejandro M. SPIOTTA ; Sami Al KASAB ;
Journal of Stroke 2024;26(1):95-103
Background:
and Purpose Outcomes following mechanical thrombectomy (MT) are strongly correlated with successful recanalization, traditionally defined as modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b. This retrospective cohort study aimed to compare the outcomes of patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS; 2–5) who achieved mTICI 2b versus those who achieved mTICI 2c/3 after MT.
Methods:
This study utilized data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combined databases from 32 thrombectomy-capable stroke centers between 2013 and 2023. The study included only patients with low ASPECTS who achieved mTICI 2b, 2c, or 3 after MT for internal carotid artery or middle cerebral artery (M1) stroke.
Results:
Of the 10,229 patients who underwent MT, 234 met the inclusion criteria. Of those, 98 (41.9%) achieved mTICI 2b, and 136 (58.1%) achieved mTICI 2c/3. There were no significant differences in baseline characteristics between the two groups. The 90-day favorable outcome (modified Rankin Scale score: 0–3) was significantly better in the mTICI 2c/3 group than in the mTICI 2b group (adjusted odds ratio 2.35; 95% confidence interval [CI] 1.18–4.81; P=0.02). Binomial logistic regression revealed that achieving mTICI 2c/3 was significantly associated with higher odds of a favorable 90-day outcome (odds ratio 2.14; 95% CI 1.07–4.41; P=0.04).
Conclusion
In patients with low ASPECTS, achieving an mTICI 2c/3 score after MT is associated with a more favorable 90-day outcome. These findings suggest that mTICI 2c/3 is a better target for MT than mTICI 2b in patients with low ASPECTS.
2.Obesity and hypertriglyceridemia: high risks for disease severity and mortality in COVID-19 patients.
Su-Jie NI ; Jian-Lin GAO ; Steven S SHEN
Acta Physiologica Sinica 2022;74(5):783-791
As COVID-19 pandemic approaching its third year, more data have shown that obesity and hypertriglyceridemia are the high-risk factors for the major complications such as acute respiratory distress syndrome, thromboembolism, coagulopathy and cytokine storm, which are responsible for the majority of disease severity and mortality. In this review article, we have analyzed the public available clinical reports and laboratory research results of the COVID-19 studies by researchers and clinicians of many nations around the world. Many of these reports covered COVID-19 patients of different ethnic groups. We suggested that obesity and high triglycerides are high risks for severe COVID-19 and death. We also summarized the possible underlying molecular mechanism likely connecting the severe COVID-19 with obesity and hypertriglyceridemia. From public health perspective, we highlight the importance of the healthy diet and lifestyle in fighting against SARS-CoV-2 virus in long period of time.
Humans
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COVID-19
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Pandemics
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SARS-CoV-2
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Hypertriglyceridemia
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Obesity
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Severity of Illness Index
3.18FMAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models.
Tuo SHAO ; Zhen CHEN ; Jian RONG ; Vasily BELOV ; Jiahui CHEN ; Andre JEYARAJAN ; Xiaoyun DENG ; Hualong FU ; Qingzhen YU ; Steve H RWEMA ; Wenyu LIN ; Mikhail PAPISOV ; Lee JOSEPHSON ; Raymond T CHUNG ; Steven H LIANG
Acta Pharmaceutica Sinica B 2022;12(1):308-315
Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an 18F-labeled MAGL inhibitor ([18F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [18F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [18F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [18F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [18F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [18F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.
4.Heart Rate Variability and Its Ability to Detect Worsening Suicidality in Adolescents: A Pilot Trial of Wearable Technology
David C. SHERIDAN ; Steven BAKER ; Ryan DEHART ; Amber LIN ; Matthew HANSEN ; Larisa G. TERESHCHENKO ; Nancy LE ; Craig D. NEWGARD ; Bonnie NAGEL
Psychiatry Investigation 2021;18(10):928-935
Objective:
Suicide is the 2nd leading cause of death in adolescence, and acute pediatric mental health emergency department (ED) visits have doubled in the past decade. The objective of this study was to evaluate physiologic parameters relationship to suicide severity.
Methods:
This was a prospective, observational study from April 2018 thru November 2019 in a tertiary care pediatric emergency department (ED) and inpatient pediatric psychiatric unit enrolling acutely suicidal adolescent patients. Patients wore a wrist device that used photoplethysmography for 7 days during their acute hospitalization to measure heart rate variability (HRV). During that time, Columbia Suicide Severity Scores (CSSRS) were assessed at 3 time points.
Results:
There was complete device data and follow-up for 51 patients. There was an increase in the high frequency (HF) component of HRV in patients that had a 25% or greater decrease in their CSSRS (mean difference 11.89 ms/ Hz ; p-value 0.005). Patients with a CSSRS≥15 on day of enrollment had a lower, although not statistically significant, HF component (mean difference -8.34 ms/ Hz; p-value 0.071).
Conclusion
We found an inverse correlation between parasympathetic activity measured through the HF component and suicidality in an acutely suicidal population of adolescents. Wearable technology may have the ability to improve outpatient monitoring for earlier detection and intervention.
5.Singapore's efforts to achieve measles elimination in 2018
Wanhan See ; Yi Kai Ng ; Lin Cui ; Yuske Kita ; Steven Peng-Lim Ooi ; Vernon Lee ; Derrick Mok Kwee Heng ; Raymond Tzer Pin Lin
Western Pacific Surveillance and Response 2021;12(3):05-16
The World Health Organization verified that Singapore had eliminated endemic transmission of measles in October 2018. This report summarizes the evidence presented to the Regional Verification Commission for Measles and Rubella Elimination, comprising information about immunization schedules; laboratory testing protocols and the surveillance system; and data on immunization coverage and the epidemiology of cases. Between 2015 and 2017, a total of 246 laboratory confirmed cases of measles were reported. The source or country of infection was unknown for most cases (195; 79.3%). There were 22 clusters, ranging from two to five cases. The most common genotypes detected were D8 and D9. Transmission of B3 was interrupted in 2017, and H1 cases were sporadic and imported. Phylogenetic analyses of the D8 isolates showed the existence of 13 lineages or clusters. Although a few lineages were circulating concurrently, no lineage propagated continuously for a prolonged period, and transmission of each lineage eventually stopped. Although cases and clusters were reported yearly, molecular data showed that none of the lineages resulted in prolonged transmission. There were fewer measles cases in 2017 compared with 2016. The higher number of clusters was likely due to the overall increase in cases because cluster sizes remained small. The occurrence of small clusters is not unexpected since measles is highly infectious. The majority of imported cases did not result in secondary transmission. With the global increase in the number of measles cases, Singapore needs to stay vigilant and continue to promptly test suspected cases; vaccination is the key to preventing infection.
6.Heart Rate Variability Analysis: How Much Artifact Can We Remove?
David C. SHERIDAN ; Ryan DEHART ; Amber LIN ; Michael SABBAJ ; Steven D. BAKER
Psychiatry Investigation 2020;17(9):960-965
Objective:
Heart rate variability (HRV) evaluates small beat-to-beat time interval (BBI) differences produced by the heart and suggested as a marker of the autonomic nervous system. Artifact produced by movement with wrist worn devices can significantly impact the validity of HRV analysis. The objective of this study was to determine the impact of small errors in BBI selection on HRV analysis and produce a foundation for future research in mental health wearable technology.
Methods:
This was a sub-analysis from a prospective observational clinical trial registered with clinicaltrials.gov (NCT03030924). A cohort of 10 subject’s HRV tracings from a wearable wrist monitor without any artifact were manipulated by the study team to represent the most common forms of artifact encountered.
Results:
Root mean square of successive differences stayed below a clinically significant change when up to 5 beats were selected at the wrong time interval and up to 36% of BBIs was removed. Standard deviation of next normal intervals stayed below a clinically significant change when up to 3 beats were selected at the wrong time interval and up to 36% of BBIs were removed. High frequency HRV shows significant changes when more than 2 beats were selected at the wrong time interval and any BBIs were removed.
Conclusion
Time domain HRV metrics appear to be more robust to artifact compared to frequency domains. Investigators examining wearable technology for mental health should be aware of these values for future analysis of HRV studies to improve data quality.
7.Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome
Christopher M DUSSIK ; Maryam HOCKLEY ; Aleksandra GROZIĆ ; Ichiro KANEKO ; Lin ZHANG ; Marya S SABIR ; Jin PARK ; Jie WANG ; Cheryl A NICKERSON ; Steven H YALE ; Christopher J RALL ; Amy E FOXX-ORENSTEIN ; Connie M BORROR ; Todd R SANDRIN ; Peter W JURUTKA
Journal of Neurogastroenterology and Motility 2018;24(1):96-106
BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifaceted disorder that afflicts millions of individuals worldwide. IBS is currently diagnosed based on the presence/duration of symptoms and systematic exclusion of other conditions. A more direct manner to identify IBS is needed to reduce healthcare costs and the time required for accurate diagnosis. The overarching objective of this work is to identify gene expression-based biological signatures and biomarkers of IBS. METHODS: Gene transcripts from 24 tissue biopsy samples were hybridized to microarrays for gene expression profiling. A combination of multiple statistical analyses was utilized to narrow the raw microarray data to the top 200 differentially expressed genes between IBS versus control subjects. In addition, quantitative polymerase chain reaction was employed for validation of the DNA microarray data. Gene ontology/pathway enrichment analysis was performed to investigate gene expression patterns in biochemical pathways. Finally, since vitamin D has been shown to modulate serotonin production in some models, the relationship between serum vitamin D and IBS was investigated via 25-hydroxyvitamin D (25[OH]D) chemiluminescence immunoassay. RESULTS: A total of 858 genetic features were identified with differential expression levels between IBS and asymptomatic populations. Gene ontology enrichment analysis revealed the serotonergic pathway as most prevalent among the differentially expressed genes. Further analysis via real-time polymerase chain reaction suggested that IBS patient-derived RNA exhibited lower levels of tryptophan hydroxylase-1 expression, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis. Finally, mean values for 25(OH)D were lower in IBS patients relative to non-IBS controls. CONCLUSIONS: Values for serum 25(OH)D concentrations exhibited a trend towards lower vitamin D levels within the IBS cohort. In addition, the expression of select IBS genetic biomarkers, including tryptophan hydroxylase 1, was modulated by vitamin D. Strikingly, the direction of gene regulation elicited by vitamin D in colonic cells is “opposite” to the gene expression profile observed in IBS patients, suggesting that vitamin D may help “reverse” the pathological direction of biomarker gene expression in IBS. Thus, our results intimate that IBS pathogenesis and pathophysiology may involve dysregulated serotonin production and/or vitamin D insufficiency.
Biomarkers
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Biopsy
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Cohort Studies
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Colon
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Diagnosis
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Gene Expression Profiling
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Gene Expression
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Gene Ontology
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Health Care Costs
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Humans
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Immunoassay
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Irritable Bowel Syndrome
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Luminescence
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Oligonucleotide Array Sequence Analysis
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Polymerase Chain Reaction
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Real-Time Polymerase Chain Reaction
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RNA
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Serotonin
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Transcriptome
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Tryptophan
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Tryptophan Hydroxylase
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Vitamin D
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Vitamins
8.Biomonitoring for traditional herbal medicinal products using DNA metabarcoding and single molecule, real-time sequencing.
Tianyi XIN ; Zhichao XU ; Jing JIA ; Christine LEON ; Songnian HU ; Yulin LIN ; Subramanyam RAGUPATHY ; Jingyuan SONG ; Steven G NEWMASTER
Acta Pharmaceutica Sinica B 2018;8(3):488-497
Global concerns have been paid to the potential hazard of traditional herbal medicinal products (THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, real-time (SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan (JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing (CCS) reads belonging to the ITS2 and regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs.
9.Protective effects of traditional Tibetan medicine Zuo-Mu-A Decoction () on the blood parameters and myocardium of high altitude polycythemia model rats.
Meng-Qian LU ; Nyima TSRING ; Tian-Yuan YU ; Jian-Cong WU ; Steven WONG ; Guo-Yong CHEN ; Pasang DEKYI ; Fan PAN ; Si-Tong XIAN ; Dorje RINCHEN ; Ying-Qiu MAO ; Lin-Feng ZHANG ; Bin-Bin YAO
Chinese journal of integrative medicine 2017;23(12):908-915
OBJECTIVETo explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats.
METHODSForty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy.
RESULTSCompared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group.
CONCLUSIONZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.
10.Effect of Functional Status on the Quality of Bowel Preparation in Elderly Patients Undergoing Screening and Surveillance Colonoscopy.
Akash KUMAR ; Lisa LIN ; Oren BERNHEIM ; Emilia BAGIELLA ; Lina JANDORF ; Steven H ITZKOWITZ ; Brijen J SHAH
Gut and Liver 2016;10(4):569-573
BACKGROUND/AIMS: Optimal bowel preparation is essential for successful screening or for surveillance colonoscopy (SC). Inadequate bowel preparation is associated with older age, the male gender, and the presence of certain comorbidities. However, the association between patients' functional status and bowel preparation quality has not been studied. We prospectively examined the relationship between functional status, namely, the ability to perform activities of daily living (ADLs) and ambulate, and the quality of bowel preparation in elderly patients undergoing SC. METHODS: Before undergoing SC, 88 elderly patients were surveyed regarding their functional status, specifically regarding their ability to perform ADLs and ambulate a quarter of a mile. Gastroenterologists then determined the quality of the bowel preparation, which was classified as either adequate or inadequate. Then, the frequency of inadequate bowel preparation in patients who did or did not experience difficulty performing ADLs and ambulating was calculated. RESULTS: Difficulty ambulating (unadjusted odds ratio [OR], 4.83; p<0.001), difficulty performing ADLs (OR, 2.93; p=0.001), and history of diabetes (OR, 2.88; p=0.007) were significant univariate predictors of inadequate bowel preparation. After adjusting for the above variables, only difficulty ambulating (adjusted OR, 5.78; p=0.004) was an independent predictor of inadequate bowel preparation. CONCLUSIONS: Difficulty with ambulation is a strong predictor of inadequate bowel preparation in elderly patients undergoing SC.
Activities of Daily Living
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Aged*
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Colonoscopy*
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Comorbidity
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Humans
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Male
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Mass Screening*
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Odds Ratio
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Prospective Studies
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Walking


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