Comparison of Quantitative and Qualitative Oxygen Extraction Fraction (OEF) in Acute Stroke Patients with Large Vessel Occlusion.

The superficial temporal artery-middle cerebral artery bypass (STA-MCA) bypass surgery developed by Donaghy and Yarsagil in 1967 provided relief for patients with acute stroke and large vessel occlusive vascular disease. Early reports showed low morbidity and good outcomes. However, a large clinical trial in 1985 reported a failure of extracranial-intracranial (EC/IC) bypass to show benefit in reducing the risk of stroke compared to best medical treatment. Problems with the study included cross overs to surgery from best medical treatment, patients unwilling to be randomized and chose EC/IC surgery, and loss of patients to follow-up. Most egregious is the fact that the study did not attempt to identify and select the patients at high risk for a second stroke. Based on these shortcomings of the EC/IC bypass study, a carotid occlusion surgery study (COSS) was proposed by Dr. William Powers and colleagues using qualitative hemispheric oxygen extraction fraction (OEF) by positron emission tomography (PET) between the contralateral and ipsilateral hemispheres with a ratio of 1.16 indicative of hemodynamic compromise. To increase patient enrollment, several compromises were made mid study. First. The ratio threshold was lowered to 1.12 and the level of occlusion in the carotid reduced from 70% to 60%. Despite these compromises the study was closed for futility, apparently because the stroke rate in the medically treated group was too low. Thus, the question as to the benefit of EC/IC bypass surgery remains unresolved. In our NIH funded study Quantitative Occlusive Vascular Disease Study (QUOVADIS), we used quantitative OEF to evaluate stroke risk and compared it to the qualitative count-rate ratio method used in the COSS study and found that these two methods did not identify the same patients at increased risk for stroke, which may explain the reason for the failure of the COSS study as our results show that qualitative OEF ratios do not identify the same patients as quantitative OEF.

Prop-2-ynyl 3-meth-oxy-4-(prop-2-yn-yloxy)benzoate.

The title compound, C14H12O4, comprises of two crystallographically independent mol-ecules in the asymmetric unit, linked via C-H⋯O inter-actions to form dimeric entities. The allylic groups are twisted out of the phenyl planes with dihedral angles varying between 7.92 (13) and 25.42 (8)°. In the crystal, the packing follows a zigzag pattern along the c-axis direction. The absolute configuration of the sample could not be determined reliably.

COVID-19 Vaccination Rates and Predictors of Uptake Among Adults With Coronary Heart Disease: Insight From the 2022 National Health Interview Survey.

INTRODUCTION: COVID-19 has become a burden to all nations across the globe, and vaccination currently remains the most effective means of fighting the SARS-COV-2 pandemic. From the time of approval and subsequent distribution of the various COVID-19 vaccines, nearly 72.3% (5.5 billion) of the globe's population have been vaccinated, leaving slightly more than a quarter of the globe's population at risk. With the approval and availability of booster vaccine dosages to individuals with chronic conditions, including coronary heart disease (CHD), it is vital to comprehend the factors underlying the uptake of COVID-19 vaccination in such subgroups. Further, the American Heart Association recommends vaccination against COVID-19 in populations with coronary heart disease (CHD). This is because they are more likely to experience severe outcomes due to COVID-19 infection. This study assesses the uptake of COVID-19 vaccines as well as predictors of its uptake. METHODS: Using the 2022 survey data from the National Health Interview Survey (NHIS), 1,708 adults ≥ 40 years with CHD who responded yes/no to whether they had received the vaccine were identified. A Pearson's chi-square test was used to ascertain differences among those who had received the vaccine and those who had not. A logistic regression (multivariate regression) was used to evaluate predictors of COVID-19 vaccination. RESULTS: About 1,491/1,708 (86.8%) adults ≥ 40 years reported being vaccinated against COVID-19. Among them, 1,065/1,491 (68.4%) had received more than two vaccination doses. The predictors of COVID-19 vaccination were older age (odds ratio (OR): 2.01 (95% confidence interval (CI): 1.40-2.89), p < 0.001), ratio of family income to poverty threshold of 1 and above (OR: 2.40 (95% CI: 1.58-3.64), p < 0.001), having a college degree (OR: 3.09 (95% CI: 1.85-5.14), p < 0.001), and being insured (OR: 3.26 (95% CI: 1.03-10.26), p = 0.044). CONCLUSION: The findings of the study have indicated that 68.4% of adults 40 years and above with CHD have been vaccinated against COVID-19 and have received more than two doses of vaccines. More than half have followed recommendations and have received booster doses of the vaccine. Old age (above 40 years) and a higher socioeconomic class are associated with being more likely to follow COVID-19 vaccination guidelines. Despite the higher vaccination rate of 68.4% in the adults with heart diseases group, strategies for improving booster vaccine awareness alongside accessibility are needed to enhance additional dosage uptake, protect them against novel COVID-19 variants, and ensure the development of sustained immunity.

Evaluation of the Influence of thiosemicarbazone-triazole hybrids on genes implicated in lipid oxidation and accumulation as potential anti-obesity agents.

A series of thiosemicarbazone-triazole hybrids 1a-h are efficiently synthesised and evaluated for their influence on the expression of genes, cpt-1, acc-1 and pgc-1, which are essential in lipid metabolism. The test results show that hybrids 1c and 1g exhibited relatively high influence on the expression of cpt-1 and pgc-1 and suppression of acc-1 as desired.

2-[(3-Oxo-1-benzofuran-6-yl)-oxy]aceto-nitrile.

The mol-ecule of the title compound, C11H8O3, is essentially planar [r.m.s. deviation = 0.025 (2) Å]. In the crystal, mol-ecules are stacked along [110] but no short π-π contacts are observed. Weak C-H⋯O inter-actions link the mol-ecules into chains along [101].

Temporal Patterns of Diabetes in Pregnancy: Analyzing Pregestational and Gestational Diabetes Mellitus Among Women Aged 15-44 Years Using the United States Diabetes Surveillance System (USDDS) Database.

BACKGROUND: Diabetes in pregnancy, including pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM), is a significant global health concern. Understanding its temporal patterns is crucial for effective healthcare planning and intervention strategies. METHODS: This retrospective observational study utilized data from the United States Diabetes Surveillance System (USDDS) spanning 2000 to 2019. We conducted a comprehensive analysis of temporal trends in PGDM and GDM prevalence among people aged 15-44 years. Additionally, age and race-based subgroup analyses were performed to identify variations in diabetes patterns. RESULTS: Over the two-decade study period, PGDM and GDM exhibited distinct temporal patterns. PGDM prevalence remained stable initially (1.1% per 100 deliveries) but gradually increased to 1.6% by 2019. In contrast, GDM prevalence showed a consistent rise, reaching 9.6% per 100 deliveries by 2019. Age-specific analysis revealed higher prevalence rates in older age groups, peaking at 40-44 years. Race-based analyses unveiled significant disparities, with Asians having the highest GDM rates and Black individuals having the highest PGDM rates. CONCLUSION: The prevalence of diabetes in pregnancy in the United States has increased significantly from 2000 to 2019, emphasizing the need for continued surveillance and tailored interventions. Age and race-specific disparities highlight the importance of the growing impact of diabetes in pregnancy on maternal and fetal health.

Epidemiology of Current Asthma in Children Under 18: A Two-Decade Overview Using National Center for Health Statistics (NCHS) Data.

OBJECTIVE:  This study conducted a comprehensive two-decade analysis of current asthma among children under 18 in the United States using National Center for Health Statistics (NCHS) data. The primary objective was to assess the prevalence of current asthma, evaluate temporal trends, and identify disparities based on gender, age, insurance status, household poverty levels, and race/ethnicity. METHODS:  Data spanning 2003-2019 from NCHS were analyzed, focusing on current asthma prevalence among children under 18. Age-adjusted prevalence rates were calculated and stratified by various factors, including gender, age groups, health insurance status, poverty levels, and race/ethnicity. RESULTS:  The study revealed substantial disparities in current asthma prevalence. Over the two-decade period, the overall prevalence of current asthma fluctuated. It increased from 2003 (8.5%) to 2009 (9.6%) and then decreased by 2019 (7.0%). Gender disparities were evident, with males (9.9%) consistently reporting a higher prevalence than females (7.5%). Older children aged between 10-17 years (10.4%) consistently had a higher prevalence of asthma than younger children aged 0-4 (5.3%) and 5-9 years (9.5%). Children with Medicaid insurance (11.2%) had the highest prevalence, followed by insured (8.9%), privately insured (7.7%), and uninsured children (6.1%). Children living below the federal poverty level (FPL) consistently reported the highest prevalence (11.3%), while children above 400% of the FPL (7.1%) had the lowest prevalence. Racial disparities were observed, with Black children (14.3%) having higher asthma prevalence, followed by White (7.6%) and Asian children (5.4%). CONCLUSION: The study highlights significant disparities in current asthma prevalence over the two-decade period analyzed. While the overall prevalence showed fluctuations, it generally increased from 2003 to 2009 and then decreased by 2019. Gender disparities were evident, with males consistently reporting a higher prevalence compared to females. Older children in the 10-17 age group consistently had a higher asthma prevalence than younger age groups. Moreover, disparities based on insurance status and income levels were also apparent, with children on Medicaid and those living below the FPL reporting higher asthma prevalence. Racial disparities were observed, with Black children having the highest prevalence, followed by White and Asian children. These findings emphasize the importance of addressing these disparities and tailoring interventions to improve asthma management and prevention across different demographic groups.

2-(2-Hy-droxy-propan-2-yl)-6-(prop-2-yn-yloxy)-1-benzofuran-3(2H)-one.

In the title compound, C14H14O4, the prop-2-yn-yloxy O-C-C C plane [maximum deviation = 0.0116 (12) Å] forms a dihedral angle of 78.44 (9)° with the benzofuran-3(2H)-one ring system. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming a tape along the a-axis direction. C-H⋯O inter-actions are observed between the tapes.

N-[4-(2-Propyn-1-yl-oxy)phen-yl]acetamide.

The title compound, C(11)H(11)NO(2), was synthesized by chemoselective N-acetyl-ation of 4-amino-phenol followed by reaction with propargyl bromide in the presence of K(2)CO(3). the acetamide and propyn-1-yloxy substituents form dihedral angles of 18.31 (6) and 7.01 (10)°, respectively, with the benzene ring. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into chains along [010]. C-H⋯O and C-H⋯π inter-actions also occur.

S-Phenyl benzothio-ate.

In the title compound, C(13)H(10)OS, the phenyl rings are inclined to one another by 51.12 (8)°. There is a short C-H⋯S contact in the molecule.In the crystal, molecules are linked via C-H⋯O hydrogen bonds forming chains along the a axis. Molecules are also linked by C-H⋯π and weak π-π interactions [centroid-centroid distance = 3.9543 (10) Å].

Diagnosis of ventriculoperitoneal shunt infection using [F-18]-FDG PET: a case report.

Infection of cerebrospinal fluid (CSF) shunts is a common occurrence and can often be difficult to diagnose using standard analysis of shunt fluid. This article presents the first case report on the diagnosis of a CSF shunt infection on FDG PET scan. A 26-year-old female underwent ventriculoperitoneal shunt placement after developing a pseudomeningocele subsequent to a suboccipital craniectomy for Chiari malformation. Two months later, the patient presented with abdominal pain and non-specific symptoms and was found to have a perisplenic abscess for which she was adequately treated. Failure of her symptoms to solve and an initial negative shunt CSF analysis prompted the search for other sources of infection. An FDG PET scan performed a week later found evidence of increase tracer uptake around the distal tip of the catheter and a repeat shunt CSF analysis showed evidence of CSF infection. FDG PET may be useful in diagnosing shunt related infections in case of high clinical suspicion when standard diagnostic modalities fail to diagnose hardware infection.

In vivo mapping of local cerebral blood flow by xenon-enhanced computed tomography.

A noninvasive technique has been developed to measure and display local cerebral blood flow (LCBF) in vivo. In this procedure, nonradioactive xenon gas is inhaled and the temporal changes in radiographic enhancement produced by the inhalation are measured by sequential computerized tomography. The time-dependent xenon concentrations in various anatomical units in the brain are used to derive both the local partition coefficient and the LCBF. Functional mapping of blood flow with excellent anatomical specificity has been obtained in the baboon brain. The response of LCBF to stimuli such as changes in carbon dioxide concentrations as well as the variability in LCBF in normal and diseased tissue can be easily demonstrated. This method is applicable to the study of human physiology and pathologic blood flow alterations.

Pretreatment ipsilateral regional cortical blood flow influences vessel recanalization in intra-arterial thrombolysis for MCA occlusion.

BACKGROUND AND PURPOSE: The aim of acute stroke interventions is to achieve recanalization of the target occluded artery. We sought to determine whether pretreatment cortical cerebral blood flow (CBF) was associated with vessel recanalization in patients undergoing intra-arterial therapy. METHODS: This is a retrospective analysis of patients who underwent a quantitative xenon CT blood flow study and were noted to have a documented M1 middle cerebral artery (MCA) or carotid terminus occlusion less than 6 hours from symptom onset between January 1997 and April 2001. Twenty-three patients who underwent intra-arterial thrombolysis were included in the analysis. Univariate and multivariate analyses were performed to determine whether pretherapy CBF was correlated to the likelihood of recanalization. RESULTS: A total of 23 patients were studied in this analysis with a median age of 69 (range 32-81) and median National Institutes of Health Stroke Score of 19 (range, 8-22). Twelve patients (52%) underwent combined intravenous/intra-arterial therapy, and 11 patients (48%) were treated with intra-arterial thrombolytics alone. Successful vessel recanalization (Thrombolysis in Myocardial Infarction classification 2 or 3 flow) occurred in 13 patients (57%). The only variable associated with recanalization in multivariate modeling was mean ipsilateral MCA CBF (odds ratio, 1.25; 95% confidence interval, 1.01-1.54; P = .035). A receiver operating characteristic curve was generated, and a mean ipsilateral MCA CBF threshold of 18 mL/100 g/min was found to be the threshold for successful recanalization. CONCLUSIONS: Our study suggests that patients with higher mean ipsilateral MCA CBF are more likely to recanalize. The threshold for successful revascularization may be 18 mL/100 g/min. Further study is required to determine whether pretreatment CBF is related to recanalization success.

Comprehensive transcript analysis in small quantities of mRNA by SAGE-lite.

Serial analysis of gene expression (SAGE) is a powerful technique that can be used for global analysis of gene expression. Its chief advantage over other methods is that SAGE does not require prior knowledge of the genes of interest and provides quantitative and qualitative data of potentially every transcribed sequence in a particular tissue or cell type. Furthermore, SAGE can quantify low-abundance transcripts and reliably detect relatively small differences in transcript abundance between cell populations. However, SAGE demands high input levels of mRNA which are often unavailable, particularly when studying human disease. To overcome this limitation, we have developed a modification of SAGE that allows detailed global analysis of gene expression in extremely small quantities of tissue or cultured cells. We have called this approach 'SAGE-Lite'. This technique was used for the global analysis of transcription in samples of normal and pathological human cerebrovasculature to study the molecular pathology of intracranial aneurysms. These samples, which are obtained during operative surgical repair, are typically no bigger than 1 or 2 mm and yield <100 ng of total RNA. In addition, we show that SAGE-Lite allows simple and rapid isolation of long cDNAs from short (15 bp) SAGE sequence tags.

Comparative overview of brain perfusion imaging techniques.

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.

Cerebrovascular reserve in patients with carotid occlusive disease assessed by stable xenon-enhanced ct cerebral blood flow and transcranial Doppler.

BACKGROUND AND PURPOSE: Cerebrovascular reserve (CVR) by both transcranial Doppler ultrasonography (TCD) and quantitative cerebral blood flow (CBF) can identify subgroups of patients at increased risk for stroke. A direct comparison of CVR measurements obtained with both technologies in patients with cerebrovascular occlusive disease is lacking. METHODS: CVRs before and after acetazolamide administration (1 g IV) were measured by TCD insonation of the middle cerebral artery (MCA) and CBF obtained with stable xenon CT (Xe/CT) in 38 patients with carotid occlusive disease. Sensitivity/specificity calculations were based on 2 Xe/CT MCA values: an average over 4 levels and the level with the lowest percent change in CBF. Compromised CVR was defined as no reactivity or a decrease in reactivity. RESULTS: Using the analysis of the systolic TCD, we found that velocity changes compared with the average Xe/CT MCA CVR showed a sensitivity of 33%, specificity of 90.6%, positive predictive value of 54.5%, and negative predictive value of 80%. The sensitivity of TCD compared with the lowest Xe/CT CBF CVR was 35.5%, specificity and positive predictive values were 100%, and negative predictive value was 66.7%. The index of validity was between 72% and 76%. CONCLUSIONS: TCD is much less sensitive than Xe/CT CBF in identifying patients with compromised CVR. This may be a result of the inability of TCD to identify patients with compromised reserves when their MCA blood flow comes from collateral sources. The lack of correlation between TCD and Xe/CT CBF for identifying patients with compromised CVR should be considered when stroke risk assessments are made by TCD.

Molecular anatomy of an intracranial aneurysm: coordinated expression of genes involved in wound healing and tissue remodeling.

BACKGROUND AND PURPOSE: Approximately 6% of human beings harbor an unruptured intracranial aneurysm. Each year in the United States, >30 000 people suffer a ruptured intracranial aneurysm, resulting in subarachnoid hemorrhage. Despite the high incidence and catastrophic consequences of a ruptured intracranial aneurysm and the fact that there is considerable evidence that predisposition to intracranial aneurysm has a strong genetic component, very little is understood with regard to the pathology and pathogenesis of this disease. METHODS: To begin characterizing the molecular pathology of intracranial aneurysm, we used a global gene expression analysis approach (SAGE-Lite) in combination with a novel data-mining approach to perform a high-resolution transcript analysis of a single intracranial aneurysm, obtained from a 3-year-old girl. RESULTS: SAGE-Lite provides a detailed molecular snapshot of a single intracranial aneurysm. These data suggest that, at least in this specific case, aneurysmal dilation results in a highly dynamic cellular environment in which extensive wound healing and tissue/extracellular matrix remodeling are taking place. Specifically, we observed significant overexpression of genes encoding extracellular matrix components (eg, COL3A1, COL1A1, COL1A2, COL6A1, COL6A2, elastin) and genes involved in extracellular matrix turnover (TIMP-3, OSF-2), cell adhesion and antiadhesion (SPARC, hevin), cytokinesis (PNUTL2), and cell migration (tetraspanin-5). CONCLUSIONS: Although these are preliminary data, representing analysis of only one individual, we present a unique first insight into the molecular basis of aneurysmal disease and define numerous candidate markers for future biochemical, physiological, and genetic studies of intracranial aneurysm. Products of these genes will be the focus of future studies in wider sample sets.

CT-based assessment of acute stroke: CT, CT angiography, and xenon-enhanced CT cerebral blood flow.

BACKGROUND AND PURPOSE: Only a small percentage of acute-stroke patients receive thrombolytic therapy because of time constraints and the risks associated with thrombolytic therapy. We sought to determine whether xenon-enhanced CT (XeCT) cerebral blood flow (CBF) and/or CT angiography (CTA) in conjunction with CT can distinguish subgroups of acute ischemic stroke victims and thereby better predict the subgroups most likely to benefit and not to benefit from thrombolytic therapy. METHODS: An analysis of 51 patients who had a CT, CTA, and stable XeCT CBF examination within 24 hours of stroke symptom onset was conducted. These initial radiographic studies and National Institutes of Health Stroke Scale score on admission were assessed to determine whether they could predict new infarction on follow-up CT or discharge disposition by use of the Fisher exact test to determine statistical significance. RESULTS: Patients with no infarction on initial CT and normal XeCT CBF had significantly fewer new infarctions and were discharged home more often than those with compromised CBF. The same held true for patients with an open internal carotid artery and middle cerebral artery by CTA and normal CT compared with those with an occluded internal carotid artery and/or middle cerebral artery by CTA. Either was superior to CT and the National Institutes of Health Stroke Scale in prediction of outcome. Both enable the selection of a group of patients not identifiable by CT alone that would do well without being exposed to the risks of thrombolytic therapy. This study included too few patients to statistically assess the role of combining CTA and XeCT CBF information. CONCLUSIONS: The combination of CT, CTA, and Xe/CT CBF does define potentially significant subgroups of patients. The utility of this classification is supported by the observation that CTA and XeCT CBF are superior to CT alone in predicting infarction on follow-up CT and clinical outcome. This information may be useful in selecting patients for acute-stroke treatment.

Effect of xenon-induced flow activation on xenon-enhanced computed tomography cerebral blood flow calculations.

Computer simulations of stable xenon ((S)Xe) uptake curves were used to evaluate the effect of xenon-induced flow activation on CBF calculations by xenon-enhanced computed tomography. Estimates of flow activation were based on repeated transcranial Doppler measurements of blood velocity during 4.5 minutes of (S)Xe inhalation. The synthetic curves were generated from a generalized Kety equation that included time-varying blood flow activation. In contrast to the peak 35% increase in blood flow velocity during (S)Xe inhalation, a standard analysis of the flow-varying synthetic curves revealed only minor 3% to 5% increases in calculated CBF. It is concluded that brief xenon inhalations can provide blood flow estimates that contain minimal bias from activation.

Regional cerebral blood flow and CO2 reactivity in fulminant hepatic failure.

Alterations in cerebral hemodynamics are postulated to contribute to brain herniation, a major cause of death in patients with severe hepatic encephalopathy due to fulminant hepatic failure (FHF). In an effort to identify these changes in cerebral hemodynamics, regional and global cerebral blood flow (CBF) and CO2 reactivity were measured using stable xenon-enhanced computed tomography (Xe/CT) in 24 patients within 72 h of onset of severe hepatic encephalopathy. Regional variations in CBF, most notably, a relative decrease in CBF in the anterior circulation and an increase in CBF in the posterior circulation were found. CBF was significantly lower in FHF patients compared with controls, however, these values are well out of the established ischemic range. FHF patients also showed significant impairment in CBF response to hypoventilation, while the CBF response to hyperventilation remained intact. This study suggests that FHF patients demonstrate early changes in both CBF patterns and CO2 reactivity. The relatively "normal" CBF values obtained in FHF patients in severe hepatic encephalopathy coupled with the lack of vasodilatation to hypoventilation suggest a state of uncoupled CBF and metabolism or "luxury perfusion" that could theoretically contribute to vasogenic edema, brain swelling, and cerebral herniation.