Detection of Single Cancer Cell Multidrug Resistance With Single Cell Bioanalyzer.

Objectives: Despite the development of various cancer treatment methods, chemotherapy remains the most common approach for treating cancer. The risk of tumors acquiring resistance to chemotherapy remains a significant hurdle to the successful treatment of various types of cancer. Therefore, overcoming or predicting multidrug resistance in clinical treatment is essential. The detection of circulating tumor cells (CTCs) is an important component of liquid biopsy and the diagnosis of cancer. This study aims to test the feasibility of single-cell bioanalyzer (SCB) and microfluidic chip technology in identifying patients with cancer resistant to chemotherapy and propose new methods to provide clinicians with new choices. Methods: In this study, we used rapidly isolated viable CTCs from the patient blood samples method combined with SCB technology and a novel microfluidic chip, to predict whether patients with cancer are resistant to chemotherapy. SCB and microfluidic chip were used to select single CTCs, and the accumulation of chemotherapy drug was fluorescently measured in real time on these cells in the absence and presence of permeability-glycoprotein inhibitors. Results: Initially, we successfully isolated viable CTCs from the blood samples of patients. Additionally, the present study accurately predicted the response of 4 lung cancer patients to chemotherapeutic drugs. In addition, the CTCs of 17 patients with breast cancer diagnosed at Zhuhai Hospital of Traditional Chinese and Western Medicine were assessed. The results indicated that 9 patients were sensitive to chemotherapeutic drugs, 8 patients were resistant to a certain degree, and only 1 was completely resistant to chemotherapy. Conclusion: The present study indicated that the SCB technology could be used as a prognostic assay to evaluate the CTCs response to available drugs and guide physicians to treatment options that are most likely to be effective.

The Curiosity Rover's Exploration of Glen Torridon, Gale Crater, Mars: An Overview of the Campaign and Scientific Results.

The Mars Science Laboratory rover, Curiosity, explored the clay mineral-bearing Glen Torridon region for 1 Martian year between January 2019 and January 2021, including a short campaign onto the Greenheugh pediment. The Glen Torridon campaign sought to characterize the geology of the area, seek evidence of habitable environments, and document the onset of a potentially global climatic transition during the Hesperian era. Curiosity roved 5 km in total throughout Glen Torridon, from the Vera Rubin ridge to the northern margin of the Greenheugh pediment. Curiosity acquired samples from 11 drill holes during this campaign and conducted the first Martian thermochemolytic-based organics detection experiment with the Sample Analysis at Mars instrument suite. The lowest elevations within Glen Torridon represent a continuation of lacustrine Murray formation deposits, but overlying widespread cross bedded sandstones indicate an interval of more energetic fluvial environments and prompted the definition of a new stratigraphic formation in the Mount Sharp group called the Carolyn Shoemaker formation. Glen Torridon hosts abundant phyllosilicates yet remains compositionally and mineralogically comparable to the rest of the Mount Sharp group. Glen Torridon samples have a great diversity and abundance of sulfur-bearing organic molecules, which are consistent with the presence of ancient refractory organic matter. The Glen Torridon region experienced heterogeneous diagenesis, with the most striking alteration occurring just below the Siccar Point unconformity at the Greenheugh pediment. Results from the pediment campaign show that the capping sandstone formed within the Stimson Hesperian aeolian sand sea that experienced seasonal variations in wind direction.

Depleted carbon isotope compositions observed at Gale crater, Mars.

Obtaining carbon isotopic information for organic carbon from Martian sediments has long been a goal of planetary science, as it has the potential to elucidate the origin of such carbon and aspects of Martian carbon cycling. Carbon isotopic values (δ13CVPDB) of the methane released during pyrolysis of 24 powder samples at Gale crater, Mars, show a high degree of variation (-137 ± 8‰ to +22 ± 10‰) when measured by the tunable laser spectrometer portion of the Sample Analysis at Mars instrument suite during evolved gas analysis. Included in these data are 10 measured δ13C values less than -70‰ found for six different sampling locations, all potentially associated with a possible paleosurface. There are multiple plausible explanations for the anomalously depleted 13C observed in evolved methane, but no single explanation can be accepted without further research. Three possible explanations are the photolysis of biological methane released from the subsurface, photoreduction of atmospheric CO2, and deposition of cosmic dust during passage through a galactic molecular cloud. All three of these scenarios are unconventional, unlike processes common on Earth.

COVID-19 Home Monitoring: An Institutional Approach to Bridging Care During a Pandemic.

Introduction: Coronavirus disease 2019 (COVID-19) has widened patient care gaps and created gaps in medical student clinical training. The care gaps are often most obvious in primary care medicine clinics (PCMCs) where residents and medical students care for a vulnerable population. Materials and Methods: We designed an outpatient telehealth program to support and monitor PCMC patients who had been diagnosed or were suspected to have COVID-19 and were confined to their homes due to public health mandated isolation. To support the program, we recruited medical student volunteers. We recruited patients from our institution's primary care clinic who were recently diagnosed with COVID-19 and were currently not hospitalized. Feasibility of the home monitoring program (HMP) was assessed and mortality data for all patients were collected. Results: Over 800 monitoring phone calls were placed during the 8-month study period to 296 patients, with an average of 2.79 calls per patient. A total of 30 medical students participated. A total of four patients died during the study period. Conclusions: Our institution was able to rapidly design and implement a COVID-19 HMP integrated with our primary care clinic to ensure continued access to care during a pandemic.

Frequency, Determinants, and Outcomes of Emboli to Distal and New Territories Related to Mechanical Thrombectomy for Acute Ischemic Stroke.

Background and Purpose: Clot fragmentation and distal embolization during endovascular thrombectomy for acute ischemic stroke may produce emboli downstream of the target occlusion or in previously uninvolved territories. Susceptibility-weighted magnetic resonance imaging can identify both emboli to distal territories (EDT) and new territories (ENT) as new susceptibility vessel signs (SVS). Diffusion-weighted imaging (DWI) can identify infarcts in new territories (INT). Methods: We studied consecutive acute ischemic stroke patients undergoing magnetic resonance imaging before and after thrombectomy. Frequency, predictors, and outcomes of EDT and ENT detected on gradient-recalled echo imaging (EDT-SVS and ENT-SVS) and INT detected on DWI (INT-DWI) were analyzed. Results: Among 50 thrombectomy-treated acute ischemic stroke patients meeting study criteria, mean age was 70 (±16) years, 44% were women, and presenting National Institutes of Health Stroke Scale score 15 (interquartile range, 8­19). Overall, 21 of 50 (42%) patients showed periprocedural embolic events, including 10 of 50 (20%) with new EDT-SVS, 10 of 50 (20%) with INT-DWI, and 1 of 50 (2%) with both. No patient showed ENT-SVS. On multivariate analysis, model-selected predictors of EDT-SVS were lower initial diastolic blood pressure (odds ratio, 1.09 [95% CI, 1.02­1.16]), alteplase pretreatment (odds ratio, 5.54 [95% CI, 0.94­32.49]), and atrial fibrillation (odds ratio, 7.38 [95% CI, 1.02­53.32]). Classification tree analysis identified pretreatment target occlusion SVS as an additional predictor. On univariate analysis, INT-DWI was less common with internal carotid artery (5%), intermediate with middle cerebral artery (25%), and highest with vertebrobasilar (57%) target occlusions (P=0.02). EDT-SVS was not associated with imaging/functional outcomes, but INT-DWI was associated with reduced radiological hemorrhagic transformation (0% versus 54%; P<0.01). Conclusions: Among acute ischemic stroke patients treated with thrombectomy, imaging evidence of distal emboli, including EDT-SVS beyond the target occlusion and INT-DWI in novel territories, occur in about 2 in every 5 cases. Predictors of EDT-SVS are pretreatment intravenous fibrinolysis, potentially disrupting thrombus structural integrity; atrial fibrillation, possibly reflecting larger target thrombus burden; lower diastolic blood pressure, suggestive of impaired embolic washout; and pretreatment target occlusion SVS sign, indicating erythrocyte-rich, friable target thrombus.

A Prehospital Acute Stroke Trial has Only Modest Impact on Enrollment in Concurrent, Post-arrival-Recruiting Stroke Trials.

BACKGROUND: Because "time is brain," acute stroke trials are migrating to the prehospital setting. The impact upon enrollment in post-arrival trials of earlier recruitment in a prehospital trial requires delineation. METHODS: We analyzed all patients recruited into acute and prevention stroke trials during an 8-year period when an academic medical center (AMC) was participating in a prehospital treatment trial - the NIH Field Administration of Stroke Treatment - Magnesium (FAST-MAG) study. RESULTS: During the study period, in addition to FAST-MAG, the AMC participated in 33 post-arrival stroke trials: 27 for acute cerebral ischemia, one for intracerebral hemorrhage, and 5 secondary prevention trials. Throughout the study period, the AMC was recruiting for at least 3 concurrent post-arrival acute trials. Among 199 patients enrolled in acute stroke trials, 98 (49%) were in FAST-MAG and 101 (51%) in concurrent, post-arrival acute trials. Among FAST-MAG patients, 67% were not eligible for any concurrent acute, post-arrival trial. Of 134 patients eligible for post-arrival acute trials, 101 (76%) were enrolled in post-arrival trials and 32 (24%) in FAST-MAG. Leading reasons FAST-MAG patients were ineligible for post-arrival acute trials were: NIHSS too low (23.4%), intracranial hemorrhage (17.9%), IV tPA used in standard management (9.0%), NIHSS too high (7.1%), and age too high (5.2%). CONCLUSIONS: A prehospital hyperacute stroke trial with wide entry criteria reduced only modestly, by one-fourth, enrollment into concurrently active, post-arrival stroke trials. Simultaneous performance of prehospital and post-arrival acute and secondary prevention stroke trials in research networks is feasible.

Frequency, Predictors, and Outcomes of Prehospital and Early Postarrival Neurological Deterioration in Acute Stroke: Exploratory Analysis of the FAST-MAG Randomized Clinical Trial.

Importance: Studies of neurological deterioration in stroke have focused on the subacute period, but stroke treatment is increasingly migrating to the prehospital setting, where the neurological course has not been well delineated. Objective: To describe the frequency, predictors, and outcomes of neurological deterioration among patients in the ultra-early period following ischemic stroke or intracranial hemorrhage. Design, Settings, and Participants: Exploratory analysis of the prehospital, randomized Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial conducted from 2005 to 2013 within 315 ambulances and 60 stroke patient receiving hospitals in Southern California. Participants were consecutively enrolled patients with suspected acute stroke who were transported by ambulance within 2 hours of stroke onset. Main Outcomes and Measures: The main outcome was neurological deterioration, defined as a worsening of 2 or more points on the Glasgow Coma Scale (GCS), a level of consciousness scale ranging from 3 to 15, with higher scores indicating more alertness. Imaging outcomes were ischemic or hemorrhagic injury extent identified during the first brain imaging scan. Outcomes at 3 months included global disability level (assessed using the modified Rankin Scale [mRS]; range, 0-6, with higher numbers indicating greater disability) and mortality. Results: Among the 1690 patients (99.4%), the mean (SD) age was 69.4 (13.5) years, and 43% were female. Final diagnoses were acute cerebral ischemia in 1237 patients (73.2%), intracranial hemorrhage in 386 patients (22.8%), and neurovascular mimic in 67 patients (4.0%). The median (interquartile range [IQR]) minutes between the last well-known time and GCS assessments were 23 (14-42) minutes for prehospital, 58 (46-79) minutes for ED arrival, and 149 (120-180) minutes for early ED course assessments. From prehospital to early postarrival, ultra-early neurological deterioration (U-END) occurred in 200 of 1690 patients (11.8%), more often among patients with intracranial hemorrhage than among those with acute cerebral ischemia (119 of 386 [30.8%] vs 75 of 1237 [6.1%], P < .001). Patterns of U-END were prehospital U-END without early recovery in 30 of 965 patients (3.1%), stable prehospital course but early ED deterioration in 49 of 965 patients (5.1%), and continuous deterioration in both prehospital and early ED phases in 27 of 965 patients (2.8%). Ultra-early neurological deterioration was associated with worse 3-month outcomes, including increased global disability (mRS score, 4.6 vs 2.4; P < .001), reduced functional independence (mRS score 0-2, 32 of 200 [16.0%] vs 844 of 1490 [56.6%]; P < .001), and increased mortality (87 of 200 [43.5%] vs 176 of 1490 [11.8%]; P < .001). Conclusions and Relevance: Ultra-early neurological deterioration occurs in 1 in 8 ambulance-transported patients with acute cerebrovascular disease, including 1 in 3 patients with intracranial hemorrhage and 1 in 16 patients with acute cerebral ischemia, and is associated with markedly reduced functional independence and increased mortality. Averting U-END may be a target for future prehospital therapeutics. Trial Registration: ClinicalTrials.gov Identifier: NCT00059332.

Stratosphere Conditions Inactivate Bacterial Endospores from a Mars Spacecraft Assembly Facility.

Every spacecraft sent to Mars is allowed to land viable microbial bioburden, including hardy endospore-forming bacteria resistant to environmental extremes. Earth's stratosphere is severely cold, dry, irradiated, and oligotrophic; it can be used as a stand-in location for predicting how stowaway microbes might respond to the martian surface. We launched E-MIST, a high-altitude NASA balloon payload on 10 October 2015 carrying known quantities of viable Bacillus pumilus SAFR-032 (4.07 × 107 spores per sample), a radiation-tolerant strain collected from a spacecraft assembly facility. The payload spent 8 h at ∼31 km above sea level, exposing bacterial spores to the stratosphere. We found that within 120 and 240 min, spore viability was significantly reduced by 2 and 4 orders of magnitude, respectively. By 480 min, <0.001% of spores carried to the stratosphere remained viable. Our balloon flight results predict that most terrestrial bacteria would be inactivated within the first sol on Mars if contaminated spacecraft surfaces receive direct sunlight. Unfortunately, an instrument malfunction prevented the acquisition of UV light measurements during our balloon mission. To make up for the absence of radiometer data, we calculated a stratosphere UV model and conducted ground tests with a 271.1 nm UVC light source (0.5 W/m2), observing a similarly rapid inactivation rate when using a lower number of contaminants (640 spores per sample). The starting concentration of spores and microconfiguration on hardware surfaces appeared to influence survivability outcomes in both experiments. With the relatively few spores that survived the stratosphere, we performed a resequencing analysis and identified three single nucleotide polymorphisms compared to unexposed controls. It is therefore plausible that bacteria enduring radiation-rich environments (e.g., Earth's upper atmosphere, interplanetary space, or the surface of Mars) may be pushed in evolutionarily consequential directions. Key Words: Planetary protection-Stratosphere-Balloon-Mars analog environment-E-MIST payload-Bacillus pumilus SAFR-032. Astrobiology 17, 337-350.

The Effect of Sterilization Methods on the Structural and Chemical Properties of Fibrin Microthread Scaffolds.

A challenge for the design of scaffolds in tissue engineering is to determine a terminal sterilization method that will retain the structural and biochemical properties of the materials. Since commonly used heat and ionizing energy-based sterilization methods have been shown to alter the material properties of protein-based scaffolds, the effects of ethanol and ethylene oxide (EtO) sterilization on the cellular compatibility and the structural, chemical, and mechanical properties of uncrosslinked, UV crosslinked, or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) crosslinked fibrin microthreads in neutral (EDCn) or acidic (EDCa) buffers are evaluated. EtO sterilization significantly reduces the tensile strength of uncrosslinked microthreads. Surface chemistry analyses show that EtO sterilization induces alkylation of EDCa microthreads leading to a significant reduction in myoblast attachment. The material properties of EDCn microthreads do not appear to be affected by the sterilization method. These results significantly enhance the understanding of how sterilization or crosslinking techniques affect the material properties of protein scaffolds.

Relationship of gastrointestinal symptoms and psychosocial distress to gastric retention in children.

OBJECTIVES: To determine whether gastrointestinal (GI) symptoms (abdominal pain, nonpain GI symptoms, nausea) and/or psychosocial distress differ between children with/without gastroparesis and whether the severity of GI symptoms and/or psychosocial distress is related to the degree of gastroparesis. STUDY DESIGN: Children aged 7-18 years (N = 100; 63 female patients) undergoing a 4-hour gastric emptying scintigraphy study completed questionnaires evaluating GI symptoms, anxiety, and somatization for this prospective study. Spearman correlation, Mann-Whitney, t-test, and χ(2) tests were used as appropriate for statistical analysis. RESULTS: Children with gastroparesis (n = 25) were younger than those with normal emptying (12.6 ± 3.5 vs 14.3 ± 2.6 years, P = .01). Because questionnaire responses from 7- to 10-year-old children were inconsistent, only patient-reported symptoms from 11- to 18-year-olds were used. Within this older group (n = 83), children with gastroparesis (n = 17) did not differ from children with normal emptying in severity of GI symptoms or psychosocial distress. In children with gastroparesis, gastric retention at 4 hours was related inversely to vomiting (r = -0.506, P = .038), nausea (r = -0.536, P = .019), difficulty finishing a meal (r = -0.582, P = .014), and Children's Somatization Inventory score (r = -0.544, P = .024) and positively correlated with frequency of waking from sleep with symptoms (r = 0.551, P = .022). CONCLUSIONS: The severity of GI symptoms and psychosocial distress do not differ between children with/without gastroparesis who are undergoing gastric emptying scintigraphy. In those with gastroparesis, gastric retention appears to be inversely related to dyspeptic symptoms and somatization and positively related to waking from sleep with symptoms.

Decreased relative diagnostic yield of esophagogastroduodenoscopy in children with gastroparesis.

BACKGROUND: Esophagogastroduodenoscopy (EGD) and gastric emptying scintigraphy (GES) are commonly performed in the evaluation of children with upper gastrointestinal symptoms. It has been presumed, but not clarified, that gastroparesis increases the likelihood of identifying abnormalities on EGD. We sought to determine whether the presence of gastroparesis influenced the diagnostic yield of EGD in children. METHODS: We conducted a retrospective chart review of children who underwent both an EGD and GES within 3 months of each other for evaluation of upper gastrointestinal symptoms (eg, abdominal pain). Clinical history (symptoms, comorbidities, medications, and surgical procedures), GES results, and EGD histology reports were captured. RESULTS: A total of 125 children (46% female) were included, of whom, 70 (56%) had gastroparesis. Thirty-three (26%) children had liquid meal GES (1.2 ± 1.1 y of age, mean ± SD) and 92 (64%) had solid meal GES (12.4 ± 3.6 y of age). There was an overall trend toward a decreased frequency of biopsy abnormalities in those with gastroparesis (P=0.09). Those with gastroparesis identified through liquid meal GES were less likely to have reflux esophagitis on biopsy (P=0.002). Those with gastroparesis identified on solid meal GES were less likely to have gastritis (P=0.04). Symptoms, comorbidities, or medications were not predictive of GES or EGD results. CONCLUSIONS: Children with gastroparesis may be less likely to have biopsy abnormalities identified on EGD in comparison to those without gastroparesis. Further prospective, larger, and multicenter studies are needed to validate our findings.

Implantable drug delivery device using frequency-controlled wireless hydrogel microvalves.

This paper reports a micromachined drug delivery device that is wirelessly operated using radiofrequency magnetic fields for implant applications. The controlled release from the drug reservoir of the device is achieved with the microvalves of poly(N-isopropylacrylamide) thermoresponsive hydrogel that are actuated with a wireless resonant heater, which is activated only when the field frequency is tuned to the resonant frequency of the heater circuit. The device is constructed by bonding a 1-mm-thick polyimide component with the reservoir cavity to the heater circuit that uses a planar coil with the size of 5-10 mm fabricated on polyimide film, making all the outer surfaces to be polyimide. The release holes created in a reservoir wall are opened/closed by the hydrogel microvalves that are formed inside the reservoir by in-situ photolithography that uses the reservoir wall as a photomask, providing the hydrogel structures self-aligned to the release holes. The wireless heaters exhibit fast and strong response to the field frequency, with a temperature increase of up to 20°C for the heater that has the 34-MHz resonant frequency, achieving 38-% shrinkage of swelled hydrogel when the heater is excited at its resonance. An active frequency range of ~2 MHz is observed for the hydrogel actuation. Detailed characteristics in the fabrication and actuation of the hydrogel microvalves as well as experimental demonstrations of frequency-controlled temporal release are reported.

Brain-derived neurotrophic factor (BDNF) gene not associated with antidepressant-induced mania.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems. Recent studies have suggested that BDNF plays a role in the pathogenesis of bipolar disorder (BPD). Moreover, increasing BDNF production might be one of the mechanisms involved in the alleviation of depression and aggravation of mania in antidepressant treatment. OBJECTIVES: Thus, we hypothesized that a genetic variant within the BDNF gene might influence susceptibility to antidepressant-induced mania, as has been suggested previously. METHODS: We performed a case-control study to test for allelic frequency and genotype distribution differences across six BDNF polymorphisms between 27 patients with antidepressant-induced mania (IM+) and 29 patients without antidepressant-induced mania (IM-). RESULTS: We did not observe any significant difference in either allelic or genotype frequencies between the two groups. CONCLUSIONS: Our results did not support the BDNF link to mania hypothesis proposed previously. However, a larger sample would allow for greater power to determine smaller effects of the BDNF gene in antidepressant-induced mania.

Association analyses of the DAOA/G30 and D-amino-acid oxidase genes in schizophrenia: further evidence for a role in schizophrenia.

A number of linkage studies have previously implicated the region of chromosome 13q34 in schizophrenia. Chumakov and colleagues (2002) identified a gene complex called G72 (now termed D-amino acid oxidase activator: DAOA)/G30 in this region and performed association analyses of the DAOA/G30 as well as the D-amino-acid oxidase (DAAO) gene with schizophrenia. DAAO oxidizes D-serine, a potent activator of the N-methyl-D-aspartate (NMDA) type glutamate receptor in the human brain whereas the DAOA protein is considered an activator of DAAO. The interaction of these two genes has thus been implicated in the NMDA receptor regulation pathway in schizophrenia. To date, several studies have shown a relatively consistent positive association between schizophrenia and DAOA/G30, but not with DAAO. The aim of our study was to further evaluate the contributions of these genes to the susceptibility to schizophrenia using two different sample sets. Our sample consisted of 168 matched case-control pairs as well as a family-based sample (n=113) for transmission disequilibrium test. Significant associations between the DAOA/G30 M-7 and M-18 polymorphisms and schizophrenia were observed in our case-control sample whereas no associations were observed for DAAO markers. We also observed significant or suggestive transmission disequilibrium for DAOA/G30 M-7, M-23, and M-24 to probands with schizophrenia in our family-based sample. Subsequent analysis of haplotypes made up of four DAOA/G30 markers, one marker selected from each of two linkage disequilibrium blocks that were observed in our sample as well as both ends (M-7 and M-25), were also associated with schizophrenia. Our data provide further evidence that the DAOA/G30 locus may play a role in the pathophysiology of schizophrenia. Although no direct link to genetic polymorphism in these genes and NMDA receptor function has been revealed, the present findings support previous reports implicating DAOA/G30 as susceptibility genes for schizophrenia. Further research is warranted to determine the functional variation underlying these findings and to relate this to the pathophysiology of schizophrenia.

N-methyl-D-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA levels.

The NR2B protein is a critical structural and functional subunit of the NMDA glutamate receptor. The glutamate neurotransmitter system has been implicated in psychosis and schizophrenia, and so we looked for genetic association and measured gene expression in human DNA and brain samples, respectively, of the GRIN2B gene that codes for the NR2B protein. We tested three genetic polymorphisms: G-200T (5'UTR), A5806C and T5988C (both 3'UTR) in 180 matched schizophrenia case-control pairs, 86 schizophrenia nuclear family trios, and 318 bipolar disorder trios (of which 158 probands had psychotic symptoms). We measured brain GRIN2B mRNA levels in schizophrenia, bipolar disorder and unaffected controls (n = 35 each). We detected genetic association between the G-200T marker and schizophrenia (p = 0.002), between T5988C and bipolar disorder (p = 0.02), and between A5806C and bipolar disorder with psychotic symptoms (p = 0.0038). The T-C-C haplotype was transmitted more frequently with bipolar disorder, but less often with schizophrenia, while the G-C-T haplotype was transmitted more often in schizophrenia. Significant differences were found in overall haplotype frequencies between schizophrenia cases and controls (p = 0.005). GRIN2B expression levels in schizophrenia, bipolar disorder and controls were not significantly different. The genetic findings suggest a role for GRIN2B in schizophrenia and bipolar disorder.

Correlation between lumenal geometry changes and hemodynamics in fusiform intracranial aneurysms.

BACKGROUND AND PURPOSE: Hemodynamics may predispose aneurysms to rupture; however, hemodynamic descriptors that can describe aneurysm growth are not well understood. We examined the relationship between hemodynamics and growth of 2 fusiform basilar artery aneurysms in an effort to define hemodynamic variables that may be helpful in predicting aneurysmal growth. METHODS: Two patients with basilar fusiform aneurysms of a similar size were followed for a 2-year period. The lumenal geometry and inflow and outflow rates were acquired by using MR angiography and velocimetry, respectively. The location of aneurysmal growth was identified by coregistering aneurysm models that were acquired at different times. Hemodynamic descriptors were calculated by using computational fluid dynamic simulations and compared with aneurysm growth pattern. RESULTS: One patient had an aneurysm that grew significantly, but a similar-sized aneurysm in the other patient remained unchanged. The largest aneurysmal growth (approximately 3 mm/year) was found at the inferior side (lower part) of the aneurysm, where the wall shear stress was very low (<0.1N/m(2)). The general flow patterns did not change with time, even in the aneurysm that grew, but histograms of wall shear stress were very different in these 2 patients. CONCLUSIONS: This study investigates whether hemodynamic descriptors can be correlated with regional changes in aneurysm lumen morphology on a patient-specific basis. That capability will permit the testing, in longitudinal studies, of hypotheses as to which mechanisms are the most important in aneurysm growth.