Cytoprotective Agents in Stroke: Still Uncertainty in the Next Frontier.

INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. Additional adjuvant therapies are needed but pharmacologic interactions among therapies may dictate how they could be used. We conducted a survey to determine physician decision-making regarding the use of cytoprotective agents in patients presenting with AIS. METHODS: The survey was structured, web-based, anonymous, and invite-only among physicians across the world treating patients presenting with AIS. Respondents were asked about the use of a hypothetical cytoprotective agent (that provided an added 10% benefit) in the context of a treatment interaction with IVT or its timing in relation to IVT. RESULTS: A total of 282 stroke physicians (74.9% males, mean age 46 years) participated in the survey. When the respondent could give both the cytoprotective agent and IVT with no treatment interaction, 177 (78.0%) chose to administer both. In the presence of treatment interaction, 88 (38.3%) would withhold IVT, 83 (36.1%) would withhold the cytoprotective agent and 56 (24.4%) were uncertain. Lastly, 111 (48.9%) were willing to administer the cytoprotective agent if it meant a necessary 10-minute delay in IVT administration. CONCLUSIONS: Pharmacologic interactions result in major uncertainty about cytoprotective treatment choices.

Reduced disease severity following therapeutic treatment with angiotensin 1-7 in a mouse model of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by autoimmune and neurodegenerative pathologies for which there is no cure and no defined etiology. Although several, modestly effective, disease modifying drugs are available to treat MS, there are presently no treatments that offer neuroprotection and prevent clinical progression. Therapies are needed that control immune homeostasis, prevent disease progression, and stimulate regeneration in the CNS. Components of the renin-angiotensin-system (RAS) have recently been identified as chemical mediators in the CNS and in neurological disease. Here we show the beneficial effect of therapeutic treatment with the Mas receptor agonist and metabolite of the protective arm of RAS, angiotensin 1-7 (A(1-7)), in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Therapeutic treatment with A(1-7) caused a dose-dependent reduction both in clinical disease severity and progression, and was dependent on Mas receptor activation. Further analysis of the most optimal dose of A(1-7) treatment revealed that the reductions in clinical disease course were associated with decreased immune infiltration and demyelination, axonal loss and oxidative stress in the spinal cord. In addition A(1-7) treatment was also associated with increases in circulating alternatively activated monocytes/macrophages.

Does injection flow rate have an impact on arterial phase image degradation in liver MRI? A comparison of gadoxetic acid versus gadobutrol.

AIM: To evaluate retrospectively the impact of injection flow rate on arterial phase image degradation in liver magnetic resonance imaging (MRI) with gadoxetic acid (Gd-EOB-DTPA) compared to gadobutrol. MATERIALS AND METHODS: Two hundred consecutive patients who had undergone liver MRI were enrolled in this Health Insurance Portability and Accountability Act (HIPAA)-compliant institutional review board (IRB)-approved study and were divided into three groups. Group 1 (50 patients) and 2 (50 patients) had undergone MRI performed with gadoxetic acid (fixed 10 ml) at flow rate of 1 and 2 ml/s, respectively. Group 3 (100 patients) had undergone MRI performed with gadobutrol (0.1 mmol/kg) at 1 ml/s. Precontrast and post-contrast (arterial, portal venous, and hepatic venous phases) image degradation was assessed by two blinded independent readers using a four-point rating scale. The numbers of patients with arterial phase image degradation were compared using the Fisher exact test among the three groups. RESULTS: The incidence of arterial phase image degradation was 12% (6/50) in group 1 and 16% (8/50) in group 2 for both readers, 6% (6/100) for reader 1 and 5% (5/100) for reader 2 in group 3. Group 2 had a higher incidence of arterial phase image degradation when compared with group 3 for reader 2 (p=0.032). Severe arterial phase image degradation, resulting in non-diagnostic image quality, occurred in 4% (2/50) of patients when performed with gadoxetic acid administration at 2 ml/s and 2% (1/50) at 1 ml/s. CONCLUSION: A slower injection flow rate has a trend to reduce the incidence and severity of arterial phase image degradation during liver MRI with gadoxetic acid when compared to gadobutrol.

Machine-learning assisted multiplex detection of catecholamine neurotransmitters with a colorimetric sensor array.

Catecholamine neurotransmitters (CNs), such as dopamine (DA), epinephrine (EP), norepinephrine (NEP), and levodopa (LD), are recognized as the primary biomarkers of a variety of neurological illnesses. Therefore, simultaneous monitoring of these biomarkers is highly recommended for clinical diagnosis and treatment. In this study, a high-performance colorimetric artificial tongue has been proposed for the multiplex detection of CNs. Different aggregation behaviors of gold nanoparticles in the presence of CNs under various buffering conditions generate unique fingerprint response patterns. Under various buffering conditions, the distinct acidity constants of CNs, and consequently their predominant species at a given pH, drive the aggregation of gold nanoparticles (AuNPs). The utilization of machine learning algorithms in this design enables classification and quantification of CNs in various samples. The response profile of the array was analyzed using the linear discriminant analysis algorithm for classification of CNs. This colorimetric sensor array is capable of accurately distinguishing between individual neurotransmitters and their combinations. Partial least squares regression was also applied for quantitation purposes. The obtained analytical figures of merit (FOMs) and linear ranges of 0.6-9 µM (R2 = 0.99) for DA, 0.1-10 µM (R2 = 0.99) for EP, 0.1-9 µM (R2 = 0.99) for NEP and 1-70 µM (R2 = 0.99) for LD demonstrated the potential applicability of the developed sensor array in precise and accurate determination of CNs. Finally, the feasibility of the array was validated in human urine samples as a complex biological fluid with LODs of 0.3, 0.5, 0.2, and 1.9 µM for DA, EP, NEP, and LD, respectively.

CT Perfusion Does Not Modify the Effect of Reperfusion in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment in the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing endovascular treatment, many patients still do poorly. We investigated whether CTP modifies the effect of near-complete reperfusion on clinical outcomes, ie, whether poor clinical outcomes despite near-complete reperfusion can be partly or fully explained by CTP findings. MATERIALS AND METHODS: Data are from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Admission CTP was processed using RAPID software, generating relative CBF and CBV volume maps at standard thresholds. CTP lesion volumes were compared in patients with-versus-without near-complete reperfusion. Associations between each CTP metric and clinical outcome (90-day mRS) were tested using multivariable logistic regression, adjusted for baseline imaging and clinical variables. Treatment-effect modification was assessed by introducing CTP lesion volume × reperfusion interaction terms in the models. RESULTS: CTP lesion volumes and reperfusion status were available in 410/1105 patients. CTP lesion volumes were overall larger in patients without near-complete reperfusion, albeit not always statistically significant. Increased CBF <34%, CBV <34%, CBV <38%, and CBV <42% lesion volumes were associated with worse clinical outcome (ordinal mRS) at 90 days. CTP core lesion volumes did not modify the treatment effect of near-complete recanalization on clinical outcome. CONCLUSIONS: CTP did not modify the effect of near-complete reperfusion on clinical outcomes. Thus, CTP cannot explain why some patients with near-complete reperfusion have poor clinical outcomes.

Interrater Agreement and Detection Accuracy for Medium-Vessel Occlusions Using Single-Phase and Multiphase CT Angiography.

BACKGROUND AND PURPOSE: Accurate and reliable detection of medium-vessel occlusions is important to establish the diagnosis of acute ischemic stroke and initiate appropriate treatment with intravenous thrombolysis or endovascular thrombectomy. However, medium-vessel occlusions are often challenging to detect, especially for unexperienced readers. We aimed to evaluate the accuracy and interrater agreement of the detection of medium-vessel occlusions using single-phase and multiphase CTA. MATERIALS AND METHODS: Single-phase and multiphase CTA of 120 patients with acute ischemic stroke (20 with no occlusion, 44 with large-vessel occlusion, and 56 with medium-vessel occlusion in the anterior and posterior circulation) were assessed by 3 readers with varying levels of experience (session 1: single-phase CTA; session 2: multiphase CTA). Interrater agreement for occlusion type (large-vessel occlusion versus medium-vessel occlusion versus no occlusion) and for detailed occlusion sites was calculated using the Fleiss κ with 95% confidence intervals. Accuracy for the detection of medium-vessel occlusions was calculated for each reader using classification tables. RESULTS: Interrater agreement for occlusion type was moderate for single-phase CTA (κ = 0.58; 95% CI, 0.56-0.62) and almost perfect for multiphase CTA (κ = 0.81; 95% CI, 0.78-0.83). Interrater agreement for detailed occlusion sites was moderate for single-phase CTA (κ = 0.55; 95% CI, 0.53-0.56) and substantial for multiphase CTA (κ = 0.71; 95% CI, 0.67-0.74). On single-phase CTA, readers 1, 2, and 3 classified 33/56 (59%), 34/56 (61%), and 32/56 (57%) correctly as medium-vessel occlusions. On multiphase CTA, 48/56 (86%), 50/56 (89%), and 50/56 (89%) medium-vessel occlusions were classified correctly. CONCLUSIONS: Interrater agreement for medium-vessel occlusions is moderate when using single-phase CTA and almost perfect with multiphase CTA. Detection accuracy is substantially higher with multiphase CTA compared with single-phase CTA, suggesting that multiphase CTA might be a valuable tool for assessment of medium-vessel occlusion stroke.

A ratiometric fluorescence nanoprobe using CdTe QDs for fast detection of carbaryl insecticide in apple.

In this study, a novel, simple and sensitive ratiometric fluorescence method is presented for the detection of very low quantities of the carbaryl in Iranian apple using cadmium telluride quantum dots (CdTe QDs) nanoprobe. The principle of the proposed strategy relies on the rapid hydrolysis of the carbaryl under an alkaline condition and production of the 1-naphthol with a blue emission at 470 nm. Besides, using the CdTe QDs with a yellow emission at 580 nm, as a reference, improves the visual tracking of carbaryl through changes in color tonality. The herein described methodology is applied for enzyme-free visual detection of carbaryl with satisfactory results in the presence of other common pesticides in Iranian apple sample. Additionally, the calculated limit of detection (LOD) of 0.12 ng mL-1 for carbaryl is much lower than the maximum residue limits of carbaryl warned value reported by the European Union and United States pesticides database, which is so promising for carbaryl sensing in the monitoring of fruits. Furthermore, the ability of the proposed method for the detection of carbaryl residues in Iranian apple was confirmed by the high-performance liquid chromatography (HPLC) method as a standard method through statistical analysis. This fast and highly sensitive naked-eye ratiometric sensor may hold great promise to provide the technical support for the rapid and valid detection of other targets in food safety fields.

Patient-Relevant Deficits Dictate Endovascular Thrombectomy Decision-Making in Patients with Low NIHSS Scores with Medium-Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: There is a paucity of evidence regarding the safety of endovascular treatment for patients with acute ischemic stroke due to primary medium-vessel occlusion. The aim of this study was to examine the willingness among stroke physicians to perform endovascular treatment in patients with mild-yet-disabling deficits due to medium-vessel occlusion. MATERIALS AND METHODS: In an international cross-sectional survey consisting of 7 primary medium-vessel occlusion case scenarios, participants were asked whether the presence of personally disabling deficits would influence their decision-making for endovascular treatment despite the patients having low NIHSS scores (<6). Decision rates were calculated on the basis of physician characteristics. Univariable logistic regression clustered by respondent and scenario identity was performed. RESULTS: Three hundred sixty-six participants from 44 countries provided 2562 answers to the 7 medium-vessel occlusion scenarios included in this study. In scenarios in which the deficit was relevant to the patient's profession, 56.9% of respondents opted to perform immediate endovascular treatment compared with 41.0% when no information regarding the patient's profession was provided (risk ratio = 1.39, P < .001). The largest effect sizes were seen for female participants (risk ratio = 1.68; 95% CI, 1.35-2.09), participants older than 60 years of age (risk ratio = 1.61; 95% CI, 1.23-2.10), those with more experience in neurointervention (risk ratio = 1.60; 95% CI, 1.24-2.06), and those who personally performed >100 endovascular treatments per year (risk ratio = 1.63; 95% CI, 1.22-2.17). CONCLUSIONS: The presence of a patient-relevant deficit in low-NIHSS acute ischemic stroke due to medium-vessel occlusion is an important factor for endovascular treatment decision-making. This may have relevance for the conduct and interpretation of low-NIHSS endovascular treatment in randomized trials.

Perceived Limits of Endovascular Treatment for Secondary Medium-Vessel-Occlusion Stroke.

BACKGROUND AND PURPOSE: Thrombus embolization during mechanical thrombectomy occurs in up to 9% of cases, making secondary medium vessel occlusions of particular interest to neurointerventionalists. We sought to gain insight into the current endovascular treatment approaches for secondary medium vessel occlusion stroke in an international case-based survey because there are currently no clear recommendations for endovascular treatment in these patients. MATERIALS AND METHODS: Survey participants were presented with 3 cases involving secondary medium vessel occlusions, each consisting of 3 case vignettes with changes in the patient's neurologic status (improvement, no change, unable to assess). Multivariable logistic regression analyses clustered by the respondent's identity were used to assess factors influencing the decision to treat. RESULTS: In total, 366 physicians (56 women, 308 men, 2 undisclosed) from 44 countries provided 3294 responses to 9 scenarios. Most (54.1%, 1782/3294) were in favor of endovascular treatment. Participants were more likely to treat occlusions in the anterior M2/3 (74.3%; risk ratio = 2.62; 95% CI, 2.27-3.03) or A3 (59.7%; risk ratio = 2.11; 95% CI, 1.83-2.42) segment compared with the M3/4 segment (28.3%; reference). Physicians were less likely to pursue endovascular treatment in patients who showed neurologic improvement than in patients with an unchanged neurologic deficit (49.9% versus 57.0% responses in favor of endovascular treatment, respectively; risk ratio = 0.88, 95% CI, 0.83-0.92). Interventionalists and more experienced physicians were more likely to treat secondary medium vessel occlusions. CONCLUSIONS: Physicians' willingness to treat secondary medium vessel occlusions endovascularly is limited and varies per occlusion location and change in neurologic status. More evidence on the safety and efficacy of endovascular treatment for secondary medium vessel occlusion stroke is needed.

MRI Head Coil Malfunction Producing Artifacts Mimicking Malformation of Cortical Development in Pediatric Epilepsy Work-Up.

We recently observed a type of MR imaging artifact that consistently mimics an abnormal appearance of the cerebral cortex, leading to initial misinterpretation and repeat scans. The artifact is caused by malfunction of part of the multichannel phased array head coil and is manifested by irregularity of cortical surface and gray-white matter junctions. The presence of such an artifact can be confirmed by assessing the background noise of the MR images and checking the coil element status on the MR imaging operator console.

FadA-positive Fusobacterium nucleatum is prevalent in biopsy specimens of Iranian patients with colorectal cancer.

Fusobacterium nucleatum has been increasingly implicated as a causative agent of various diseases, such as inflammatory bowel disease. Moreover, the gastrointestinal tracts of patients with colorectal cancer (CRC) also have been shown to be colonized by this bacterium. We aimed to determine the prevalence of F. nucleatum among CRC and non-CRC Iranian patients and to investigate potential associations between fadA-positive F. nucleatum and diagnosed CRC cases. Eighty patients admitted to two main hospitals in Tehran, Iran, were enrolled. The patients were aged between 20 and 75 and were diagnosed by a gastroenterologist. A trained surgeon used standard surgical protocols to collect two CRC biopsy samples per patient. One of the samples was used for pathologic examination, and the other was subjected to DNA extraction and PCR. Lesion colonization by F. nucleatum and expression of its major virulence factor, fadA, were investigated. The fadA-positive F. nucleatum strain was absent in all the lesions obtained from non-CRC patients. All patients with lesions that were colonized with fadA-positive F. nucleatum were diagnosed as CRC (p < 0.05); selected patients were sent for further intensive treatment. We found a significant association between the presence of F. nucleatum colonization and lesions from CRC patients (p  0.0001; odds ratio, 6.74; 95% confidence interval, 2.5-18.07). Our study confirmed colonization of the fadA-positive F. nucleatum on lesions from 80 Iranian CRC patients. New therapeutic strategies to achieve eradication of F. nucleatum are necessary for clinical management of patients suspected of having or prone to developing CRC.

Endovascular Treatment Decisions in Patients with M2 Segment MCA Occlusions.

BACKGROUND AND PURPOSE: Endovascular therapy in acute ischemic stroke is rapidly evolving. We explored physicians' treatment attitudes and practice in patients with acute ischemic stroke due to M2 occlusion, given the absence of Level-1 guidelines. MATERIALS AND METHODS: We conducted an international multidisciplinary survey among physicians involved in acute stroke care. Respondents were presented with 10 of 22 case scenarios (4 with proximal M2 occlusions and 1 with a small-branch M2 occlusion) and asked about their treatment approach under A) current local resources, and B) assumed ideal conditions (no monetary or infrastructural restraints). Overall treatment decisions were evaluated; subgroup analyses by physician and patient baseline characteristics were performed. RESULTS: A total of 607 physicians participated. Most of the respondents decided in favor of endovascular therapy in M2 occlusions, both under current local resources and assumed ideal conditions (65.4% versus 69.6%; P = .017). Under current local resources, older patient age (P < .001), longer time since symptom onset (P < .001), high center endovascular therapy volume (P < .001), high personal endovascular therapy volume (P = .005), and neurosurgeons (P < .001) were more likely to favor endovascular therapy. European respondents were less likely to favor endovascular therapy (P = .001). Under assumed ideal conditions, older patient age (P < .001), longer time since symptom onset (P < .001), high center endovascular therapy volume (P = .041), high personal endovascular therapy volume (P = .002), and Asian respondents were more likely to favor endovascular therapy (P = .037). Respondents with more experience (P = .048) and high annual stroke thrombolysis treatment volume (P = .001) were less likely to favor endovascular therapy. CONCLUSIONS: Patients with M2 occlusions are considered appropriate candidates for endovascular therapy by most respondents in this survey, especially by those performing endovascular therapy more often and those practicing in high-volume centers.

Displaying Multiphase CT Angiography Using a Time-Variant Color Map: Practical Considerations and Potential Applications in Patients with Acute Stroke.

Various imaging protocols exist for the identification of vessel occlusion and assessment of collateral flow in acute stroke. CT perfusion is particularly popular because the color maps are a striking visual indicator of pathology. Multiphase CTA has similar diagnostic and prognostic ability but requires more expertise to interpret. This article presents a new multiphase CTA display format that incorporates vascular information from all phases of the multiphase CTA series in a single time-variant color map, thereby facilitating multiphase CTA interpretation, particularly for less experienced readers. Exemplary cases of multiphase CTA from this new display format are compared with conventional multiphase CTA, CT perfusion, and follow-up imaging to demonstrate how time-variant multiphase CTA color maps facilitate assessment of collateral flow, detection of distal and multiple intracranial occlusions, differentiation of pseudo-occlusion from real occlusion, and assessment of flow relevance of stenoses, ante- and retrograde flow patterns, and clot permeability.

How Do Physicians Approach Intravenous Alteplase Treatment in Patients with Acute Ischemic Stroke Who Are Eligible for Intravenous Alteplase and Endovascular Therapy? Insights from UNMASK-EVT.

BACKGROUND AND PURPOSE: With increasing use of endovascular therapy, physicians' attitudes toward intravenous alteplase in endovascular therapy-eligible patients may be changing. We explored current intravenous alteplase treatment practices of physicians in endovascular therapy- and alteplase-eligible patients with acute stroke using prespecified case scenarios and compared how their current local treatment practices differ compared with an assumed ideal environment. MATERIALS AND METHODS: In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 of 22 case scenarios, among them 14 with guideline-based alteplase recommendations (9 with level 1A and 5 with level 2B recommendation) and were asked how they would treat the patient: A) under their current local resources, and B) under assumed ideal conditions. Answer options were the following: 1) anticoagulation/antiplatelet therapy, 2) endovascular therapy, 3) endovascular therapy plus intravenous alteplase, and 4) intravenous alteplase. Decision rates were calculated, and multivariable regression analysis was performed to determine variables associated with the decision to abandon intravenous alteplase. RESULTS: In cases with guideline recommendations for alteplase, physicians favored alteplase in 82.0% under current local resources and in 79.3% under assumed ideal conditions (P < .001). Under assumed ideal conditions, interventional neuroradiologists would refrain from intravenous alteplase most often (6.28%, OR = 2.40; 95% CI, 1.01-5.71). When physicians' current and ideal decisions differed, most would like to add endovascular therapy to intravenous alteplase in an ideal setting (196/3861 responses, 5.1%). CONCLUSIONS: In patients eligible for endovascular therapy and intravenous alteplase, we observed a slightly lower decision rate in favor of intravenous alteplase under assumed ideal conditions compared with the decision rate under current local resources.

Endovascular Treatment Decision Making in Octogenarians and Nonagenarians : Insights from UNMASK EVT an International Multidisciplinary Study.

BACKGROUND: Evidence for efficacy and safety in stroke patients ≥80 years is limited, since they were underrepresented in randomized thrombectomy trials. This study sought to explore how physicians approach endovascular therapy (EVT) decision making in octogenarians and nonagenarians under their current local resources under assumed ideal conditions, i.e. without external (monetary or infrastructural) limitations. METHODS: In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 out of a pool of 22 case scenarios with different evidence levels for EVT, 4 of which involved octogenarians and 2 nonagenarians, and asked how they would treat the patient in the given scenario A) under their current local resources and B) under assumed ideal conditions, i.e. with no external restraints. Decision rates were calculated and clustered multivariable regression analysis performed to determine adjusted measures of effect size for patient age. RESULTS: In octogenarians, physicians decided in favor of EVT in 76.7% (all of which were level 2B evidence scenarios) under current local resources and in 80.2% under assumed ideal conditions. In nonagenarians, 74.0% decided in favor of EVT under current local resources (level 1A scenarios: 87.7%, level 2B scenarios: 60.3%) and 79.2% would offer EVT under assumed ideal conditions (level 1A scenarios: 91.3%, level 2B scenarios: 67.2%). Age was not a significant predictor for treatment decision under current local resources (adjusted odds ratio, OR: 0.99, confidence interval, CI: 0.96-1.02 per decile increase) and under assumed ideal conditions (adjusted OR: 1.00, CI 0.97-1.03 per decile increase). CONCLUSION: The vast majority of physicians participating in this survey would offer EVT to acute ischemic stroke patients above 80 years.

Ultrabroadband 3D invisibility with fast-light cloaks.

An invisibility cloak should completely hide an object from an observer, ideally across the visible spectrum and for all angles of incidence and polarizations of light, in three dimensions. However, until now, all such devices have been limited to either small bandwidths or have disregarded the phase of the impinging wave or worked only along specific directions. Here, we show that these seemingly fundamental restrictions can be lifted by using cloaks made of fast-light media, termed tachyonic cloaks, where the wave group velocity is larger than the speed of light in vacuum. On the basis of exact analytic calculations and full-wave causal simulations, we demonstrate three-dimensional cloaking that cannot be detected even interferometrically across the entire visible regime. Our results open the road for ultrabroadband invisibility of large objects, with direct implications for stealth and information technology, non-disturbing sensors, near-field scanning optical microscopy imaging, and superluminal propagation.

Validation of the diagnostic criteria for atopic dermatitis.

OBJECTIVE: To validate the accuracy of newly proposed diagnostic criteria for atopic dermatitis (AD). DESIGN: Double-blind, cross-sectional study comparing the achievement of new criteria with the diagnosis of a dermatologist. SETTING: A private, general dermatology, outpatient clinic. PATIENTS: A sample of 416 consecutive patients attending the clinic within 2 months (146 males and 270 females), consisting of 60 patients with AD and 356 control patients with other skin diseases. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of proposed criteria in the diagnosis of AD. RESULTS: Sensitivity, specificity, and positive and negative predictive values of proposed diagnostic criteria for AD were 10.0% (95% confidence interval [CI], 4.1%-21.2%), 98.3% (95% CI, 96.2%-99.3%), 50.0% (95% CI, 22.3%-77.7%), and 86.6% (95% CI, 82.8%-89.7%), respectively. CONCLUSIONS: These diagnostic criteria for AD are highly specific and are suitable for clinical trials. However, they may not achieve enough sensitivity to be useful for large, population-based epidemiological studies or for routine clinical practice, at least in Iran.

The factor V Leiden mutation increases the risk of venous thrombosis in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). The aim of this study was to determine the incidence and possible association of the factor V Leiden mutation with the development of thrombosis in patients with IBD. METHODS: This retrospective study included 11 patients with IBD and arterial or venous thrombosis and 51 patients with IBD and no history of thrombosis who were matched for age, sex, ethnic/racial origin, and type of IBD (controls). The presence of the factor V Leiden mutation was determined by coagulation assay and confirmed by a polymerase chain reaction method. RESULTS: Four of 11 IBD patients (36%) with thrombosis and 2 of 51 IBD controls (4%) were heterozygotes for the factor V Leiden mutation (relative risk, 14.00; 95% confidence interval, 1.55-169.25; P = 0.009, Fisher exact test). All thrombotic events in the patients with activated protein C resistance were venous with a calculated prevalence of 50% (4 of 8 patients) and a relative risk of venous thrombosis in IBD patients with factor V Leiden of 23 (95% confidence interval, 2-294; P = 0.005). CONCLUSIONS: In patients with IBD, inheritance of the factor V Leiden mutation results in a significant increased risk of venous thrombosis.

Land barriers and open oceans: effects on gene diversity and population structure in Avicennia germinans L. (Avicenniaceae).

Avicennia germinans L. is a widespread mangrove species occupying the west coast of Africa and the Atlantic and Pacific coasts of the Americas from the Bahamas to Brazil and Baja California to Peru. An amplified fragment length polymorphism (AFLP) molecular analysis was carried out to assess genetic architecture within this species and to evaluate the effects of the Atlantic Ocean and the Central American Isthmus (CAI) on population and regional genetic diversity and differentiation. In total, 349 polymorphic AFLP fragments were identified among 144 individuals from 14 populations from the east Atlantic, west Atlantic and east Pacific. Levels of genetic diversity varied considerably among populations, but were generally higher in populations from the east Atlantic. Regional differentiation between the Pacific coast and Atlantic populations was greater than between east and west Atlantic populations, suggesting that the CAI has had an important influence on population genetic structure in this species. The lower level of divergence of east Atlantic from west Atlantic populations suggests some dispersal across the Atlantic Ocean, although migration rates are probably low; Nm from GST equal to 0.41 and accumulation of private and rare alleles in the east Atlantic. Population differentiation did not appear to follow an isolation by distance model and has probably resulted from complex patterns of population bottlenecks, and founder events due to landscape changes during the Pleistocene, particularly in the west Atlantic. The molecular data provide no support for the treatment of east Atlantic populations as a separate species A. africana.