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Traditional developmental toxicity testing practice examines fetal apical endpoints to identify a point of departure (POD) for risk assessment. A potential new testing paradigm involves deriving a POD from a comprehensive analysis of molecular-level change. Here, the rat ketoconazole endocrine-mediated developmental toxicity model was used to test the hypothesis that maternal epigenomic (miRNA) and transcriptomic (mRNA) PODs are similar to fetal apical endpoint PODs. Sprague-Dawley rats were exposed from gestation day (GD) 6-21 to 0, 0.063, 0.2, 0.63, 2, 6.3, 20, or 40 mg/kg/day ketoconazole. Dam systemic, liver, and placenta PODs, along with GD 21 fetal resorption, body weight, and skeletal apical PODs were derived using BMDS software. GD 21 dam liver and placenta miRNA and mRNA PODs were obtained using three methods: a novel individual molecule POD accumulation method, a first mode method, and a gene set method. Dam apical POD values ranged from 2.0 to 38.6 mg/kg/day; the lowest value was for placenta histopathology. Fetal apical POD values were 10.9-20.3 mg/kg/day; the lowest value was for fetal resorption. Dam liver miRNA and mRNA POD values were 0.34-0.69 mg/kg/day, and placenta miRNA and mRNA POD values were 2.53-6.83 mg/kg/day. Epigenomic and transcriptomic POD values were similar across liver and placenta. Deriving a molecular POD from dam liver or placenta was protective of a fetal apical POD. These data support the conclusion that a molecular POD can be used to estimate, or be protective of, a developmental toxicity apical POD.

Aim: The neutropenic diet is commonly prescribed to cancer patients with neutropenia with the goal of reducing infections. However, multiple randomized trials have proved no benefit with neutropeni...

Introduction: The ADAPT technique uses large bore aspiration catheters for mechanical thrombectomy. Several aspiration catheters are now available. We report a bench-top exploration of a beveled-tip catheter, and our experience in treating large vessel occlusions using next-generation aspiration catheters. Methods: Twenty experiments were conducted with either a Sofia Plus or a Zoom71 using a vascular phantom in which a clot model was introduced. Rate of ingestion, complete recanalization after a single attempt, and pressure at the catheter tip for both devices were recorded. A retrospective analysis from a prospectively-maintained database was performed. Patient demographics, periprocedural metrics, discharge and 90-day modified Rankin Scales were collected. Patients were divided into two groups based on which aspiration catheter was used. Results: In our bench-top experiment, complete ingestion of the clot occurred in 90% of beveled tip and 20% of control device experiments (p=0.006). Our clinical data demonstrated no significant difference in age, gender, IV tPA administration, admission NIHSS, baseline mRS, or LVO location between the beveled tip and flat tip groups. With the beveled tip, TICI 2C or better recanalization was more frequent (93.2% vs 74.2%, p-value 0.017), stent retriever usage was lower (9.1% versus 29%, p-value 0.024), and patients had lower mRS on discharge (median 3 vs 4, p less than 0.001) and at 90 days (median 2 vs 4, p=0.008). Conclusion: The beveled tip design leads to more frequent clot ingestion in a bench top model, which may translate into a more efficacious thrombectomy device with improved outcomes.

Considerations of human relevance and animal use are driving research to identify new approaches to inform risk assessment of chemicals and replace guideline-based rodent carcinogenicity tests. Here, the hypothesis was tested across four agrochemicals that 1) a rat 90-day transcriptome-based BEPOD is protective of a rat carcinogenicity study and 2) a subchronic liver or kidney BEPOD would approximate a cancer bioassay apical POD derived from other organs and a rat subchronic BEPOD would approximate a mouse cancer bioassay apical POD. Using RNA sequencing and BMDExpress software, liver and/or kidney BEPOD values were generated in male rats exposed for 90 days to either Triclopyr Acid, Pronamide, Sulfoxaflor, or Fenpicoxamid. BEPOD values were compared to benchmark dose-derived apical POD values generated from rat 90-day and rodent carcinogenicity studies. Across all four agrochemicals, findings showed that a rat 90-day study BEPOD approximated the most sensitive apical POD (within 10-fold) generated from the 90-day rat study and long-term rodent carcinogenicity studies. This study supports the conclusion that a subchronic transcriptome-based BEPOD could be utilized to estimate an apical POD within a risk-based approach of chronic toxicity and carcinogenicity agrochemical assessment, abrogating the need for time- and resource-intensive rodent carcinogenicity studies and minimizing animal testing.

BackgroundDirect aspiration thrombectomy techniques use large bore aspiration catheters for mechanical thrombectomy. Several aspiration catheters are now available. We report a bench top exploration of a novel beveled tip catheter and our experience in treating large vessel occlusions (LVOs) using next-generation aspiration catheters.MethodsA retrospective analysis from a prospectively maintained database comparing the bevel shaped tip aspiration catheter versus non-beveled tip catheters was performed. Patient demographics, periprocedural metrics, and discharge and 90-day modified Rankin Scale (mRS) scores were collected. Patients were divided into two groups based on which aspiration catheter was used.ResultsOur data showed no significant difference in age, gender, IV tissue plasminogen activator administration, admission NIH Stroke Scale score, baseline mRS, or LVO location between the beveled tip and flat tip groups. With the beveled tip, Thrombolysis in Cerebral Infarction (TICI) 2C or better recanalization was more frequent overall (93.2% vs 74.2%, p=0.017), stent retriever usage was lower (9.1% vs 29%, p=0.024), and patients had lower mRS on discharge (median 3 vs 4, pConclusionPatients who underwent mechanical thrombectomy with the beveled tip catheter had a higher proportion of TICI 2C or better and had a significantly lower mRS score on discharge and at 90 days.

There are few data comparing outcomes of transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) in patients with chronic kidney disease. In this retrospective cohort study using the National Inpatient Sample 2011 to 2014, we included a total of 2,820 TAVI and 4,054 SAVR procedures, representative of 14,039 TAVI and 19,835 SAVR procedures nationally. Co-primary outcomes were in-hospital mortality, acute kidney injury (AKI), dialysis-requiring AKI, and postoperative stroke. In multivariate analysis, TAVI was associated with a lower in-hospital mortality (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.32 to 0.69, p 0.001), rates of AKI (OR 0.18, 95% CI 0.14 to 0.22, p 0.001), dialysis-requiring AKI (OR 0.30, 95% CI 0.20 to 0.44, p 0.001), and postoperative stroke (OR 0.27, 95% CI 0.13 to 0.53, p 0.001) compared with SAVR. In 1001 propensity-matched pairs of TAVI and SAVR procedures, TAVI was associated with lower in-hospital mortality (OR 0.67, 95% CI 0.45 to 0.99, p = 0.047) rates of AKI (OR 0.39, 95% CI 0.32 to 0.46, p 0.001), dialysis-requiring AKI (OR 0.53, 95% CI 0.35 to 0.81, p 0.001), postoperative stroke (OR 0.46, 95% CI 0.20 to 0.98, p = 0.045), significantly shorter length of stay (OR 0.35, 95% CI 0.29 to 0.42, p 0.001), and nonsignificant difference in cost (OR 1.05, 95% CI 0.88 to 1.26, p = 0.57) compared with SAVR. In conclusion, TAVI may be a preferable approach to SAVR in patients with severe aortic stenosis in the setting of chronic kidney disease.

The carbohydrate-binding molecule galectin-3 has garnered significant attention recently as a biomarker for various conditions ranging from cardiac disease to obesity. Although there have been several recent studies investigating its role in stroke and other cerebrovascular diseases, awareness of this emerging biomarker in the wider neurology community is limited. We performed a systematic search in PubMed, Embase, Scopus, CINAHL, Clinicaltrials.gov and the Cochrane library in November and December 2016 for articles related to galectin-3 and cerebrovascular disease. We included both human and pre-clinical studies in order to provide a comprehensive view of the state of the literature on this topic. The majority of the relevant literature focuses on stroke, cerebral ischemia and atherosclerosis, but some recent attention has also been devoted to intracranial and subarachnoid hemorrhage. Higher blood levels of galectin-3 correlate with worse outcomes in atherosclerotic disease as well as in intracranial and subarachnoid hemorrhage in human studies. However, experimental evidence supporting the role of galectin-3 in these phenotypes is not as robust. It is likely that the role of galectin-3 in the inflammatory cascade within the central nervous system following injury is responsible for many of its effects, but its varied physiological functions and multiple sites of expression mean that it may have different effects depending on the nature of the disease condition and the time since injury. In summary, experimental and human research raises the possibility that galectin-3, which is closely linked to the inflammatory cascade, could be of value as a prognostic marker and therapeutic target in cerebrovascular disease.

ObjectiveThe efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs.MethodsWe searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model.ResultsInclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management).ConclusionIAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty.

Background and Aims: Many studies have conclusively proven that meditative techniques derived from the Indian systems of philosophy, meditation and ritual classified as “Tantra” can bring about sustained changes in the structure and function of the nervous system of practitioners. The aim of this study is to provide neuroscientists a framework through which to interpret Tantra, and thereby provide a foundation upon which future interdisciplinary study can be built. Methods: We juxtapose Tantric concepts such as the subtle body, nadis and mantras with relevant neuroscientific findings. Our premise is that through sustained internalization of attention, Tantric practitioners were able to identify and document subtle changes in their field of awareness, which usually do not cross the threshold to come into our perception. Results: The descriptions left by Tantric philosophers are often detailed and empirical, but they are about subjective phenomena, rather than external objects. They also focus on individual experiences, rather than the group-level analyses favored by modern medical science. Conclusion: Systematic exploration of Tantric texts can be of tremendous value in expanding our understanding of human beings' experiential reality, by enabling us to build bridges between first-person and third-person approaches to the nervous system. This may open up new avenues for cognitive enhancement and treating neurological diseases.

The ataxic syndrome associated with Anti‐Yo antibody, or Purkinje cell cytoplasmic antibody type 1 (PCA1), is the most common variant of paraneoplastic cerebellar degeneration (PCD). The typical presentation involves the subacute development of pancerebellar deficits with a clinical plateau within 6 months. The vast majority of cases have been reported in women with pelvic or breast tumors. Magnetic resonance imaging of the brain is often normal in the early stages, with cerebellar atrophy seen later. The underlying mechanism is believed to be an immunological reaction to cerebellar degeneration‐related protein 2 (CDR2), a protein usually found in the cerebellum that is ectopically produced by tumor cells. Although both B‐ and T‐cell abnormalities are seen, there is debate about the relative importance of the autoantibodies and cytotoxic T lymphocytes in the neuronal loss. Cerebrospinal fluid abnormalities, primarily elevated protein, lymphocytic pleocytosis, and oligoclonal bands, are common in the early stages. The low prevalence of this condition has not allowed for large‐scale randomized controlled trials. Immunotherapies, such as steroids, intravenous immune globulins, and plasma exchange, have been extensively used in managing this condition, with limited success. Although some reports indicate benefit from antitumor therapies like surgery and chemotherapy, this has not been consistently observed. The prognosis for anti‐Yo PCD is almost uniformly poor, with most patients left bedridden. Further studies are required to clarify the pathophysiology and provide evidence‐based treatment options.

The carbohydrate binding molecule Galectin-3 has been the focus of recent study in a variety of disease processes, and there is evidence that it plays a role in diseases of the cerebrovascular system. In this review, we summarize the relevant clinical literature on the role of Galectin-3 in ischemic stroke, intracranial hemorrhage and subarachnoid hemorrhage. We also provide a brief overview of the cellular and molecular mechanisms behind the role played by Galectin-3 following ischemic brain injury. Our review is aimed at clinicians who manage these conditions, and neuroscientists who study the role of biomarkers in cerebrovascular disease.

Introduction The relationship between serum galectin-3 and incident cognitive impairment was analyzed in the Reasons for Geographic and Racial Differences in Stroke study. Methods Baseline galectin-3 was measured in 455 cases of incident cognitive impairment and 546 controls. Galectin-3 was divided into quartiles based on the weighted distribution in the control group, and the first quartile was the referent. Results There was an increasing odds of cognitive impairment across quartiles of galectin-3 (odds ratios, 1.00 [0.68–1.46], 1.45 [1.01–2.10], and 1.58 [1.10–2.27] relative to the quartile 1; P trend = .003) in an unadjusted model, which persisted after adjusting for age, sex, and race (P = .004). Adjustment for cardiovascular risk factors greatly attenuated this association (odds ratios, 0.97 [0.60–1.57], 1.52 [0.94–2.46], and 1.27 [0.76–2.12]; P = .15). The association differed by diabetes status (P interaction, .007). Among nondiabetics (293 cases, 411 controls), those with galectin-3 in the fourth compared with first quartile had an odds ratio of 1.6 (0.95–2.99; P trend, .02). In diabetics, the odds ratio was 0.23 (0.04–1.33). Discussion Serum galectin-3 was associated with increased risk of incident cognitive impairment in a large cohort study of blacks and whites but only in nondiabetics.

BACKGROUND Control of systolic blood pressure (SBP) after primary intracerebral hemorrhage improves outcomes. Factors determining the number of blood pressure medications (BPM) required for goal SBP

Aim: End-stage renal disease is a prevalent and growing health problem worldwide. With increasing Internet use, video-sharing websites could potentially serve as a powerful platform for dissemination of information on dialysis. We conducted a cross-sectional study to assess the accuracy, content and viewership of YouTube videos on dialysis. Methods: YouTube videos identified using the search term 'dialysis' were classified independently by two physicians as 'useful,' 'misleading' and 'patient's personal experiences'. Five-point ordinal scales were used to grade reliability and quality. Information regarding source of upload, content in seven pre-defined domains and various viewer interaction metrics was collected. Results: Of the 115 videos with cumulative duration of 16.2 h and viewership of approximately 2.7 million, 67 (58.3%) were useful, 19 (16.5%) were misleading and 29 (25.2%) represented patient's personal experiences; kappa statistic for inter-observer agreement was 0.985. Useful videos were the most comprehensive and had the highest reliability and quality scores. However, viewership per day was the lowest for useful videos at a median of 3 (interquartile range (IQR) 1-17), as compared with 11 (IQR 4-43) for misleading videos and 14 (IQR 5-30) for patient experiences (P = 0.013). All misleading videos were uploaded by individual users with unknown credentials. Of these, 68.4% promoted alternative therapies such as herbs and osmotherapy; 47.4% included advertisements for related services. Conclusions: Viewers favoured misleading videos and patient narratives over scientifically accurate information. Authoritative sources should use popular social media websites to provide relevant and easy-to-understand information on dialysis; including patient stories can make this material more engaging.

Introduction It is suspected that Web 2.0 web sites, with a lot of user-generated content, often support viewpoints that link autism to vaccines. Methods We assessed the prevalence of the views supporting a link between vaccines and autism online by comparing YouTube, Google and Wikipedia with PubMed. Freedom of speech is highest on YouTube and progressively decreases for the others. Results Support for a link between vaccines and autism is most prominent on YouTube, followed by Google search results. It is far lower on Wikipedia and PubMed. Anti-vaccine activists use scientific arguments, certified physicians and official-sounding titles to gain credibility, while also leaning on celebrity endorsement and personalized stories. Conclusions Online communities with greater freedom of speech lead to a dominance of anti-vaccine voices. Moderation of content by editors can offer balance between free expression and factual accuracy. Health communicators and medical institutions need to step up their activity on the Internet.

We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids.

Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably alter the lipid profile. We sought to examine the rates of ischaemic stroke and neurocognitive deficits in patients treated with and without PCSK9 inhibitors. Methods and results Randomized controlled trials (RCTs) reporting rates of ischaemic stroke and neurocognitive deficits in patients using PCSK9 inhibitors were identified. Standard meta-analysis techniques were used to compare these outcomes among patients treated with and without PCSK9 inhibitors and the two US Food and Drug Administration-approved PCSK9 inhibitors, evolocumab and alirocumab. The results were presented in terms of risk ratio (RR) with 95% confidence intervals (CIs). Sixteen RCTs with 39 104 patients were included. Evolocumab was used in six RCTs with 33 450 patients, whereas alirocumab was used in 10 RCTs with 5654 patients. We observed a significantly lower risk of ischaemic stroke among those treated with PCSK9 inhibitors (RR 0.77, 95% CI 0.64-0.93) when compared with those without. We did not observe any difference in the risk of neurocognitive deficits between the aforementioned groups (RR 1.11, 95% CI 0.93-1.32). The lower stroke risk in the PCSK9 inhibitors group was driven by evolocumab studies. We observed no difference in the risk of neurocognitive deficits among evolocumab and alirocumab when compared with no PCSK9 inhibitors group. Conclusion Treatment with PCSK9 inhibitors significantly lowers the risk of ischaemic stroke, without any increased risk of neurocognitive deficits. PCSK9 inhibitors are neuroprotective due to the decrease in ischaemic-mediated neurovascular events and should be considered cognitively innocuous medications.

Background and purpose Galectin-3 is a biomarker of atherosclerotic and cardiovascular disease, and may be a useful marker for ischaemic stroke risk. Methods The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled and examined 30 239 US participants between 2003 and 2007 (41% black, 59% white and 55% in the southeastern stroke belt). Baseline galectin-3 was measured in 526 subjects with incident ischaemic stroke over 5.4 years and in a cohort random sample (CRS) of 947 participants. Cox proportional hazards models were used to calculate hazard ratios (HRs) of ischaemic stroke by quartiles of galectin-3. Results In the CRS, galectin-3 was significantly higher with older age, black race, female sex, body mass index, hypertension, diabetes mellitus and kidney disease, and also in those who developed incident stroke. Participants with galectin-3 levels in the fourth versus first quartile had a 2.3-fold increased stroke risk [95% confidence interval (CI) 1.6, 3.4] in an unadjusted model. An interaction with age was found (P = 0.06), and therefore age-stratified analyses were performed. Amongst those younger than age 64, baseline galectin-3 in the second–fourth quartiles was associated with increased stroke risk (HR 3.0, 95% CI 1.6, 5.5) compared to the first quartile in an age-, race- and sex-adjusted model. The HR was 2.0 (95% CI 1.0, 4.0) with multivariable adjustment. There was no association amongst older participants. Conclusions Galectin-3 was associated with incident ischaemic stroke in younger but not older individuals. Confirmation of this finding, and elucidation of its implications for stroke pathophysiology and prevention, is needed.

Dear Editor, We read with great interest, the recent article by Ling et al. who hypothesized that following the launch of a campaign for a medical condition, information seeking behavior pertaining to the condition would increase as well1. They used data from Google Trends (Google Inc., CA) on 4 different diseases (including Colon Cancer) to conclude that the use of infoveillance shows promise as an alternative and inexpensive solution for disease surveillance and health care campaign evaluation. Cancer awareness has massively benefitted from rapid growth of internet and mass media and the evolution of social marketing strategies around the promotion of healthcare2,3. This has resulted in the development of cancer oriented societies, websites, public campaigns and specifically earmarked Cancer Awareness Months (CAMs) directed at changing public attitudes towards prevention, screening, treatment and informed decision making. However, despite the significant impact of cancer awareness on screening of preventable cancers4, the impact of CAMs on cancer-related internet search activity has not been well studied. Breast (BC), Lung (LC) and Colorectal Cancers (CRC) are the leading causes of cancer incidence and mortality among women 5 and have their respective CAMs during October, November and March respectively 6. Using Google Trends, a public web facility of Google Inc. based on Google Search, we compared the relative frequency of search of terms ‘Breast Cancer’,‘Lung Cancer’ and ‘Colon Cancer’ between 1st January 2004 and 31st January 2017 (n=158 months). The program assigns a reference value of 100 for the point of maximum popularity from among the search terms, and provides relative monthly scores for all terms, which we termed interest scores (IS). IS were then compared among cancers for the overall period (n=158 months) and specifically during their CAMs (n=13 months). Within each cancer, IS were then compared during the CAMs (n=13 months) as compared to the remaining months (n=145 months). Parametric and non-parametric analyses were carried out (wherever applicable) using ANOVA and Kruskal-Wallis tests respectively. A p-value of

Background: Patients with primary intracerebral hemorrhage (pICH) are at risk of airway compromise and commonly undergo intubation. Poor outcomes have been reported for these patients. Factors predicting intubation prior to admission (PTA), and after admission are unknown. These factors may be helpful in predicting which pICH patients require intubation, and its optimal timing. Methods: Patients with pICH directly admitted or transferred from another facility to our center were included. Patients with SAH, SDH, epidural hemorrhage, underlying lesions, or infarct with hemorrhagic transformation were excluded. Intubation note from medical chart was used to determine the timing of intubation. Demographic and clinical data were recorded. The primary outcome was a discharge mRS (dmRS) of 4-6. Results: A total of 370 patients were included. Patients intubated PTA had a lower average GCS (6 vs. 9; p=0.0003) and a higher average NIHSS (26 vs. 18; p=0.0007) than those intubated after admission. Higher incidences of hematoma expansion (30.9% vs. 16.3%; p=0.0253), tracheostomies performed (17.5% vs. 4.8%; p=0.0004), ICH volumes > 30cc (40% vs. 25.5%; p=0.0352), and pneumonia (35.1% vs. 5.4%; p Conclusions: Lower GCS and higher NIHSS significantly predict intubation in pICH patients PTA. ICH volumes > 30cc, hematoma expansion and pneumonia significantly predict intubation after admission. Intubation is significantly associated with poor functional outcomes independent of ICH score and pneumonia. Location of ICH does not predict intubation.

Summary Chordomas are rare tumors that can develop anywhere along the craniospinal axis. These tumors present challenges with respect to diagnosis and treatment due to a high rate of recurrence, even after multiple surgeries, and the propensity to involve any region within the craniospinal axis. New developments in radiation therapy have improved recurrence-free survival in patients with chordomas. Different regimens of chemotherapy and molecularly-targeted therapies, as adjuvants to surgery, have been described in individual case reports and case series. The purpose of this paper is to describe a case of clival chordoma and review recent developments in diagnostic and therapeutic options. A 77-year-old female was referred because of diplopia and progressively worsening headaches. Head imaging revealed a large expansile and erosive mass in the skull base. The patient underwent a successful endoscopic endonasal trans-sphenoidal resection of the mass, with biopsy confirming the diagnosis of chordoma. Postoperatively, the patient experienced an improvement in neurological symptoms. Chordomas can present a diagnostic challenge due to the rare occurrence and a tendency to involve any region within the craniospinal axis.

Summary: Lateralized periodic discharges (LPDs) are commonly seen on EEG in critically ill patients. They are often associated with seizures, but some patients may have them without seizures. Therefore, they are considered to lie in the ictal–interictal continuum. When ictal, they require multiple antiepileptic drugs to treat effectively, which can expose the patient to iatrogenic complications. Therefore, optimal management is controversial. We present here two cases where perfusion-weighted MRI was useful in distinguishing ictal from interictal LPDs. In the first patient, hyperperfusion in the area showing LPDs was considered an indication that the LPDs were ictal, and aggressive treatment led to clinical improvement. The second patient had no asymmetry on perfusion-weighted MRI, and therefore, we did not escalate antiepileptic therapy, and the LPDs resolved spontaneously over the next few days. Perfusion-weighted MRI offers several advantages over other techniques, such as single-photon emission computerized tomography that have been used for this purpose before. It does not expose the patient to radiation, and newer techniques like arterial spin labeling can even obviate the need for intravenous contrast. Larger scale studies using perfusion-weighted MRI will be of great value to clinical practice.

Objective: Previous meta-analyses have not reported pooled estimates of response to the treatment of vasospasm with intra-arterial vasodilators (IADs) in aneurysmal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to pool estimates of angiographic & clinical response, good outcome, & mortality rates following treatment of vasospasm with IADs. Methods: We searched PubMed using MeSH terms for “Subarachnoid Hemorrhage" AND ("Endovascular Procedures" OR "Infusions, Intra-Arterial") AND "Vasodilator Agents". Bibliographies of retrieved articles were also searched. Studies reporting clinical and angiographic response, mortality, and outcome, following IAD treatment of vasospasm in adult humans with aSAH were included. All IADs were allowed. Two authors independently selected studies & abstracted data. Mean weighted probabilities (MWP) were calculated using random effects model. Results: Inclusion criteria were met by 48 studies (n=1264). Heterogeneity was significant in all syntheses (I2 ≥50%; P< 0.5) and studies were of poor quality. Publication bias was significant for the synthesis of mortality. MWP for immediate angiographic response to IAD treatment was 90% (95% CI 84-95%), post-IAD neurological improvement 59% (95% CI 47-71%), good outcome 56% (95% CI 49-63%), and Mortality rate was 9% (95% CI 6-12%). Subgroup analysis is shown in the table. Conclusion: IAD treatment leads to a fair angiographic and neurologic response but the impact on outcome is unknown. Studies were of poor quality and bias was significant. Current evidence does not support the use of IADs for the treatment of cerebral vasospasm in aSAH. Randomized/pragmatic trials are needed to elucidate the role of IADs in vasospasm in aSAH.

In view of the reported association of SNPs in the paraoxonase (PON1) gene with coronary artery disease (CAD), and the absence of conclusive data from India, we investigated the relationship of three SNPs at different loci (-108C/T, L55M and Q192R) of the PON1 gene and their haplotypes with CAD among people residing in the northern plains of India.One hundred and seventy-eight healthy controls and two hundred and four angiographically-proven CAD patients were genotyped using PCR-RFLP.Of the three SNPs, only the R allele of Q192R polymorphism was associated with CAD (p0.05). Two locus haplotypes QT (OR 0.55, p=0.0004, 95% CI 0.39-0.77, significant) and LQ (odds ratio 0.73, p=0.03, 95% CI 0.55-0.97, trend) showed protective effects, while haplotypes MR (OR=5.36, p=0.0001, 95% CI 2.045-14.049) and MC (OR=2.71, p=0.011, 95% CI 1.221-6.046) were associated with increased risk of CAD. MRT, a minor three-locus haplotype also displayed significant association (OR 4.93, 95% CI 1.7-13.5) with the disease. Significance was assessed after applying Bonferroni's correction.Our study revealed that only one SNP at a single locus but several haplotype combinations of PON1 coding and promoter-region polymorphisms were associated with the risk of or protection against CAD. Thus, haplotype analysis brought better insights into the association of PON1 gene polymorphisms with CAD in Asian Indians.

The Gene Ontology Normal Usage Tracking System (GONUTS) is a community-based browser and usage guide for Gene Ontology (GO) terms and a community system for general GO annotation of proteins. GONUTS uses wiki technology to allow registered users to share and edit notes on the use of each term in GO, and to contribute annotations for specific genes of interest. By providing a site for generation of third-party documentation at the granularity of individual terms, GONUTS complements the official documentation of the Gene Ontology Consortium. To provide examples for community users, GONUTS displays the complete GO annotations from seven model organisms: Saccharomyces cerevisiae, Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus and Arabidopsis thaliana. To support community annotation, GONUTS allows automated creation of gene pages for gene products in UniProt. GONUTS will improve the consistency of annotation efforts across genome projects, and should be useful in training new annotators and consumers in the production of GO annotations and the use of GO terms. GONUTS can be accessed at http://gowiki.tamu.edu. The source code for generating the content of GONUTS is available upon request.

EcoliWiki is the community annotation component of the PortEco (http://porteco.org; formerly EcoliHub) project, an online data resource that integrates information on laboratory strains of Escherichia coli, its phages, plasmids and mobile genetic elements. As one of the early adopters of the wiki approach to model organism databases, EcoliWiki was designed to not only facilitate community-driven sharing of biological knowledge about E. coli as a model organism, but also to be interoperable with other data resources. EcoliWiki content currently covers genes from five laboratory E. coli strains, 21 bacteriophage genomes, F plasmid and eight transposons. EcoliWiki integrates the Mediawiki wiki platform with other open-source software tools and in-house software development to extend how wikis can be used for model organism databases. EcoliWiki can be accessed online at http://ecoliwiki.net.

A single-nucleotide promoter region polymorphism (-108C/T) of the paraoxonase (PON1) gene had been suggested to influence an individual's susceptibility to coronary artery disease (CAD). No data is available on this polymorphism from India. One hundred seventy-eight healthy individuals and 204 angiographically proven CAD patients were recruited to get baseline data on the frequency distribution of the -108C/T polymorphism in normal people of Asian Indian ethnicity and its relation with the risk of CAD. Polymerase chain reaction followed by restriction fragment length analysis was used as the method for genotyping. Blood samples were used for DNA isolation. In the normal subjects, the genotypes were distributed as CT (43.26%) > CC (30.34%), >TT (26.4%). The allele frequency of the C allele was 0.52, and that of the T allele was 0.48. The patients showed a similar pattern, but the TT genotype was about two times more frequent in the controls than in patients. Odds ratios for developing CAD for individuals with CT, TT, and CT + TT genotypes were 0.89 (0.50–1.59), 0.56 (0.27–1.08), and 0.76 (0.44–1.29), respectively (at 95% confidence interval), when compared to CC homozygous people (age- and sex-adjusted, p = 0.114, all genotypes compared). This suggested a trend for the T allele as protective against CAD. This first report on the frequency distribution of the -108C/T polymorphism in people of Asian Indian ethnicity suggests that the normal distribution is similar to that observed for the Chinese, Japanese, and Latino people, but the disease association is unique. The TT genotype and the T allele which are widely found associated with the risk of CAD showed a protective trend in this study.

e18940Background: Neutropenic Diet (ND) is commonly recommended and widely practiced for cancer patients with neutropenia with the goal of reducing infections. However, multiple randomized trials s...

Background and objectives: There are limited data on racial differences in clinical and economic outcomes of acute ischemic stroke (AIS) hospitalizations in the US. We sought to ascertain the effect of race on AIS outcomes in a population based retrospective cohort study. Methods: We used the 2012 National Inpatient Sample (NIS), which is the largest database of inpatient stays in the US, to identify cases of AIS using ICD9-CM codes 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91 and 437.1 in patients >=18 years of age. Cases with missing data on race were excluded (5% of study sample). Primary outcome was in-hospital mortality. Secondary outcomes included proportion receiving endovascular mechanical thrombectomy (EMT) or thrombolysis, mean inflation adjusted charges and length of stay. Linear and logistic regression was used to test differences in continuous and categorical outcomes respectively. Survey techniques were used for all analyses. Results: There were 452, 330 hospitalizations for AIS in patients >=18 years in 2012. In univariate logistic regression using race as predictor, in-hospital mortality was significantly lower for Blacks (p Conclusions: Blacks hospitalized for AIS have significantly lower in-hospital mortality compared to whites but are significantly less likely to receive thrombolysis compared to whites. Total charges and length of stay are significantly higher for racial minorities. Future studies should investigate mechanisms of this apparent protective effect of black race on in-hospital mortality in AIS.

Background and objectives: Seasonal patterns in incidence and mortality are well known for cardiovascular diseases (CVD) including acute myocardial infarction and arrhythmias. It is unclear whether in-hospital mortality in patients with acute ischemic stroke (AIS) exhibits seasonal variation. Methods: We searched the 2011 Nationwide Inpatient Sample for discharges with a principal diagnosis of AIS using the ICD-9 codes 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91 and 437.1. Seasonal variation in in-hospital mortality was tested using logistic regression with admission season and month as categorical predictors in separate models. In addition to annual variation, we tested for the “July effect” of increase in mortality in teaching hospitals. Results: There was an estimated 467, 849 discharges for AIS of which 21,149 (4.53%) died in the hospital. Compared to summer months, the risk of in-hospital mortality was 12.6% higher in winter and 10.2% higher in the fall (p=0.004 for winter vs. summer, p=0.024 for fall vs. summer). Compared to August, mortality was 18.20% higher in January (p=0.026 for comparison) and 24.3% higher in December (p=0.003 for comparison) (Table shows odds ratio of death compared to reference season/month). We did not find any evidence of a “July effect” of increased mortality, often attributed to new trainees, in teaching hospitals (p=0.830 for June vs. July) Conclusions: In a large national database of hospital discharges related to AIS, mortality was significantly higher in colder months compared to warmer months. Our study adds to the growing body of evidence that links winter season to worse outcomes in CVD.

End-stage renal disease is a prevalent and growing health problem worldwide. With increasing Internet use, video-sharing websites could potentially serve as a powerful platform for dissemination of information on dialysis. We conducted a cross-sectional study to assess the accuracy, content and viewership of YouTube videos on dialysis.YouTube videos identified using the search term 'dialysis' were classified independently by two physicians as 'useful,' 'misleading' and 'patient's personal experiences'. Five-point ordinal scales were used to grade reliability and quality. Information regarding source of upload, content in seven pre-defined domains and various viewer interaction metrics was collected.Of the 115 videos with cumulative duration of 16.2 h and viewership of approximately 2.7 million, 67 (58.3%) were useful, 19 (16.5%) were misleading and 29 (25.2%) represented patient's personal experiences; kappa statistic for inter-observer agreement was 0.985. Useful videos were the most comprehensive and had the highest reliability and quality scores. However, viewership per day was the lowest for useful videos at a median of 3 (interquartile range (IQR) 1-17), as compared with 11 (IQR 4-43) for misleading videos and 14 (IQR 5-30) for patient experiences (P = 0.013). All misleading videos were uploaded by individual users with unknown credentials. Of these, 68.4% promoted alternative therapies such as herbs and osmotherapy; 47.4% included advertisements for related services.Viewers favoured misleading videos and patient narratives over scientifically accurate information. Authoritative sources should use popular social media websites to provide relevant and easy-to-understand information on dialysis; including patient stories can make this material more engaging.

Investigators at the Baylor College of Medicine Human Genome Sequencing Center (BCM–HGSC) and BeeBase organized a community-wide effort to manually annotate the honey bee (Apis mellifera) genome. Although various strategies for manual annotation have been used in the past, the value of dispersed community annotation has not yet been demonstrated. Here we make a case for the merit of dispersed community annotation. We present annotation procedures, standard protocols, and tools used for sequence analysis, data submission, and data management. We also report lessons learned from this dispersed community annotation effort for a metazoan genome.

Background: Transcatheter Aortic Valve Replacement (TAVR) has been found to be a safe and effective alternative to Surgical Aortic Valve Replacement (SAVR) in patients with a high/intermediate surgical risk. Comparative outcomes of TAVR vs. SAVR have not been well studied in patients with CKD.

Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease caused by a pathogenic glutamine repeat expansion in the protein ataxin-1 (ATXN1). One likely mechanism mediating pathogenesis is excessive transcriptional repression induced by the expanded ATXN-1. Because ATXN1 binds HDAC3, a Class I histone deacetylase (HDAC) that we have found to be required for ATXN1-induced transcriptional repression, we tested whether genetically depleting HDAC3 improves the phenotype of the SCA1 knock-in mouse (SCA1(154Q/2Q)), the most physiologically relevant model of SCA1. Given that HDAC3 null mice are embryonic lethal, we used for our analyses a combination of HDAC3 haploinsufficient and Purkinje cell (PC)-specific HDAC3 null mice. Although deleting a single allele of HDAC3 in the context of SCA1 was insufficient to improve cerebellar and cognitive deficits of the disease, a complete loss of PC HDAC3 was highly deleterious both behaviorally, with mice showing early onset ataxia, and pathologically, with progressive histologic evidence of degeneration. Inhibition of HDAC3 may yet have a role in SCA1 therapy, but our study provides cautionary evidence that this approach could produce untoward effects. Indeed, the neurotoxic consequences of HDAC3 depletion could prove relevant, wherever pharmacologic inhibition of HDAC3 is being contemplated, in disorders ranging from cancer to neurodegeneration.

Hypertension (HTN) is a prevalent and growing public health problem in the United States and worldwide. Video sharing Web sites such as YouTube could potentially influence patient behaviors via properties of interpersonal and mass media communication. We conducted this cross-sectional study to assess the accuracy and content of YouTube videos on HTN and understand how viewers interact with this online information. We analyzed 209 videos (31.57 hours) of which 63% were classified as useful, 33% as misleading, and 4% represented patient's personal experiences. Number of views per day and "likes" were significantly lower for useful videos. Approximately half the misleading videos contained product advertisements, 70% advocated unproven alternative treatments, and 91% targeted patients. Viewer engagement (number of views) was a poor predictor of usefulness and/or content whereas source of upload, and target audiences were good predictors of usefulness and/or content. Videos uploaded by university channels and/or professional organizations that targeted physicians had a 99.4% (P .001) probability of being useful whereas videos uploaded by individuals with unknown credentials that targeted patients had a 21.2% (P .001) probability of being useful. A majority of HTN-related videos on YouTube are useful. Viewer engagement is significantly higher with videos that contain misleading and/or erroneous information in comparison to videos that contain useful information.