Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate.We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjectivemethod and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients

Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle

Citation: Wendel, S. O., Menon, S., Alshetaiwi, H., Shrestha, T. B., Chlebanowski, L., Hsu, W. W., . . . Troyer, D. L. (2015). Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle. Plos One, 10(5), 13. doi:10.1371/journal.pone.0128144The recent WHO report on antibiotic resistances shows a dramatic increase of microbial resistance against antibiotics. With only a few new antibiotics in the pipeline, a different drug delivery approach is urgently needed. We have obtained evidence demonstrating the effectiveness of a cell based drug delivery system that utilizes the innate immune system as targeting carrier for antibacterial drugs. In this study we show the efficient loading of neutrophil granulocytes with chlorhexidine and the complete killing of E. coli as well as Fusobacterium necrophorum in in-vitro studies. Fusobacterium necrophorum causes hepatic abscesses in cattle fed high grain diets. We also show in a mouse model that this delivery system targets infections of F. necrophorum in the liver and reduces the bacterial burden by an order of magnitude from approximately 2.10(6) to 1.10(5)

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age \u3e60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p\u3c0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality

Air Pollution in Delhi: A Review of Past and Current Policy Approches

Delhi National Capital Region (Delhi NCR) is facing serious challenges linked to worrying levels of air pollution (mainly NO2, PM10 and PM2.5). The CADTIME prject (Clean Air in Delhi through Implementation, Mitigation and Engagement) aims to understand what is required to deliver significant reductions in levels of air pollution. This paper presents the results of the first stage of the project: it firstly contextualises the challenges of air quality management in Delhi within the broader evolution of environmental policies and governance in India, with particular consideration to the tensions between environmental protection and the country’s development objectives. Secondly, it sets out how CADTIME will combine multiple source qualitative and quantitative data to develop an air quality action plan and an implementation strategy. In particular, through two workshops with local and national experts and stakeholders, and two rounds of focus groups with citizens of Delhi we will contrast stakeholders’ priorities and preferences for existing and potential solutions to air pollution with citizens’ lived experiences, thus assessing the political/technical feasibility and public acceptability of current and proposed measures. Furthermore, we will complement the primary qualitative data with a critical review examining the successes and failures of UK and European policies to draw lessons that can be relevant for Delhi and to avoid ineffective policies and achieve cost-effective solutions for the city in the shortest possible time

महिषासुर: मिथक व परंपराएं

इक्कसवीं सदी के दूसरे दशक में भारत में महिषासुर आंदोलन द्विज संस्कृति के लिए चुनौती बनकर उभरा। इसके माध्यम से आदिवासियों, पिछड़ों और दलितों के एक बड़े हिस्से ने अपनी सांस्कृतिक दावेदारी पेश की। लेकिन यह आंदोलन क्या है, इसकी जड़ें समाज में कहां तक फैली हैं, बहुजनों की सांस्कृतिक परंपरा में इसका क्या स्थान है, मौजूदा लोक-जीवन में महिषासुर की उपस्थिति किन-किन रूपों में है, इसके पुरातात्विक साक्ष्य क्या हैं? गीतों-कविताओं व नाटकों में महिषासुर किस रूप में याद किए जा रहे हैं और अकादमिक-बौद्धिक वर्ग को इस आंदोलन ने किस रूप में प्रभावित किया है, उनकी प्रतिक्रियाएं क्या हैं? आदि प्रश्नों पर विमर्श हमें एक ऐसी बौद्धिक यात्रा की ओर ले जाने में सक्षम हैं, जिससे हममें अधिकांश अभी तक अपरिचित रहे हैं। क्या महिषासुर दक्षिण एशिया के अनार्यों के पूर्वज थे, जो बाद में एक मिथकीय चरित्र बन कर बहुजन संस्कृति के प्रतीक पुरुष बन गए? क्या यह बहुत बाद की परिघटना है, जब माकण्डेय पुराण, दुर्गासप्तशती जैसे ग्रंथ रच कर, एक कपोल-कल्पित देवी के हाथों महिषासुर की हत्या की कहानी गढ़ी गई? इस आंदोलन की सैद्धांतिकी क्या है? प्रमोद रंजन द्वारा संपादित किताब “महिषासुर: मिथक व परंपराएं” में लेखकों ने उपरोक्त प्रश्नों पर विचार किया है तथा विलुप्ति के कगार पर खड़े असुर समुदाय का विस्तृत नृवंशशास्त्रीय अध्ययन भी प्रस्तुत किया है। इस पुस्तक में समकालीन भारतीय साहित्य में महिषासुर पर लिखी गई कविताओं व गीतों का प्रतिनिधि संकलन भी है तथा महिषासुर की बहुजन कथा पर आधारित एक नाटक भी प्रकाशित है। समाज-विज्ञान व सांस्कृतिक विमर्श के अध्येताओं, सामाजिक-राजनीतिक कार्यकर्ताओं, साहित्य प्रेमियों के लिए यह एक आवश्यक पुस्तक है

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau-Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers.

Importance: Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. Objective: To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. Design, Setting, and Participants: In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau-T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively). Conclusions and Relevance: Plasma P-tau levels and P-tau-T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau-T-tau ratios show more robust and sustained elevations among patients with chronic TBI.This study was supported in part by the Office of the Assistant Secretary of Defense for Health Affairs through the Department of Defense (DOD) Broad Agency Announcement under award numbers W81XWH-11-2-0069 (Dr Rubenstein) and W81XWH-14-2-0166 (Dr Rubenstein). It was also supported in part by National Institutes of Health (NIH) grant RC2 NS069409 (Dr Manley), NIH grant 1U01 NS086090-01 (Dr Manley), US DOD grant W81XWH-14-2-0176 (Dr Manley), US DOD grant W81XWH-13-1-04 (Dr Manley), NIH grant R21NS085455-01 (Dr Wang), and University of Florida McKnight Brain Institute BSCIRTF fund (Dr Wang)

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Irradiation induced optical and electrical modification of Lexan films

591-594Low energy Argon ions have been irradiated on to the surface of Lexan polycarbonate (PC) films using an electron cyclotron resonance ion source (ECRIS). Different energy of Argon ions have been used for the study by limiting the value of fluence to 1.04×1016 ions/cm2. The ion irradiation has brought changes in electrical, optical and chemical properties of Lexan films. The results obtained from the study show an increase in the surface conductivity after irradiation, shift in optical absorption edge with decrease in optical energy gap and decrease in the intensity of peaks related to C=O, C-C, C-O groups. The irradiated films can find its application in antireflection materials, microelectronics devices and other surface coating applications

The expanding spectrum of pediatric anti-glutamic acid decarboxylase antibody mediated CNS disease - a chance association?

Central nervous system autoimmunity in the pediatric age group represents an evolving constellation of various syndromes distinct from the adult age group. One of the rarely described pathogenic auto-antibodies (ab) is the one directed against glutamic acid decarboxylase (GAD). While its pathogenic role is controversial, literature concerning adult patients abounds with heterogeneous presentations with epilepsy often as part of limbic encephalitis or chronic temporal lobe epilepsy and cerebellar ataxia accompanying endocrinopathies or paraneoplastic disorders. Diagnosis is often delayed until late adulthood. The authors report hitherto under-reported syndromes in the pediatric age group. The first case was a 3-year-old boy with sub-acute myoclonus-ataxia following a flu-like illness akin to para-infectious cerebellitis. The second case was a 7-year-old girl with long-standing chronic extratemporal partial epilepsy and electrical status epilepticus in sleep (ESES) with right hemiparesis and developmental delay. Investigations revealed two-four fold elevations in titres of GAD-65-ab. The absence of systemic diseases like diabetes and the dramatic clinical response to steroids as well as intravenous immunoglobulin in both the cases argued for GAD-ab mediated neuronal injury rather than a chance association. The concern exists regarding other potentially co-existent auto-ab to gamma-amino butyric acid and glycine receptors, and demonstration of intrathecal synthesis of GAD-ab would be ideal. This entity should be contemplated in children presenting with acute/sub-acute onset episodic or progressive ataxia or refractory cryptogenic focal epilepsy syndromes, epileptic encephalopathy such as ESES and worsening neurological deficits. These children ought to be maintained on regular follow-up for monitoring evolution of other autoimmune disorders in adult life