Search

Background: The optimal endovascular management of cervical carotid dissection causing tandem occlusion remains uncertain. We investigated the impact of emergent carotid stenting during endovascular treatment (EVT) for acute ischemic stroke (AIS) in patients with tandem occlusion secondary to cervical carotid artery dissection. Methods: This was a secondary analysis of patients treated with EVT for AIS due to occlusive carotid artery dissection and tandem occlusion included in the retrospective international Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD) study. We compared patients with and without emergent stenting. The primary efficacy and safety outcomes were 90-day functional independence (modified Rankin Scale 0-2) and symptomatic intracranial hemorrhage (sICH) within 24h after EVT. Procedural outcome was successful intracranial recanalization (mTICI 2b/3). We used mixed-effect logistic regression adjusting for site, age, and NIHSS. In additional analyses, we used inverse probability of treatment weighting and adjusted for ASPECTS. Results: Of the 4023 patients enrolled in STOP-CAD, 328 presented with anterior circulation AIS due to tandem occlusion and underwent EVT. The median age was 51 years (interquartile range 44-58), and 96 patients (29.3%) were female. One hundred fifty patients (45.7%) underwent emergent stenting. There was no significant association between stenting and 90-day functional independence (62.0% vs 59.7%; aOR 1.23, 95% CI 0.82-1.86, p=0.315) or sICH (7.3% vs 7.9%; aOR OR 0.95, 95% CI 0.41-2.2, p=0.913). Emergent carotid stenting was associated with successful intracranial recanalization (81.8% vs 76.6% aOR 2.62, 95% CI 1.52-4.5, p<0.001). Results did not meaningfully change in additional analyses. Conclusion: In patients presenting with an acute anterior circulation tandem occlusion secondary to cervical carotid artery dissection, emergent stenting was associated with a higher likelihood of successful intracranial recanalization but not improved functional outcomes or increased sICH. It remains unclear whether emergent stenting led to successful intracranial recanalization or patients with successful intracranial recanalization were more likely to be stented. Randomized trials are warranted.

Giant cell arteritis (GCA) is an inflammatory vasculitis affecting large and medium-sized arteries, leading to complications such as arterial dissection, blindness, and stroke. Rarely, GCA presents with Horner's syndrome due to sympathetic neuron involvement from arterial inflammation. This case report discusses an 82-year-old female with hypertension, atrial fibrillation, and arthritis who presented with a 24 h history of right eye ptosis, blurred vision, dizziness, and aching eye pain. She had a mild headache and tenderness over the right temporomandibular joint but no temporal artery tenderness. Examination revealed right eye ptosis and miosis, indicative of Horner's syndrome, with no other neurological deficits. Lab results showed elevated ESR (68 mm/h) and CRP (16 mg/L). MRI with contrast revealed mild to moderate stenosis and enhancement in bilateral MCAs and basilar artery with inflammation in the right distal extracranial ICA, suggesting an inflammatory process. The patient was started on prednisone 40 mg daily. A temporal artery biopsy confirmed GCA with characteristic histopathological findings. Her prednisone dosage was increased to 60 mg/day, and she was started on tocilizumab. This case underscores the need to consider GCA in patients with Horner's syndrome and the importance of vessel wall imaging, as early corticosteroid treatment can prevent complications like vision loss and stroke., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Emily Barr et al.)

Parkinson's disease (PD) is associated with both genetic and environmental factors; however, sporadic forms of PD account for > 90 % of cases, and PD prevalence has doubled in the past 25 years. Depending on the importance of the environmental factors, various neurotoxins are used to induce PD both in vivo and in vitro. Unlike other neurodegenerative diseases, PD can be induced in vivo using specific neurotoxic chemicals. However, no chemically induced PD model is available because of the sporadic nature of PD. Rotenone is a pesticide that accelerates the induction of PD and exhibits the highest toxicity in fish, unlike other pesticides. Therefore, in this study, we aimed to establish a model exhibiting PD pathologies such as dysfunction of DArgic neuron, aggregation of ɑ-synuclein, and behavioral abnormalities, which are known features of PD pathology, by rotenone exposure at an environmentally relevant concentration (30 nM) in developing zebrafish embryos. Our results provide direct evidence for the association between PD and muscle degeneration by confirming rotenone-induced muscle atrophy. Therefore, we conclude that the rotenone-induced model presents non-motor and motor defects with extensive studies related to muscle atrophy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear., Methods: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization., Results: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%)., Conclusions: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.)., (Copyright © 2024 Massachusetts Medical Society.)

Bagauda aelleni Villiers, 1970 (Hemiptera: Heteroptera: Reduviidae: Emesinae: Leistarchini), described from Sri Lanka, is reported from India for the first time. Based on specimens collected at Sirumalai, Tamil Nadu, the species is redescribed and various aspects of its morphology and life history are highlighted and illustrated.

This study focuses on Macrognathus pentophthalmos, one of the two freshwater spiny eel species in Sri Lanka, which was once abundant in lowland floodplains. However, since the 1980s, this species has experienced a significant population decline, the causes of which remain unknown. It is presently assessed as Critically Endangered in the National Red List. Here, we report on a juvenile and an adult M. pentophthalmos discovered in the dry zone lowlands of the island. Using the mitochondrial cytochrome oxidase subunit 1 marker, we reveal subtle genetic differences between M. pentophthalmos and its Indian congener, M. aral. Additionally, we delve into the historical records of M. pentophthalmos in Sri Lanka, tracing its decline, and suggest strategic hotspots for further investigation into its current status. This study aims to contribute insights into the enigmatic decline of this species while shedding light on its genetic relationships and proposing targeted areas for conservation efforts.

Three nominal species of the killifish genus Aplocheilus are reported from the lowlands of Sri Lanka. Two of these, Aplocheilus dayi and Aplocheilus werneri, are considered endemic to the island, whereas Aplocheilus parvus is reported from both Sri Lanka and Peninsular India. Here, based on a collection from 28 locations in Sri Lanka, also including a dataset of Asian Aplocheilus downloaded from GenBank, we present a phylogeny constructed from the mitochondrial cytochrome b (cytb), mitochondrial cytochrome c oxidase subunit 1 (cox1), and nuclear recombination activating protein 1 (rag1), and investigate the interrelationships of the species of Aplocheilus in Sri Lanka. The endemic Sri Lankan aplocheilid clade comprising A. dayi and A. werneri is recovered as the sister group to the clade comprising A. parvus from Sri Lanka and Aplocheilus blockii from Peninsular India. The reciprocal monophyly of A. dayi and A. werneri is not supported in our molecular phylogeny. A. dayi and A. werneri display strong sexual dimorphism, but species-level differences are subtle, explained mostly by pigmentation patterns. Their phenotypes exhibit a parapatric distribution and may represent locally adapted forms of a single species. Alternatively, the present study does not rule out the possibility that A. dayi and A. werneri may represent an incipient species pair or that they have undergone introgression or hybridization in their contact zones. We provide evidence that the Nilwala-Gin region of southwestern Sri Lanka may have acted as a drought refugium for these fishes., (© 2024 Fisheries Society of the British Isles.)

Background: Understanding how landscape characteristics affect animal movement is essential for conservation in human-dominated habitats. A fundamental question is how monoculture agroforests, including rubber and tea plantations, affect wildlife and its movement. Experimental translocations represent an important technique to assess animals' habitat selection while moving through agricultural matrices, especially when complemented with observations of birds' natural movements, and with "control" translocations, in which birds are moved within their natural habitat such as forest. Yet, experimental translocations have been little used for birds outside the Western Hemisphere., Methods: We conducted experimental translocations and home-range measurements on an understory forest specialist, Brown-capped Babbler (BCBA, Pellorneum fuscocapillus), and a forest generalist, Tickell's Blue Flycatcher (TBFL, Cyornis tickelliae). These species were studied in three rubber plantations, which also included some open areas mostly planted with tea, and in three forest reserves of Sri Lanka., Results: Four of the five BCBAs translocated within disturbed habitats (rubber plantations) could not return to their capture locations. However, all four individuals within undisturbed habitats (forest reserves) successfully returned to their point of origin within 10.5 daytime hours. In contrast, all TBFLs returned to their capture locations in both disturbed (n = 7) and undisturbed habitats (n = 3) within 11.3 daytime hours. A Cox-proportional survival model demonstrated that the percentage of rubber cover decreased return time, similar to the effect of open-area cover. The home range surveys (n = 13 for BCBA, n = 10 for TBFL) revealed that very little of the birds' natural home-ranges was covered by rubber (0.2% for BCBA, 13.1% for TBFL at 50% Kernel Density Estimates KDE). Home range size for BCBA was approximately half the size in disturbed habitats compared to undisturbed ones, although there was no significant difference between habitats for TBFL., Conclusions: We conclude that rubber plantations can be impermeable to understory habitat specialist birds, and even generalist species may avoid them long-term. Our findings highlight the potential utility of strips of native vegetation, particularly those featuring understory layers, as corridors to facilitate the movement of forest specialists in landscapes dominated by rubber plantations and other types of disturbed habitats., (© 2024. The Author(s).)

SummaryHereditary haemorrhagic telangiectasia (HHT) has an estimated prevalence of 1 in 5000-8000 individuals globally with pulmonary arteriovenous malformations (PAVMs) affecting approximately 15%-50% of HHT patients. Ischaemic stroke is a known complication of PAVMs that affects ≤30% of patients with PAVMs. Studies have shown that patients with PAVMs have ischaemic stroke a decade earlier than routine stroke. The predominant mechanism of ischaemic stroke in HHT patients is paradoxical embolism due to PAVMs, but most HHT-related PAVMs are asymptomatic. Additionally, HHT is often underdiagnosed in patients and poses a challenge to physicians due to its rarity. We present a case of a patient with ischaemic stroke who was subsequently diagnosed with HHT and found to have a PAVM on further evaluation. This case highlights the importance of using an individualised patient-centred stroke evaluation and screening for PAVMs in patients who had a stroke with possible or suspected HHT and definite HHT., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation., Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments., Results: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; P interaction =0.009)., Conclusions: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings., Competing Interests: Disclosures Disclosures provided by Dr Nguyen in compliance with American Heart Association annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. Dr Arnold reports compensation from Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic, Novo Nordisk, and Amgen for consultant services. Dr Lester reports a provisional patent for Methods and compositions for disrupting tau aggregates. Dr Touze reports compensation from Elsevier for other services and employment by Caen. J.E. Kaufman reports grants from Goldschmidt Jacobson-Stiftung. Dr Traenka reports travel support from Bayer Healthcare. Dr Aguiar de Sousa reports compensation from Daiichi Sankyo, Bayer, AstraZeneca, Johnson & Johnson, and Fundação Bial for other services; compensation from the University of British Columbia for data and safety monitoring services; compensation from Organon & Co for consultant services. Dr Rosa reports grants from Merck Sharp & Dohme Corporation. Dr Field reports compensation from HLS Therapeutics, AstraZeneca Canada, and Roche for consultant services; service as a board member for Destine Health; and compensation from the Canadian Medical Protective Association for expert witness services; and grants from Bayer. Dr Leker reports compensation from Medtronic, Ischemaview, Bayer, Abbott Diabetes Care, Biogen, Janssen Biotech, and Boehringer Ingelheim for other services. Dr Nolte reports compensation from Daiichi Sankyo Europe GmbH, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Alexion Pharmaceuticals for consultant services; and compensation from AstraZeneca, Abbott Canada, Deutsches Zentrum für Neurodegenerative Erkrankungen, Novartis, Portola Pharmaceuticals, Deutsches Zentrum für Herz-Kreislaufforschung, and Novartis for other services. Dr Poppe reports grants from Foundation Brain Canada, Heart and Stroke Foundation of Canada, and Stryker; and compensation from Roche for other services. Dr Liebeskind reports compensation from Medtronic, Genentech, Cerenovus, Stryker, and Rapid Medical Ltd, for consultant services. B. Mac Grory reports grants from the National Institutes of Health; employment by Duke University Medical Center; compensation from Bayer for other services; grants from the American Heart Association, Duke Bass Connections, and the Duke Office of Physician Scientist Development. Dr Al Kasab reports compensation from Stryker for other services and employment by Medical University of South Carolina. Dr Kicielinski reports compensation from Stryker, Penumbra Inc, Medtronic, and MicroVention Inc, for other services; travel support from MicroVention Inc; and employment by Medical University of South Carolina and Elsevier. Dr de Havenon reports stock options in TitinKM and Certus; grants from the National Institutes of Health; and compensation from Novo Nordisk for consultant services. Dr Siegler reports grants from Philips and employment by the University of Chicago. Dr Willey reports compensation from Edwards Lifesciences Corporation and Abbott Fund for end point review committee services; compensation from Uptodate for other services; and compensation from the Abbott Laboratories for consultant services. Dr Sharma reports a provisional patent for a stroke etiology classifier algorithm and grants from the National Institutes of Health Clinical Center. Dr Martins reports compensation from Pfizer, Medtronic, Servier Affaires Medicales, Daiichi Sankyo, Bayer, Novo Nordisk, Novartis, Penumbra Inc, and Boehringer Ingelheim for other services. Dr Simpkins reports grants from the National Institutes of Health. Dr Stretz reports grants from Massachusetts General Hospital. Dr Furie reports compensation from Janssen Biotech for consultant services. The other authors report no conflicts

As there are limited data on B-cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron, and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n = 30), WT infected (n = 30), delta infected (n = 30), omicron infected + vaccinated (n = 20) and Sinopharm (BBIBP-CorV) vaccinees (n = 30). We then investigated the sensitivity and specificity of these immunodominant regions and analyzed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses, and bat Sarbecoviruses. We identified four immunodominant regions aa 29-52, aa 155-178, aa 274-297, and aa 365-388, which were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Food allergy (FA), which is a condition that has no effective cure and can result in severe life-threatening allergic reactions, remains a global public health concern; however, little is known about how FAs are currently managed in the Asia-Pacific region., Objective: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia., Methods: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey., Results: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories., Conclusions: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies., Competing Interests: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2023 The Author(s).)

Sri Lanka's biota is derived largely from Southeast Asian lineages which immigrated via India following its early-Eocene contact with Laurasia. The island is now separated from southeastern India by the 30 km wide Palk Strait which, during sea-level low-stands, was bridged by the 140 km-wide Palk Isthmus. Consequently, biotic ingress and egress were mediated largely by the climate of the isthmus. Because of their dependence on perennial aquatic habitats, freshwater fish are useful models for biogeographic studies. Here we investigate the timing and dynamics of the colonization of-and diversification on-Sri Lanka by a group of four closely-related genera of cyprinid fishes (Puntius sensu lato). We construct a molecular phylogeny based on two mitochondrial and two nuclear gene markers, conduct divergence timing analyses and ancestral-range estimations to infer historical biogeography, and use haplotype networks to discern phylogeographic patterns. The origin of Puntius s.l. is dated to ~ 20 Ma. The source of diversification of Puntius s.l. is Sri Lanka-Peninsular India. Species confined to perhumid rainforests show strong phylogeographic structure, while habitat generalists show little or no such structure. Ancestral range estimations for Plesiopuntius bimaculatus and Puntius dorsalis support an 'Out of Sri Lanka' scenario. Sri Lankan Puntius s.l. derive from multiple migrations across the Palk Isthmus between the early Miocene and the late Pleistocene. Species dependent on an aseasonal climate survived aridification in rainforest refugia in the island's perhumid southwest and went on to recolonize the island and even southern India when pluvial conditions resumed. Our results support an historical extinction of Sri Lanka's montane aquatic fauna, followed by a recent partial recolonization of the highlands, showing also that headwater stream capture facilitated dispersal across basin boundaries., (© 2023. The Author(s).)

A comprehensive evaluation is necessary to identify the etiologic factors in order to select optimal stroke-prevention measures. Atrial fibrillation is one of the most important stroke causes. Although anticoagulant therapy is the treatment of choice for patients with nonvalvular atrial fibrillation, it should not be considered uniformly to treat all patients given the high mortality associated with anticoagulant-related hemorrhages. The authors propose a risk-stratified individualized approach for stroke prevention in patients with nonvalvular atrial fibrillation by considering nonpharmacologic approaches for patients at high hemorrhage risk or otherwise unsuitable for lifelong anticoagulation., Competing Interests: Disclosure T. Ranasinghe: no disclosures. M.E. Gurol: Neurocardiology section editor, American Heart Association Stroke journal; Chair, WSO Task Force on Cerebral Small Vessel Diseases and Vascular Cognitive Impairment; Member, WSO Brain & Heart Task Force; M.E.G.’s hospital received research funding from AVID, Pfizer, and Boston Scientific Corporation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Large vessel occlusion (LVO) stroke is a common presentation of acute ischemic stroke and is often unknown or cryptogenic in etiology. There is a strong association between atrial fibrillation (AF) and cryptogenic LVO stroke, making it a unique stroke subgroup. Therefore, we propose that any LVO stroke meeting the criteria for an embolic stroke of an undetermined source (ESUS) be classified as large ESUS (LESUS). The purpose of this retrospective cohort study was to report the etiology of anterior LVO strokes that underwent endovascular thrombectomy., Methods: This was a single-center retrospective cohort study characterizing the etiology of acute anterior circulation LVO strokes that received emergent endovascular thrombectomy from 2011 to 2018. Patients with LESUS designation at hospital discharge were changed to cardioembolic etiology if AF was discovered during the two-year follow-up period.  Results: Overall, 155 (45%) of 307 patients in the study were found to have AF. New onset AF was discovered in 12 (23%) of 53 LESUS patients after hospitalization. Furthermore, eight (35%) of 23 LESUS patients who received extended cardiac monitoring were found to have AF., Conclusion: Nearly half the patients with LVO stroke who received endovascular thrombectomy were found to have AF. With the use of extended cardiac monitoring devices after hospitalization, AF is frequently discovered in patients with LESUS and may change the secondary stroke prevention strategy., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Seachrist et al.)

Background: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine., Methods: Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19., Results: We identified four immunodominant regions aa 29-52, aa 155-178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses., Conclusions: N-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines.

The kinetics and magnitude of antibody responses to different proteins of the SARS-CoV-2 virus in Sinopharm/BBIBP-CorV vaccinees has not been previously studied. Therefore, we investigated antibody responses to different SARS-CoV-2 proteins at 2 weeks, 3 months, and 6 months post-second dose in previously infected (n = 20) and uninfected (n = 20) Sinopharm/BBIBP-CorV vaccinees. The IgG antibodies to the S, S1 and S2 and N were several folds higher in those who had natural infection compared to uninfected individuals at all time points. We then compared the persistence of antibody responses and effect of natural omicron infection or BNT162b2 booster in Sinopharm/BBIBP-CorV vaccinees. We measured the total antibodies to the RBD, ACE2 blocking antibodies and antibody responses to different SARS-CoV-2 proteins in Sinopharm vaccinees at 7 months post second dose, including those who remained uninfected and not boosted (n = 21), or those who had previous infection and who did not obtain the booster (n = 17), those who were not infected, but who received a BNT162b2 booster (n = 30), or those who did not receive the booster but were infected with omicron (n = 29). At 7 months post second dose uninfected (no booster) had the lowest antibody levels to the RBD, while omicron infected vaccinees showed significantly higher anti-RBD antibody levels (p = 0.04) than vaccinees who received the booster. Only 3/21 cohort A (14.3%) had ACE2 blocking antibodies, while higher frequencies were observed in naturally infected individuals (100%), those who received the booster (18/21, 85.7%), and omicron infected individuals (100%). Pre-vaccination, naturally infected had the highest antibody levels to the N protein. These data suggest that those previously infected Sinopharm/BBIBP-CorV vaccinees have a robust antibody response, 7 months post vaccination, while vaccinees who were naturally infected with omicron had a similar immune response to those who received the booster. It will be important to investigate implications for subsequent clinical protection., Competing Interests: The authors have declared that no competing interests exist.

As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. SARS-CoV-2-specific antibodies were measured in 282 individuals who were seronegative at baseline, and ACE2 receptor blocking antibodies, antibodies to the receptor-binding domain (RBD) of the wild-type (WT), alpha, beta and delta variants, ex vivo and cultured IFNγ ELISpot assays, intracellular cytokine secretion assays and B cell ELISpot assays were carried out in a sub cohort of the vaccinees at 4 and 6 weeks (2 weeks after the second dose). Ninety-five percent of the vaccinees seroconverted, although the seroconversion rates were significantly lower (p < 0.001) in individuals >60 years (93.3%) compared to those who were 20-39 years (98.9%); 81.25% had ACE2 receptor blocking antibodies at 6 weeks, and there was no difference in these antibody titres in vaccine sera compared to convalescent sera (p = 0.44). Vaccinees had significantly less (p < 0.0001) antibodies to the RBD of WT and alpha, although there was no difference in antibodies to the RBD of beta and delta compared to convalescent sera; 27.7% of 46.4% of vaccinees had ex vivo IFNγ and cultured ELISpot responses respectively, and IFNγ and CD107a responses were detected by flow cytometry. Sinopharm/BBIBP-CorV appeared to induce a similar level of antibody responses against ACE2 receptor, delta and beta as seen following natural infection., (© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)

To determine the antibody responses elicited by different vaccines against SARS-CoV-2, we compared antibody responses in individuals 3 months post-vaccination in those who had received different vaccines in Sri Lanka. Abs to the receptor binding domain (RBD) of the ancestral (wild type) virus (WT) as well as to variants of concern (VoCs), and ACE2 blocking Abs, were assessed in individuals vaccinated with Moderna (n = 225), Sputnik V (n = 128) or Sputnik light (n = 184) and the results were compared with previously reported data on Sinopharm and AZD1222 vaccinees. A total of 99.5% of Moderna, >94% of AZD1222 or Sputnik V and >70% of Sputnik light, >60% of Sinopharm vaccine recipients, had a positive response to ACE2 blocking antibodies. The ACE2 blocking antibody levels were highest to lowest was Moderna > Sputnik V/AZD1222 (had equal levels) > Sputnik light > Sinopharm. All Moderna recipients had antibodies to the RBD of WT, alpha and beta, while positivity rates for delta variant was 80%. The positivity rates for Sputnik V vaccinees for the WT and VoCs were higher than for AZD1222 vaccinees while those who received Sinopharm had the lowest positivity rates (<16.7%). The total antibodies to the RBD were highest for the Sputnik V and AZD1222 vaccinees. The Moderna vaccine elicited the highest ACE2 blocking antibody levels followed by Sputnik V/AZD1222, while those who received Sinopharm had the lowest levels. These findings highlight the need for further studies to understand the effects on clinical outcomes., (© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)

Background: There are limited data regarding the safety and immunogenicity of the Sinopharm/BBIBP-CorV vaccine in pregnancy. Therefore, we sought to investigate the antibody responses and maternal and fetal adverse events following this vaccine in pregnant mothers in Sri Lanka., Methods and Findings: SARS-CoV-2 receptor binding domain (RBD) specific total antibodies and ACE2 blocking antibodies were measured by ELISA in pregnant mothers (n = 94) who received the vaccine in the first (n = 2), second (n = 57) and third (n = 33) trimester of pregnancy. Data regarding adverse events and fetal and maternal outcomes were obtained from the women once they delivered. No adverse maternal or fetal complications reported such as miscarriage, thrombotic events, hypertensive disorders, fetal death, preterm delivery, or congenital anomalies were reported. 58/94 (61.7%) had RBD binding antibodies and were found to be seropositive at the time of recruitment. All women seroconverted after the second dose and 31/36 previously uninfected women and 57/58 previously infected women gave a positive response to ACE2 blocking antibodies. The RBD binding antibody levels (p = 0.0002) and ACE2 blocking antibodies (p<0.0001) were significantly higher in previously infected individuals post-second dose compared to uninfected individuals., Conclusions: The Sinopharm/ BBIBP-CorV vaccine appeared safe and induced high seroconversion rates and ACE2 blocking antibodies in pregnant mothers in the second and third trimester in pregnancy. However, the RBD binding antibodies and ACE2 blocking antibodies post-second dose were significantly higher in previously infected pregnant mothers post-second dose, suggesting that two doses of the vaccine are likely to be less immunogenic in previously unexposed individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Jeewandara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222 (Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD, and N proteins in patients at 4 weeks and 12 weeks since the onset of illness or following vaccination. Antibodies to the receptor-binding domain of SARS-CoV-2 wild type (WT), α, β, and λ and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. For those with mild illness and in vaccines, the IgG responses to S1, S2, RBD, and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccines, IgG antibodies to the S2 subunit had the highest significant rise (P < 0.0001). Vaccines had several-fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the haemagglutination test (HAT) titres were significantly lower to the α in vaccines and significantly lower in those with mild illness and in vaccines to β and for λ. No such difference was seen in those with moderate/severe illness. Vaccines had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccines had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.)

Ricefishes of the genus Oryzias occur commonly in the fresh and brackish waters in coastal lowlands ranging from India across Southeast Asia and on to Japan. Among the three species of Oryzias recorded from peninsular India, two widespread species, O. carnaticus and O. dancena , have previously been reported from Sri Lanka based on museum specimens derived from a few scattered localities. However, members of the genus are widespread in the coastal lowlands of Sri Lanka, a continental island separated from India by the shallow Palk Strait. Although recent molecular phylogenies of Adrianichthyidae represent near-complete taxon representation, they lack samples from Sri Lanka. Here, based on sampling at 13 locations representative of the entire geographic and climatic regions of the island's coastal lowlands, we investigate for the first time the molecular phylogenetic relationships and phylogeography of Sri Lankan Oryzias based on one nuclear and two mitochondrial markers. Sri Lankan Oryzias comprise two distinct non-sister lineages within the javanicus species group. One of these is represented by samples exclusively from the northern parts of the island; it is recognized as O. dancena . This lineage is recovered as the sister group to the remaining species in the javanicus group. The second lineage represents a species that is widespread across the island's coastal lowlands. It is recovered as the sister group of O. javanicus and is identified as O . cf. carnaticus . Ancestral-range estimates suggest two independent colonizations of Indian subcontinent and Sri Lanka by widespread ancestral species of Oryzias during two discrete temporal windows: late Miocene and Plio-Pleistocene. No phylogeographic structure is apparent in Sri Lankan Oryzias , suggesting that there are no strong barriers to gene flow and dispersal along the coastal floodplains, as is the case also for other generalist freshwater fishes in the island., Competing Interests: The authors declare no competing interests., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals., Methods: SARS-CoV-2 specific total antibodies were measured in 20-39 years (n = 61), 40-59 years (n = 120) and those >60 years of age (n = 22) by enzyme-linked immunosorbent assay, 12 weeks after the second dose of the vaccine. Angiotensin-converting enzyme 2 (ACE2) receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor-binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays., Results: A total of 193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. A total of 14.3%-16.7% individuals in the 20-39 age groups had detectable antibodies to the RBD of the WT and variants of concern, while the positivity rates of those ≥60 years of age was <10%. A total of 14/49 (28.6%) had Interferon gamma ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined from 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40-59 (p = .0007) and ≥60 (p = .005) age groups., Conclusions: Antibody responses declined in all age groups, especially in those ≥60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

A comprehensive evaluation is necessary to identify the etiologic factors in order to select optimal stroke-prevention measures. Atrial fibrillation is one of the most important stroke causes. Although anticoagulant therapy is the treatment of choice for patients with nonvalvular atrial fibrillation, it should not be considered uniformly to treat all patients given the high mortality associated with anticoagulant-related hemorrhages. The authors propose a risk-stratified individualized approach for stroke prevention in patients with nonvalvular atrial fibrillation by considering nonpharmacologic approaches for patients at high hemorrhage risk or otherwise unsuitable for lifelong anticoagulation., Competing Interests: Disclosure T. Ranasinghe: no disclosures. M.E. Gurol: Neurocardiology section editor, American Heart Association Stroke journal; Chair, WSO Task Force on Cerebral Small Vessel Diseases and Vascular Cognitive Impairment; Member, WSO Brain & Heart Task Force; M.E.G.’s hospital received research funding from AVID, Pfizer, and Boston Scientific Corporation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps., Methods: Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2-blocking antibodies (ACE2-blocking Abs), antibodies to the receptor-binding domain (RBD) of  variants of concern (VOC), and ex vivo T cell responses were assessed in a subcohort., Results: All individuals (100%) had SARS-CoV-2-specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2-blocking Abs. There was no difference in antibody titers or positivity rates in different age groups in both cohorts. The ACE2-blocking Abs (p < .0001) and antibodies to the RBD of the VOCs were significantly higher in cohort 2 compared to cohort 1. 41.2% to 65.8% of different age groups gave a positive response by the hemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6%-90% gave a positive response in cohort 2. 17/57 (29.8%) of cohort 1 and 17/29 (58.6%) of cohort 2 had ex vivo interferon (IFN)γ ELISpot responses above the positive threshold. The ACE2-blocking antibodies (Spearman's r = .46, p = .008) and ex vivo IFNγ responses (Spearman's r = .71, p < .0001) at 12 weeks post first dose, significantly correlated with levels 12 weeks post second dose., Conclusions: Both dosing schedules resulted in high antibody and T cell responses post vaccination, although those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

A national programme to universally screen the population between 35 and 65 years for non-communicable diseases was established at 'Healthy Lifestyle Centres (HLCs)' in 2011 in Sri Lanka. Despite several efforts by policymakers, the uptake of screening remained <10% of the target population and with disparities in uptake across districts and among men and women. Considering service beneficiaries as a vital stakeholder, a discrete choice experiment was carried out to estimate people's preference for a non-communicable disease screening service delivery model in rural, urban and estate sectors in a district in Sri Lanka. The choice design and the general survey questionnaire was developed through focus group discussions, literature reviews and stakeholder consultations. Data were collected by stratified random sampling, with 187 participants from the urban sector, 253 from the rural sector and 152 from the estate/plantation sector. People's preference was assessed as utility estimates derived using multinomial logistic regression. Reliability was assessed within test among all study participants and with test-retest among 40 participants showed 80% precision. Urban and rural sectors gave the highest priority to workplace screening over screening at HLCs. The estates attributed the highest priority for cost-free screening. If cost-free screening is offered with having to spend 1-2 hours at the most preferred opening times for each sector with warm and friendly staff, the uptake of screening can predicted to be increased by 65, 29 and 21 times in urban, rural and estate sectors, respectively, relative to having to attend HLCs from 8 a.m. to 4 p.m., spending >2 hours and Rs. 1000 with unfriendly staff. Thus, people's preferences on service delivery aspects seemed to have differed from government priorities. Preferences when ill and apparently healthy differed, as they preferred to spend less time and money when healthy than when ill., (© The Author(s) 2021. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial., (© 2022. The Author(s).)