The Involvement of Complement Factor B and Complement Component C2 in an Indian Cohort with Age-Related Macular Degeneration

PURPOSE. Genes involved in the complement cascade such as complement factor B (CFB) and complement component C2 have been implicated in age-related macular degeneration (AMD) worldwide. In continuation of the analysis of CFH and LOC387715/HTRA1, this study was conducted to gain understanding of the role of CFB and C2 in an Indian AMD cohort. METHODS. Single nucleotide polymorphisms in CFB and C2 were screened in a cohort of clinically well-characterized patients with AMD (n ϭ 177) and unaffected normal control subjects (n ϭ 175). Screening was accomplished by a combination of customized genotyping followed by validation through resequencing. In addition, genotyping of two CFB variants (rs12614 and rs641153) that were in close proximity had to be resolved by resequencing. Estimates of allele and genotype frequencies, odds ratios, Hardy-Weinberg equilibrium, linkage disequilibrium (LD), and haplotype frequencies were also performed. RESULTS. Three SNPs in C2 (rs547154 [IVS10] ; P ϭ 5.4 ϫ 10 Ϫ11 ) and CFB (rs641153 [R32Q], P ϭ 2.2 ϫ 10 Ϫ7 and rs2072633 [IVS17]; P ϭ 2.0 ϫ 10 Ϫ4 ) were strongly associated with reduced risk of AMD. The rs547154 and rs641153 were in strong LD (DЈ ϭ 0.90, 95% CI ϭ 0.81-0.96) and a protective haplotype T-A was observed (OR ϭ 0.10, 95% CI ϭ 0.05-0.20). LD was moderate (DЈ ϭ 0.77, 95% CI ϭ 0.67-0.85) between the rs547154 and the rs2072633 SNPs, and the haplotype T-T generated with these SNPs was relatively less protective (OR ϭ 0.28, 95% CI ϭ 0.18 -0.44). CONCLUSIONS. The results of the present study provide an independent validation of the association of rs547154 (C2) and rs641153 (CFB) SNPs with reduced risk of AMD in an Indian cohort. (Invest Ophthalmol Vis Sci

Hybrid‐Mobile Stroke Unit: Opening the Indication Spectrum for Stroke Mimics and Beyond

Background Despite proven benefits, the use of single‐purpose mobile stroke units (MSUs) has raised concerns about their effective and cost‐efficient integration into clinical practice, especially when considered for operation in nonurban areas. The MSU concept may benefit from opening the indication spectrum to include frequent stroke mimics and additional emergencies. Methods The current observational study evaluated benefits for the treatment and triage decision‐making of use of an MSU with extended capabilities (Hybrid‐MSU), also including radiography, ultrasonography, extended point‐of‐care laboratory, ECG, electroencephalography, and advanced medications. Apart from patients with a dispatch code for “stroke”, the ambulance was also dispatched to those with codes for “seizures”, “falls with head trauma”, “headache”, “unconsciousness”, “infection and pandemic”, “chest pain”, and “breathing problems”. Results For 250 patients treated by the Hybrid‐MSU, but not for 250 conventionally treated patients, the prehospital diagnostic workup allowed, apart from treatment with stroke thrombolytics (n=15), prehospital administration of specific anticonvulsants (n=15), antibiotics (n=5), early secondary stroke prophylaxis with aspirin (n=49), and the Sepsis Six bundle (n=2). Prehospital diagnosis avoided 215 (86.0%) admissions to the emergency department, either by management at home (n=116, 46.4%) or by directly transferring patients to the required specialized wards (n=99, 39.6%). Conclusion The current study demonstrates the feasibility of the use of a Hybrid‐MSU and indicates its potential benefits for prehospital treatment and triage decision‐making. Opening the indication spectrum, together with an act‐alone ability, could be a key in the future integration of MSUs into routine health care

Mobile Stroke Unit in the UK Healthcare System:Avoidance of Unnecessary Accident and Emergency Admissions for the Majority of Patients

Background And Aims: Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay. To explore the benefit of a Mobile Stroke Unit (MSU) in the United Kingdom (UK) National Health Service for reduction of hospital admissions.Methods: Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea. Emergency patients categorised as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to accident and emergency (A&E) department, rate of admission directly to target ward and stroke management metrics were assessed.Results: In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); other conditions, n = 38 (32.8%). Prehospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Prehospital diagnosis avoided hospital admission for 29 (25.0%) patients. If hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the A&E department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40–60).Conclusions: This first deployment of an MSU in the UK National Health Service demonstrated improved triage decision-making for or against hospital admission and to the appropriate target ward, thereby potentially reducing pressure on strained A&E departments

Hypolipidemic Effect of Celastrus paniculatus in Experimentally Induced Hypercholesterolemic Wistar Rats

The objective of the present study was to evaluate hypolipidemic effect of methanolic extract of Celastrus paniculatus in experimentally induced hypercholesterolemic rats. Hypercholesterolemia was induced by feeding the animals with high fat diet. Oral administration of methanolic seed extract (50%) of Celastrus paniculatus at the optimized dose of 65 mg/kg body weight, substantially reduced the plasma total cholesterol, triglycerides and LDL cholesterol in comparison with induced hypercholesterolemic animal group and the results were comparable with the standard hypocholesterolemic drug and almost similar to the control group. Atherogenic index and liver weight of treated animals also showed significant decrease compared to the hypercholesterolemic animals. It substantially increased the HDL cholesterol level as compared to control group. A significant increase in the activities of lipoprotein lipase and plasma LCAT enhanced hepatic bile acid synthesis and thereby, increased degradation of cholesterol to neutral sterols. Furthermore, the activities of HMG-CoA reductase, glucose 6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Histological studies showed less cholesterol deposits in the aorta of animals fed with seed extract of C. paniculatus compared to the induced hypercholesterolemic animals not given C. paniculatus supplement