Detecting the Effect of Umckaloabo/EPs®7630 Liquid Extract after its Therapeutic Purposed Usage in Calves Showing Symptoms of Respiratory Tract Infection

Background: Respiratory tract diseases are commonly seen in beef cattle. Young calves are affected with many respiratory pathogens. Viral pathogens are particularly seen. There are many causative factors, e.g. environmental conditions, immune system of calves. Therefore, alternative treatments are needed for viral respiratory infections. The purpose of the current study was to investigate effectiveness of Umckaloabo/EPs®7630 liquid extract in some bovine viral pathogens of young beef calves.Materials, Methods & Results: Antibody presence in terms of bovine herpesvirus type 1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine parainfluenza virus type 3 (BPIV-3), bovine respiratory syncytial virus (BRSV) and bovine adenovirus type 3 (BAV-3) was searched in blood serum samples of 40 Holstein calves aged 6 months and over showing respiratory tract infection symptoms. All animals were found seronegative in terms of other factors except BRSV. Out of 20 BRSV seropositive calves, 10 of them were classified as control group and the other ten as testing group. BRSV antibody titers were also detected in blood samples of both groups on day 0. Umckaloabo/EPs®7630 liquid extract was given through oral route to animals in testing group according to their weights for 14 days morning, noon and night. No application was performed on animals in control group. BRSV antibody titers were detected in blood samples of animals in both groups taken on days 1st, 3rd, 5th, 7th, 10th and 14th. At the end of day 14th, BRSV antibody titer increased in 9 out of 10 animals (90%) in testing group that were given Umckaloabo/EPs® 7630 liquid extract while one of them (10%) showed no variability. BRSV antibody titer increased in 6 out of 10 animals (60%) in control group while it decreased in one of them (10%) and 3 of them (30%) showed no variability. In testing group, BRSV antibody titer started to increase on day 3rd in 6 out of 10 animals (60%), on day 5th in one (10%), on day 10th in one (10%) and on day 14th in another (10%). In control group, BRSV antibody titer started to increase on day 3rd in 3 out of 10 animals (30%) and on day 5th in 3 of them (30%). When haematologic values of blood samples taken from animals in testing and control groups on day 14th were studied comparatively, no statistical importance (P < 0.01 or P < 0.05) and difference was detected. As a result, in stock calves showing respiratory tract infection symptoms, applying Umckaloabo/EPs® 7630 liquid extract helped BRSV antibody titer to increase and symptoms decreased. The increase in antibody titers started from day 3rd especially after applying Umckaloabo/EPs® 7630 liquid extract.Discussion: Respiratory system infections are contagious and fatal in calves. Respiratory tract bacterial and viral vaccinations are applied in order to prevent losses of calves due to these problems. However, these vaccinations are not sufficient most of the time and antibiotics+supportive treatment applications follow afterwards. Therefore, we advise to use a herbal product, Umckaloabo/ EPs®7630 liquid extract, that has both an antiviral efficiency and a feature of supporting immune system in order to prevent mortalities in stock calves, to stop the infection from spreading on all the herd and to decrease the symptoms of respiratory system. We believe that the obtained data should be supported with more examples and more wide-ranging studies

AI as a Medical Device for Ophthalmic Imaging in Europe, Australia, and the United States: Protocol for a Systematic Scoping Review of Regulated Devices

\ua9 2024 JMIR Publications Inc.. All rights reserved.Background: Artificial intelligence as a medical device (AIaMD) has the potential to transform many aspects of ophthalmic care, such as improving accuracy and speed of diagnosis, addressing capacity issues in high-volume areas such as screening, and detecting novel biomarkers of systemic disease in the eye (oculomics). In order to ensure that such tools are safe for the target population and achieve their intended purpose, it is important that these AIaMD have adequate clinical evaluation to support any regulatory decision. Currently, the evidential requirements for regulatory approval are less clear for AIaMD compared to more established interventions such as drugs or medical devices. There is therefore value in understanding the level of evidence that underpins AIaMD currently on the market, as a step toward identifying what the best practices might be in this area. In this systematic scoping review, we will focus on AIaMD that contributes to clinical decision-making (relating to screening, diagnosis, prognosis, and treatment) in the context of ophthalmic imaging.Objective: This study aims to identify regulator-approved AIaMD for ophthalmic imaging in Europe, Australia, and the United States; report the characteristics of these devices and their regulatory approvals; and report the available evidence underpinning these AIaMD.Methods: The Food and Drug Administration (United States), the Australian Register of Therapeutic Goods (Australia), the Medicines and Healthcare products Regulatory Agency (United Kingdom), and the European Database on Medical Devices (European Union) regulatory databases will be searched for ophthalmic imaging AIaMD through a snowballing approach. PubMed and clinical trial registries will be systematically searched, and manufacturers will be directly contacted for studies investigating the effectiveness of eligible AIaMD. Preliminary regulatory database searches, evidence searches, screening, data extraction, and methodological quality assessment will be undertaken by 2 independent review authors and arbitrated by a third at each stage of the process.Results: Preliminary searches were conducted in February 2023. Data extraction, data synthesis, and assessment of methodological quality commenced in October 2023. The review is on track to be completed and submitted for peer review by April 2024.Conclusions: This systematic review will provide greater clarity on ophthalmic imaging AIaMD that have achieved regulatory approval as well as the evidence that underpins them. This should help adopters understand the range of tools available and whether they can be safely incorporated into their clinical workflow, and it should also support developers in navigating regulatory approval more efficiently

OCT Assisted Quantification of Vitreous Inflammation in Uveitis

Purpose: Vitreous haze (VH) is a key marker of inflammation in uveitis but limited by its subjectivity. Optical coherence tomography (OCT) has potential as an objective, noninvasive method for quantifying VH. We test the hypotheses that OCT can reliably quantify VH and the measurement is associated with slit-lamp based grading of VH. Methods: In this prospective study, participants underwent three repeated OCT macular scans to evaluate the within-eye reliability of the OCT vitreous intensity (VI). Association between OCT VI and clinical findings (including VH grade, phakic status, visual acuity [VA], anterior chamber cells, and macular thickness) were assessed. Results: One hundred nineteen participants were included (41 healthy participants, 32 patients with uveitis without VH, and 46 patients with uveitis with VH). Within-eye test reliability of OCT VI was high in healthy eyes and in all grades of VH (intraclass correlation coefficient [ICC] > 0.79). Average OCT VI was significantly different between healthy eyes and uveitic eyes without and uveitic eyes with VH, and was associated with increasing clinical VH grade (P < 0.05). OCT VI was significantly associated with VA, whereas clinical VH grading was not. Cataract was also associated with higher OCT VI (P = 0.03). Conclusions: OCT VI is a fast, noninvasive, objective, and automated method for measuring vitreous inflammation. It is associated with clinician grading of vitreous inflammation and VA, however, it can be affected by media opacities. Translational Relevance: OCT imaging for quantifying vitreous inflammation shows high within-eye repeatability and is associated with clinical grading of vitreous haze. OCT measurements are also associated with visual acuity but may be affected by structures anterior to the acquisition window, such as lens opacity and other anterior segment changes

A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset

Purpose: Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset. / Design: Dataset descriptor for routinely collected eye screening data. / Participants: All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme. / Methods: The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)–led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program. / Main Outcome Measures: This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients’ diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below. / Results: At the time point of this analysis (December 31, 2019), the dataset comprised 6 202 161 images from 246 180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1 360 547 grading episodes between R0M0 and R3M1. / Conclusions: This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/

Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review

Purpose: New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. Methods: Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading. Results: From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66–0.87 and 0.06–0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73–0.97) than in the inferior AC (0.06–0.56). Conclusion: AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity

Assessment of a treatment guideline to improve home management of malaria in children in rural south-west Nigeria

<p>Abstract</p> <p>Background</p> <p>Many Nigerian children with malaria are treated at home. Treatments are mostly incorrect, due to caregivers' poor knowledge of appropriate and correct dose of drugs. A comparative study was carried out in two rural health districts in southwest Nigeria to determine the effectiveness of a guideline targeted at caregivers, in the treatment of febrile children using chloroquine.</p> <p>Methods</p> <p>Baseline and post intervention knowledge, attitude and practice household surveys were conducted. The intervention strategy consisted of training a core group of mothers ("mother trainers") in selected communities on the correct treatment of malaria and distributing a newly developed treatment guideline to each household. "Mother trainers" disseminated the educational messages about malaria and the use of the guideline to their communities.</p> <p>Results</p> <p>Knowledge of cause, prevention and treatment of malaria increased with the one-year intervention. Many, (70.4%) of the respondents stated that they used the guideline each time a child was treated for malaria. There was a significant increase in the correct use of chloroquine from 2.6% at baseline to 52.3% after intervention among those who treated children at home in the intervention arm compared with 4.2% to 12.7% in the control arm. The correctness of use was significantly associated with use of the guideline. The timeliness of commencing treatment was significantly earlier in those who treated febrile children at home using chloroquine than those who took their children to the chemist or health facility (p < 0.005). Mothers considered the guideline to be explicit and useful. Mother trainers were also considered to be effective and acceptable.</p> <p>Conclusion</p> <p>The use of the guideline with adequate training significantly improved correctness of malaria treatment with chloroquine at home. Adoption of this mode of intervention is recommended to improve compliance with drug use at home. The applicability for deploying artemisinin-based combination therapy at the community level needs to be investigated.</p

Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses

The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV

Polymorphic Structures of Alzheimer's β-Amyloid Globulomers

Misfolding and self-assembly of Amyloid-β (Aβ) peptides into amyloid fibrils is pathologically linked to the development of Alzheimer's disease. Polymorphic Aβ structures derived from monomers to intermediate oligomers, protofilaments, and mature fibrils have been often observed in solution. Some aggregates are on-pathway species to amyloid fibrils, while the others are off-pathway species that do not evolve into amyloid fibrils. Both on-pathway and off-pathway species could be biologically relevant species. But, the lack of atomic-level structural information for these Aβ species leads to the difficulty in the understanding of their biological roles in amyloid toxicity and amyloid formation.Here, we model a series of molecular structures of Aβ globulomers assembled by monomer and dimer building blocks using our peptide-packing program and explicit-solvent molecular dynamics (MD) simulations. Structural and energetic analysis shows that although Aβ globulomers could adopt different energetically favorable but structurally heterogeneous conformations in a rugged energy landscape, they are still preferentially organized by dynamic dimeric subunits with a hydrophobic core formed by the C-terminal residues independence of initial peptide packing and organization. Such structural organizations offer high structural stability by maximizing peptide-peptide association and optimizing peptide-water solvation. Moreover, curved surface, compact size, and less populated β-structure in Aβ globulomers make them difficult to convert into other high-order Aβ aggregates and fibrils with dominant β-structure, suggesting that they are likely to be off-pathway species to amyloid fibrils. These Aβ globulomers are compatible with experimental data in overall size, subunit organization, and molecular weight from AFM images and H/D amide exchange NMR.Our computationally modeled Aβ globulomers provide useful insights into structure, dynamics, and polymorphic nature of Aβ globulomers which are completely different from Aβ fibrils, suggesting that these globulomers are likely off-pathway species and explaining the independence of the aggregation kinetics between Aβ globulomers and fibrils

Shiga Toxin Binding to Glycolipids and Glycans

Background: Immunologically distinct forms of Shiga toxin (Stx1 and Stx2) display different potencies and disease outcomes, likely due to differences in host cell binding. The glycolipid globotriaosylceramide (Gb3) has been reported to be the receptor for both toxins. While there is considerable data to suggest that Gb3 can bind Stx1, binding of Stx2 to Gb3 is variable. Methodology: We used isothermal titration calorimetry (ITC) and enzyme-linked immunosorbent assay (ELISA) to examine binding of Stx1 and Stx2 to various glycans, glycosphingolipids, and glycosphingolipid mixtures in the presence or absence of membrane components, phosphatidylcholine, and cholesterol. We have also assessed the ability of glycolipids mixtures to neutralize Stx-mediated inhibition of protein synthesis in Vero kidney cells. Results: By ITC, Stx1 bound both Pk (the trisaccharide on Gb3) and P (the tetrasaccharide on globotetraosylceramide, Gb4), while Stx2 did not bind to either glycan. Binding to neutral glycolipids individually and in combination was assessed by ELISA. Stx1 bound to glycolipids Gb3 and Gb4, and Gb3 mixed with other neural glycolipids, while Stx2 only bound to Gb3 mixtures. In the presence of phosphatidylcholine and cholesterol, both Stx1 and Stx2 bound well to Gb3 or Gb4 alone or mixed with other neutral glycolipids. Pre-incubation with Gb3 in the presence of phosphatidylcholine and cholesterol neutralized Stx1, but not Stx2 toxicity to Vero cells