Mapping the functional B-cell epitopes of Shigella invasion plasmid antigen D (IpaD).

Shigella bacteria utilize the type III secretion system (T3SS) to invade host cells and establish local infection. Invasion plasmid antigen D (IpaD), a component of Shigella T3SS, has garnered extensive interest as a vaccine target, primarily due to its pivotal role in the Shigella invasion, immunogenic property, and a high degree of conservation across Shigella species and serotypes. Currently, we are developing an epitope- and structure-based multivalent vaccine against shigellosis and require functional epitope antigens of key Shigella virulence determinants including IpaD. However, individual IpaD B-cell epitopes, their contributions to the overall immunogenicity, and functional activities attributing to bacteria invasion have not been fully characterized. In this study, we predicted continuous B-cell epitopes in silico and fused each epitope to a carrier protein. Then, we immunized mice intramuscularly with each epitope fusion protein, examined the IpaD-specific antibody responses, and measured antibodies from each epitope fusion for the activity against Shigella invasion in vitro. Data showed that all epitope fusion proteins induced similar levels of anti-IpaD IgG antibodies in mice, and differences were noted for antibody inhibition activity against Shigella invasion. IpaD epitope 1 (SPGGNDGNSV), IpaD epitope 2 (LGGNGEVVLDNA), and IpaD epitope 5 (SPNNTNGSSTET) induced antibodies significantly better in inhibiting invasion from Shigella flexneri 2a, and epitopes 1 and 5 elicited antibodies more effectively at preventing invasion of Shigella sonnei. These results suggest that IpaD epitopes 1 and 5 can be the IpaD representative antigens for epitope-based polyvalent protein construction and protein-based cross-protective Shigella vaccine development.IMPORTANCEShigella is a leading cause of diarrhea in children younger than 5 years in developing countries (children's diarrhea) and continues to be a major threat to public health. No licensed vaccines are currently available against the heterogeneous Shigella species and serotype strains. Aiming to develop a cross-protective multivalent vaccine against shigellosis and dysentery, we applied novel multiepitope fusion antigen (MEFA) technology to construct a broadly immunogenic polyvalent protein antigen, by presenting functional epitopes of multiple Shigella virulence determinants on a backbone protein. The functional IpaD epitopes identified from this study will essentially allow us to construct an optimal polyvalent Shigella immunogen, leading to the development of a cross-protective vaccine against shigellosis (and dysentery) and the improvement of global health. In addition, identifying functional epitopes from heterogeneous virulence determinants and using them as antigenic representatives for the development of cross-protective multivalent vaccines can be applied generally in vaccine development.

Snellen iPad App versus Traditional Light-Box Snellen Chart in Distance Visual Acuity.

This study aimed to discover distance visual acuity (VA) assessments through the display of the Snellen chart on the iPad tablet. The findings are equivalent to those obtained using the conventional light-box Snellen chart. In this work, the Snellen iPad app and Eye Chart HD iOS app are utilized among the participants in the Ophthalmology Outpatient Department (OPD) for determining VA. A cross-sectional method was used for the examination, which included 100 new patients who were chosen by random selection. The age requirement for new patients was 8 years and up for both genders. Patients with a VA of less than 6/30 were disqualified from the experiment. Two testing modalities are used to measure VA, such as the iPad Mini 2 with the iOS software Eye Chart HD and the classic Snellen light-box chart. The observation revealed that the Snellen iPad app and the classic light-box Snellen chart produced equivalent findings. The classic Snellen chart may have been memorized by participants before their eye examination, undermining the accuracy of the conclusions of the initial testing modality used. Patient-related variables were also identified as confounders. Future studies should adjust the brightness of the iPad Mini 2 and the traditional light-box Snellen chart to make sure that neither experiment modality's brightness affects the accuracy of the findings. Future research should also investigate the use of premium apps, use both devices, and employ a bigger sample size.

Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies.

The brain's network of perivascular channels for clearance of excess fluids and waste plays a critical role in the pathogenesis of several neurodegenerative diseases including cerebral amyloid angiopathy (CAA). CAA is the main cause of hemorrhagic stroke in the elderly, the most common vascular comorbidity in Alzheimer's disease and also implicated in adverse events related to anti-amyloid immunotherapy. Remarkably, the mechanisms governing perivascular clearance of soluble amyloid ß-a key culprit in CAA-from the brain to draining lymphatics and systemic circulation remains poorly understood. This knowledge gap is critically important to bridge for understanding the pathophysiology of CAA and accelerate development of targeted therapeutics. The authors of this review recently converged their diverse expertise in the field of perivascular physiology to specifically address this problem within the framework of a Leducq Foundation Transatlantic Network of Excellence on Brain Clearance. This review discusses the overarching goal of the consortium and explores the evidence supporting or refuting the role of impaired perivascular clearance in the pathophysiology of CAA with a focus on translating observations from rodents to humans. We also discuss the anatomical features of perivascular channels as well as the biophysical characteristics of fluid and solute transport.

Evaluation of a self-administered iPad®-based processing speed assessment for people with multiple sclerosis in a clinical routine setting.

BACKGROUND: Limited resources often hinder regular cognitive assessment of people with multiple sclerosis (pwMS) in standard clinical care. A self-administered iPad®-based cognitive screening-tool (Processing Speed Test; PST) might mitigate this problem. OBJECTIVE: To evaluate the PST in clinical routine. METHODS: We investigated the feasibility of the PST in both a quiet and a waiting room setting. We assessed the validity of the PST in comparison with the established Symbol Digit Modalities Test (SDMT). We explored associations between processing speed assessments and the Brief International Cognitive Assessment for MS (BICAMS), magnetic resonance imaging (MRI) parameters, and psychological factors. Additionally, we explored the ability of the PST to detect impairment in processing speed compared to the SDMT. RESULTS: The PST was feasible in the waiting room setting. PST and SDMT correlated comparably with the BICAMS, MRI parameters, and psychological variables. Of 172 pwMS, 50 (30.8%) showed cognitive impairment according to the BICAMS; respective values were 47 (27.3%) for the SDMT and 9 (5.2%) for the PST. CONCLUSIONS: The PST performed in a waiting room setting correlates strongly with established cognitive tests. It thus may be used to assess processing speed in a resource-efficient manner and complement cognitive assessment in clinical routine. Despite comparable validity of the PST and SDMT, we identified more pwMS with impaired processing speed using normative data of the SDMT compared to the PST and advise caution, that the common cut-off score of - 1.5 SD from the current PST is not appropriate in Europe.

Production of egg yolk antibody (IgY) against a chimeric protein containing IpaD, StxB, and TolC antigens from Shigella: An investigation of its prophylactic effects against Shiga toxin (Stx) and Shigella dysenteriae in vitro and in vivo.

Shigella is a major problem in developing countries. Immunoglobulin Y (IgY) can be used for prophylaxis and neutralize bacteria. The aim of this study was to produce IgY against the chimeric protein containing IpaD, StxB, and TolC antigens from Shigella, investigate its prophylactic and neutralizing effects against Stx and Shigella dysenteriae. The nucleotide sequence corresponding to the chimeric protein was cloned into pET28a plasmid and expressed in E. coli BL21 (DE3). Protein expression was confirmed by SDS-PAGE and the recombinant protein was purified by Ni-NTA affinity chromatography. The 150 µg of chimeric protein was mixed with Freund's adjutant and injected into laying hens (Leghorn). IgY was purified using PEG6000 precipitation. Antibody titer in the serum and egg yolk was evaluated by ELISA. IgY challenge against 1,10 and 50 LD50 of Stx and S. dysenteriae was investigated. A 60.6 kDa recombinant protein was confirmed by SDS-PAGE. ELISA showed that the antibody titer was significantly increased. MTT assay [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] showed that at 16 µmol/L, IgY protected HeLa cells against Stx. Treatment of mice with 1000 and 1500 µg IgY leads to complete survival of the mice against 1LD50 toxin and 4000 µg of IgY led to complete survival against 1LD50, also 70% and 30% survival against 10 and 50 LD50S. dysenteriae. This study showed that IgY produced against Stx and Shigella virulence factors could cause high protective effects against bacteria and toxins.

Accuracy and tracing time of cephalometric analyses on a tablet or desktop computer : A prospective study.

BACKGROUND: This prospective study aimed to evaluate the influence of the computer type (tablet or desktop) on accuracy and tracing time of cephalometric analyses. METHODS: Dental students used a web-based application specifically developed for this purpose to perform cephalometric analyses on tablet and desktop computers. Landmark locations and timestamps were exported to measure the accuracy, successful detection rate and tracing time. Reference landmarks were established by six experienced orthodontists. Statistical analysis included reliability assessment, descriptive statistics, and linear mixed effect models. RESULTS: Over a period of 8 semesters a total of 277 cephalometric analyses by 161 students were included. The interrater reliability of the orthodontists establishing the reference coordinates was excellent (ICC > 0.9). For the students, the mean landmark deviation was 2.05 mm and the successful detection rate for the clinically acceptable threshold of 2 mm suggested in the literature was 68.6%, with large variations among landmarks. No effect of the computer type on accuracy and tracing time of the cephalometric analyses could be found. CONCLUSION: The use of tablet computers for cephalometric analyses can be recommended.

TECH preserves global cognition of older adults with MCI compared with a control group: a randomized controlled trial.

BACKGROUND: Cognitive training using touchscreen tablet casual game applications (apps) has potential to be an effective treatment method for people with mild cognitive impairment (MCI). AIMS: This study aimed to establish the effectiveness of 'Tablet Enhancement of Cognition and Health' (TECH), a novel cognitive intervention for improving/preserving cognition in older adults with MCI. METHODS: A single-blind randomized controlled trial with assessments pre-, post-, and at 6-month follow-up was conducted. TECH entailed 5 weeks of daily self-training utilizing tablet apps, facilitated by weekly group sessions. Global cognition was assessed by the Montreal Cognitive Assessment (MoCA), and specific cognitive components were assessed using WebNeuro computerized battery. Short Form Health Survey (SF-12) assessed health-related quality of life (HRQoL). Intention-to-treat analysis was conducted and the %change was calculated between pre-post and between pre-follow-up. Cohen's d effect size was also calculated. RESULTS: Sixty-one participants aged 65-89 years were randomly allocated to TECH (N = 31, 14 women) or to standard care (N = 30, 14 women). Pre-post and pre-follow-up MoCA %change scores were significantly higher in TECH than control (U = 329.5, p < .05; U = 294.5, p < .05) with intermediate effect size values (Cohen's d = .52, Cohen's d = .66). Forty percent of TECH participants versus 6.5% of control participants achieved a minimal clinical important difference in MoCA. Pre-post between-group differences for specific cognitive components were not found and HRQoL did not change. DISCUSSION AND CONCLUSIONS: TECH encouraged daily self-training and showed to preserve global cognition of older adults with MCI. The implementation of TECH is recommended for older adults with MCI, who are at risk for further cognitive decline.

Novel Three-Dimensional Image-Guided Surgery: Application of a Computed Tomography-Based Three-Dimensional Model Using a Tablet Device

OBJECTIVE: A tablet device has several medical applications because it's portability. Most importantly, its powerful graphics and touch-based features have several benefits in the surgical field, especially for generating three-dimensional (3D) images based on patients' computed tomography (CT) scans. METHODS: In this study, 3D objects were manipulated by an operator on an iPad during several laparoscopic surgeries of intra-abdominal organs. Before surgery, 3D structures, such as vessels, soft tissues, and bones, were reconstructed by the surgeon using the patients' CT scans on the patients' bed-side personal computer. RESULTS: In this study, 3D image-guided surgeries were performed using an iPad in five patients. The benefits of this technique were recorded and analyzed in detail by the surgeon. CONCLUSION: Although in a pilot phase with unresolved issues, direct intra-operative handling of a patient-tailored 3D model developed using a tablet device could be useful compared with conventional two-dimensional imaging.

Korean Version Self-testing Application for Reading Speed

PURPOSE: This study introduces a reading chart application for the iPad tablet in the Korean language and investigates the reading speed in a normal-sighted population according to age group. METHODS: Sixty-three Korean sentences were selected from textbooks for second grade elementary school students. A commonly used typeface in everyday printed material, “BatangChe,” was used. Letter size was presented in logarithm of the minimum angle of resolution (logMAR) 0.0 to 1.0 at 0.1 logMAR steps at a reading distance of 40 cm. A third generation retina display iPad was used to present the chart, and the sentences were presented randomly for each size of letter. The subjects repeated the test silently (reading only) and out loud (reading and speaking) to prevent them from skipping reading words. Pilot testing followed in 65 normal vision adults under 60 years of age. RESULTS: The mean reading only speed for logMAR 0.5 optotype (point 10) was 121.1 ± 47.2 words per minute (wpm) for people in their 20s (n=21), 116.5 ± 38.3 in their 30s (n=27), 93.8 ± 12.6 in their 40s (n=9), and 56.5 ± 42.7 (n=8) in their 50s. There was a significant correlation between age and reading and speaking speed (r=−0.48, p<0.001). The mean reading only speed for logMAR 0.5 optotype (point 10) was 202.3 ± 88.4 wpm and the mean reading and speaking speed was 129.7 ± 25.9 wpm, with significantly different (p<0.001). CONCLUSIONS: This Korean reading chart application could present a new standard when checking reading speed according to age groups.

Visual Fatigue Induced by Viewing a Tablet Computer with a High-resolution Display

PURPOSE: In the present study, the visual discomfort induced by smart mobile devices was assessed in normal and healthy adults. METHODS: Fifty-nine volunteers (age, 38.16 ± 10.23 years; male : female = 19 : 40) were exposed to tablet computer screen stimuli (iPad Air, Apple Inc.) for 1 hour. Participants watched a movie or played a computer game on the tablet computer. Visual fatigue and discomfort were assessed using an asthenopia questionnaire, tear film break-up time, and total ocular wavefront aberration before and after viewing smart mobile devices. RESULTS: Based on the questionnaire, viewing smart mobile devices for 1 hour significantly increased mean total asthenopia score from 19.59 ± 8.58 to 22.68 ± 9.39 (p < 0.001). Specifically, the scores for five items (tired eyes, sore/aching eyes, irritated eyes, watery eyes, and hot/burning eye) were significantly increased by viewing smart mobile devices. Tear film break-up time significantly decreased from 5.09 ± 1.52 seconds to 4.63 ± 1.34 seconds (p = 0.003). However, total ocular wavefront aberration was unchanged. CONCLUSIONS: Visual fatigue and discomfort were significantly induced by viewing smart mobile devices, even though the devices were equipped with state-of-the-art display technology.

A randomised, double-blinded clinical study on the efficacy of multimedia presentation using an iPad for patient education of postoperative hip surgery patients in a public hospital in Singapore

<p><b>INTRODUCTION</b>This study compared patient satisfaction and recall of physiotherapy patient education among patients who had undergone hip surgery, with information presented via an iPad versus a standard paper booklet.</p><p><b>METHODS</b>Patients who had undergone hip surgery joined and completed this single-centre study, which utilised a randomised parallel group design. They were randomly allocated to either Group A (received information on hip surgery physiotherapy via an iPad) or Group B (received the same information via a paper booklet). The participants were blinded to the intervention received by the other group and the testers were blinded to the intervention received by the participants. The interventions were carried out during the patients' first four postoperative physiotherapy sessions. The outcome measures were recorded using pre-validated questionnaires.</p><p><b>RESULTS</b>A total of 42 participants (mean age 70 ± 12 years) were recruited. After the intervention, patients in both groups had improved recall of the information presented during patient education. However, the patients in Group A had a significantly better recall score than those in Group B (4.0 points higher, p < 0.001). The level of patient satisfaction was also significantly higher in Group A than in Group B (8.5 points higher, p < 0.001).</p><p><b>CONCLUSION</b>While the use of an iPad and a paper booklet both had positive outcomes for patient recall and satisfaction, the use of an iPad was found to be more effective at improving patient satisfaction and recall of physiotherapy patient education in the present study.</p>

A comparative study of postoperative pain for open thyroidectomy versus bilateral axillo-breast approach robotic thyroidectomy using a self-reporting application for iPad

PURPOSE: Postoperative pain for robotic thyroid surgeries including bilateral axillo-breast approach (BABA) has not been well studied. In this study, we have developed a self-reporting application (SRA) for iPad and prospectively collected pain scores from open thyroidectomy (OT) and BABA robotic thyroidectomy (RT) patients. METHODS: Female patients who underwent total thyroidectomy for papillary thyroid carcinoma were included. Patients recorded pain scores for throat, anterior neck, posterior neck, chest, and back on postoperative days 1, 2, and 3. Once discharged, on postoperative day 14, a survey was also conducted on satisfaction of SRA and cosmesis. RESULTS: A total of 54 patients were enrolled (27 BABA RT and 27 OT). There were no significant differences between the 2 groups in clinicopathological characteristics and postoperative complication rates. Postoperative pain scores at days 1, 2, 3, and 14 were not significantly different between the groups for throat, anterior neck, posterior neck, or back. Postoperative analgesic requirements were similar between the 2 groups. Wound satisfaction scores were significantly higher in the BABA RT group (BABA RT 7.4 vs. OT 5.7; P = 0.016). Satisfaction scores for the usefulness of SRA were above 7.2 for all four questionnaire items on the 10-point scale. CONCLUSION: Postoperative pain for BABA RT is equivalent to OT but offers greater cosmetic satisfaction for patients. A mobile device application such as SRA may facilitate proper assessment and management of pain in postoperative patients.

Validity of Korean Version Reading Speed Application and Measurement of Reading Speed: Pilot Study

PURPOSE: Reading speed is one of the methods used to measure near visual function. Although several versions of reading charts in different languages have been introduced, there is no Korean version of the reading chart yet. Therefore, we investigated the reading speed of normal-sighted Korean people using a recently developed reading speed application for the iPad tablet in Korea. METHODS: Normal-sighted participants without presbyopia were included and a third generation retina display iPad was used to measure reading speed. The iPad screen was set to maximum brightness and the examination was performed at a distance of 40 cm. Reading speeds were recorded twice: one for reading the sentence silently (reading only) and one for reading the sentence out loud (reading & speaking). RESULTS: The test sentences used in the application had 18.9 ± 2.6 letters and 6.5 ± 0.7 words on average. Twenty-five males and seventeen females were included. The average of the reading only speed was 202.3 ± 88.4 words per minute (WPM), and that of the reading & speaking speed was 129.7 ± 25.9 WPM, showing a statistically significant difference (p < 0.001). CONCLUSIONS: This Korean reading chart application is the first self-reporting reading chart in Korean. This chart could present a new standard for measuring both reading only and reading & speaking speeds.

Application of iPad and its Software in Rehabilitation of Children with Autism:Four Cases Report / 中国康复理论与实践

Objective To explore the application of iPad-based software Let'S Talk in the rehabilitation of children with autism. Meth-ods From March to September, 2015, iPad-based software Let'S Talk was applied in four children with autism. The language ability, emo-tion and behavior control ability, self-consciousness and eye contact were observed. The Psycho-educational Profile-3rd (PEP-3), Autism Be-havior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to access the months of age, behavior characteristics, and the severity of autism before and after application. Results The language ability and behavior control ability improved, as well as the self-consciousness and eye contact, and the bad behaviors reduced. The months of age rose in PEP-3, and the scores of ABC and CARS de-creased. Conclusion IPad-based software Let'S Talk could be applied in the rehabilitation of children with autism.

Research on Ocular Fatigability Induced by Multimedia and Instrument Features

PURPOSE: The aim of the present study was to evaluate the different features of such instruments and how they cause ocular fatigability. METHODS: Under the same settings and circumstances, 75 participants were asked to read the novel, "You without me?" in different formats including paper book, E-book (biscuit(R), Interpark Inc., LG INNOTECK LTD, Korea) and LCD reader (iPad(R), Apple Inc., United States). For every 10 minutes of reading, 10 minutes of rest was provided. After finishing the novel, the participants were asked to complete a questionnaire, and the data obtained were statistically analyzed using univariate analysis. RESULTS: Compared to paper book readers (1.93), LCD readers (2.40) complained of insufficient lubrication in the eye (p = 0.038), and experience more letter-floating illusions (1.92) than did paper book readers (1.49) (p = 0.043). Moreover, compared to the other formats including the E-book (20%) and paper book (8%), LCD readers (72%) experienced more significant glare symptoms (n = 23) and could read at a faster rate than the other groups of readers (n = 26). CONCLUSIONS: In the present study, the I-Pad caused ocular fatigability more easily than the other formats examined. No statistical significance of ocular discomfort or fatigability was observed among the different format groups. Further investigation with a greater number of age-controlled participants should be conducted prior to designing a study to determine the best format for reading.