Mitochondrion to endoplasmic reticulum apposition length in zebrafish embryo spinal progenitors is unchanged in response to perturbations associated with Alzheimer’s disease

Published: June 21, 2017Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD). The length of mitochondrion-endoplasmic reticulum (M-ER) appositions is increased in Psen1-/-/Psen2-/- double knockout murine embryonic fibroblasts and in fibroblasts from AD-affected individuals. Development of an easily accessible, genetically manipulable, in vivo system for studying M-ER appositions would be valuable so we attempted to manipulate M-ER apposition length in zebrafish (Danio rerio) embryos. We injected fertilized zebrafish eggs with antisense morpholino oligonucleotides (MOs) that inhibit expression of zebrafish familial AD gene orthologues psen1 and psen2. Furthermore, we treated zebrafish embryos with DAPT (a highly specific γ-secretase inhibitor) or with sodium azide (to mimic partially hypoxic conditions). We then analyzed M-ER apposition in an identified, presumably proliferative neural cell type using electron microscopy. Our analysis showed no significant differences in M-ER apposition lengths at 48 hours post fertilization (hpf) between psen1 & psen2 MO co-injected embryos, embryos treated with DAPT, or sodium azide, and control embryos. Instead, the distribution of M-ER apposition lengths into different length classes was close to identical. However, this indicates that it is feasible to reproducibly measure M-ER size distributions in zebrafish embryos. While our observations differ from those of murine and human studies, this may be due to differences in cellular differentiation and metabolic state, cell age, or species-specific responses. In particular, by focusing on a presumably proliferative embryonic cell type, we may have selected a cell heavily already reliant on anaerobic glycolysis and less responsive to factors affecting M-ER apposition. Future examination of more differentiated, more secretory cell types may reveal measurable responses of M-ER apposition to environmental and genetic manipulation.Morgan Newman, Lena Halter, Anne Lim, Michael Lardell

Let\u27s Go

Illustration of a woman in a blue dress dancing with a man in a top hat.https://scholarsjunction.msstate.edu/cht-sheet-music/9202/thumbnail.jp

Using Natural Language Processing and Sentiment Analysis to Augment Traditional User-Centered Design: Development and Usability Study

Background: Sarcopenia, defined as the age-associated loss of muscle mass and strength, can be effectively mitigated through resistance-based physical activity. With compliance at approximately 40% for home-based exercise prescriptions, implementing a remote sensing system would help patients and clinicians to better understand treatment progress and increase compliance. The inclusion of end users in the development of mobile apps for remote-sensing systems can ensure that they are both user friendly and facilitate compliance. With advancements in natural language processing (NLP), there is potential for these methods to be used with data collected through the user-centered design process. Objective: This study aims to develop a mobile app for a novel device through a user-centered design process with both older adults and clinicians while exploring whether data collected through this process can be used in NLP and sentiment analysis. Methods: Through a user-centered design process, we conducted semistructured interviews during the development of a geriatric-friendly Bluetooth-connected resistance exercise band app. We interviewed patients and clinicians at weeks 0, 5, and 10 of the app development. Each semistructured interview consisted of heuristic evaluations, cognitive walkthroughs, and observations. We used the Bing sentiment library for a sentiment analysis of interview transcripts and then applied NLP-based latent Dirichlet allocation (LDA) topic modeling to identify differences and similarities in patient and clinician participant interviews. Sentiment was defined as the sum of positive and negative words (each word with a +1 or −1 value). To assess utility, we used quantitative assessment questionnaires—System Usability Scale (SUS) and Usefulness, Satisfaction, and Ease of use (USE). Finally, we used multivariate linear models—adjusting for age, sex, subject group (clinician vs patient), and development—to explore the association between sentiment analysis and SUS and USE outcomes. Results: The mean age of the 22 participants was 68 (SD 14) years, and 17 (77%) were female. The overall mean SUS and USE scores were 66.4 (SD 13.6) and 41.3 (SD 15.2), respectively. Both patients and clinicians provided valuable insights into the needs of older adults when designing and building an app. The mean positive-negative sentiment per sentence was 0.19 (SD 0.21) and 0.47 (SD 0.21) for patient and clinician interviews, respectively. We found a positive association with positive sentiment in an interview and SUS score (ß=1.38; 95% CI 0.37 to 2.39; P=.01). There was no significant association between sentiment and the USE score. The LDA analysis found no overlap between patients and clinicians in the 8 identified topics. Conclusions: Involving patients and clinicians allowed us to design and build an app that is user friendly for older adults while supporting compliance. This is the first analysis using NLP and usability questionnaires in the quantification of user-centered design of technology for older adults

The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review

Background: Electrical impedance technology has been well established for the last 20 years. Recently research has begun to emerge into its potential uses in the detection and diagnosis of pre-malignant and malignant conditions. The aim of this study was to systematically review the clinical application of electrical impedance technology in the detection of malignant neoplasms. Methods: A search of Embase Classic, Embase and Medline databases was conducted from 1980 to 22/02/2018 to identify studies reporting on the use of bioimpedance technology in the detection of pre-malignant and malignant conditions. The ability to distinguish between tissue types was defined as the primary endpoint, and other points of interest were also reported. Results: 731 articles were identified, of which 51 reported sufficient data for analysis. These studies covered 16 different cancer subtypes in a total of 7035 patients. As the studies took various formats, a qualitative analysis of each cancer subtype’s data was undertaken. All the studies were able to show differences in electrical impedance and/or related metrics between malignant and normal tissue. Conclusions: Electrical impedance technology provides a novel method for the detection of malignant tissue, with large studies of cervical, prostate, skin and breast cancers showing encouraging results. Whilst these studies provide promising insights into the potential of this technology as an adjunct in screening, diagnosis and intra-operative margin assessment, customised development as well as multi-centre clinical trials need to be conducted before it can be reliably employed in the clinical detection of malignant tissue

The Physicist's Guide to the Orchestra

An experimental study of strings, woodwinds (organ pipe, flute, clarinet, saxophone and recorder), and the voice was undertaken to illustrate the basic principles of sound production in music instruments. The setup used is simple and consists of common laboratory equipment. Although the canonical examples (standing wave on a string, in an open and closed pipe) are easily reproduced, they fail to explain the majority of the measurements. The reasons for these deviations are outlined and discussed.Comment: 11 pages, 10 figures (jpg files). Submitted to European Journal of Physic

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation

Background: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. Methods: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). Results: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5% (1/8). Conclusions: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infectio

Detection and Monitoring of Repetitions Using an mHealth-Enabled Resistance Band

Sarcopenia is defined as an age-related loss of muscle mass and strength which impairs physical function leading to disability and frailty. Resistance exercises are effective treatments for sarcopenia and are critical in mitigating weight-loss induced sarcopenia in older adults attempting to lose weight. Yet, adherence to home-based regimens, which is a cornerstone to lifestyle therapies, is poor and cannot be ascertained by clinicians as no objective methods exist to determine patient compliance outside of a supervised setting. Our group developed a Bluetooth connected resistance band that tests the ability to detect exercise repetitions. We recruited 6 patients aged 65 years and older and recorded 4 specific, physical therapist-led exercises. Three blinded reviewers examined the findings and we also applied a peak finding algorithm to the data. There were 16.6 repetitions per exercise across reviewers, with an intraclass correlation of 0.912 (95%CI: $0.853-0.953$, $p\u3c0.001$) between reviewers and the algorithm. Using this novel resistance band, we feasibly detected repetition of exercises in older adults. Sarcopenia is defined as an age-related loss of muscle mass and strength which impairs physical function leading to disability and frailty. Resistance exercises are effective treatments for sarcopenia and are critical in mitigating weight-loss induced sarcopenia in older adults attempting to lose weight. Yet, adherence to home-based regimens, which is a cornerstone to lifestyle therapies, is poor and cannot be ascertained by clinicians as no objective methods exist to determine patient compliance outside of a supervised setting. Our group developed a Bluetooth connected resistance band that tests the ability to detect exercise repetitions. We recruited 6 patients aged 65 years and older and recorded 4 specific, physical therapist-led exercises. Three blinded reviewers examined the findings and we also applied a peak finding algorithm to the data. There were 16.6 repetitions per exercise across reviewers, with an intraclass correlation of 0.912 (95%CI: $0.853-0.953$, $p\u3c0.001$) between reviewers and the algorithm. Using this novel resistance band, we feasibly detected repetition of exercises in older adults

Modulatory Effects of Motor State During Paired Associative Stimulation on Motor Cortex Excitability and Motor Skill Learning

Repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) representation for a target muscle can induce neuroplastic adaptations in the human brain related to motor learning. The extent to which the motor state during this form of paired associative stimulation (PAS) influences the degree and mechanisms of neuroplasticity or motor learning is unclear. Here, we investigated the effect of volitional muscle contraction during PAS on: (1) measures of general corticomotor excitability and intracortical circuit excitability; and (2) motor performance and learning. We assessed measures of corticomotor excitability using TMS and motor skill performance during a serial reaction time task (SRTT) at baseline and at 0, 30, 60 min post-PAS. Participants completed a SRTT retention test 1 week following the first two PAS sessions. Following the PAS intervention where the hand muscle maintained an active muscle contraction (PASACTIVE), there was lower short interval intracortical inhibition compared to PAS during a resting motor state (PASREST) and a sham PAS condition (PASCONTROL). SRTT performance improved within the session regardless of PAS condition. SRTT retention was greater following both PASACTIVE and PASREST after 1 week compared to PASCONTROL. These findings suggest that PAS may enhance motor learning retention and that motor state may be used to target different neural mechanisms of intracortical excitation and inhibition during PAS. This observation may be important to consider for the use of therapeutic noninvasive brain stimulation in neurologic patient populations