Concurrent Validity of Equine Joint Range of Motion Measurement: A Novel Digital Goniometer versus Universal Goniometer

Simple SummaryWith the growth of the field of equine rehabilitation, there is an increased demand on rehabilitation clinicians to utilize simple and reliable objective outcome assessment tools. Goniometry, the measurement of joint angles, traditionally performed with a universal goniometer (UG), is a commonly utilized assessment tool in monitoring problems of the musculoskeletal system, as well as the progression of rehabilitation interventions. Goniometry has been demonstrated to be of value, being both reliable and valid, in humans and other animal species. There are different types of goniometers, each of which has some benefit, but varies in accessibility, cost, and user-friendliness. This study examined the use of a novel digital goniometer (DG) in the measurement of angles of two joints in a horse, and comparing the measurements to those taken with a UG. The study demonstrated significant differences in range of motion for the carpus and fetlock joint, a 2-3 degrees difference comparing measurements on a sedated horse with corresponding radiographs, a "fair" to "excellent" inter-tester reliability and a "fair" to "almost perfect" intra-tester reliability. The novel DG was found to be easier to use than the UG. In conclusion, the novel DG may serve as a simple tool for measuring joint motion in equine rehabilitation patients.Goniometry is the measurement of joint angles with a conventional universal goniometer (UG) or a digital goniometer (DG). The UG is validated for use in dogs and cats. However, it demands both of the user's hands when measuring. To avoid this, a novel type of DG has been developed, simplifying measurement by offering single-hand usage. The objective of this study is to examine the concurrent validity of the DG. The study consists of measurement with the DG and UG for flexion of the carpus and fetlock on ten horses, and with the DG in flexion and neutral positioning of the fetlock on a sedated horse and corresponding radiographs, intra- and inter-tester reliability and a survey on user-friendliness. The data were analyzed with ANOVA and intraclass correlation coefficient (ICC), with a significance of p < 0.05. The study showed significant differences in range of motion for the carpus and fetlock joint, a 2-3 degrees difference comparing measurements on a sedated horse with corresponding radiographs, a "fair" to "excellent" inter-tester reliability and a "fair" to "almost perfect" intra-tester reliability, and the DG was easier to use than the UG. In conclusion, the novel DG may serve as a simple tool for measuring joint motion in equine rehabilitation patients

Goniometer measurement in carpus and fetlock on horse with manual and digital goniometer

Skäl att utföra studien: Radiografi har länge använts som ”Gold Standard” vid mätningar av ROM. Då radiografi både är dyrt, tidskrävande och utsätter patienter och personal för strålning behövs en objektiv och validerad metod för att mäta ROM som saknar radiografins nackdelar. Goniometri är en mät-metod som är billig, snabb och saknar skadlig påverkan på patienter och per-sonal. På humansidan är goniometri en validerad metod men tekniken är inte validerad på hästar. Mål: Att undersöka mätsäkerheten hos en digital goniometer vid mätning av maximal passiv flektion i karpus och kotled på häst. Målet var också att un-dersöka dess användarvänlighet. Metoder: Studien består av tre delar; 1) jämförande mätningar med en digital och en manuell goniometer i maximal passiv flektion i karpus och kotled på tio vakna hästar; 2) jämförande mätningar med en digital goniometer på se-derad häst med flekterad och belastad kotled samt på radiografiska bilder av samma led och vinklar; 3) intra- och interbedömarreliabiliteten för en manuell och en digital goniometer räknas ut för alla utredare enskilt samt för hela stu-dien; 4) de båda goniometrarnas användarvänlighet utvärderades genom en enkät. Intraclass Correlation Coefficient (ICC) eller P-värde användes vid analys av data. Resultat: 1) Signifikanta skillnader i ROM registrerades i karpus (17°) och kotled (10°) vid jämförande mätning med en manuell och en digital gonio-meter. (P <0,001), 2) på flekterad kotled registrerades 3° skillnad och på flekterad kotled registrerades 2° skillnad vid jämförande mätningar på se-derad häst med radiografiska bilder, 3) interbedömarreliabiliteten för karpus var bra (ICC 0,77-0,77) och för kotled låg (ICC 0,25-0,39). Intrabedömarre-liabiliteten för kotled var bra till mycket bra (ICC 0,66-0,90) och för karpus låg till mycket bra (ICC 0,33-0,81), 4) Resultatet visar att den digitala goni-ometern EasyAngle enligt studien var lättare att lära sig använda och en-klare att använda än den manuella goniometern samt att utredarna kände sig något tryggare med att använda EasyAngle. De båda goniometrarna skiljde sig inte nämnvärt i hur utredarna upplevde noggrannheten och tillförlitlig-heten. Slutsats: En digital goniometer är ett lovande verktyg vid mätningar av kar-pus och kotled i maximal passiv flektion på häst om den används av samma person. Mer studier behövs dock för att validera metoden ytterligare.Reason for the study: Radiography has been used as the ”gold standard” for measuring ROM for some time. As radiography is both expensive and time consuming, and exposes both patients and staff to radiation, there is a need for an objective and validated method for measuring ROM which eliminates the fore mentioned disadvantages. Goniometry is a measurement method which is cheap, quick and does not harm the patient or the staff. Goniometry is a validated method for humans but is yet to be validated on horses. Objective: Examine the measurement accuracy with a digital goniometer when measuring maximum passive flexion in carpus and fetlock with horses. The objective is also to examine these to see how user friendly they are. Another objective was to determine the user friendliness of the method? Methods: The study consists of three parts, 1) comparative measurement between a digital and a manual goniometer in maximum passive flexion in carpus and fetlock on ten unsedated horses 2) comparative measurements between a digital goniometer on a sedated horse in flexed and loaded fetlock as well as radiographic images of the same joint and angles, 3) intra and in-terreliability for manual and a digital goniometer is to be calculated sepa-rately for each examiner as well as the whole study. 4) User friendliness evaluated on a digital and a manual goniometer where the examiners in the study had to answer a questionnaire about both the goniometers. Intraclass Correlation Coefficient (ICC) or P-värde (P-value) was used for analysis of the data. Results: 1) Significant differences in ROM were recorded in carpus (17 °) and vertically (10 °) when comparing with a manual and a digital goniome-ter. (P <0.001), 2) on the spotted vertebrae, 3 ° difference was recorded and 2 ° difference was recorded on the reflected vertebrae when comparing measurements on sedated horse with radiographic images; and for vertebral low (ICC 0.25-0.39). The intracellularity of vertebrae was good to very good (ICC 0.66-0.90) and for carpus was very good (ICC 0.33-0.81), 4) The result shows that the digital goniometer EasyAngle according to the study was easier to learn to use and easier to use than the manual goniometer and the investigators felt somehow safer with using EasyAngle. The two goni-ometers did not differ significantly in how the investigators experienced the accuracy and reliability

Healthcare ecosystems research in mental health: a scoping review of methods to describe the context of local care delivery

Background: Evidence from the context of local health ecosystems is highly relevant for research and policymaking to understand geographical variations in outcomes of health care delivery. In mental health systems, the analysis of context presents particular challenges related to their complexity and to methodological difficulties. Method guidelines and standard recommendations for conducting context analysis of local mental health care are urgently needed. This scoping study reviews current methods of context analysis in mental health systems to establish the parameters of research activity examining availability and capacity of care at the local level, and to identify any gaps in the literature. Methods: A scoping review based on a systematic search of key databases was conducted for the period 2005– 2016. A systems dynamics/complexity approach was adopted, using a modified version of Tansella and Thornicroft’s matrix model of mental health care as the conceptual framework for our analysis. Results: The lack of a specific terminology in the area meant that from 10,911 titles identified at the initial search, only 46 papers met inclusion criteria. Of these, 21 had serious methodological limitations. Fifteen papers did not use any kind of formal framework, and five of those did not describe their method. Units of analysis varied widely and across different levels of the system. Six instruments to describe service availability and capacity were identified, of which three had been psychometrically validated. A limitation was the exclusion of grey literature from the review. However, the imprecise nature of the terminology, and high number of initial results, makes the inclusion of grey literature not feasible. Conclusion: We identified that, in spite of its relevance, context studies in mental health services is a very limited research area. Few validated instruments are available. Methodological limitations in many papers mean that the particular challenges of mental health systems research such as system complexity, data availability and terminological variability are generally poorly addressed, presenting a barrier to valid system comparison. The modified Thornicroft and Tansella matrix and related ecological production of care model provide the main model for research within the area of health care ecosystems

Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells

A proteolytic cascade ensures that OMA1 cleaves and inactivates mitochondrial fusion protein OPA1 in times of stress, preventing damaged mitochondria from fusing with healthy organelles. (See also companion paper from Ehses et al. in this issue.

A Conditional Yeast E1 Mutant Blocks the Ubiquitin–Proteasome Pathway and Reveals a Role for Ubiquitin Conjugates in Targeting Rad23 to the Proteasome

E1 ubiquitin activating enzyme catalyzes the initial step in all ubiquitin-dependent processes. We report the isolation of uba1-204, a temperature-sensitive allele of the essential Saccharomyces cerevisiae E1 gene, UBA1. Uba1-204 cells exhibit dramatic inhibition of the ubiquitin–proteasome system, resulting in rapid depletion of cellular ubiquitin conjugates and stabilization of multiple substrates. We have employed the tight phenotype of this mutant to investigate the role ubiquitin conjugates play in the dynamic interaction of the UbL/UBA adaptor proteins Rad23 and Dsk2 with the proteasome. Although proteasomes purified from mutant cells are intact and proteolytically active, they are depleted of ubiquitin conjugates, Rad23, and Dsk2. Binding of Rad23 to these proteasomes in vitro is enhanced by addition of either free or substrate-linked ubiquitin chains. Moreover, association of Rad23 with proteasomes in mutant and wild-type cells is improved upon stabilizing ubiquitin conjugates with proteasome inhibitor. We propose that recognition of polyubiquitin chains by Rad23 promotes its shuttling to the proteasome in vivo

Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy

Defects in mitochondrial fusion or fission are associated with many pathologies, raising the hope that pharmacological manipulation of mitochondrial dynamics may have therapeutic benefit. This approach assumes that organ physiology can be restored by rebalancing mitochondrial dynamics, but this concept remains to be validated. We addressed this issue by analyzing mice deficient in Mff, a protein important for mitochondrial fission. Mff mutant mice die at 13 wk as a result of severe dilated cardiomyopathy leading to heart failure. Mutant tissue showed reduced mitochondrial density and respiratory chain activity along with increased mitophagy. Remarkably, concomitant deletion of the mitochondrial fusion gene Mfn1 completely rescued heart dysfunction, life span, and respiratory chain function. Our results show for the first time that retuning the balance of mitochondrial fusion and fission can restore tissue integrity and mitochondrial physiology at the whole-organ level. Examination of liver, testis, and cerebellum suggest, however, that the precise balance point of fusion and fission is cell type specific

Targeting and Function of the Mitochondrial Fission Factor GDAP1 Are Dependent on Its Tail-Anchor

Proteins controlling mitochondrial dynamics are often targeted to and anchored into the mitochondrial outer membrane (MOM) by their carboxyl-terminal tail-anchor domain (TA). However, it is not known whether the TA modulates protein function. GDAP1 is a mitochondrial fission factor with two neighboring hydrophobic domains each flanked by basic amino acids (aa). Here we define GDAP1 as TA MOM protein. GDAP1 carries a single transmembrane domain (TMD) that is, together with the adjacent basic aa, critical for MOM targeting. The flanking N-terminal region containing the other hydrophobic domain is located in the cytoplasm. TMD sequence, length, and high hydrophobicity do not influence GDAP1 fission function if MOM targeting is maintained. The basic aa bordering the TMD in the cytoplasm, however, are required for both targeting of GDAP1 as part of the TA and GDAP1-mediated fission. Thus, this GDAP1 region contains critical overlapping motifs defining intracellular targeting by the TA concomitant with functional aspects

Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission

Mitochondrial morphology depends on the balance between fission and fusion events. This study identifies a receptor for the fission factor Drp1 within the mitochondrial outer membrane, which inhibits Drp1-mediated fission and activates fusion

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER

This is the final version of the article. Available from the publisher via the DOI in this record.Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering.This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/K006231/1 and BB/ N01541X/1 to M. Schrader). J. Metz and M. Schrader are supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF and WT105618MA) and L.F. Godinho by a fellowship from Fundação para a Ciência e a Tecnologia, Portugal (SFRH/ BPD/90084/2012). M. Schrader and A.S. Azadi are supported by Marie Curie Initial Training Network action PerFuMe (316723). M. Islinger is supported by MEAMEDMA Anschubförderung, Medical Faculty Mannheim, University of Heidelberg