Partial weight-bearing following ankle fracture: what's the actual load in early recovery?

PURPOSE: This study investigates the learning efficacy for partial weight load before discharge as well as the impact of biofeedback during the learning process. METHODS: We monitored weight-bearing in 57 patients who had surgery for ankle fractures. Continuous measurements without and with biofeedback were performed in the early postoperative stage in order to, first, assess how well these patients could apply what they have learned before being discharged, and second, to examine the influence of biofeedback. RESULTS: Using conventional teaching methods, only about one-third of patients (36.8% on the ground and 29.2% on the stairs) were able to maintain a satisfactory load. One-fourth of the patients did not place any weight on their leg, which was shown to be due to excessive pain at the time of the measurement (p < 0.05). A further one-fourth loaded inadequately low, while the remainder loaded excessively. Patients benefited significantly from the activation of audio-visual biofeedback in real time. As a result, loads in a target zone between 15 and 30 kg could be significantly increased (p < 0.05). CONCLUSION: We conclude that the majority of ankle fracture patients were unable to learn partial weight bearing in the early postoperative stage using traditional techniques. Additionally, each patient's ability to carry out a given loading varied. Using an audio-visual real-time biofeedback modality led to significantly improved performance. These findings support the proposed utility of audiovisual feedback in early rehabilitation. With the use of outpatient real-time biofeedback systems, therapists will be able to respond specifically to the needs of each individual patient. TRIAL REGISTRATION: Trial registration: DRKS00031136, Registered 01.02.2023 - Retrospectively registered, https://www.drks.de/DRKS00031136.

Continuous real-time biofeedback in orthosis improves partial weight bearing on stairs.

INTRODUCTION: Climbing up and down stairs with crutches is a particular challenge. The current study evaluates a commercially available insole orthosis device for weighing an affected limb and for biofeedback training of gait. This study was done on healthy, asymptomatic individuals before applying to the intended postoperative patient. The outcomes should demonstrate whether a continuous real-time biofeedback (BF) system is more effective on stairs than the current protocol involving a bathroom scale. MATERIALS AND METHODS: 59 healthy test subjects received both crutches and an orthosis and learned to apply a 3-point gait with a partial load of 20 kg using a bathroom scale. Thereafter, the participants were asked to complete an up-and-down course, first without (control group) and then with (test group) an audio-visual real-time biofeedback (BF). Compliance was evaluated using an insole pressure measurement system. RESULTS: Using the conventional therapy technique, 36.6% of the steps up and 39.1% of the steps down in the control group were loaded with < 20 kg. By activating continuous biofeedback, steps with < 20 kg could be increased significantly to 61.1% upstairs (p < 0.001) and 66.1% downstairs (p < 0.001). All subgroups profited from the BF system, independent of age, gender, side relieved, dominant or non-dominant side. CONCLUSIONS: Traditional training without biofeedback led to poor performance for partial weight bearing on stairs, even among young and healthy individuals. However, continuous real-time biofeedback clearly improved compliance, indicating its potential to enhance training and support future research in patient populations.

Efficient and precise editing of endogenous transcripts with SNAP-tagged ADARs.

Molecular tools that target RNA at specific sites allow recoding of RNA information and processing. SNAP-tagged deaminases guided by a chemically stabilized guide RNA can edit targeted adenosine to inosine in several endogenous transcripts simultaneously, with high efficiency (up to 90%), high potency, sufficient editing duration, and high precision. We used adenosine deaminases acting on RNA (ADARs) fused to SNAP-tag for the efficient and concurrent editing of two disease-relevant signaling transcripts, KRAS and STAT1. We also demonstrate improved performance compared with that of the recently described Cas13b-ADAR.

Shoulder function after helical long PHILOS plate.

BACKGROUND: In order to minimize the risk of damaging the radial nerve while using a long PHILOS plate for proximal humerus fractures, recent studies have proposed twisting the plate in a helical form. This implies a modified surgical approach being yet unclear whether it leads to different middle to long-term shoulder function. This study compares the one-year shoulder functional outcomes of both techniques (helical vs. control). METHODS: In this retrospective comparative study, we analyzed 30 patients that fit the inclusion criteria, being 14 treated with a helical plate and 16 with a conventional straight long PHILOS plate. The primary endpoint was the normalized constant score after a minimum follow up of one year. RESULTS: Both groups had a good one-year shoulder function, and no significant difference between the normalized constant scores was seen. There was no significant difference in the surgical complications as well. CONCLUSION: Opting for a helical long PHILOS plate in order to avoid radial nerve damage provided a safe treatment with similarly good one-year shoulder function compared to straight PHILOS plates. LEVEL OF EVIDENCE: Level 3, Retrospective Cohort Study.

Comparing iatrogenic radial nerve lesions in humeral shaft fractures treated with helical or straight PHILOS plates: a 10-year retrospective cohort study of 62 cases.

BACKGROUND: Humerus shaft fractures are common and often treated surgically with a proximal humerus internal locking system like the long PHILOS® plate. Due to its close anatomical proximity to the humerus, the radial nerve is particularly susceptible to traumatic and iatrogenic damage. The iatrogenic radial nerve damage associated with internal locking systems is described in about 7% of the cases. In order to avoid this lesion, helical plates have been suggested since 1999. This technique continues to not being used as standard as there is still a clear lack of evidence. This study aimed to understand if twisting a long PHILOS plate can reduce the rate of iatrogenic radial nerve damage in humerus shaft fractures. METHODS: In this 10-year retrospective comparative study, patients with primary traumatic proximal humerus shaft fracture treated with a straight or twisted helical PHILOS® plate were analyzed and compared. Among the 62 patients meeting the inclusion criteria between 2008 and 2018, 33 received a conventional straight plate, while 29 were treated with a helical plate. The primary endpoint was iatrogenic radial nerve damage immediately after surgery with a follow-up of at least 3 months. RESULTS: No case of radial nerve damage was reported in the helical group. In the control group, iatrogenic radial nerve damage occurred in two cases (6%), which was not statistically significant when comparing both groups (p = 0.18). CONCLUSION: Manually twisting long PHILOS® plates is a safe procedure to avoid radial nerve lesion in humerus shaft fractures. Even though the group size did not allow a statistically relevant difference, we underline that only the helical group showed no iatrogenic radial lesion. This technique deserves further attention. LEVEL OF EVIDENCE: Level 3, retrospective cohort study.

A simple mathematical model using centred loops and random perturbations accurately reconstructs search patterns observed in desert ants.

This paper describes a new mathematical model that is based on centred loops to reconstruct the "Systematic Search" behaviour of Cataglyphis desert ants. The notable advantage of this model is the combination of simplicity, efficiency and performance. All model input is kept to a minimum, using only parameters that previous research has shown to be available to the animals at all times: distance from the origin, direction of the last step and home vector. Outbound and inbound search paths are being combined into loops that return to the origin, sampling this area more intensely. A stochastic element is added by random perturbations during the next step, mimicking unsystematic errors during the process of path integration and yielding the typical search patterns observed in Cataglyphis desert ants. The model output is compared to runs observed in the field.

Shoulder joint replacement can improve quality of life and outcome in patients with dysmelia: a case series.

BACKGROUND: Arthroplasty is a proven treatment option for glenohumeral osteoarthritis. Common indications include primary or posttraumatic osteoarthritis, avascular necrosis of the humeral head, rotator cuff tear arthropathy and rheumatoid osteoarthritis. Arthroplasty is rarely performed among patients with glenohumeral dysmelia. An overuse of the upper limb in patients with thalidomide-induced phocomelia and people with similar congenital deformities like dysmelia results in premature wear of the shoulder joint. This study aims to evaluate our experience with cases of glenohumeral osteoarthritis caused by dysmelia and treated with arthroplasty. To date, few reports on the outcome of shoulder arthroplasty exist on this particular patient group. CASE PRESENTATION: We included four dysmelic patients (five shoulders) with substantial glenoid dysplasia in a prospective database after approval by the local ethics committee. Once conservative treatment options had been exhausted, the patients were treated with shoulder arthroplasty and assessed clinically and radiographically before and after surgery. The mean patient age at the time of surgery was 50.4 years. The minimum follow-up time was 24 months (24-91 months). All patients experienced a considerable improvement of range of motion (ROM) and a relief of pain. No intra- or postoperative complications appeared. CONCLUSION: Patients with dysmelia have acceptable short and mid-term results with resurfacing hemiarthroplasty. It is an effective although somewhat complicated method to relieve pain and improve movement. Long-term performance of arthroplasty in patients with dysmelia remains to be seen, particularly with regard to the remaining problem of the altered and often deficient glenoid.

Interactions between Flavins and Quadruplex Nucleic Acids.

Quadruplex nucleic acids are widespread in genomes. They influence processes such as transcription, translation, replication, recombination, and the regulation of gene expression. Several synthetic ligands have been demonstrated to target quadruplex nucleic acids. However, only very few metabolites have been reported to interact with quadruplexes. In principle, an intracellular metabolite that selectively binds to four-stranded sequences could modulate quadruplex formation, stability, and thus functions in a riboswitch (or deoxyriboswitch) manner. Here we report quadruplex interactions with flavin derivatives such as FMN and FAD. The affinities were highest with parallel quadruplexes, with low (14-20 µm) dissociation constants. Taking into account combined intracellular flavin concentrations of 243 µm in E. coli, the observed interactions in principle open up the possibility of flavin levels affecting gene expression and other processes by modulating quadruplex formation.

Can elderly individuals perform partial weight bearing on their lower limbs? A prospective cohort study using ambulatory real-time biofeedback.

BACKGROUND: Partial weight bearing in an orthosis and with forearm crutches is a widespread and well-accepted therapeutic principle after an injury of the lower extremity during early rehabilitation. Complying may be challenging to do under these circumstances, especially for elderly people. This study compares the spatiotemporal parameters and peak loads performed by a group of older participants before and after activating real-time biofeedback (BF) to determine whether they benefit from a biofeedback. METHODS: Twenty-four healthy subjects between 61 and 80 years learned how to walk using forearm crutches in a lower leg orthosis while performing a weight of 20 kg using a bathroom scale with the aim of loading in a zone between 15 and 30 kg. After that, they completed a course that was on level ground (50 m) and another course on stairs (11 steps). They did a walk without BF first, and then with BF. Each step was given a maximum load, which was determined and statistically checked. In addition, spatiotemporal parameters were collected. RESULTS: The classical teaching method with a bathroom scale was ineffective. Only 32.3% of the loads could be adequately carried by a person on level ground in the 15-30 kg target zone. On the stairs, it was 48.2% and 34.3%, respectively. Thus, on level ground, 52.7% of loads exceeded 30 kg. Downstairs it was 46.4%, and upstairs it was 41.6%. Subjects clearly benefit from activated biofeedback. Biofeedback significantly reduced missteps > 30 kg in every course. The loads decreased significantly to 25.0% on level ground, to 23.0% upstairs, and to 24.4% downstairs. At the same time, speed and stride length decreased per course while total time increased. CONCLUSION: Partial weight bearing is more complex and difficult for the elderly. These study results may help better understand 3-point gait in older adults in an outpatient setting. When partial weight bearing is recommended, special follow-up attention must be given for this group. Age-based therapy strategies can be developed and monitored with the assistance of ambulatory biofeedback devices. Trial registration Retrospectively registered, https://www.drks.de/DRKS00031136 .

Biomechanical testing of osteosynthetic locking plates for proximal humeral shaft fractures - a systematic literature review.

Proximal humeral shaft fractures can be treated with helically deformed bone plates to reduce the risk of iatrogenic nerve lesion. Controversially to this common surgical technique that was first established in 1999, no biomechanical investigation on humeral helical plating is recorded by other reviews, which focus on proximal fractures exclusively. Does an additional scope for shaft fractures reveal findings of helical testing? The present systematic literature review was performed based on guidelines by Kitchenham et al. to systematically search and synthesize literature regarding biomechanical testing of osteosynthetic systems for proximal humeral shaft fractures. Therefore, a systematic approach to search and screen literature was defined beforehand and applied on the findings of the database PubMed®. Synthesized information of the included literature was categorized, summarized and analyzed via descriptive statistics. Out of 192 findings, 22 publications were included for qualitative synthesis. A wide range of different test methods was identified, leading to a suboptimal comparability of specific results between studies. Overall, 54 biomechanical test scenarios were identified and compared. Physiological based boundary conditions (PB-BC) were referenced in 7 publications only. One study of testing straight and helical dynamic compression plates without PB-BCs was identified, showing significant differences under compressional loading. The absence of test standards of specific fields like humeral fractures lead to a high variance in biomechanical testing of osteosynthetic locking plates for proximal humeral shaft fractures. Physiological approaches offer realistic test scenarios but need to be uniformed for enhanced comparability between studies. The impact of helically deformed locking plates under PB-BC was not identified in literature.

Path integration mediated systematic search: a Bayesian model.

The systematic search behaviour is a backup system that increases the chances of desert ants finding their nest entrance after foraging when the path integrator has failed to guide them home accurately enough. Here we present a mathematical model of the systematic search that is based on extensive behavioural studies in North African desert ants Cataglyphis fortis. First, a simple search heuristic utilising Bayesian inference and a probability density function is developed. This model, which optimises the short-term nest detection probability, is then compared to three simpler search heuristics and to recorded search patterns of Cataglyphis ants. To compare the different searches a method to quantify search efficiency is established as well as an estimate of the error rate in the ants' path integrator. We demonstrate that the Bayesian search heuristic is able to automatically adapt to increasing levels of positional uncertainty to produce broader search patterns, just as desert ants do, and that it outperforms the three other search heuristics tested. The searches produced by it are also arguably the most similar in appearance to the ant's searches.

Protective and Risk Factors for Humerus Head Necrosis After Proximal Humerus Fracture Treated with Internal Locking Plate.

BACKGROUND: Proximal humerus fractures (PHF) are common and lead to post-traumatic humerus head necrosis (HHN) in 3-35% after ORIF with an internal locking plate. Few studies focus on this condition and risk factors remain a discussion topic. Hertel's criteria for initial head ischemia right after fracture (fracture complexity, medial hinge displacement and short metaphyseal head extension) have recently been correlated to HHN, but there is still a clear lack of evidence on the topic. Due to its anatomical similarities to the proximal femur, some authors argue that PHF may as well benefit from early surgery to avoid head necrosis. METHODS: In this 10-year retrospective study, we assessed 305 patients from a single center. All cases were treated with a PHILOS plate through a deltopectoral approach. The mean follow-up time was 467 days. The primary endpoint was HHN. RESULTS: HHN was diagnosed in 12 patients (4%), 10 of which were diagnosed within the first year and one case 4 years after surgery. A positive correlation (p < 0.04) was found between HHN and fracture type (both in AO and Neer's classification), initial neck-shaft-angle (NSA) and metaphyseal head extension (MHE). Medial hinge displacement (MHD) occurred in all HHN cases. Achieving perfect reduction (< 2 mm dislocation) was relevant to avoiding HHN (p = 0.035). Although HHN developed in 32% of the high risk cases (four-part fractures with a short MHE), it was completely avoided (0%) when perfect reduction was achieved. Time until surgery after admission was neither a protective nor a risk factor for HHN. CONCLUSION: We conclude that fracture complexity (four-part and C-fractures) as well as disruption of the medial hinge with a metaphyseal head extension smaller than 8 mm are relevant risk factors for humerus head necrosis. A combination of these criteria generated an high risk pattern with a 32% rate of HHN. Though often difficult to achieve, perfect reduction was a clear protective factor and reduced HHN to 0%. Perfect reduction may be key to inosculation and, therefore, salvage of the humerus head, especially in high risk cases. Surgery timing did not correlate with HHN. LEVEL OF EVIDENCE: Level 3, retrospective cohort study.

New Frontiers for Site-Directed RNA Editing: Harnessing Endogenous ADARs.

RNA editing activity can be exploited for the restoration of disease-causing nonsense and missense mutations and as a tool to manipulate the transcriptome in a simple and programmable way. The general concept is called site-directed RNA editing and has high potential for translation into the clinics. Due to its different mode of action RNA editing may well complement gene editing and other gene therapy options. In this method chapter, we particularly highlight RNA editing strategies that harness endogenous ADARs. Such strategies circumvent the delivery and expression of engineered editases and are notably precise and simple. This is particularly true if endogenous ADARs are recruited with chemically modified antisense oligonucleotides, an approach we call RESTORE (recruiting endogenous ADAR to specific transcripts for oligonucleotide-mediated RNA editing). To foster the research and development of RESTORE we now report a detailed protocol for the procedure of editing reactions, and a protocol for the generation of partly chemically modified RESTORE ASOs with a combination of in vitro transcription and ligation.

High stimulus specificity characterizes anti-predator habituation under natural conditions.

Habituation is one of the most fundamental learning processes that allow animals to adapt to dynamic environments. It is ubiquitous and often thought of as a simple form of non-associative learning. Very little is known, though, about the rules that govern habituation and their significance under natural conditions. Questions about how animals incorporate habituation into their daily behaviour and how they can assure only to habituate to non-relevant stimuli are still unanswered. Animals under threat of predation should be particularly selective about which stimuli they habituate to, since ignoring a real threat could be fatal. In this study, we tested the response of fiddler crabs, Uca vomeris, to repeatedly approaching dummy predators to find out whether these animals habituate to potential predators and to test the selectivity of the habituation process. The crabs habituated to model predators, even though they were confronted with real predators during the same habituation process. They showed remarkable selectivity towards the stimulus: a simple change in the approach distance of the stimulus led to a recovery in their responses. The results strongly indicate that in the context of predator avoidance, habituation under natural conditions is highly selective and a stimulus is not defined just by its current sensory signature, but also its spatio-temporal history.

Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides.

Site-directed RNA editing might provide a safer or more effective alternative to genome editing in certain clinical scenarios. Until now, RNA editing has relied on overexpression of exogenous RNA editing enzymes or of endogenous human ADAR (adenosine deaminase acting on RNA) enzymes. Here we describe the engineering of chemically optimized antisense oligonucleotides that recruit endogenous human ADARs to edit endogenous transcripts in a simple and programmable way, an approach we call RESTORE (recruiting endogenous ADAR to specific transcripts for oligonucleotide-mediated RNA editing). We observed almost no off-target editing, and natural editing homeostasis was not perturbed. We successfully applied RESTORE to a panel of standard human cell lines and human primary cells and demonstrated repair of the clinically relevant PiZZ mutation, which causes α1-antitrypsin deficiency, and editing of phosphotyrosine 701 in STAT1, the activity switch of the signaling factor. RESTORE requires only the administration of an oligonucleotide, circumvents ectopic expression of proteins, and represents an attractive approach for drug development.

Surface structure helps desert ants return to known feeding sites.

Desert ants, Cataglyphis fortis, return to their nest when they are disturbed during their foraging trips. Training them to a landmark corridor enabled us to induce ants that were captured immediately after leaving the nest and transferred to an unknown area to start their foraging trips.1 However, most of the ants never traveled the entire foraging distance to the feeder, but aborted their runs after the landmark corridor was no longer visible. Therefore, apart from landmark information and path integrator, there are additional cues that determine the ants' foraging behavior. Considering the reduced straightness of the outbound runs, I argue that surface structure might have a remarkable impact on foraging desert ants.

Landmark cues can change the motivational state of desert ant foragers.

Desert ants of the genus Cataglyphis rely on path integration vectors to return to the nest (inbound runs) and back to frequently visited feeding sites (outbound runs). If disturbed, e.g., experimentally displaced on their inbound runs, they continue to run off their home-bound vector, but if disturbed in the same way on their outbound runs, they do not continue their feeder-based vector, but immediately switch on the home-bound state of their path integration vector and return to the nest. Here we show that familiar landmarks encountered by the ants during their run towards the feeder can change the ants' motivational state insofar that the ants even if disturbed continue to run in the nest-to-feeder direction rather than reverse their courses, as they do in landmark-free situations. Hence, landmark cues can cause the ants to change their motivational state from homing to foraging.

Landmark guidance and vector navigation in outbound desert ants.

This study deals with the influence landmark information has on the foraging behaviour of the desert ant, Cataglyphis fortis, especially with the interaction of such landmark information with the ants' path integration system. We show in the first experiment that desert ants that are captured immediately after leaving their nest and then transferred to a remote test area search for the nest rather than activate their previous path integration vector. In a second experiment, the ants had been trained to a landmark corridor on their way to the feeder. In the critical test situation, they were again captured immediately after they had left the nest and transferred to a test field where they faced one of the following three situations: (1) the same landmark corridor as used during the training phase, (2) no landmarks at all and (3) a landmark corridor rotated by 90 deg. as compared with the training situation. Nearly all ants in test situation (1) eventually followed the landmark corridor but most of them never reached the fictive feeder. In situation (2), the ants searched around the nest entrance. In situation (3), approximately one half of the ants searched for the nest, whereas most of the other ants followed the landmark corridor, i.e. headed in a completely wrong direction. Hence, familiar landmarks do not only influence the foraging behaviour of desert ants, e.g. in making the ants start their foraging runs but can even out-compete the ants' path integration system.

Egocentric path integration models and their application to desert arthropods.

Path integration enables desert arthropods to find back to their nest on the shortest track from any position. To perform path integration successfully, speeds and turning angles along the preceding outbound path have to be measured continuously and combined to determine an internal global vector leading back home at any time. A number of experiments have given an idea how arthropods might use allothetic or idiothetic signals to perceive their orientation and moving speed. We systematically review the four possible model descriptions of mathematically precise path integration, whereby we favour and elaborate the hitherto not used variant of egocentric cartesian coordinates. Its simple and intuitive structure is demonstrated in comparison to the other models. Measuring two speeds, the forward moving speed and the angular turning rate, and implementing them into a linear system of differential equations provides the necessary information during outbound route, reorientation process and return path. In addition, we propose several possible types of systematic errors that can cause deviations from the correct homeward course. Deviations have been observed for several species of desert arthropods in different experiments, but their origin is still under debate. Using our egocentric path integration model we propose simple error indices depending on path geometry that will allow future experiments to rule out or corroborate certain error types.

Uncertainty about nest position influences systematic search strategies in desert ants.

Foraging desert ants return to their starting point, the nest, by means of path integration. If the path-integration vector has been run off but the nest has not yet been reached, the ants engage in systematic search behavior. This behavior results in a system of search loops of ever increasing size and finally leads to a search density profile peaking at the location where the path integration system has been reset to zero. In this study we investigate whether this systematic search behavior is adapted to the uncertainty resulting from the preceding foraging run. We show first that the longer the distances of the foraging excursions, the larger the errors occurring during path integration, and second that the ants adapt their systematic search strategy to their increasing uncertainty by extending their search pattern. Hence, the density of the systematic search pattern is correlated with the ants' confidence in their path integrator. This confidence decreases with increasing foraging distances.