The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

Barriers to physical activity during the COVID-19 pandemic in adults: a cross-sectional study

Sport Sciences for Health - Social isolation due to the coronavirus disease 2019 (COVID-19) pandemic has reduced physical activity levels in both men and women. The identification of barriers to...     

Engram Size Varies with Learning and Reflects Memory Content and Precision

Memories are rarely acquired under ideal conditions, rendering them vulnerable to profound omissions, errors, and ambiguities. Consistent with this, recent work using context fear conditioning has shown that memories formed after inadequate learning time display a variety of maladaptive properties, including overgeneralization to similar contexts. However, the neuronal basis of such poor learning and memory imprecision remains unknown. Using c-fos to track neuronal activity in male mice, we examined how these learning-dependent changes in context fear memory precision are encoded in hippocampal ensembles. We found that the total number of c-fos-encoding cells did not correspond with learning history but instead more closely reflected the length of the session immediately preceding c-fos measurement. However, using a c-fos-driven tagging method (TRAP2 mouse line), we found that the degree of learning and memory specificity corresponded with neuronal activity in a subset of dentate gyrus cells that were active during both learning and recall. Comprehensive memories acquired after longer learning intervals were associated with more double-labeled cells. These were preferentially reactivated in the conditioning context compared with a similar context, paralleling behavioral discrimination. Conversely, impoverished memories acquired after shorter learning intervals were associated with fewer double-labeled cells. These were reactivated equally in both contexts, corresponding with overgeneralization. Together, these findings provide two surprising conclusions. First, engram size varies with learning. Second, larger engrams support better neuronal and behavioral discrimination. These findings are incorporated into a model that describes how neuronal activity is influenced by previous learning and present experience, thus driving behavior.SIGNIFICANCE STATEMENT Memories are not always formed under ideal circumstances. This is especially true in traumatic situations, such as car accidents, where individuals have insufficient time to process what happened around them. Such memories have the potential to overgeneralize to irrelevant situations, producing inappropriate fear and contributing to disorders, such as post-traumatic stress disorder. However, it is unknown how such poorly formed fear memories are encoded within the brain. We find that restricting learning time results in fear memories that are encoded by fewer hippocampal cells. Moreover, these fewer cells are inappropriately reactivated in both dangerous and safe contexts. These findings suggest that fear memories formed at brief periods overgeneralize because they lack the detail-rich information necessary to support neuronal discrimination.     

Characterization of the orientation and isometry of Humphrey's ligament

Objectives/purposeThe purpose of this study was to examine the effect of flexion angle on isometry and fiber obliquity of the anterior meniscofemoral ligament (Humphrey's ligament (HL)).MethodsFollowing a medial parapatellar arthrotomy on 7 fresh frozen cadavers, the insertion points of the anterolateral (AL) and posteromedial (PM) bundles of the PCL, and HL were identified. Using a 9 mm circular software tool, virtual fibers were created. Within each virtual graft, a central fiber was calculated and used to generate anisometry profiles for the AL and PM bundles and HL at flexion angles of 0°, 30°, 60°, 90°, and 120°. Previously validated computer navigation software was used to re-create three dimensional bundles to measure fiber obliquity in the sagittal, frontal, and axial planes.ResultsHL length increased with knee flexion from 0 to 120°, and underwent similar length changes as the PCL bundles. In full extension and at 90°, the average length of the PM and AL bundles were not statistically different (p = 0.13 and p = 0.85 respectively). From 0 to 120°, the PM bundle was the most isometric, but the anisometry profile was statistically similar to the AL bundle and HL. In general, HL and the PM bundle had similar graphic trends in terms of fiber obliquity in all planes.ConclusionsUsing computer navigation, we have demonstrated that HL has similar isometry profiles as the PM and AL bundles of the PCL, and “mirrored” the obliquity of the PM bundle in all planes throughout flexion to 120°.     

Self-rehabilitation combined with botulinum toxin to improve arm function in people with chronic stroke. A randomized controlled trial

BackgroundBotulinum toxin injection (BTI) reduces muscle hyperactivity, but its effect on active upper-limb function is limited. Intensive rehabilitation could optimize the effects; however, outpatient post-stroke rehabilitation is usually not intensive. One solution could be self-rehabilitation.ObjectivesThe aim of this randomized controlled trial was to determine the effect of a self-rehabilitation program combined with BTI on upper-limb function in individuals with chronic hemiparesis.MethodsIn total, 33 outpatients were randomly allocated to receive BTI + self-rehabilitation (R group: n = 17) or BTI alone (C group: n = 16). Outcomes evaluated just before the BTI and 4 weeks later included the Wolf Motor Function Test (WMFT time: primary outcome), Action Research Arm Test, fatigue and quality of life.ResultsChange in WMFT did not differ between groups at 4 weeks (WMFT time: ?14% for R group, ?4% for C group. WFMT score: +12% for R group, 0% in C group). WFMT time and score improved significantly in the R group only (?14%, P = 0.01, and +12%, P = 0.02). In addition, the proportion of patients with improved WMFT time and score was higher in the R than C group (R group: 71% improved score, 77% improved time; C group: 43% improved score, 50% improved time). Also, passive range of shoulder flexion (P = 0.03) and wrist extension (P = 0.01) improved only in the R group. No other variables changed significantly. Compliance was excellent; average daily training time was greater than that prescribed.ConclusionsThe addition of a self-rehabilitation program to BTI did not significantly improve functional outcomes more than BTI alone; however, movement quality and speed improved only in the self-rehabilitation group. Participants in the self-rehabilitation group trained more than they were asked to, which suggests that they found the program worthwhile. These clinically relevant findings justify larger-scale studies of the effects of self-rehabilitation to enhance the effects of BTI. Clinical trial: NCT02699762.