Dynamic actin/septin network in megakaryocytes coordinates proplatelet elaboration

Megakaryocytes (MK) undergo extensive cytoskeletal rearrangements as they give rise to platelets. While cortical microtubule sliding has been implicated in proplatelet formation, the role of the actin cytoskeleton in proplatelet elongation is less understood. It is assumed that actin filament reorganization is important for platelet generation given that mouse models with mutations in actin-associated proteins exhibit thrombocytopenia. However, due to the essential role of the actin network during MK development, a differential understanding of the contribution of the actin cytoskeleton on proplatelet release is lacking. Here, we reveal that inhibition of actin polymerization impairs the formation of elaborate proplatelets by hampering proplatelet extension and bead formation along the proplatelet shaft, which was mostly independent of changes in cortical microtubule sliding. We identify Cdc42 and its downstream effectors, septins, as critical regulators of intracellular actin dynamics in MK, inhibition of which, similarly to inhibition of actin polymerization, impairs proplatelet movement and beading. Super-resolution microscopy revealed a differential association of distinctive septins with the actin and microtubule cytoskeleton, respectively, which was disrupted upon septin inhibition and diminished intracellular filamentous actin dynamics. In vivo, septins, similarly to F-actin, were subject to changes in expression upon enforcing proplatelet formation through prior platelet depletion. In summary, we demonstrate that a Cdc42/septin axis is not only important for MK maturation and polarization, but is further required for intracellular actin dynamics during proplatelet formation

The relationship between rowing related low back pain and rowing biomechanics: a systematic review

Background Low back pain (LBP) is common in rowers. Understanding rowing biomechanics may help facilitate prevention and improve rehabilitation. Objectives To define the kinematics and muscle activity of rowers and to compare with rowers with current or LBP history. Design Systematic review. Data sources EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science and Scopus from inception to December 2019. Grey literature was searched. Study eligibility criteria Experimental and non-experimental designs. Methods Primary outcomes were kinematics and muscle activity. Modified Quality Index (QI) checklist was used. Results 22 studies were included (429 participants). Modified QI score had a mean of 16.7/28 points (range: 15–21). Thirteen studies investigated kinematics and nine investigated muscle activity. Rowers without LBP (‘healthy’) have distinct kinematics (neutral or anterior pelvic rotation at the catch, greater hip range of motion, flatter low back spinal position at the finish) and muscle activity (trunk extensor dominant with less flexor activity). Rowers with LBP had relatively greater posterior pelvic rotation at the catch, greater hip extension at the finish and less efficient trunk muscle activity. In both groups fatigue results in increased lumbar spine flexion at the catch, which is greater on the ergometer. There is insufficient evidence to recommend one ergometer type (fixed vs dynamic) over the other to avoid LBP. Trunk asymmetries are not associated with LBP in rowers. Conclusion Improving clinicians’ and coaches’ understanding of safe and effective rowing biomechanics, particularly of the spine, pelvis and hips may be an important strategy in reducing incidence and burden of LBP

?There's definitely something wrong but we just don't know what it is? : A qualitative study exploring rowers' understanding of low back pain

Objectives: Low back pain is highly prevalent in rowing and can be associated with significant disability and premature retirement. A previous qualitative study in rowers revealed a culture of concealment of pain and injury due to fear of judgement by coaches or teammates. The aim of this study was to explore rowers' perspectives in relation to diagnosis, contributory factors, and management of low back pain. Design: Qualitative secondary analysis. Methods: We conducted a secondary analysis of interview data previously collected from 25 rowers (12 in Australia and 13 in Ireland). A reflexive thematic analysis approach was used. Results: We identified three themes: 1) Rowers attribute low back pain to structural/physical factors. Most rowers referred to structural pathologies or physical impairments when asked about their diagnosis. Some participants were reassured if imaging results helped to explain their pain, but others were frustrated if findings on imaging did not correlate with their symptoms. 2) Rowing is viewed as a risky sport for low back pain. Risk factors proposed by the rowers were primarily physical and included ergometer training, individual technique, and repetitive loading. 3) Rowers focus on physical strategies for the management and prevention of low back pain. In particular, rowers considered stretching and core-strengthening exercise to be important components of treatment. Conclusions: Rowers' understanding of low back pain was predominantly biomedical and focused on physical impairments. Further education of rowers, coaches and healthcare professionals in relation to the contribution of psychosocial factors may be helpful for rowers experiencing low back pain. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of Sports Medicine Australia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

“There's definitely something wrong but we just don't know what it is”: a qualitative study exploring rowers' understanding of low back pain

Objectives: Low back pain is highly prevalent in rowing and can be associated with significant disability and premature retirement. A previous qualitative study in rowers revealed a culture of concealment of pain and injury due to fear of judgement by coaches or teammates. The aim of this study was to explore rowers' perspectives in relation to diagnosis, contributory factors, and management of low back pain.Design: Qualitative secondary analysis.Methods: We conducted a secondary analysis of interview data previously collected from 25 rowers (12 in Australia and 13 in Ireland). A reflexive thematic analysis approach was used.Results: We identified three themes: 1) Rowers attribute low back pain to structural/physical factors. Most rowers referred to structural pathologies or physical impairments when asked about their diagnosis. Some participants were reassured if imaging results helped to explain their pain, but others were frustrated if findings on imaging did not correlate with their symptoms. 2) Rowing is viewed as a risky sport for low back pain. Risk factors proposed by the rowers were primarily physical and included ergometer training, individual technique, and repetitive loading. 3) Rowers focus on physical strategies for the management and prevention of low back pain. In particular, rowers considered stretching and core-strengthening exercise to be important components of treatment.Conclusions: Rowers' understanding of low back pain was predominantly biomedical and focused on physical impairments. Further education of rowers, coaches and healthcare professionals in relation to the contribution of psychosocial factors may be helpful for rowers experiencing low back pain.</p

Brachydactyly type B: linkage to chromosome 9q22 and evidence for genetic heterogeneity.

Brachydactyly type B (BDB), an autosomal dominant disorder, is the most severe of the brachydactylies and is characterized by hypoplasia or absence of the terminal portions of the index to little fingers, usually with absence of the nails. The thumbs may be of normal length but are often flattened and occasionally are bifid. The feet are similarly but less severely affected. We have performed a genomewide linkage analysis of three families with BDB, two English and one Portugese. The two English families show linkage to the same region on chromosome 9 (combined multipoint maximum LOD score 8.69 with marker D9S257). The 16-cM disease interval is defined by recombinations with markers D9S1680 and D9S1786. These two families share an identical disease haplotype over 18 markers, inclusive of D9S278-D9S280. This provides strong evidence that the English families have the same ancestral mutation, which reduces the disease interval to <12.7 cM between markers D9S257 and D9S1851 in chromosome band 9q22. In the Portuguese family, we excluded linkage to this region, a result indicating that BDB is genetically heterogeneous. Reflecting this, there were atypical clinical features in this family, with shortening of the thumbs and absence or hypoplasia of the nails of the thumb and hallux. These results enable a refined classification of BDB and identify a novel locus for digit morphogenesis in 9q22