The use of electromyography interference pattern analysis to determine muscle force of the deep digital flexor muscle in healthy and laminitic horses

BACKGROUND: In equine laminitis, the deep digital flexor muscle (DDFM) appears to have increased muscle force, but evidence-based confirmation is lacking. OBJECTIVES: The purpose of this study was to test if the DDFM of laminitic equines has an increased muscle force detectable by needle electromyography interference pattern analysis (IPA). ANIMALS AND METHODS: The control group included six Royal Dutch Sport horses, three Shetland ponies and one Welsh pony [10 healthy, sound adults weighing 411 ± 217 kg (mean ± SD) and aged 10 ± 5 years]. The laminitic group included three Royal Dutch Sport horses, one Friesian, one Haflinger, one Icelandic horse, one Welsh pony, one miniature Appaloosa and six Shetland ponies (14 adults, weight 310 ± 178 kg, aged 13 ± 6 years) with acute/chronic laminitis. The electromyography IPA measurements included firing rate, turns/second (T), amplitude/turn (M) and M/T ratio. Statistical analysis used a general linear model with outcomes transformed to geometric means. RESULTS: The firing rate of the total laminitic group was higher than the total control group. This difference was smaller for the ponies compared to the horses; in the horses, the geometric mean difference of the laminitic group was 1.73 [geometric 95% confidence interval (CI) 1.29-2.32], and in the ponies this value was 1.09 (geometric 95% CI 0.82-1.45). CONCLUSION AND CLINICAL RELEVANCE: In human medicine, an increased firing rate is characteristic of increased muscle force. Thus, the increased firing rate of the DDFM in the context of laminitis suggests an elevated muscle force. However, this seems to be only a partial effect as in this study, the unchanged turns/second and amplitude/turn failed to prove the recruitment of larger motor units with larger amplitude motor unit potentials in laminitic equids.

Dual Role of Mesenchymal Stem Cells Allows for Microvascularized Bone Tissue-Like Environments in PEG Hydrogels.

In vitro engineered tissues which recapitulate functional and morphological properties of bone marrow and bone tissue will be desirable to study bone regeneration under fully controlled conditions. Among the key players in the initial phase of bone regeneration are mesenchymal stem cells (MSCs) and endothelial cells (ECs) that are in close contact in many tissues. Additionally, the generation of tissue constructs for in vivo transplantations has included the use of ECs since insufficient vascularization is one of the bottlenecks in (bone) tissue engineering. Here, 3D cocultures of human bone marrow derived MSCs (hBM-MSCs) and human umbilical vein endothelial cells (HUVECs) in synthetic biomimetic poly(ethylene glycol) (PEG)-based matrices are directed toward vascularized bone mimicking tissue constructs. In this environment, bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor-2 (FGF-2) promotes the formation of vascular networks. However, while osteogenic differentiation is achieved with BMP-2, the treatment with FGF-2 suppressed osteogenic differentiation. Thus, this study shows that cocultures of hBM-MSCs and HUVECs in biological inert PEG matrices can be directed toward bone and bone marrow-like 3D tissue constructs.

Anatomy of the nail unit and the nail biopsy

The nail unit is the largest and a rather complex skin appendage. It is located on the dorsal aspect of the tips of fingers and toes and has important protective and sensory functions. Development begins in utero between weeks 7 and 8 and is fully formed at birth. For its correct development, a great number of signals are necessary. Anatomically, it consists of 4 epithelial components: the matrix that forms the nail plate; the nail bed that firmly attaches the plate to the distal phalanx; the hyponychium that forms a natural barrier at the physiological point of separation of the nail from the bed; and the eponychium that represents the undersurface of the proximal nail fold which is responsible for the formation of the cuticle. The connective tissue components of the matrix and nail bed dermis are located between the corresponding epithelia and the bone of the distal phalanx. Characteristics of the connective tissue include: a morphogenetic potency for the regeneration of their epithelia; the lateral and proximal nail folds form a distally open frame for the growing nail; and the tip of the digit has rich sensible and sensory innervation. The blood supply is provided by the paired volar and dorsal digital arteries. Veins and lymphatic vessels are less well defined. The microscopic anatomy varies from nail subregion to subregion. Several different biopsy techniques are available for the histopathological evaluation of nail alterations.

Three-dimensional culture and characterization of mononuclear cells from human bone marrow

BACKGROUND AIMS The diverse phenotypic changes and clinical and economic disadvantages associated with the monolayer expansion of bone marrow-derived mesenchymal stromal cells (MSCs) have focused attention on the development of one-step intraoperative cells therapies and homing strategies. The mononuclear cell fraction of bone marrow, inclusive of discrete stem cell populations, is not well characterized, and we currently lack suitable cell culture systems in which to culture and investigate the behavior of these cells. METHODS Human bone marrow-derived mononuclear cells were cultured within fibrin for 2 weeks with or without fibroblast growth factor-2 supplementation. DNA content and cell viability of enzymatically retrieved cells were determined at days 7 and 14. Cell surface marker profiling and cell cycle analysis were performed by means of multi-color flow cytometry and a 5-ethynyl-2'-deoxyuridine incorporation assay, respectively. RESULTS Total mononuclear cell fractions, isolated from whole human bone marrow, was successfully cultured in fibrin gels for up to 14 days under static conditions. Discrete niche cell populations including MSCs, pericytes and hematopoietic stem cells were maintained in relative quiescence for 7 days in proportions similar to that in freshly isolated cells. Colony-forming unit efficiency of enzymatically retrieved MSCs was significantly higher at day 14 compared to day 0; and in accordance with previously published works, it was fibroblast growth factor-2-dependant. CONCLUSIONS Fibrin gels provide a simple, novel system in which to culture and study the complete fraction of bone marrow-derived mononuclear cells and may support the development of improved bone marrow cell-based therapies.

Ultrastructure and Pathoanatomy of the Rotator Cuff

The rotator cuff is a complex musculotendinous unit, which plays a major role in glenohumeral joint stability and mobilization. Tears of the rotator cuff tendon and its subsequent changes of the rotator cuff muscle are common, and the incidence increases with age. Several structures such as the muscle, tendon, and bone may contribute to the development of a tear as well as on the outcome following a rotator cuff repair. Knowledge of these structures may help to improve rotator cuff healing after rotator cuff tear. The goal of this chapter is to discuss the evidence which exists with regard to the pathophysiological changes in the muscle, tendon, and bone that lead to a rotator cuff rupture as well as the changes that occur in these structures after a tear has occurred.

Pelvic floor muscle displacement during voluntary and involuntary activation in continent and incontinent women: a systematic review.

INTRODUCTION Investigations of the dynamic function of female pelvic floor muscles (PFM) help us to understand the pathophysiology of stress urinary incontinence (SUI). Displacement measurements of PFM give insight into muscle activation and thus help to improve rehabilitation strategies. This systematic review (PROSPERO 2013: CRD42013006409) was performed to summarise the current evidence for PFM displacement during voluntary and involuntary activation in continent and incontinent women. METHODS MEDLINE, EMBASE, Cochrane and SPORTDiscus databases were searched using selected terminology reflecting the PICO approach. Screening of Google Scholar and congress abstracts added to further information. Original articles investigating PFM displacement were included if they reported on at least one of the aims of the review, e.g., method, test position, test activity, direction and quantification of displacement, as well as the comparison between continent and incontinent women. Titles and abstracts were screened by two reviewers. The papers included were reviewed by two individuals to ascertain whether they fulfilled the inclusion criteria and data were extracted on outcome parameters. RESULTS Forty-two predominantly observational studies fulfilled the inclusion criteria. A variety of measurement methods and calculations of displacement was presented. The sample was heterogeneous concerning age, parity and continence status. Test positions and test activities varied among the studies. CONCLUSIONS The findings summarise the present knowledge of PFM displacement, but still lack deeper comprehension of the SUI pathomechanism of involuntary, reflexive activation during functional activities. We therefore propose that future investigations focus on PFM dynamics during fast and stressful impact tasks.

Dislocated Tongue Muscle Attachment and Cleft Palate Formation

In Pierre Robin sequence, a retracted tongue due to micrognathia is thought to physically obstruct palatal shelf elevation and thereby cause cleft palate. However, micrognathia is not always associated with palatal clefting. Here, by using the Bmp7-null mouse model presenting with cleft palate and severe micrognathia, we provide the first causative mechanism linking the two. In wild-type embryos, the genioglossus muscle, which mediates tongue protrusion, originates from the rostral process of Meckel's cartilage and later from the mandibular symphysis, with 2 tendons positive for Scleraxis messenger RNA. In E13.5 Bmp7-null embryos, a rostral process failed to form, and a mandibular symphysis was absent at E17.5. Consequently, the genioglossus muscle fibers were diverted toward the lingual surface of Meckel's cartilage and mandibles, where they attached in an aponeurosis that ectopically expressed Scleraxis. The deflection of genioglossus fibers from the anterior-posterior toward the medial-lateral axis alters their direction of contraction and necessarily compromises tongue protrusion. Since this muscle abnormality precedes palatal shelf elevation, it is likely to contribute to clefting. In contrast, embryos with a cranial mesenchyme-specific deletion of Bmp7 (Bmp7:Wnt1-Cre) exhibited some degree of micrognathia but no cleft palate. In these embryos, a rostral process was present, indicating that mesenchyme-derived Bmp7 is dispensable for its formation. Moreover, the genioglossus appeared normal in Bmp7:Wnt1-Cre embryos, further supporting a role of aberrant tongue muscle attachment in palatal clefting. We thus propose that in Pierre Robin sequence, palatal shelf elevation is not impaired simply by physical obstruction by the tongue but by a specific developmental defect that leads to functional changes in tongue movements.

Dysfunction of respiratory muscles in critically ill patients on the intensive care unit.

Muscular weakness and muscle wasting may often be observed in critically ill patients on intensive care units (ICUs) and may present as failure to wean from mechanical ventilation. Importantly, mounting data demonstrate that mechanical ventilation itself may induce progressive dysfunction of the main respiratory muscle, i.e. the diaphragm. The respective condition was termed 'ventilator-induced diaphragmatic dysfunction' (VIDD) and should be distinguished from peripheral muscular weakness as observed in 'ICU-acquired weakness (ICU-AW)'. Interestingly, VIDD and ICU-AW may often be observed in critically ill patients with, e.g. severe sepsis or septic shock, and recent data demonstrate that the pathophysiology of these conditions may overlap. VIDD may mainly be characterized on a histopathological level as disuse muscular atrophy, and data demonstrate increased proteolysis and decreased protein synthesis as important underlying pathomechanisms. However, atrophy alone does not explain the observed loss of muscular force. When, e.g. isolated muscle strips are examined and force is normalized for cross-sectional fibre area, the loss is disproportionally larger than would be expected by atrophy alone. Nevertheless, although the exact molecular pathways for the induction of proteolytic systems remain incompletely understood, data now suggest that VIDD may also be triggered by mechanisms including decreased diaphragmatic blood flow or increased oxidative stress. Here we provide a concise review on the available literature on respiratory muscle weakness and VIDD in the critically ill. Potential underlying pathomechanisms will be discussed before the background of current diagnostic options. Furthermore, we will elucidate and speculate on potential novel future therapeutic avenues.