Muscular dystrophies are a group of genetic muscle disorders that cause progressive muscle weakness and degeneration. Within this group, Duchenne muscular dystrophy (DMD) is the most common and one ...of the most severe. DMD is an X chromosome linked disease that occurs to 1 in 3500 to 1 in 5000 boys. The cause of DMD is a mutation in the dystrophin gene, whose encoded protein provides both structural support and cell signaling capabilities. So far, there are very limited therapeutic options available and there is no cure for this disease. In this review, we discuss the existing cell therapy research, especially stem cell-based, which utilize myoblasts, satellite cells, bone marrow cells, mesoangioblasts and CD133+ cells. Finally, we focus on human pluripotent stem cells (hPSCs) which hold great potential in treating DMD. hPSCs can be used for autologous transplantation after being specified to a myogenic lineage. Over the last few years, there has been a rapid development of isolation, as well as differentiation, techniques in order to achieve effective transplantation results of myogenic cells specified from hPSCs. In this review, we summarize the current methods of hPSCs myogenic commitment/differentiation, and describe the current status of hPSC-derived myogenic cell transplantation.
•Myogenic progenitor cells could provide a source for cell therapy for DMD to regenerate and replace the diseased tissue•An orchestration of signaling molecules directing the lineage determination sets the basis for PSC differentiation in vitro•There is a need to develop more cell therapy options (e.g iPSC) for DMD due to limited success of current ones•The review describes the most recent studies of hiPSC muscle lineage specification and the potential of their application
The topic of analogical relationship between hearing and meaning has strong repercussions in the history of musical understanding. The high-low couple, the ground of spatial dimension in music, turns ...in a lot of metaphorical meanings which show the way that draws from perceptual data to imaginative values. In this paper, I reconstruct a shirt history of the relationship between hearing and imagination starting from the metaphorical conception of musical hearing from Aristotelian environment to phenomenological perspective.
During muscle regeneration, the mechanism integrating environmental cues at the chromatin of muscle progenitors is unknown. We show that inflammation-activated MKK6-p38 and insulin growth factor 1 ...(IGF1)-induced PI3K/AKT pathways converge on the chromatin of muscle genes to target distinct components of the muscle transcriptosome. p38 α/β kinases recruit the SWI/SNF chromatin-remodeling complex; AKT1 and 2 promote the association of MyoD with p300 and PCAF acetyltransferases, via direct phosphorylation of p300. Pharmacological or genetic interference with either pathway led to partial assembly of discrete chromatin-bound complexes, which reflected two reversible and distinct cellular phenotypes. Remarkably, PI3K/AKT blockade was permissive for chromatin recruitment of MEF2-SWI/SNF complex, whose remodeling activity was compromised in the absence of MyoD and acetyltransferases. The functional interdependence between p38 and IGF1/PI3K/AKT pathways was further established by the evidence that blockade of AKT chromatin targets was sufficient to prevent the activation of the myogenic program triggered by deliberate activation of p38 signaling.
Asomatognosia designates the experience that one's body has faded from awareness. It is typically a somaesthetic experience but may target the visual modality ("asomatoscopy"). Frequently associated ...symptoms are the loss of ownership or agency over a limb. Here, we elaborate on the rigorous nosographic classification of asomatognosia and introduce a structured interview to capture both its core symptoms and associated signs of bodily estrangement. We additionally report the case of a pure left-sided hemiasomatognosia occurring after surgical removal of a meningioma in the right atrium. Despite the wide lesions of the right angular gyrus and of the temporo-parietal junction, the patient did not present visuospatial deficits or bodily awareness disorders other than hemiasomatognosia. The patient and 10 matched controls' motor imagery was formally assessed with a limb laterality task in which they had to decide whether hands and feet presented under different angles of rotation depicted a left or a right limb. Bayesian statistics showed that patient's reaction times were significantly impaired exclusively for the left foot and especially for mental rotations requiring somatomotor rather than visual limb representations. This was in accordance with a more enduring left-sided hemiasomatognosia for the lower limbs confined to the somesthetic modality. Our findings shed new light on motor imagery in asomatognosia and encourage the future use of the structured interview introduced here. In addition, the limb laterality task may capture phenomenological elements of a case by chronometric means. This allows a more standardized reporting of phenomenological detail and improves communication across different clinical facilities.
Prolactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine, metabolic, and inflammatory ...profiles in PRL patients, aiming to identify potential prognostic markers.
The study comprised data from 59 PRL patients gathered in a registry at the University Hospital of Zurich. Diagnostic criteria included MRI findings and elevated serum prolactin levels. We assessed baseline and follow-up clinical demographics, metabolic markers, serum inflammation-based scores, and endocrine parameters. Treatment outcomes were evaluated based on prolactin normalization, tumor shrinkage, and cabergoline dosage.
The PRL cohort exhibited a higher prevalence of overweight/obesity, prediabetes/diabetes mellitus, and dyslipidemia compared to the general population. Significant correlations were found between PRL characteristics and BMI, HbA1c, and fT4 levels. Follow-up data indicated decreases in tumor size, tumor volume, prolactin levels, and LDL-cholesterol, alongside increases in fT4 and sex hormones levels. No significant associations were observed between baseline parameters and tumor shrinkage at follow-up. A positive association was noted between PRL size/volume and the time to achieve prolactin normalization, and a negative association with baseline fT4 levels.
This study underscores the metabolic significance of PRL, with notable correlations between PRL parameters and metabolic indices. However, inflammatory markers were not significantly correlated with patient stratification or outcome prediction. These findings highlight the necessity for standardized follow-up protocols and further research into the metabolic pathogenesis in PRL patients.
Background
The extent of resection (EOR) is a crucial outcome parameter in transsphenoidal pituitary surgery (TSS), and is linked to endocrinological outcome, postoperative morbidity, and mortality. ...We aimed to build a robust, quantitative, and easily reproducible imaging score able to predict EOR in TSS.
Methods
The ratio (R) between the maximum horizontal adenoma diameter and intercarotid distance at the horizontal C4 segment was used to stratify our patient series in four classes: class I R ≤ 0.75, class II 0.75 < R ≤ 1.25, and class III R ≥ 1.25. Class IV included adenomas which completely encased the internal carotid artery. The resulting score was internally validated for robustness.
Results
One hundred sixteen patients were included in the study, of which 96 (83%) for derivation and 20 (17%) for validation. EOR showed significant differences between grades (grade I, 100%; II, 97.9%; III, 94.2%; IV, 87.2%; all
P
< 0.05). The same applied to residual volume (RV) (grade I, 0 cm
3
; II, 0.08 cm
3
; III, 1.11 cm
3
; IV, 1.63 cm
3
; all
P
< 0.05). Differences in gross total resection (GTR) were statistically significant among classes I, II, and III (
P
< 0.05). The incidence of residual adenoma in the cavernous sinus increased also constantly from grade I up to grade IV although a significant difference was only found between grades III and II (
P
= 0.004). The score performed equally well in the validation cohort. Inter-observer agreement was high, with intraclass correlation coefficients > 0.89 for measurement of both the horizontal tumor diameter and the ICD among two independent raters (
P
< 0.001).
Conclusions
The proposed score is a simple and reproducible tool which reliably predicts surgical outcome including EOR, RV, and GTR of pituitary adenoma patients undergoing TSS.
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