A Rare Case of a Solitary Fibrous Tumor of the Spermatic Cord.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors, originally identified in the pleura. Even though they have subsequently been described in several extrapleural sites, the incidence of SFTs in the spermatic cord is particularly rare. Here, we report a case of a 27-year-old male that presented with a 3-year history of left scrotal swelling.

Modulation of the Acetylcholine Receptor Clustering Pathway Improves Neuromuscular Junction Structure and Muscle Strength in a Mouse Model of Congenital Myasthenic Syndrome.

Congenital myasthenic syndromes (CMS) are a diverse group of inherited neuromuscular disorders characterized by a failure of synaptic transmission at the neuromuscular junction (NMJ). CMS often present early with fatigable weakness and can be fatal through respiratory complications. The gene is one of over 30 genes known to harbor mutations causative for CMS.

Influence of cosmetic formulations on the skin's circadian clock.

Objective: The circadian rhythm was set into focus by awarding the Nobel Price of Physiology/Medicine to Jeffrey Hall, Michael Rosbash and Michael Young in late 2017. Numerous publications elucidated the molecular mechanisms driving the circadian biorhythms of our body, peripheral organs and each single cell. However, there is minor knowledge on the circadian rhythm of the skin, which has its own peripheral circadian clock in contact with cosmetic formulations.

Modulation of Agrin and RhoA Pathways Ameliorates Movement Defects and Synapse Morphology in MYO9A-Depleted Zebrafish.

Congenital myasthenic syndromes (CMS) are a group of rare, inherited disorders characterised by impaired function of the neuromuscular junction (NMJ). This is due to defects in one of the many proteins associated with the NMJ. In three patients with CMS, missense mutations in a gene encoding an unconventional myosin protein, MYO9A, were identified as likely causing their disorder.

Plasma C-terminal agrin fragment and rapid kidney function decline in chronic kidney disease patients.

C-terminal agrin fragment (tCAF) is a promising biomarker for glomerular filtration. Data regarding biomarkers that have the ability to predict rapid progression of chronic kidney disease (CKD) are sparse but necessary in order to identify patients at high risk for rapid progression. This study addresses the value of tCAF as a predictor of rapid kidney function decline in CKD patients.

MYO9A deficiency in motor neurons is associated with reduced neuromuscular agrin secretion.

Congenital myasthenic syndromes (CMS) are a group of rare, inherited disorders characterized by compromised function of the neuromuscular junction, manifesting with fatigable muscle weakness. Mutations in MYO9A were previously identified as causative for CMS but the precise pathomechanism remained to be characterized. On the basis of the role of MYO9A as an actin-based molecular motor and as a negative regulator of RhoA, we hypothesized that loss of MYO9A may affect the neuronal cytoskeleton, leading to impaired intracellular transport.

Increasing Agrin Function Antagonizes Muscle Atrophy and Motor Impairment in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a pediatric genetic disease, characterized by motor neuron (MN) death, leading to progressive muscle weakness, respiratory failure, and, in the most severe cases, to death. Abnormalities at the neuromuscular junction (NMJ) have been reported in SMA, including neurofilament (NF) accumulation at presynaptic terminals, immature and smaller than normal endplates, reduced transmitter release, and, finally, muscle denervation. Here we have studied the role of agrin in SMAΔ7 mice, the experimental model of SMAII.

Engineered agrin attenuates the severity of experimental autoimmune myasthenia gravis.

Introduction: Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG).

Testosterone does not affect agrin cleavage in mobility-limited older men despite improvement in physical function.

In a subset of men, sarcopenia and physical dysfunction occur due to destabilization of the neuromuscular junction (NMJ), which is manifested by elevated serum concentrations of C-terminal agrin fragment (CAF). Testosterone administration improves physical function in some studies; however, its effects on serum circulating CAF concentrations remain unknown. Here we evaluate the effects of testosterone administration on circulating CAF levels in mobility-limited men with low testosterone aged 65 or older participating in the Testosterone in Older Men with Mobility Limitations (TOM) Trial.

Grifolin derivatives from Albatrellus ovinus as TRPV1 receptor blockers for cosmetic applications.

Objective: Blocking the TRPV1 receptor is an interesting approach for the treatment of sensitive skin. Here we investigated the potential of grifolin derivatives from Albatrellus ovinus to act as TRPV1 receptor blockers and their potential to serve as cosmetic active ingredients.

Methods: Binding characteristics of grifolin derivatives from Albatrellus ovinus were determined in competitive and functional in vitro assays to achieve IC values.

Denervation drives mitochondrial dysfunction in skeletal muscle of octogenarians.

Key Points: Mitochondria are frequently implicated in the ageing of skeletal muscle, although the role of denervation in modulating mitochondrial function in ageing muscle is unknown. We show that increased sensitivity to apoptosis initiation occurs prior to evidence of persistent denervation and is thus a primary mitochondrial defect in ageing muscle worthy of therapeutic targeting. However, at more advanced age, mitochondrial function changes are markedly impacted by persistent sporadic myofibre denervation, suggesting the mitochondrion may be a less viable therapeutic target.

Failed reinnervation in aging skeletal muscle.

Background: Skeletal muscle displays a marked accumulation of denervated myofibers at advanced age, which coincides with an acceleration of muscle atrophy.

Methods: In this study, we evaluated the hypothesis that the accumulation of denervated myofibers in advanced age is due to failed reinnervation by examining muscle from young adult (YA) and very old (VO) rats and from a murine model of sporadic denervation secondary to neurotrypsin over-expression (Sarco mouse).

Results: Both aging rat muscle and Sarco mouse muscle exhibited marked fiber-type grouping, consistent with repeating cycles of denervation and reinnervation, yet in VO muscle, rapsyn at the endplate increased and was associated with only a 10 % decline in acetylcholine receptor (AChR) intensity, whereas in Sarco mice, there was a decline in rapsyn and a 25 % decrease in AChR intensity.

The C-Terminal Fragment of Agrin (CAF), a Novel Marker of Renal Function, Is Filtered by the Kidney and Reabsorbed by the Proximal Tubule.

Agrin, a multidomain proteoglycan and neurotrypsin, a neuronal serine protease, are important for forming (neuromuscular) synapses. Proteolytical activity of neurotrypsin produces a C-terminal fragment of agrin, termed CAF, of approximately 22 kDA molecular size which also circulates in blood. The presence of CAF in urine suggests either glomerular filtration or secretion into urine.

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation.

Background: C-terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub-fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke.

Comparison of Peritoneal Low-Molecular-Weight-Protein-Removal in CCPD and CAPD Patients Based on C-Terminal Agrin Fragment Clearance.

Background/aims: This study compares the peritoneal elimination of the low-molecular-weight-protein (LMWP) C-terminal agrin fragment (tCAF, size 22 kDa), a promising biomarker for kidney function, in continuous cycling peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD).

Methods: 103 sets of serum, 24h-urine and dialysate samples were obtained in 15 CCPD (63 sets) and 11 CAPD (40 sets) patients. Total, renal and peritoneal substrate removals/clearances were measured/calculated for tCAF, creatinine, blood-urea-nitrogen (BUN), cystatin C and albumin and correlated with the peritoneal transport type.

Plasma total C-terminal agrin fragment (tCAF) as a marker for kidney function in patients with chronic kidney disease.

Background: Total C-terminal agrin fragment (tCAF) is a new biomarker that was previously correlated with kidney function. This article studies the validity of tCAF as a biomarker for kidney function in chronic kidney disease (CKD).

Methods: Plasma tCAF, serum creatinine (Cr), cystatin C (CyC), blood urea-nitrogen (BUN) concentrations and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals [71 without CKD (CKD 0°) and 355 CKD patients].

C-Terminal Fragment of Agrin (CAF): A Novel Marker for Progression of Kidney Disease in Type 2 Diabetics.

Background: Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics.

Effects of a One-Year Physical Activity Program on Serum C-Terminal Agrin Fragment (CAF) Concentrations among Mobility-Limited Older Adults.

Objectives: C-terminal Agrin Fragment (CAF) has been proposed as a potential circulating biomarker for predicting changes in physical function among older adults. To determine the effect of a one-year PA intervention on changes in CAF concentrations and to evaluate baseline and longitudinal associations between CAF concentrations and indices of physical function.

Design: Ancillary study to the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P), a multi-site randomized clinical trial designed to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability.

Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

Aims: Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting.

Early postoperative C-terminal agrin fragment (CAF) serum levels predict graft loss and proteinuria in renal transplant recipients.

Background: C-terminal agrin fragment (CAF), cleavage product of agrin, was previously correlated with kidney function in renal transplant patients. This article studies the predictive value of CAF for long-term outcomes in renal transplant recipients.

Methods: In this observational cohort study, serum CAF, creatinine and blood-urea-nitrogen (BUN) concentrations and eGFR (CKD-EPI) were assessed 1-3 months after transplantation in 105 patients undergoing kidney transplantation.

C-terminal agrin fragment (CAF) reflects renal function in patients suffering from severe sepsis or septic shock.

Background: One of the main causes of acute kidney injury (AKI) in patients treated on an intensive care unit (ICU) is sepsis. The identification of new biomarkers indicating the early development and future course of AKI are of utmost medical interest. The C-terminal agrin fragment (CAF) is measurable in blood serum and might reflect kidney function.

C-terminal agrin fragment (CAF) as a serum biomarker for residual renal function in peritoneal dialysis patients.

Background: C-terminal agrin fragment (CAF, size 22 kDa) is a promising new biomarker for kidney function. This study evaluated the usefulness of CAF as a serum biomarker for residual renal function (RRF) in patients undergoing automated peritoneal dialysis (APD).

Patients And Methods: Serum, urine and dialysate samples were obtained in 12 end-stage renal disease patients undergoing APD.

Influence of high-flux hemodialysis and hemodiafiltration on serum C-terminal agrin fragment levels in end-stage renal disease patients.

C-terminal agrin fragment (CAF, 22 kDa) has been shown to be a promising new rapid biomarker for kidney function. This study evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) treatment on serum CAF concentrations in patients with end-stage renal disease (ESRD). A total of 36 patients with ESRD undergoing chronic HD/HDF treatment were enrolled (21 high-flux-HD/Fx60 membrane, 7 high-flux-HD/Elisio19H membrane, and 8 HDF/Elisio19H membrane).

Motoneuron loss is associated with sarcopenia.

Objectives: Sarcopenia, age-related muscle wasting, is associated with increased morbidity and mortality in the affected individuals. The pathogenesis of sarcopenia is not yet fully understood. A multifactorial concept is currently favored.

Elevated troponin in septic patients in the emergency department: frequency, causes, and prognostic implications.

Background: According to the "Third Universal Definition of Myocardial Infarction", cardiac troponin (cTn) is defined to be elevated, if the value is above the 99th percentile of a normal reference population. Especially in emergency medicine, this leads to pathological values more often than before this definition has been founded. Severe sepsis and septic shock frequently cause a rise of cTn, but there is only limited data about its role in septic patients in the emergency department (ED).