Polyglutamine diseases: looking beyond the neurodegenerative universe

正Multisystem disorders are often manifested by affecting more than one bodily system or tissue.We have recently reported a significantly higher prevalence of coexisting conditions in the cohorts of both pre-and symptomatic Huntington's disease(HD) gene carriers.     

Can Achilles and patellar tendon structures predict musculoskeletal injuries in combat soldiers?

Aiming to investigate whether Achilles tendon (AT) structure and patellar tendon (PT) structure are risk factors for musculoskeletal injuries in combat soldiers, 168 participants were recruited from an infantry commander's course. The AT and PT were examined pre‐course using UTC to capture the structure of four echo‐type fibers (I–IV). All injuries were assessed by military physicians pre‐course and throughout the 14‐week course. Soldiers who were injured during the course had a significantly higher pre‐course prevalence of AT and PT echo‐type III and echo‐type IV compared to soldiers that were not injured during the course. Variables that were found to be associated with injured/non‐injured participants were echo‐type III + IV of the PT (OR = 1.44, 95% CI = 1.24‐1.68) and echo‐type III of the AT (OR = 1.69, 95% CI = 1.35‐2.12). ROC analyses showed that the best model, exhibiting both high sensitivity and low specificity, was that participants with PT echo‐type III + IV > 10% or AT echo‐type III >8.5% had the highest risk of being injured during the course. In conclusions, the tendon structure at the beginning of high‐intensity activity or physical training program might be a risk factor for subsequent injury during the course. Soldiers and high‐level athletes should be aware of the cutoff points for fiber types in tendon structure that might put them at high risk for future injury. At‐risk soldiers/athletes should be provided with an intervention program before they start their training program, with the aim of improving the tendon structure and preventing subsequent injury.     

Spinal extradural solitary fibrous tumor with retiform and papillary features

We report a 66-year-old man with a spinal, extradural solitary fibrous tumor showing unique retiform and papillary architecture. The patient presented in May 2008 with worsening right-sided lower back pain and urinary frequency. Magnetic resonance imaging of the spine documented a heterogeneously enhancing dumbbell-shaped extradural lesion causing cord compression at T11/12 level. The tumor extended to the paravertebral soft tissue and invaded the right adjacent vertebral pedicles and laminae. An angiogram showed prominent vascular supply mainly from the right T11 radicular artery. The patient underwent surgery to relieve cord compression in May 2008 and a second operation following embolization with coils in October 2009. No recurrence was observed at the last neuroimaging follow-up in June 2012. The tumor was composed of vimentin, CD34, Bcl-2, and CD99-positive rounded or slightly elongated cells with scant cytoplasm and oval to spindle nuclei. Several pseudovascular spaces reminiscent of the rete testis were present, and several of them contained papillary projections. Cytologic atypia was minimal, and mitotic activity was low. Focal infiltration of the paraspinal adipose tissue was seen at microscopic level. To our knowledge, retiform and papillary features have never been reported in a solitary fibrous tumor.     

Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy: Two case reports and literature review

BACKGROUNDMuscle growth promoters are being developed for the treatment of disease-induced loss of muscle mass. Ligandrol and ostarine are selective androgen receptor modulators (SARMs) with a non-steroidal structure and a presumably more favorable side effect profile. In recent years, these substances with or without “post-cycle therapy” (PCT) are often misused by amateur athletes aiming to promote muscle growth. At the same time, reports on their toxic effects on organ systems are emerging.CASE SUMMARYWe report two cases of liver injury in young men who used ligandrol and/or ostarine for a few weeks followed by the use of substances for PCT. Acute liver injury occurred in both cases after stopping SARMs while on PCT. The clinical picture was dominated by jaundice and fatigue. The biochemical pattern showed a mixed type of injury with normal alkaline phosphatase and high concentrations of bilirubin and serum bile acids. Histological evidence showed predominantly cholestatic injury with canalicular bile plugs, ductopenia, and mild hepatocellular damage without significant fibrosis. The patients recovered from the condition after 3 mo. The off target effects of SARMs were likely idiosyncratic, but our report highlights the yet unrecognized effects of other toxic substances used for PCT, supra-therapeutic doses, and the complete absence of monitoring for adverse effects.CONCLUSIONAmong muscle-building amateur athletes, SARMs (ligandrol or ostarine) and/or substances in PCT may cause cholestatic liver injury with prolonged recovery.     

Vitamin D and Clinical Outcomes in Dialysis

Most dialysis patients are vitamin D deficient, including deficiencies in both activated vitamin D (1, 25‐dihydroxyvitamin D) and the less active 25‐hydroxyvitamin D. These and other abnormalities associated with chronic kidney disease (CKD), if they remain untreated, lead to secondary hyperparathyroidism and bone changes, such as osteitis fibrosa cystica. Activated vitamin D has been proven to decrease parathyroid hormone (PTH) levels in dialysis patients and is currently used for this indication. There are multiple other potential “pleotrophic” effects associated with vitamin D therapy. These include associations with lower all‐cause and cardiovascular mortality, lower rates of infections and improved glycemic indexes. Meta‐analyses of multiple observational studies have shown activated vitamin D therapy to be associated with improved survival. Observational data also suggest fewer infections and better glucose control. There have been no randomized clinical trials powered to evaluate mortality or other clinical outcomes. Small trials of nutritional vitamin D (ergocalciferol and cholecalciferol) showed increases in 25‐hydroxyvitamin D levels without hypercalcemia or hyperphosphatemia, even when given in addition to activated vitamin D therapy. While activated vitamin D therapy is associated with improved outcomes, it also leads to higher fibroblast growth factor 23 (FGF‐23) levels, which may be detrimental in dialysis patients. Further research is needed to evaluate whether activated or nutritional vitamin D therapy are beneficial in dialysis patients for outcomes other than secondary hyperparathyroidism.     

Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells

We report that angiotensin-converting enzyme (ACE), a critical physiologic regulator of blood pressure, angiogenesis, and inflammation, is a novel marker for identifying hemangioblasts differentiating from human embryonic stem cells (hESC). We demonstrate that ACE+CD45-CD34+/- hemangioblasts are common yolk sac (YS)-like progenitors for not only endothelium but also both primitive and definitive human lymphohematopoietic cells. Thrombopoietin and basic fibroblast growth factor are identified as critical factors for the proliferation of human hemangioblasts. The developmental sequence of human embryoid body hematopoiesis is remarkably congruent to the timeline of normal human YS development, which occurs during weeks 2 to 6 of human gestation. Furthermore, ACE and the renin-angiotensin system (RAS) directly regulate hemangioblast expansion and differentiation via signaling through the angiotensin II receptors AGTR1 and AGTR2. ACE enzymatic activity is required for hemangioblast expansion, and differentiation toward either endothelium or multipotent hematopoietic progenitors is dramatically augmented after manipulation of angiotensin II signaling with either AGTR1- or AGTR2-specific inhibitors. The RAS can therefore be exploited to direct the hematopoietic or endothelial fate of hESC-derived hemangioblasts, thus providing novel opportunities for human tissue engineering. Moreover, the initial events of human hematoendotheliogenesis can be delineated in a manner previously impossible because of inaccessibility to early human embryonic tissues.     

Relation between actual heart rate and autonomic effects of beta blockade in healthy men

This study evaluated the effect of beta blockade on cardiac autonomic control and its dependence on heart rate change. The relations between RR interval duration, heart rate variability (HRV), and baroreflex sensitivity (BRS) were studied in 111 healthy men and in 21 male volunteers before and after a 100-mg oral dose of metoprolol. HRV and BRS correlated significantly with mean RR (r = 0.39, r = 0.57). Metoprolol administration increased both mean RR (from 996 to 1,176 ms, p <0.001), BRS from 24 to 36 ms/mm Hg (p = 0.003), and the SD of RR from 61 to 74 ms (p = 0.05). However, metoprolol-induced changes of HRV and BRS became insignificant (p = 0.69 and 0.48) after they were normalized to the same cycle length, suggesting that the improvement of cardiac autonomic control after beta blockade could be explained by a change of heart rate.     

The Impact of Graphene and Diatomite Admixtures on the Performance and Properties of High-Performance Magnesium Oxychloride Cement Composites

A high-performance magnesium oxychloride cement (MOC) composite composed of silica sand, diatomite powder, and doped with graphene nanoplatelets was prepared and characterized. Diatomite was used as a 10 vol.% replacement for silica sand. The dosage of graphene was 0.5 wt.% of the sum of the MgO and MgCl₂·6H₂O masses. The broad product characterization included high-resolution transmission electron microscopy, X-ray diffraction, X-ray fluorescence, scanning electron microscopy and energy dispersive spectroscopy analyses. The macrostructural parameters, pore size distribution, mechanical resistance, stiffness, hygric and thermal parameters of the composites matured for 28-days were also the subject of investigation. The combination of diatomite and graphene nanoplatelets greatly reduced the porosity and average pore size in comparison with the reference material composed of MOC and silica sand. In the developed composites, well stable and mechanically resistant phase 5 was the only precipitated compound. Therefore, the developed composite shows high compactness, strength, and low water imbibition which ensure high application potential of this novel type of material in the construction industry.