Brandstruphedegaard1181

As the induction of RACK1 expression can be blocked by the antagonist G15, induced by the agonist G1 and by the non-cell permeable 17β-estradiol conjugated with BSA, a role of GPER (previously named GPR30) activation in estrogen-induced RACK1 expression could be demonstrated. In addition, a role of androgen receptor (AR) in RACK1 transcription was also demonstrated by the ability of flutamide, a nonsteroidal antiandrogen, to completely prevent diethylstilbestrol-induced RACK1 transcriptional activity and protein expression. Altogether, our data suggest that RACK1 may represent an interesting target of steroid-active compounds, and its evaluation may offer the opportunity to screen the immunotoxic potential of hormone-active substances.PURPOSE To assess current surgical preferences and practice patterns regarding primary anterior cruciate ligament (ACL) repair among European Society for Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) members. METHODS A web-based survey was designed, including questions regarding indications for primary repair, outcomes of primary repair, and rehabilitation protocols. An invitation for study participation was sent by email to all ESSKA e-mail contacts. Descriptive statistics were performed. RESULTS A total of 169 surgeons responded to the survey (7% response rate of active members). Lack of supporting scientific evidence is the main reason for not using repair as a surgical treatment (63%). Most important indications were proximal avulsion tears (84%), younger age (49%), and older age (34%). Among those currently utilizing repair as a treatment option, transosseous tunnel fixation repair (34%) and repair with internal brace using transosseous tunnel fixation (32%) were the most preferred techniques. Eleven percent indicated dynamic intraligamentary stabilization as their preferred technique. A similar rate of progression for rehabilitation for repair and reconstruction techniques was noted among respondents. CONCLUSION This practice survey shows that the majority of surgeons indicated the main reason for not incorporating primary repair in their current practices was a lack of supporting scientific evidence. Among those holding favourable attitudes and beliefs, most surgeons indicated patients with proximal tears, younger-aged, and older-aged patients might be eligible for repair. Prospective studies with higher levels of evidence are warranted to establish guidelines for repair, including indications, optimal surgical technique, and rehabilitation protocols. LEVEL OF EVIDENCE V (expert opinion).PURPOSE To compare the postoperative rotatory knee laxity between ACL-reconstructed knees with different meniscus treatments using an electromagnetic pivot-shift measurement. METHODS Forty-six patients with unilateral ACL reconstructions were enrolled (21 males/25 females, 25 ± 12 y.o.). Concomitant meniscus tears, if any, were repaired whenever possible during primary ACL reconstruction. At 1 year postoperatively, pivot-shift test was performed under anaesthesia during screw removal surgery and quantitatively evaluated by tibial acceleration using an electromagnetic system. The acceleration was compared between ACL-reconstructed knees with different meniscal treatments intact, repaired and unrepaired. RESULTS A concomitant meniscus tear was found in 28 knees preoperatively lateral tears in 11 knees, medial tears in 11 knees and both medial and lateral tears in 6 knees. Postoperatively, 19 ACL-reconstructed knees had a repaired meniscus for either medial, lateral or bilateral menisci tears, and 18 knees had intact menisci pre- and post-operatively. Meanwhile, nine lateral meniscus tears were irreparable and treated by partial meniscectomy or left in situ. ACL-reconstructed knees with unrepaired lateral menisci had significantly larger pivot-shift acceleration (0.9 ± 0.7 m/s2) than those with intact menisci (0.5 ± 0.2 m/s2, p  less then  0.05), whereas rotatory knee laxity was similar between the knees with fully repaired menisci (0.6 ± 0.3 m/s2) and intact menisci (n.s.). CONCLUSION An unrepaired lateral meniscus tear in an ACL-reconstructed knee could lead to remaining pivot-shift postoperatively. A concomitant meniscus tear should be repaired during ACL reconstruction to restore normal rotational laxity. LEVEL OF EVIDENCE Therapeutic Study, Level III.Great strides over the past few decades have increased our understanding of the pathophysiology of hypophosphatemic disorders. Phosphate is critically important to a variety of physiologic processes, including skeletal growth, development and mineralization, as well as DNA, RNA, phospholipids, and signaling pathways. Consequently, hypophosphatemic disorders have effects on multiple systems, and may cause a variety of nonspecific signs and symptoms. The acute effects of hypophosphatemia include neuromuscular symptoms and compromise. However, the dominant effects of chronic hypophosphatemia are the effects on musculoskeletal function including rickets, osteomalacia and impaired growth during childhood. While the most common causes of chronic hypophosphatemia in children are congenital, some acquired conditions also result in hypophosphatemia during childhood through a variety of mechanisms. Improved understanding of the pathophysiology of these congenital conditions has led to novel therapeutic approaches. This article will review the pathophysiologic causes of congenital hypophosphatemia, their clinical consequences and medical therapy.BACKGROUND Little is known about the relationships between MRI splenic T1 relaxation measurements and other radiologic and clinical markers of chronic liver disease, including the presence of radiologic portal hypertension. OBJECTIVE To evaluate the relationships between MRI splenic T1 relaxation and other radiologic and clinical biomarkers of liver fibrosis, including the presence of radiologic portal hypertension, in children and young adults with autoimmune liver diseases (AILD). MATERIALS AND METHODS Research MRI examinations performed at 1.5 T from 63 AILD registry participants were identified. Spleen T1 and iron-corrected T1 (cT1) relaxation measurements, liver cT1, liver/spleen stiffness, splenic length percentile for age, and presence of radiologic portal hypertension were recorded, along with demographic and laboratory data. The Mann-Whitney U test was used to compare continuous data between groups; Spearman correlation was used to evaluate associations. Areas-under-the-receiver operating characteristic curve (AuROC) was used to assess diagnostic performance. RESULTS Mean age was 15.2 ± 4.1 years. Mean splenic T1 and cT1 values for the study population were 1158.0 ± 70.9 ms and 1436.0 ± 68.9 ms, respectively. Splenic T1 and cT1 values positively correlated with APRI and FIBROSIS-4 scores, splenic length percentile, liver cT1 values, and liver and spleen stiffnesses (p-values  0.05). Splenic T1 and cT1 values were higher in participants with vs. without radiologic portal hypertension (n = 18) (1213.4 ± 69.6 vs. 1135.4 ± 58.5 ms; p = 0.0001, and 1488.2 ± 64.8 vs. 1415.1 ± 59.1 ms; p = 0.0002). Splenic T1 and cT1 both demonstrated an AuROC of 0.81 for discriminating patients without and with portal hypertension (p-values  less then  0.0001). CONCLUSION Splenic T1 relaxation is associated with other radiologic and clinical biomarkers of liver fibrosis, including radiologic portal hypertension, in children and young adults with AILD.In this study, we demonstrated nano-flow injection analysis (nano-FIA) with quadrupole time-of-flight mass spectrometry (Q-TOFMS) for 17 highly polar intermediates produced during glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway (PPP). We optimized the analytical conditions for nano-flow injection/Q-TOFMS, and set the flow rate and ion source temperature to 1000 nL/min and 150 °C, respectively. Under optimal conditions, a single run was finished within 3 min, and the RSD value of 50 sequential injections was 4.2%. The method also showed quantitativity of four stable-isotope-labeled compounds (r2 > 0.99), demonstrating its robustness, high repeatability, and specificity. In addition, we compared three sample-preparation methods for rodent blood samples and found that protein precipitation with threefold methanol was the most effective. Finally, we applied the method to plasma samples from the serotonin syndrome (SS) model and control rats, the results of which were evaluated by principal component analysis (PCA). The two groups showed clearly separated PCA score plots, suggesting that the method could successfully catch the differences in metabolic profiles between SS and control rats. The results obtained from our new method were further validated by using the established gas chromatography/tandem mass spectrometry method, which demonstrated that there were good correlations between the two methods (R = 0.902 and 0.958 for lactic acid and malic acid, respectively, each at p  less then  0.001), thus proving the validity of our method. The method described here enables high-throughput analysis of metabolites and will be of use for the rapid analysis of metabolic profiles. Graphical abstract.Food products and botanicals on the global market need to be investigated in a more comprehensive way to detect effects, falsifications or adulterations. This is especially true for such ones containing Stevia leaves, Stevia extracts, or steviol glycosides. A multi-imaging profiling was developed exploiting hydrophilic interaction liquid chromatography (HILIC). A minimalistic sample preparation, different mixtures of acetonitrile and water/buffer on the silica gel phase as well as derivatization reagents and optional hyphenation with high-resolution mass spectrometry were exploited. The hydrophilic interaction high-performance thin-layer chromatography (HI-HPTLC) development took 10 min for 48 analyses. selleck inhibitor It was used to screen Stevia leaf extracts and 20 different food products. For the first time, the biological and biochemical profiling of Stevia leaf products by HI-HPTLC-UV/Vis/FLD-assay pointed to 19 different bioactive compound bands found in the more natural multicomponent Stevia leaf extracts, whereas most of these activities were not existent for the steviol glycosides. The chemically isolated, purified, and EU-regulated steviol glycosides ease risk assessment and food product development. However, multipotent botanicals may have subtle impact on homeostasis via several metabolic pathways, providing benefits for the consumer's health. Analyzed side by side by means of the effect-directed profiling, their individual activity profiles were visualized as image and individual substances of importance were pointed out. Multi-imaging (comprehensive detection) plus non-targeted bioprofiling (focus on known and unknown bioactivity) allows for a fast detection of questionable product changes that occur along the global food chain and are particularly related to food safety. Graphical abstract.Future proliferation of biological expertise and new technology may increasingly lower the difficulty to produce biological organisms for misuse. Rapid attribution of a biological attack is needed to quickly identify the person or lab responsible and prevent additional attacks by enabling the apprehension of suspects. Here, triplicate batches of Bacillus anthracis Sterne strain (BaSt) spores were grown in a total of seven amateur and professional media. Multiple orthogonal analytical signatures (peptides, metabolites, lipids by fatty acid methyl ester (FAME) analysis, bulk organic profile, and trace elements) were collected from the BaSt spores. The proteomics and metabolomics analyses identified promising attribution signature compounds that are unique to each of the seven production methods. In addition, while each of the signature types showed varying degrees of value individually for attributing BaSt spores to the culture medium used to prepare them, fusing results from all five signatures types to increase sourcing robustness and using a random forest sourcing algorithm yielded 100% hold-one-batch-out cross-validation classification accuracy and an average relative source probability for the correct source 5.