Comparison of three commercially available radio frequency coils for human brain imaging at 3 Tesla

Objective: To evaluate a transverse electromagnetic (TEM), a circularly polarized (CP) (birdcage), and a 12-channel phased array head coil at the clinical field strength of B 0 = 3T in terms of signal-to-noise ratio (SNR), signal homogeneity, and maps of the effective flip angle α. Materials and methods: SNR measurements were performed on low flip angle gradient echo images. In addition, flip angle maps were generated for αnominal= 30° using the double angle method. These evaluation steps were performed on phantom and human brain data acquired with each coil. Moreover, the signal intensity variation was computed for phantom data using five different regions of interest. Results: In terms of SNR, the TEM coil performs slightly better than the CP coil, but is second to the smaller 12-channel coil for human data. As expected, both the TEM and the CP coils show superior image intensity homogeneity than the 12-channel coil, and achieve larger mean effective flip angles than the combination of body and 12-channel coil with reduced radio frequency power deposition. Conclusion: At 3T the benefits of TEM coil design over conventional lumped element(s) coil design start to emerge, though the phased array coil retains an advantage with respect to SNR performanc

Proenkephalin and risk of developing chronic kidney disease:The Prevention of Renal and Vascular End-stage Disease study

BACKGROUND: Proenkephalin (pro-ENK) was recently found to be associated with low estimated glomerular filtration rate (eGFR). The association of pro-ENK with urinary albumin excretion (UAE), another marker for chronic kidney disease (CKD), has not been investigated. We examined the association of pro-ENK with eGFR and UAE as markers of CKD. METHODS: We included 4375 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. CKDeGFR was defined as development of eGFR <60 ml/min/1.73 m2 and CKDUAE as albuminuria >30 mg/24 h. RESULTS: Baseline median pro-ENK was 52.2 (IQR: 44.9-60.5) pmol/L. After a median follow-up of 8.4 (IQR: 7.9-8.9) years, 183 subjects developed CKDeGFR and 371 developed CKDUAE. The association of pro-ENK with CKDeGFR was modified by sex (Pinteraction < 0.1), in such a way that after adjustment, the association only remained significant in men (adjusted hazard ratio per SD increase in 10log-transformed pro-ENK, 1.65; 95% CI: 1.15-2.36) and not in women (0.83; 0.58-1.20). No significant association was observed between pro-ENK and CKDUAE risk (0.83; 0.58-1.20). CONCLUSIONS: High pro-ENK is associated with increased risk of CKDeGFR in men, but not in women. No association of pro-ENK with CKDUAE was observed. These results should be interpreted with caution, since residual confounding and potential overfitting of models could have influenced the results

Frauenforschung in der Soziologie - quo vadis?

It is widely accepted that the devastating consequences of spinal cord injury are due to the failure of lesioned CNS axons to regenerate. The current study of the spontaneous tissue repair processes following dorsal hemisection of the adult rat spinal cord demonstrates a phase of rapid and substantial nerve fibre in‐growth into the lesion that was derived largely from both rostral and caudal spinal tissues. The response was characterized by increasing numbers of axons traversing the clearly defined interface between the lesion and the adjacent intact spinal cord, beginning by 5 days post operation (p.o.). Having penetrated the lesion, axons became associated with a framework of NGFr‐positive non‐neuronal cells (Schwann cells and leptomeningeal cells). Surprisingly few of these axons were derived from CGRP‐ or SP‐immunoreactive dorsal root ganglion neurons. At the longest survival time (56 days p.o.), there was a marked shift in the overall orientation of fibres from a largely rostro‐caudal to a dorso‐ventral axis. Attempts to identify which recognition molecules may be important for these re‐organizational processes during attempted tissue repair demonstrated the widespread and intense expression of the cell adhesion molecules (CAM) L1 and N‐CAM. Double immunofluorescence suggested that both Schwann cells and leptomeningeal cells contributed to the pattern of CAM expression associated with the cellular framework within the lesion

Cancer Stemness in Apc- vs. Apc/KRAS-Driven Intestinal Tumorigenesis

Constitutive activation of the Wnt pathway leads to adenoma formation, an obligatory step towards intestinal cancer. In view of the established role of Wnt in regulating stemness, we attempted the isolation of cancer stem cells (CSCs) from Apc- and Apc/KRAS-mutant intestinal tumours. Whereas CSCs are present in Apc/KRAS tumours, they appear to be very rare (®-catenin intracellular stabilization

Steroid Binding to Autotaxin Links Bile Salts and Lysophosphatidic Acid Signalling

Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial [study protocol].

BACKGROUND Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506

Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity

Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery

PDB_REDO: automated re-refinement of X-ray structure models in the PDB

The majority of previously deposited X-ray structures can be improved by applying current refinement methods

Plasma Proenkephalin and Poor Long-Term Outcome in Renal Transplant Recipients

BACKGROUND: Proenkephalin (pro-ENK), a stable and reliable surrogate marker for unstable enkephalins, was found to be associated with acute kidney injury and chronic renal failure in previous studies. We aimed to investigate whether pro-ENK is linked to chronic kidney injury and poor long-term outcome in renal transplant recipients (RTR). METHODS: We included 664 stable RTR and 95 healthy kidney donors. Pro-ENK was measured in plasma with a double monoclonal sandwich immunoassay. Graft failure was defined as return to dialysis therapy or retransplantation. RESULTS: Median pro-ENK was 110 pmol/L (interquartile range [IQR], 85-148 pmol/L) in RTR and 48 pmol/L (IQR, 42-55 pmol/L) in kidney donors. Pro-ENK was correlated with estimated glomerular filtration rate (GFR) (rs = -0.80, P < 0.001) in RTR and with measured GFR (rs = -0.74, P < 0.001) in kidney donors. During a median follow-up of 3.1 years (IQR, 2.7-3.9 years), 45 RTR developed graft failure and 76 died. Pro-ENK was positively associated with risk (hazard ratio [HR] per standard deviation increment of the logarithm of pro-ENK; 95% confidence interval [CI]) of graft failure (HR, 4.80; 95% CI, 3.55-6.48) and mortality (HR, 1.50; 95% CI, 1.22-1.85). After adjustment of age, sex, and estimated GFR, the association of pro-ENK with graft failure remained significant (HR, 2.36; 95% CI, 1.37-4.06), whereas no significant association of pro-ENK with risk of all-cause mortality was observed (HR, 1.34; 95% CI, 0.90-2.09). CONCLUSIONS: Plasma pro-ENK is associated with kidney function as reflected by correlations with measured GFR in both RTR and kidney donors. In addition, pro-ENK was independently associated with increased risk of graft failure in RTR. Pro-ENK may aid in identification of RTR at risk for late graft failure