Pelvic Intraoperative Neuromonitoring Prevents Dysfunction in Patients With Rectal Cancer: Results From a Multicenter, Randomized, Controlled Clinical Trial of a NEUROmonitoring System (NEUROS).

Objective: This NEUROmonitoring System (NEUROS) trial assessed whether pelvic intraoperative neuromonitoring (pIONM) could improve urogenital and ano-(neo-)rectal functional outcomes in patients who underwent total mesorectal excisions (TMEs) for rectal cancer.

Background: High-level evidence from clinical trials is required to clarify the benefits of pIONM.

Methods: NEUROS was a 2-arm, randomized, controlled, multicenter clinical trial that included 189 patients with rectal cancer who underwent TMEs at 8 centers, from February 2013 to January 2017.

Effect of High-Caloric Nutrition on Survival in Amyotrophic Lateral Sclerosis.

Objective: Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high-caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high-caloric fatty diet (HCFD) for increasing survival.

Methods: A 1:1 randomized, placebo-controlled, parallel-group, double-blinded trial (LIPCAL-ALS study) was conducted between February 2015 and September 2018.

Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomised controlled trial.

Stimulants and caffeine have been proposed for cognitive enhancement by healthy subjects. This study investigated whether performance in chess - a competitive mind game requiring highly complex cognitive skills - can be enhanced by methylphenidate, modafinil or caffeine. In a phase IV, randomized, double-blind, placebo-controlled trial, 39 male chess players received 2×200mg modafinil, 2×20mg methylphenidate, and 2×200mg caffeine or placebo in a 4×4 crossover design.

Continuous intraoperative monitoring of pelvic autonomic nerves during TME to prevent urogenital and anorectal dysfunction in rectal cancer patients (NEUROS): a randomized controlled trial.

Background: Urinary, sexual and anorectal sequelae are frequent after rectal cancer surgery and were found to be related to intraoperative neurogenic impairment. Neuromonitoring methods have been developed to identify and preserve the complex pelvic autonomic nervous system in order to maintain patients' quality of life. So far no randomized study has been published dealing with the role of neuromonitoring in rectal cancer surgery.

Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression--The EMC trial.

Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures.

Background: Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)).

Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder.

Background: In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment.

Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with major depressive disorder--the EMC trial.

Background: In major depressive disorder (MDD), the traditional belief of a delayed onset of antidepressants' effects has lead to the concept of current guidelines that treatment durations should be between 3-8 weeks before medication change in case of insufficient outcome. Post hoc analyses of clinical trials, however, have shown that improvement usually occurs within the first 10-14 days of treatment and that such early improvement (Hamilton Depression Rating Scale [HAMD] decrease >or=20%) has a substantial predictive value for final treatment outcome. Even more important, non-improvement (HAMD decrease <20%) after 14 days of treatment was found to be highly predictive for a poor final treatment outcome.

Molecular mechanism and structural aspects of transporter associated with antigen processing inhibition by the cytomegalovirus protein US6.

The human cytomegalovirus (HCMV) has evolved a set of elegant strategies to evade host immunity. The HCMV-encoded type I glycoprotein US6 inhibits peptide trafficking from the cytosol into the endoplasmic reticulum and subsequent peptide loading of major histocompatibility complex I molecules by blocking the transporter associated with antigen processing (TAP). We studied the molecular mechanism of TAP inhibition by US6 in vitro.

Allosteric crosstalk between peptide-binding, transport, and ATP hydrolysis of the ABC transporter TAP.

The transporter associated with antigen processing (TAP) is essential for intracellular transport of protein fragments into the endoplasmic reticulum for loading of major histocompatibility complex (MHC) class I molecules. On the cell surface, these peptide-MHC complexes are monitored by cytotoxic T lymphocytes. To study the ATP hydrolysis of TAP, we developed an enrichment and reconstitution procedure, by which we fully restored TAP function in proteoliposomes.