Super elongation complex (SEC) is a positive regulator of RNA polymerase II, which is required for HIV-1 proviral transcription. AFF1/4 is the scaffold protein that recruits other components of SEC and forms dimer depending on its THD domain (TPRL with Handle Region Dimerization Domain). Here we report the crystal structure of the human AFF4-THD at the resolution of 2.4 Å. 1-NM-PP1 manufacturer The α4, α5, and α6 of one AFF4-THD mediate the formation of a dimer and pack tightly against the equivalent part of the second molecule in the dimer of AFF-THD. Mutagenesis analysis revealed that single mutations of either Phe1014 or Tyr1096 of AFF4 to alanine impair the formation of the AFF4 dimer. In addition, transactivation assay also indicated that Phe1014 and Tyr1096 of AFF4 are critical to the transactivation activity of AFF4. Interestingly, the corresponding residues Phe1063 and Tyr1145 in AFF1 have an effect on the transactivation of HIV-1 provirus. However, such mutations of AFF1/4 have no effect on the interaction of AFF1/4 with other subunits of the SEC. Together, our data demonstrated that the dimerization of AFF1/4 is essential to transactivation of HIV-1 provirus. © The Author(s) 2020.Background One of the core symptoms of behavioural variant frontotemporal dementia (bvFTD) is the early loss of social cognitive abilities, which has a deteriorating impact on everyday interaction and the quality of dyadic relationships. Marte Meo® (MM) counselling is a video-based intervention that aims to maintain or improve the quality of dyadic relationships. This non-randomized mixed-method study aimed to evaluate the feasibility of the intervention in practice with primary carers of persons with bvFTD as well as the feasibility of a future confirmatory trial. Methods A pilot effect study with a quasi-experimental, one-group, pre-post design and double pre-measurement was conducted. Data were collected at three time points (t0, t1 after 2 weeks, and t2 after 6 weeks) using videography and several measurement instruments. Between t1 and t2, each primary carer received five MM counselling sessions. The outcomes included positive and negative affect, behavioural and psychological symptoms in dementia (BPSD)rial, certain outcomes, particularly positive affect, distress due to BPSD, and the quality of the dyadic relationship, seem to be appropriate for describing possible effects. Conclusion Overall, the intervention seems feasible for this target group. A future confirmatory trial should be planned as a multicentre pilot trial with an extension option. Trial registration DRKS00014377. Registered retrospectively on April 11, 2018. © The Author(s). 2020.Background Stress induced by pain and anxiety is common in pediatric intensive care unit (PICU) patients. Sedation/analgesia in PICU is usually achieved through various analgesics and sedatives. Excessive use of these drugs can put patients at risk for hemodynamic/respiratory instability, prolonged ventilation, withdrawal, delirium, and critical illness polyneuromyopathy.The use of non-pharmacologic interventions has been recommended by sedation guidelines. However, non-pharmacological measures in PICU, including music and noise reduction, have been inadequately studied. Methods The Music Use for Sedation in Critically ill Children (MUSiCC trial) pilot study is an investigator-initiated, three-arm, randomized controlled trial (RCT) on the use of music for sedation in PICU. The main goal of the study is to demonstrate feasibility of a music trial in PICU and to obtain the necessary information to plan a larger trial. The study compares music versus noise cancelation versus control in sedated and mechanically vssary information to plan a larger trial focusing on the effectiveness of the intervention. Trial registration The study was registered at ClinicalTrials.gov (NCT03497559) on April 13, 2018. © The Author(s). 2020.Objective Increased foot-ground contact loading engenders adaptive glabrous skin thickening and can decrease mechanoreceptor acuity and alter plantar cutaneous sensation. There has not been any research on whether overweight and obesity are similarly associated with normal plantar cutaneous sensation scores in children. This study investigated the associations between normal plantar cutaneous sensation scores and weight status (i.e., healthy weight, overweight, and obesity) in a sample of youth. Methods Plantar sensation was tested among 122 participants aged 8 to 16 years (10.3 ± 1.8 years; 140.0 ± 11.2 cm; 44.2 ± 16.0 kg) across the forefoot, midfoot, and rearfoot using Semmes-Weinstein pressure aesthesiometry (0.07 g and 0.4 g monofilaments). Weight status was determined using the Centers for Disease Control and Prevention growth charts. Age- and sex-adjusted models were used to explore the relationships between normal plantar sensation scores and weight status. Significant two-tailed tests were set at p nd John Wiley & Sons Ltd.Objectives S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. Methods Sixty-five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty-nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. Results Circulating S100A4 levels were increased in both children (P = .002) and adults (P less then .001) with obesity compared with their normal-weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment-insulin resistance (HOMA-IR) in adults (βstd = .42, P = .008) but not in children (βstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. Conclusions Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti-inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity. © 2019 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.