Systemic disruption of the homeostasis of transfer RNA isopentenyltransferase causes growth and development abnormalities in Bombyx mori

Isopentenylation at A37 (i⁶A37) of some transfer RNAs (tRNAs) plays a vital role in regulating the efficiency and fidelity of protein synthesis. However, whether insects, which are well known for their highly efficient protein synthesis machinery, employ this regulatory mechanism remains uninvestigated. In the current study, a candidate tRNA isopentenyltransferase (IPT) gene with three alternative splicing isoforms (BmIPT1–BmIPT3) was identified in Bombyx mori (silkworm). Only BmIPT1 could complement a yeast mutant lacking tRNA IPT. Phylogenetic analysis showed that silkworm tRNA IPT is conserved in the Lepidoptera. BmIPT was expressed in all B. mori tissues and organs that were investigated, but was expressed at a significantly higher level in silk glands of the fourth instar compared to the first day of the fifth instar. Interestingly, BmIPT was expressed at a significantly higher level in the domesticated silkworm, B. mori, than in wild Bombyx mandarina in multiple tissues and organs. Knock‐down of BmIPT by RNA interference caused severe abnormalities in silk spinning and metamorphosis. Constitutive overexpression of BmIPT1 using a cytoplasmic actin 4 promoter in B. mori raised its messenger RNA level more than sixfold compared with nontransgenic insects and led to significant decreases in the body weight and cocoon shell ratio. Together, these results confirm the first functional tRNA IPT in insects and show that a suitable expression level of tRNA IPT is vital for silk spinning, normal growth, and metamorphosis. Thus, i⁶A modification at position A37 in tRNA probably plays an important role in B. mori protein synthesis.     

Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery

Background

Perioperative studies of patients following hip fracture have large heterogeneity within their reported outcomes. This study aimed to develop a core outcome set for use in perioperative studies comparing the types of anaesthesia for hip fracture surgery.

Extracapsular extension in oral cavity cancers—predictive factors and impact on recurrence pattern and survival

Extracapsular extension (ECE) has long been considered a poor prognostic factor in oral cavity cancer, the presence of which warrants intensification of adjuvant therapy. This study was done to analyze the survival of patients with ECE who received adjuvant chemoradiation. Patients with pathologically confirmed squamous cell carcinoma of the oral cavity, with a minimum of 2 years of follow-up, who were treated at a tertiary cancer centre in New Delhi, India during the years 2009–2017, were included. On multivariate analysis, ECE was significantly associated with depth of invasion >10 mm and tumour deposit size >5 mm. Among the node-positive group, patients without ECE had a 5-year disease-free survival (DFS) and 5-year overall survival (OS) advantage over ECE-positive patients of 7.8% (63.8% vs. 56.0%) and 16.5% (87.2% vs. 70.7%), respectively. For patients with ECE, the hazard ratio for DFS and OS was 1.3 (95% confidence interval 0.97–1.75, P = 0.078) and 2.30 (95% confidence interval 1.35–3.92, P = 0.002), respectively. ECE remains one of the strongest predictors of recurrence and survival in oral cancer patients, and despite aggressive adjuvant therapy, distant recurrence is still significantly high.     

Three-dimensional soft tissue prediction in orthognathic surgery: a clinical comparison of Dolphin,ProPlan CMF,and probabilistic finite element modelling

Three-dimensional surgical planning is used widely in orthognathic surgery. Although numerous computer programs exist, the accuracy of soft tissue prediction remains uncertain. The purpose of this study was to compare the prediction accuracy of Dolphin, ProPlan CMF, and a probabilistic finite element method (PFEM). Seven patients (mean age 18 years; five female) who had undergone Le Fort I osteotomy with preoperative and 1-year postoperative cone beam computed tomography (CBCT) were included. The three programs were used for soft tissue prediction using planned and postoperative maxillary position, and these were compared to postoperative CBCT. Accurate predictions were obtained with each program, indicated by root mean square distances: RMS_Dolphin = 1.8 ± 0.8 mm, RMS_ProPlan = 1.2 ± 0.4 mm, and RMS_PFEM = 1.3 ± 0.4 mm. Dolphin utilizes a landmark-based algorithm allowing for patient-specific bone-to-soft tissue ratios, which works well for cephalometric radiographs but has limited three-dimensional accuracy, whilst ProPlan and PFEM provide better three-dimensional predictions with continuous displacements. Patient or population-specific material properties can be defined in PFEM, while no soft tissue parameters are adjustable in ProPlan. Important clinical considerations are the topological differences between predictions due to the three algorithms, the non-negligible influence of the mismatch between planned and postoperative maxillary position, and the learning curve associated with sophisticated programs like PFEM.     

A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis

Atopic dermatitis (AD, atopic eczema) is a very common skin condition affecting 10-20% of children. It affects children of all skin colours and seems to occur more often in Asian children and children with dark skin types. However, most research is performed on children with light skin types. This study, performed in Amsterdam, the Netherlands, aimed to investigate differences between AD in children with dark and light skin types. To study this, the investigators took tape strips from 53 AD children aged 0-12 years and 50 healthy children as control (comparison). Tape stripping is a painless procedure which is ideal to perform in children, in which a small round sticker is attached to the skin. When removing this special sticker, a thin layer of skin cells remains attached to the sticker, allowing the investigators to study several aspects of skin inflammation and skin barrier. The authors found that AD skin from children with light and dark skin have similar levels and types of skin inflammation. However, they found differences in skin barrier markers between these two groups. In light skinned children, markers of good skin barrier were lower in AD skin when compared to healthy children's skin, while in dark AD skin these skin barrier markers were not significantly different from healthy dark skin. This study showed that dark-skinned and light-skinned AD children are similar when it concerns skin inflammation, but in light skinned AD children the skin barrier dysfunction may play an additional role in the development of AD. This suggests that AD in light and dark skin has different mechanisms of development.