Impaired Insulin Profiles Following a Single Night of Sleep Restriction: The Impact of Acute Sprint Interval Exercise

Experimental sleep restriction (SR) has demonstrated reduced insulin sensitivity in healthy individuals. Exercise is well-known to be beneficial for metabolic health. A single bout of exercise has the capacity to increase insulin sensitivity for up to 2 days. Therefore, the current study aimed to determine if sprint interval exercise could attenuate the impairment in insulin sensitivity after one night of SR in healthy males. Nineteen males were recruited for this randomized crossover study which consisted of four conditions—control, SR, control plus exercise, and sleep restriction plus exercise. Time in bed was 8 hr (2300–0700) in the control conditions and 4 hr (0300–0700) in the SR conditions. Conditions were separated by a 1-week entraining period. Participants slept at home, and compliance was assessed using wrist actigraphy. Following the night of experimental sleep, participants either conducted sprint interval exercise or rested for the equivalent duration. An oral glucose tolerance test was then conducted. Blood samples were obtained at regular intervals for measurement of glucose and insulin. Insulin concentrations were higher in SR than control (p = .022). Late-phase insulin area under the curve was significantly lower in sleep restriction plus exercise than SR (862 ± 589 and 1,267 ± 558; p = .004). Glucose area under the curve was not different between conditions (p = .207). These findings suggest that exercise improves the late postprandial response following a single night of SR

The Effect of Carbohydrate Mouth Rinsing on Multiple Choice Reaction Time During Amateur Boxing

Purpose: To examine whether the use of a carbohydrate mouth rinse (CMR) can improve multiple choice reaction time in amateur boxers during sparring. Methods: A total of 8 male amateur boxers (age 22 [3] y, stature 1.78 [0.07] m, mass 73.6 [14.2] kg) with at least 18 months of experience in the sport volunteered to participate in the study. All participants attended a familiarization session, followed by an experimental (CMR; 6% dextrose) and placebo trials in a randomized order. Participants undertook 3 × 2 minutes of sparring against an ability- and size-matched (stature and mass) opponent. Multiple choice reaction time and perceived exertion were measured before round 1 and then after each round. The respective mouth rinse was administered in a 25-mL solution for 10 seconds before each round. Magnitude-based inferences were used to compare the results of each round (mean difference; ±90% confidence limits). Results: The CMR was unlikely to have a beneficial effect on multiple choice reaction time compared with placebo (mean ± 90% confidence limits: 5 ± 9.5, 4 ± 3.4, −1 ± 8.5 lights for rounds 1 to 3, respectively) and had a possibly harmful effect on perceived exertion in round 1 (10 ± 20). There was an unlikely harmful effect on perceived exertion in rounds 2 (1 ± 12) and 3 (9 ± 23). Conclusion: There is no evidence to support the use of CMR during sparring in amateur boxers

Advanced auricular prosthesis development by 3D modelling and multi-material printing

We investigate the use of medical imaging, digital design and 3D printing technologies as a viable means of reproducing a person’s anatomy, with the intension of producing a working, patient specific prosthesis. This approach offers several advantages over traditional techniques, as data capture is non-intrusive, models can be made using quantitative methodologies, design iterations can be digitally stored for future reproduction, and additive manufacturing ensures no loss of quality when converting the digital model into a physical part. We also present a combined model segmentation with multi-material printing approach to increase the colour complexity of the final model. When combined with multi-material printing using elastic materials, our approach provides a comprehensive strategy to accurately realising mimic of both skin pigmentation and the tactile feel of human tissues. Ultimately, we believe our approach provides an innovative strategy for prosthesis production which could have considerable potential for implementation in a clinical setting

Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants

Background Tetralogy of Fallot (TOF) is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor TBX1.Objective To assess the contribution of common and rare TBX1 genetic variants to TOF.Design Rare TBX1 variants were sought by resequencing coding exons and splice-site boundaries. Common TBX1 variants were investigated by genotyping 20 haplotype-tagging SNPs capturing all the common variations present at the locus. Association analysis was performed using the program UNPHASED.Patients TBX1 exons were sequenced in 93 patients with non-syndromic TOF. Single nucleotide polymorphism analysis was performed in 356 patients with TOF, their parents and healthy controls.Results Three novel variants not present in 1000 chromosomes from healthy ethnically matched controls were identified. One of these variants, an in-frame 57 base-pair deletion in the third exon which removed 19 evolutionarily conserved residues, decreased transcriptional activity by 40% in a dual luciferase assay (p=0.008). Protein expression studies demonstrated that this mutation affected TBX1 protein stability. After correction for multiple comparisons, no significant associations between common genetic variants and TOF susceptibility were found.Conclusion This study demonstrates that rare TBX1 variants with functional consequences are present in a small proportion of non-syndromic TOF

Genetic Variation in VEGF Does Not Contribute Significantly to the Risk of Congenital Cardiovascular Malformation

Several previous studies have investigated the role of common promoter variants in the vascular endothelial growth factor (VEGF) gene in causing congenital cardiovascular malformation (CVM). However, results have been discrepant between studies and no study to date has comprehensively characterised variation throughout the gene. We genotyped 771 CVM cases, of whom 595 had the outflow tract malformation Tetralogy of Fallot (TOF), and carried out TDT and case-control analyses using haplotype-tagging SNPs in VEGF. We carried out a meta-analysis of previous case-control or family-based studies that had typed VEGF promoter SNPs, which included an additional 570 CVM cases. To identify rare variants potentially causative of CVM, we carried out mutation screening in all VEGF exons and splice sites in 93 TOF cases. There was no significant effect of any VEGF haplotype-tagging SNP on the risk of CVM in our analyses of 771 probands. When the results of this and all previous studies were combined, there was no significant effect of the VEGF promoter SNPs rs699947 (OR 1.05 [95% CI 0.95–1.17]); rs1570360 (OR 1.17 [95% CI 0.99–1.26]); and rs2010963 (OR 1.04 [95% CI 0.93–1.16]) on the risk of CVM in 1341 cases. Mutation screening of 93 TOF cases revealed no VEGF coding sequence variants and no changes at splice consensus sequences. Genetic variation in VEGF appears to play a small role, if any, in outflow tract CVM susceptibility

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Augmented patient-specific facial prosthesis production using medical imaging modelling and 3D printing technologies for improved patient outcomes

Facial prosthetic offer patients a low risk and high impact treatment option to address underlying facial defects. Such devices are generally handmade, requiring several labour-intensive manufacturing phases and numerous patient consultations to develop the final device. Therefore, production is a time-consuming and costly process with significant inconvenience to the patient and highly dependent on the skills of the prosthetists, making the whole process highly subjective. We investigate the potential of medical imaging, 3D design modelling and high-resolution 3D printing to augment the production of an auricular prosthesis for a patient who was previously using a handmade prosthesis. We reproduce the patient’s uncompromised anatomy from CT scan data, before printing a mirrored template to use in the casting process for a silicone prosthesis. This technique realises a superior end prosthesis with a realistic look on the patient while streamlining the current production methodology

Augmented patient-specific facial prosthesis production using medical imaging modelling and 3D printing technologies for improved patient outcomes

Facial prosthetic offer patients a low risk and high impact treatment option to address underlying facial defects. Such devices are generally handmade, requiring several labour-intensive manufacturing phases and numerous patient consultations to develop the final device. Therefore, production is a time-consuming and costly process with significant inconvenience to the patient and highly dependent on the skills of the prosthetists, making the whole process highly subjective. We investigate the potential of medical imaging, 3D design modelling and high-resolution 3D printing to augment the production of an auricular prosthesis for a patient who was previously using a handmade prosthesis. We reproduce the patient’s uncompromised anatomy from CT scan data, before printing a mirrored template to use in the casting process for a silicone prosthesis. This technique realises a superior end prosthesis with a realistic look on the patient while streamlining the current production methodology

Applications of 3D topography scanning and multi-material additive manufacturing for facial prosthesis

Prosthetic based rehabilitation offers several advantages over surgical intervention, however, devices are generally handmade using labour intensive and subjective manufacturing techniques. We investigate the use of optical scanning to capture the surface topography from a volunteer’s facial anatomy, reconstruct this into a 3D CAD model, and from that design a patient specific prosthesis. This approach offers many advantages over existing techniques as data collection is non-intrusive, rapid and provides anatomically precise information. A CAD approach affords greater flexibility when evaluating design iterations and allows for the creation of ‘parts libraries’ for use with patients with no initial reference anatomy. The final prosthesis is realised through high resolution, multi-material 3D printing for precise model reproduction and to add functionalities such as mimicry of soft and hard tissues. Ultimately,we believe our approach provides an optimised, low-cost approach for streamlining the complete methodology for prosthesis production