Dietary fat oxidation is elevated in middle-aged type 2 diabetes

This is the author accepted manuscript. The final version is available from the publisher via the link in this record.N/

Editorial: Improving reliability of brain stimulation: What works and what doesn't?

Editorial on the Research Topic: Improving reliability of brain stimulation: What works and what doesn't

Preserved collagen reveals species identity in archaeological marine turtle bones from Caribbean and Florida sites

Advancements in molecular science are continually improving our knowledge of marine turtle biology and evolution. However, there are still considerable gaps in our understanding, such as past marine turtle distributions, which can benefit from advanced zooarchaeological analyses. Here, we apply collagen fingerprinting to 130 archaeological marine turtle bone samples up to approximately 2500 years old from the Caribbean and Florida's Gulf Coast for faunal identification, finding the vast majority of samples (88%) to contain preserved collagen despite deposition in the tropics. All samples can be identified to species-level with the exception of the Kemp's ridley (Lepidochelys kempii) and olive ridley (L. olivacea) turtles, which can be separated to genus level, having diverged from one another only approximately 5 Ma. Additionally, we identify a single homologous peptide that allows the separation of archaeological green turtle samples, Chelonia spp., into two distinct groups, which potentially signifies a difference in genetic stock. The majority of the archaeological samples are identified as green turtle (Chelonia spp.; 63%), with hawksbill (Eretmochelys imbricata; 17%) and ridley turtles (Lepidochelys spp.; 3%) making up smaller proportions of the assemblage. There were no molecular identifications of the loggerhead turtle (Caretta caretta) in the assemblage despite 9% of the samples being morphologically identified as such, highlighting the difficulties in relying on morphological identifications alone in archaeological remains. Finally, we present the first marine turtle molecular phylogeny using collagen (I) amino acid sequences and find our analyses match recent phylogenies based on nuclear and mitochondrial DNA. Our results highlight the advantage of using collagen fingerprinting to supplement morphological analyses of turtle bones and support the usefulness of this technique for assessing their past distributions across the Caribbean and Florida's Gulf Coast, especially in these tropical environments where DNA preservation may be poor

Weighted vests in CrossFit increase physiological stress during walking and running without changes in spatiotemporal gait parameters

This study quantified the physiological and biomechanical effects of the 20 lb (9.07 kg, males) and 14 lb (6.35 kg, females) weighted vest used in CrossFit, and whether they were predisposed to injury. Twenty subjects (10 males, 10 females) undertook walking (0%, 5% and 10% gradient) and running trials in two randomised study visits (weighted vest/no weighted vest). Physiological demand during walking was increased with the vest at 10% but not 5% or 0% with no change in gait variables. In the running trial, the weighted vest increased oxygen uptake (males; females) (+0.22L/min, p < 0.01; +0.07 L/min, p < 0.05), heart rate (+11bpm, p < 0.01; +11bpm, p < 0.05), carbohydrate oxidation (+0.6 g/min, p < 0.001; +0.2 g/min, p < 0.01), and energy expenditure (+3.8 kJ/min, p < 0.001; +1.5 kJ/min, p < 0.05) whilst blood lactate was increased only in males (+0.6 mmol/L, p < 0.05). There was no change in stride length or frequency. Weighted vest training increases physiological stress and carbohydrate oxidation without affecting measured gait parameters. Practitioner summary: We examined the effect of weighted vest training prescribed in CrossFit (20 lb/9.07 kg, males and 14 lb/6.35 kg, females) in a randomised controlled trial. We found that physiological stress is increased in both sexes, although three-fold greater in males, but with no change in biomechanical gait that predisposes to lower-limb injury

Flagellar ultrastructure suppresses buckling instabilities and enables mammalian sperm navigation in high-viscosity media

Eukaryotic flagellar swimming is driven by a slender motile unit, the axoneme, which possesses an internal structure that is essentially conserved in a tremendous diversity of sperm. Mammalian sperm, however, which are internal fertilizers, also exhibit distinctive accessory structures that further dress the axoneme and alter its mechanical response. This raises the following two fundamental questions. What is the functional significance of these structures? How do they affect the flagellar waveform and ultimately cell swimming? Hence we build on previous work to develop a mathematical mechanical model of a virtual human sperm to examine the impact of mammalian sperm accessory structures on flagellar dynamics and motility. Our findings demonstrate that the accessory structures reinforce the flagellum, preventing waveform compression and symmetry-breaking buckling instabilities when the viscosity of the surrounding medium is increased. This is in agreement with previous observations of internal and external fertilizers, such as human and sea urchin spermatozoa. In turn, possession of accessory structures entails that the progressive motion during a flagellar beat cycle can be enhanced as viscosity is increased within physiological bounds. Hence the flagella of internal fertilizers, complete with accessory structures, are predicted to be advantageous in viscous physiological media compared with watery media for the fundamental role of delivering a genetic payload to the egg

A prospective observational study comparing proficiency of obstetrics & gynaecology trainees with general surgical trainees using simulated laparoscopic tasks in Health Education England, North-West

BACKGROUND: Training programmes for obstetrics and gynaecology (O&G) and general surgery (GS) vary significantly, but both require proficiency in laparoscopic skills. We sought to determine performance in each specialty. DESIGN: Prospective, Observational study. SETTING: Health Education England North-West, UK. PARTICIPANTS: 47 surgical trainees (24 O&G and 23 GS) were sub-divided into four groups: 11 junior O&G, 13 senior O&G, 11 junior GS, and 12 senior GS trainees. OBJECTIVES: Trainees were tested on four simulated laparoscopic tasks; laparoscopic camera navigation (LCN), hand eye co-ordination (HEC), bimanual co-ordination (BMC) and suturing with intracorporeal knot tying (suturing). RESULTS: O&G trainees completed LCN (P <0.001), HEC (P <0.001) and BMC (P <0.001) significantly slower than GS trainees. Furthermore, O&G found fewer number of targets in LCN (P =0.001) and dropped a greater number of pins than the GS trainees in BMC (P =0.04). In all three tasks, there were significant differences between O&G and GS trainees but no difference between the juniors and senior groups within each specialty. Performance in suturing also varied by specialty; senior O&G trainees scored significantly lower than senior GS trainees; O&G 11.4 ± 4.4 vs GS 16.8 ± 2.1, P = 0.03. Whilst suturing scores improved with seniority among O&G trainees, there was no difference between the junior and senior GS trainees; senior O&G 11.4 ± 4.4 vs junior O&G 3.6 ± 2.1, P = 0.004. DISCUSSION: GS trainees performed better than O&G trainees in core laparoscopic skills and the structure of obstetrics and gynaecology training may require modification

Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

<p>Abstract</p> <p>Background</p> <p>Low serum paraoxonase (PON) activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE). Our prior studies have shown that the <it>PON1</it>/rs662 (p.Gln192Arg), <it>PON1</it>/rs854560 (p.Leu55Met), <it>PON3</it>/rs17884563 and <it>PON3</it>/rs740264 SNPs (single nucleotide polymorphisms) significantly affect serum PON activity. Since <it>PON1, PON2 </it>and <it>PON3 </it>share high degree of structural and functional properties, in this study, we examined the role of <it>PON2 </it>genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample.</p> <p>Methods</p> <p><it>PON2 </it>SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen <it>PON2 </it>SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP) or TaqMan allelic discrimination methods.</p> <p>Results</p> <p>Our pair-wise linkage disequilibrium (LD) analysis, using an <it>r</it>^{<it>2 </it>}cutoff of 0.7, identified 14 <it>PON2 </it>tagSNPs that captured all 19 <it>PON2 </it>variants in our sample, 12 of which were not in high LD with known <it>PON1 </it>and <it>PON3 </it>SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five <it>PON2 </it>SNPs [rs6954345 (p.Ser311Cys), rs13306702, rs987539, rs11982486, and rs4729189; <it>P </it>= 0.005 to 2.1 × 10^-6] that were significantly associated with PON activity. We found no association of <it>PON2 </it>SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183) and immunologic disorder (rs11981433) in SLE patients (<it>P </it>= 0.013 to 0.042).</p> <p>Conclusions</p> <p>Our data indicate that <it>PON2 </it>genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.</p

Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans

This is the final version. Available on open access from the National Academy of Sciences via the DOI in this recordData, Materials, and Software Availability: All study data are included in the article and/or supporting information. The raw RNA sequencing data can be found within the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under the Sequence Read Archive (SRA) accession PRJNA996496 (93).Living longer without simultaneously extending years spent in good health ("health span") is an increasing societal burden, demanding new therapeutic strategies. Hydrogen sulfide (H2S) can correct disease-related mitochondrial metabolic deficiencies, and supraphysiological H2S concentrations can pro health span. However, the efficacy and mechanisms of mitochondrion-targeted sulfide delivery molecules (mtH2S) administered across the adult life course are unknown. Using a Caenorhabditis elegans aging model, we compared untargeted H2S (NaGYY4137, 100 µM and 100 nM) and mtH2S (AP39, 100 nM) donor effects on life span, neuromuscular health span, and mitochondrial integrity. H2S donors were administered from birth or in young/middle-aged animals (day 0, 2, or 4 postadulthood). RNAi pharmacogenetic interventions and transcriptomics/network analysis explored molecular events governing mtH2S donor-mediated health span. Developmentally administered mtH2S (100 nM) improved life/health span vs. equivalent untargeted H2S doses. mtH2S preserved aging mitochondrial structure, content (citrate synthase activity) and neuromuscular strength. Knockdown of H2S metabolism enzymes and FoxO/daf-16 prevented the positive health span effects of mtH2S, whereas DCAF11/wdr-23 - Nrf2/skn-1 oxidative stress protection pathways were dispensable. Health span, but not life span, increased with all adult-onset mtH2S treatments. Adult mtH2S treatment also rejuvenated aging transcriptomes by minimizing expression declines of mitochondria and cytoskeletal components, and peroxisome metabolism hub components, under mechanistic control by the elt-6/elt-3 transcription factor circuit. H2S health span extension likely acts at the mitochondrial level, the mechanisms of which dissociate from life span across adult vs. developmental treatment timings. The small mtH2S doses required for health span extension, combined with efficacy in adult animals, suggest mtH2S is a potential healthy aging therapeutic.US Army Research OfficeUnited Mitochondrial Disease FoundationUniversity of ExeterUK Space AgencyBiotechnology and Biological Sciences Research Council (BBSRC)NASAOsteopathic Heritage Foundatio

Surgical Stress: The Muscle and Cognitive Demands of Robotic and Laparoscopic Surgery

Introduction: Surgeons are among the most at-risk professionals for work-related musculoskeletal decline and experience high mental demands. This study examined the electromyographic (EMG) and electroencephalographic (EEG) activities of surgeons during surgery. Methods: Surgeons who performed live laparoscopic (LS) and robotic (RS) surgeries underwent EMG and EEG measurements. Wireless EMG was used to measure muscle activation in 4 muscle groups bilaterally (biceps brachii, deltoid, upper trapezius, and latissimus dorsi), and an 8-channel wireless EEG device was used to measure cognitive demand. EMG and EEG recordings were completed simultaneously during (1) noncritical bowel dissection, (2) critical vessel dissection, and (3) dissection after vessel control. Robust ANOVA was used to compare the %MVCRMS and alpha power between LS and RS. Results: Thirteen male surgeons performed 26 LS and 28 RS. Muscle activation was significantly higher in the right deltoid (P = 0.006), upper trapezius (left, P = 0.041; right, P = 0.032), and latissimus dorsi (left, P = 0.003; right, P = 0.014) muscles in the LS group. There was greater muscle activation in the right biceps than in the left biceps in both surgical modalities (both P = 0.0001). There was a significant effect of the time of surgery on the EEG activity (P < 0.0001). A significantly greater cognitive demand was observed in the RS than in the LS with alpha, beta, theta, delta, and gamma (P = 0.002 – P <0.0001). Conclusions: These data suggest greater muscle demands in laparoscopic surgery, but greater cognitive demands in RS. This trial was registered at Clinicaltrials.gov (NCT04477746)

Contextual adaptation of the Personnel Evaluation Standards for assessing faculty evaluation systems in developing countries: the case of Iran

<p>Abstract</p> <p>Background</p> <p>Faculty evaluations can identify needs to be addressed in effective development programs. Generic evaluation models exist, but these require adaptation to a particular context of interest. We report on one approach to such adaptation in the context of medical education in Iran, which is integrated into the delivery and management of healthcare services nationwide.</p> <p>Methods</p> <p>Using a triangulation design, interviews with senior faculty leaders were conducted to identify relevant areas for faculty evaluation. We then adapted the published checklist of the Personnel Evaluation Standards to fit the Iranian medical universities' context by considering faculty members' diverse roles. Then the adapted instrument was administered to faculty at twelve medical schools in Iran.</p> <p>Results</p> <p>The interviews revealed poor linkages between existing forms of development and evaluation, imbalance between the faculty work components and evaluated areas, inappropriate feedback and use of information in decision making. The principles of Personnel Evaluation Standards addressed almost all of these concerns and were used to assess the existing faculty evaluation system and also adapted to evaluate the core faculty roles. The survey response rate was 74%. Responses showed that the four principles in all faculty members' roles were met <it>occasionally </it>to <it>frequently</it>. Evaluation of teaching and research had the highest mean scores, while clinical and healthcare services, institutional administration, and self-development had the lowest mean scores. There were statistically significant differences between small medium and large medical schools (p < 0.000).</p> <p>Conclusion</p> <p>The adapted Personnel Evaluation Standards appears to be valid and applicable for monitoring and continuous improvement of a faculty evaluation system in the context of medical universities in Iran. The approach developed here provides a more balanced assessment of multiple faculty roles, including educational, clinical and healthcare services. In order to address identified deficiencies, the evaluation system should recognize, document, and uniformly reward those activities that are vital to the academic mission. Inclusion of personal developmental concerns in the evaluation discussion is essential for evaluation systems.</p