Bite force and cranial bone strain in four species of lizards

In vivo bone strain data provide direct evidence of strain patterns in the cranium during biting. Compared to mammals, in vivo bone strains in lizard skulls are poorly documented. This paper presents strain data from the skulls of Anolis equestris, Gekko gecko, Iguana iguana and Salvator merianae during transducer biting. Analysis of variance was used to investigate effects of bite force, bite point, diet, cranial morphology and cranial kinesis on strain magnitudes. Within individuals the most consistent determinants of variance in bone strain magnitudes are gage location and bite point, with the importance of bite force varying between individuals. Inter-site variance in strain magnitudes—strain gradient—is present in all individuals, and varies with bite point. Between individuals within species, variance in strain magnitude is driven primarily by variation in bite force, not gage location or bite point, suggesting that inter-individual variation in patterns of strain magnitude is minimal. Between species, variation in strain magnitudes is significantly impacted by bite force and species membership, as well as by interactions between gage location, species, and bite point. Independent of bite force, species differences in cranial strain magnitudes may reflect selection for different cranial morphology in relation to feeding function, but what these performance criteria are is not clear. The relatively low strain magnitudes in Iguana and Uromastyx compared to other lizards may be related to their herbivorous diet. Cranial kinesis and the presence or absence of postorbital and supratemporal bars are not important determinants of inter-specific variation in strain magnitudes

The biomechanics of chewing and suckling in the infant: A potential mechanism for physiologic metopic suture closure

Craniosynostosis is a condition with neurologic and aesthetic sequelae requiring invasive surgery. Understanding its pathobiology requires familiarity with the processes underlying physiologic suture closure. Animal studies have shown that cyclical strain from chewing and suckling influences the closure of cranial vault sutures, especially the metopic, an important locus of craniosynostosis. However, there are no human data correlating strain patterns during chewing and suckling with the physiologically early closure pattern of the metopic suture. Furthermore, differences in craniofacial morphology make it challenging to directly extrapolate animal findings to humans. Eight finite-element analysis (FEA) models were built from craniofacial computer tomography (CT) scans at varying stages of metopic suture closure, including two with isolated non-syndromic metopic craniosynostosis. Muscle forces acting on the cranium during chewing and suckling were simulated using subject-specific jaw muscle cross-sectional areas. Chewing and suckling induced tension at the metopic and sagittal sutures, and compressed the coronal, lambdoid, and squamous sutures. Relative to other cranial vault sutures, the metopic suture experienced larger magnitudes of axial strain across the suture and a lower magnitude of shear strain. Strain across the metopic suture decreased during suture closure, but other sutures were unaffected. Strain patterns along the metopic suture mirrored the anterior to posterior sequence of closure: strain magnitudes were highest at the glabella and decreased posteriorly, with minima at the nasion and the anterior fontanelle. In models of physiologic suture closure, increased degree of metopic suture closure correlated with higher maximum principal strains across the frontal bone and mid-face, a strain regime not observed in models of severe metopic craniosynostosis. In summary, our work provides human evidence that bone strain patterns from chewing and suckling correlate with the physiologically early closure pattern of the metopic suture, and that deviations from physiologic strain regimes may contribute to clinically observed craniofacial dysmorphism

Skull shape and the demands of feeding: a biomechanical study of peccaries (Mammalia, Cetartiodactyla)

A primary requirement of the mammalian skull is to exert forces on different foods and to resist the forces imposed on it during feeding. Skull shape patterns within and among mammals are generally well known, but the biomechanical relevance of this variation remains limited for some groups. By integrating geometric morphometric and biomechanical analyses, we test the hypothesis that skull shape in peccaries reflects biomechanical attributes to generate and dissipate powerful forces, presumably in response to tough foods. We obtained skull shape and size from 213 specimens of the three living peccary species and estimated bite force, bite stress at molars, bending and shear stress on the mandibular corpus, and condylar stress. We found larger estimated bite forces, greater resistance to bending loads, and lower stress emerging from the larger muscle attachment areas and shorter and deeper mandibular corpora for both Pecari tajacu and Tayassu pecari relative to Parachoerus wagneri. Peccaries (P. tajacu and T. pecari) with more powerful biomechanical attributes feed mainly on tougher foods (e.g., palm fruits). These results support the hypothesis that species eating tough foods tend to have a feeding morphology mechanically adapted to stronger bites and greater biting resistance, which must be closely reflected in their craniomandibular shape.Um requerimento primário do crânio de um mamífero é exercer forças em diferentes alimentos e resistir às forças impostas nele durante a alimentação. Os padrões de forma do crânio dentro e entre mamíferos são geralmente bem conhecidos, entretanto a relevância biomecânica desta variação permanece limitada a alguns grupos. Integrando análises de morfometria geométrica e de biomecânica nós testamos a hipótese de que a forma do crânio de tayassuídeos reflete atributos biomecânicos para gerar e dissipar forças de grande magnitude, tal como em resposta à alimentos duros. Nós obtivemos a forma e o tamanho do crânio de 213 espécimes das três espécies de tayassuídeos viventes e estimamos a força de mordida e o stress nos molares, no corpo mandibular e no côndilo. Nós encontramos maiores forças de mordida e de resistência e baixo stress emergindo de áreas mais amplas de inserção muscular e de corpos mandibulares mais curtos e altos de Pecari tajacu e Tayassu pecari em relação a Parachoerus wagneri. Tayassuídeos (P. tajacu and T. pecari) com atributos biomecânicos mais poderosos se alimentam principalmente de alimentos duros (por exemplo, frutos de palmeiras). Estes resultados suportam a hipótese de que espécies que se alimentam de alimentos duros tendem a apresentar uma morfologia do aparato alimentar mecanicamente adaptada a mordidas fortes e grande resistência de mordida, que deve estar intimamente associada as suas formas craniomandibulares.Facultad de Ciencias Naturales y Muse

Comparative cranial biomechanics in two lizard species: impact of variation in cranial design

Cranial morphology in lepidosaurs is highly disparate and characterised by the frequent loss or reduction of bony elements. In varanids and geckos, the loss of the postorbital bar is associated with changes in skull shape, but the mechanical principles underlying this variation remain poorly understood. Here, we sought to determine how the overall cranial architecture and the presence of the postorbital bar relate to the loading and deformation of the cranial bones during biting in lepidosaurs. Using computer-based simulation techniques, we compared cranial biomechanics in the varanid Varanus niloticus and the teiid Salvator merianae, two large, active foragers. The overall strain magnitude and distribution across the cranium were similar in the two species, despite lower strain gradients in V. niloticus. In S. merianae, the postorbital bar is important for resistance of the cranium to feeding loads. The postorbital ligament, which in varanids partially replaces the postorbital bar, does not affect bone strain. Our results suggest that the reduction of the postorbital bar impaired neither biting performance nor the structural resistance of the cranium to feeding loads in V. niloticus. Differences in bone strain between the two species might reflect demands imposed by feeding and non-feeding functions on cranial shape. Beyond variation in cranial bone strain related to species-specific morphological differences, our results reveal that similar mechanical behaviour is shared by lizards with distinct cranial shapes. Contrary to the situation in mammals, the morphology of the circumorbital region, calvaria and palate appears to be important for withstanding high feeding loads in these lizards

Organometallic Pillarplexes That Bind DNA 4-Way Holliday Junctions and Forks

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination, and repair) and are dynamic structures that adopt either open or closed conformations, the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core, an ideal structure to interact with open DNA junction cavities. Combining experimental studies and MD simulations, we show that an Au pillarplex can bind DNA 4-way (Holliday) junctions in their open form, a binding mode not accessed by synthetic agents before. Pillarplexes can bind 3-way junctions too, but their large size leads them to open up and expand that junction, disrupting the base pairing, which manifests in an increased hydrodynamic size and lower junction thermal stability. At high loading, they rearrange both 4-way and 3-way junctions into Y-shaped forks to increase the available junction-like binding sites. Isostructural Ag pillarplexes show similar DNA junction binding behavior but lower solution stability. This pillarplex binding contrasts with (but complements) that of metallo-supramolecular cylinders, which prefer 3-way junctions and can rearrange 4-way junctions into 3-way junction structures. The pillarplexes’ ability to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures. In human cells, the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher-order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction binders into organometallic chemistry

Organometallic Pillarplexes that bind DNA 4-way Holliday Junctions and Forks.

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination and repair) and are dynamic structures which adopt either open or closed conformations, with the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core giving them an ideal structure to interact with the central cavities of open DNA junctions. Combining experimental studies and MD simulations we show that an Au pillarplex can bind DNA 4-way junctions (Holliday junctions) in their open form, a binding mode not accessed by synthetic agents before. The Au pillarplexes can bind designed 3-way junctions too but their large size leads them to open up and expand that junction, disrupting the base pairing which manifests in an increase in hydrodynamic size and a lower junction thermal stability. At high loading they re-arrange both 4-way and 3-way junctions into Y-shaped DNA forks to increase the available junction-like binding sites. The structurally related Ag pillarplexes show similar DNA junction binding behaviour, but a lower solution stability. This pillarplex binding contrasts with (but complements) that of the metallo-supramolecular cylinders, which prefer 3-way junctions and we show can rearrange 4-way junctions into 3-way junction structures. The ability of pillarplexes to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures where they are key interconnecting components. Studies in human cells, confirm that the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction-binders into organometallic chemistry

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Perturbed autophagy and DNA repair converge to promote neurodegeneration in amyotrophic lateral sclerosis and dementia

Maintaining genomic stability constitutes a major challenge facing cells. DNA breaks can arise from direct oxidative damage to the DNA backbone, the inappropriate activities of endogenous enzymes such as DNA topoisomerases, or due to transcriptionallyderived RNA/DNA hybrids (R-loops). The progressive accumulation of DNA breaks has been linked to several neurological disorders. Recently, however, several independent studies have implicated nuclear and mitochondrial genomic instability, perturbed co-transcriptional processing, and impaired cellular clearance pathways as causal and intertwined mechanisms underpinning neurodegeneration. Here, we discuss this emerging paradigm in the context of amyotrophic lateral sclerosis and frontotemporal dementia, and outline how this knowledge paves the way to novel therapeutic interventions

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo