Comapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy.

Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for acquiring and comapping local vascular wall biology data with local hemodynamic data. Here, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was developed to obtain three-dimensional (3D) datasets for smooth muscle actin, collagen, and elastin in intact vascular specimens. A cluster analysis was introduced to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC actin density. Finally, direct quantitative comparison of local flow and wall biology in 3D intact specimens was achieved by comapping both heterogeneous SMC data and wall thickness to patient-specific hemodynamic results.

Validation of a sub-epidermal moisture scanner for early detection of pressure ulcers in an ex vivo porcine model of localized oedema.

Pressure ulcers (PUs) remain a chronic health problem with severe impacts on healthcare systems. Early detection is crucial to providing effective interventions. However, detecting PUs currently relies on subjective tissue evaluations, such as visual skin assessment, precluding interventions prior to the development of visible tissue damage. There is an unmet need for solutions that can detect early tissue damage before visual and tactile signs occur. Assessments based on sub-epidermal moisture (SEM) measurements represent an opportunity for robust and objective early detection of PUs, preventing broken skin PUs in more high-risk patients at high-risk anatomical locations. While SEM assessment technology has been validated in computational, bench and tissue phantom models, validation in soft tissue was absent. In this study, we successfully validated the ability of a commercially available SEM assessment device to measure and detect sub-epidermal moisture changes in a novel ex vivo porcine soft tissue model of localised oedema. When controlled and incremental fluid volumes (Phosphate Buffer Solution) were injected into porcine soft tissues, statistically significant differences were found in SEM values between fluid-injected sites, representing an inflammatory oedematous condition, and healthy tissue control sites, as measured by the SEM device. The device provided reproducible readings by detecting localised oedema changes in soft tissues, reflecting the build-up of fluid as small as 1 ml into the underlying tissue. Spatial characterization experiments described the ability of the device technology to differentiate between healthy and oedematous tissue. Our findings validate the use of SEM assessment technology to measure and quantify localized oedema.

A hyperacute immune map of ischaemic stroke patients reveals alterations to circulating innate and adaptive cells.

Systemic immune changes following ischaemic stroke are associated with increased susceptibility to infection and poor patient outcome due to their role in exacerbating the ischaemic injury and long-term disability. Alterations to the abundance or function of almost all components of the immune system post-stroke have been identified, including lymphocytes, monocytes and granulocytes. However, subsequent infections have often confounded the identification of stroke-specific effects. Global understanding of very early changes to systemic immunity is critical to identify immune targets to improve clinical outcome. To this end, we performed a small, prospective, observational study in stroke patients with immunophenotyping at a hyperacute time point (< 3 h) to explore early changes to circulating immune cells. We report, for the first time, decreased frequencies of type 1 conventional dendritic cells (cDC1), haematopoietic stem and progenitor cells (HSPCs), unswitched memory B cells and terminally differentiated effector memory T cells re-expressing CD45RA (TEMRA). We also observed concomitant alterations to human leucocyte antigen D-related (HLA-DR), CD64 and CD14 expression in distinct myeloid subsets and a rapid activation of CD4+ T cells based on CD69 expression. The CD69+ CD4+ T cell phenotype inversely correlated with stroke severity and was associated with naive and central memory T (TCM) cells. Our findings highlight early changes in both the innate and adaptive immune compartments for further investigation as they could have implications the development of post-stroke infection and poorer patient outcomes.

A Modified AUGIS Delphi Process to Establish Future Research Priorities in Benign Upper Gastrointestinal Surgery.

BACKGROUND: The aim of our study was to use a modified Delphi process to determine the research priorities amongst benign upper gastrointestinal (UGI) surgeons in the United Kingdom. METHODS: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland were invited to submit individual research questions via an online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high-priority research questions. RESULTS: Four hundred and twenty-seven questions were submitted in phase I, and 51 with a benign UGI focus were taken forward for prioritisation in phase II. Twenty-eight questions were ranked in phase III. A final list of 11 high-priority questions had an emphasis on acute pancreatitis, Barrett's oesophagus and benign biliary disease. CONCLUSION: A modified Delphi process has produced a list of 11 high-priority research questions in benign UGI surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research.

The Positive Impact of Bariatric Surgery on Sleep.

Between June 2009 and July 2012, Apnoea-Hypopnoea Index (AHI) and Functional Outcomes of Sleep Questionnaires Scores (FOSQ) were prospectively evaluated pre- and post-operatively in patients undergoing bariatric surgery. A total of 167 subjects were studied, 75.4% were females. The median age was 46 (14-75) years and BMI 49 (36-69) kg/m2. Ninety two (55.0%) patients were diagnosed with Obstructive Sleep Apnoea (OSA) preoperatively. Fifty (54.0%) required positive airway pressure (PAP) therapy. The mean reduction in BMI post bariatric surgery was 12.2 ± 4.52 kg/m2 at 6.56 ± 2.70 months. Eighty (87.9%) reported improved sleep quality reflected in improved scores in all domains of the FOSQ (p < 0.001, paired t-test). Improvement in FOSQ scores remained significant (p < 0.05) in those with and without OSA. Thirty-nine (90.7%) patients discontinued PAP due to resolution of daytime sleepiness. In conclusion, weight loss following bariatric surgery has a positive impact on sleep in-patients with and without OSAS.

Quantitative analysis of the nonlinear displacement-load behavior of the lumbar spine.

There is currently no universal model or fitting method to characterize the visco-elastic behavior of the lumbar spine observed in displacement versus load hysteresis loops. In this study, proposed methods for fitting these loops, along with the metrics obtained, were thoroughly analyzed. A spline fitting technique was shown to provide a consistent approximation of spinal kinetic behavior that can be differentiated and integrated. Using this tool, previously established metrics were analyzed using data from two separate studies evaluating different motion preservation technologies. Many of the metrics, however, provided no significant differences beyond range of motion analysis. Particular attention was paid to how different definitions of the neutral zone capture the high-flexibility region often seen in lumbar hysteresis loops. As a result, the maximum slope was introduced and shown to be well defined. This new parameter offers promise as a descriptive measurement of spinal instability in vitro and may have future implications in clinical diagnosis and treatment of spinal instability. In particular, it could help in assigning treatments to specific stabilizing effects in the lumbar spine.

Are carfentanil and acrylfentanyl naloxone resistant?

The rapid rise in deaths since 2012 due to opioid poisoning is correlated with the proliferation of potent synthetic opioid agonists such as fentanyl, acrylfentanyl, and carfentanil. The efficacy of frontline antidotes such as naloxone in reversing such poisoning events has been questioned, and the possibility of naloxone-resistant synthetic opioids has been raised. In this manuscript, we applied in vitro techniques to establish the median effective inhibitory concentrations for fentanyl, acrylfentanyl, and carfentanil and subsequently evaluate naloxone's ability to reverse agonist-receptor interactions.

The Categorization of Perinatal Derivatives for Orthopedic Applications.

Musculoskeletal (MSK) pathology encompasses an array of conditions that can cause anything from mild discomfort to permanent injury. Their prevalence and impact on disability have sparked interest in more effective treatments, particularly within orthopedics. As a result, the human placenta has come into focus within regenerative medicine as a perinatal derivative (PnD). These biologics are sourced from components of the placenta, each possessing a unique composition of collagens, proteins, and factors believed to aid in healing and regeneration. This review aims to explore the current literature on PnD biologics and their potential benefits for treating various MSK pathologies. We delve into different types of PnDs and their healing effects on muscles, tendons, bones, cartilage, ligaments, and nerves. Our discussions highlight the crucial role of immune modulation in the healing process for each condition. PnDs have been observed to influence the balance between anti- and pro-inflammatory factors and, in some cases, act as biologic scaffolds for tissue growth. Additionally, we assess the range of PnDs available, while also addressing gaps in our understanding, particularly regarding biologic processing methods. Although certain PnD biologics have varying levels of support in orthopedic literature, further clinical investigations are necessary to fully evaluate their impact on human patients.

Effect of device constraint: a comparative network meta-analysis of ACDF and cervical disc arthroplasty.

BACKGROUND CONTEXT: Clinical trials have demonstrated that cervical disc arthroplasty (CDA) is an effective and safe alternative treatment to anterior cervical discectomy and fusion (ACDF) for cervical degenerative disc disease in the appropriately indicated patient population. Various devices for CDA exist, differing in the level of device constraint. PURPOSE: To investigate outcomes following Anterior Cervical Discectomy and Fusion (ACDF) versus CDA stratified based on the level of device constraint: Constrained, Semiconstrained, and Unconstrained. STUDY DESIGN: Systematic review and network meta-analysis. PATIENT SAMPLE: A total of 2,932 CDA patients (979 Constrained, 1,214 Semiconstrained, 739 Unconstrained) and 2,601 ACDF patients from 41 studies that compared outcomes of patients undergoing CDA or ACDF at a single level at a minimum of 2 years follow-up. OUTCOME MEASURES: Outcomes of interest included the development of adjacent segment degeneration (ASD), index and adjacent segment reoperation rates, range of motion (ROM), high-grade heterotopic ossification (HO, McAfee Grades 3/4), and patient-reported outcomes (NDI/VAS). METHODS: CDA devices were grouped based on the degrees of freedom (DoF) allowed by the device, as either Constrained (3 DoF), Semiconstrained (4 or 5 DoF), or Unconstrained (6 DoF). A random effects network meta-analysis was conducted using standardized mean differences (SMD) and log relative risk (RR) were used to analyze continuous and categorical data, respectively. RESULTS: Semiconstrained (p=.03) and Unconstrained CDA (p=.01) demonstrated a significantly lower risk for ASD than ACDF. All levels of CDA constraint demonstrated a significantly lower risk for subsequent adjacent segment surgery than ACDF (p<.001). Semiconstrained CDA also demonstrated a significantly lower risk for index level reoperation than both ACDF and Constrained CDA (p<.001). Unconstrained devices retained significantly greater ROM than both Constrained and Semiconstrained CDA (p<.001). As expected, all levels of device constraint retained significantly greater ROM than ACDF (p<.001). Constrained and Unconstrained devices both demonstrated significantly lower levels of disability on NDI than ACDF (p=.02). All levels of device constraint demonstrated significantly less neck pain than ACDF (p<.05), while Unconstrained CDA had significantly less arm pain than ACDF (p=.02) at final follow-up greater than 2 years. CONCLUSION: CDA, particularly the unconstrained and semiconstrained designs, appears to be more effective than ACDF in reducing the risk of adjacent segment degeneration and the need for further surgeries, while also allowing for greater range of motion and better patient-reported outcomes. Less constrained CDA conferred a lower risk for index level reoperation, while also retaining more range of motion than more constrained devices.

Evaluation of Self-Inflicted versus Non-Self-Inflicted Gunshot Wounds and Associated Injuries Involving the Hand and Upper Extremity.

Orthopedic costs associated with gunshot wounds (GSWs) totaled approximately USD 510 million from 2005 to 2014. Previous studies have identified differences in injuries associated with self-inflicted (SI) GSWs; however, there remains a gap in understanding injury patterns. This study aims to expand upon the current literature and shed light on injury patterns and outcomes associated with SI vs. non-self-inflicted (NSI) GSWs. This is a retrospective cohort study of upper extremity GSWs from January 2012 to December 2022. Data were analyzed using the two-sample t-test, Pearson's chi-squared test, and Fisher's exact test. SI GSWs tended to be high-velocity GSWs and occurred more often in distal locations compared to NSI GSWs (p = 0.0014 and p < 0.0001, respectively). SI GSWs were associated with higher Gustilo-Anderson (GA) and Tscherne classifications (p < 0.0001 and p = 0.0048, respectively) and with a greater frequency of neurovascular damage (p = 0.0048). There was no difference in fracture rate or need for operative intervention between the groups. GA and Tscherne classifications were associated with the need for and type of surgery (p < 0.0001), with a higher classification being associated with more intricate operative intervention; however, GSW velocity was not associated with operative need (p = 0.42). Our findings demonstrate that velocity, wound grading systems, and other factors are associated with the manner in which GSWs to the upper extremity are inflicted and may thus have potential for use in the prediction of injury patterns and planning of trauma management and surgical intervention.

The Osteogenic Peptide P-15 for Bone Regeneration: A Narrative Review of the Evidence for a Mechanism of Action.

Bone regeneration is a complex multicellular process involving the recruitment and attachment of osteoprogenitors and their subsequent differentiation into osteoblasts that deposit extracellular matrixes. There is a growing demand for synthetic bone graft materials that can be used to augment these processes to enhance the healing of bone defects resulting from trauma, disease or surgery. P-15 is a small synthetic peptide that is identical in sequence to the cell-binding domain of type I collagen and has been extensively demonstrated in vitro and in vivo to enhance the adhesion, differentiation and proliferation of stem cells involved in bone formation. These events can be categorized into three phases: attachment, activation and amplification. This narrative review summarizes the large body of preclinical research on P-15 in terms of these phases to describe the mechanism of action by which P-15 improves bone formation. Knowledge of this mechanism of action will help to inform the use of P-15 in clinical practice as well as the development of methods of delivering P-15 that optimize clinical outcomes.

An Immunologic and Biomechanical Comparison of Polyether Ether Ketone-Zeolite and Polyether Ether Ketone Interbody Fusion Devices.

STUDY DESIGN: A laboratory study comparing polyether ether ketone (PEEK)-zeolite and PEEK spinal implants in an ovine model. OBJECTIVE: This study challenges a conventional spinal implant material, PEEK, to PEEK-zeolite using a nonplated cervical ovine model. SUMMARY OF BACKGROUND DATA: Although widely used for spinal implants due to its material properties, PEEK is hydrophobic, resulting in poor osseointegration, and elicits a mild nonspecific foreign body response. Zeolites are negatively charged aluminosilicate materials that are hypothesized to reduce this pro-inflammatory response when used as a compounding material with PEEK. MATERIALS AND METHODS: Fourteen skeletally mature sheep were, each, implanted with one PEEK-zeolite interbody device and one PEEK interbody device. Both devices were packed with autograft and allograft material and randomly assigned to one of 2 cervical disc levels. The study involved 2 survival time points (12 and 26 weeks) and biomechanical, radiographic, and immunologic endpoints. One sheep expired from complications not related to the device or procedure. A biomechanical evaluation was based on measures of segmental flexibility, using 6 degrees of freedom pneumatic spine tester. Radiographic evaluation was performed using microcomputed tomography scans in a blinded manner by 3 physicians. Levels of the pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha at the implant, were quantified using immunohistochemistry. RESULTS: PEEK-zeolite and PEEK exhibited an equivalent range of motion in flexion extension, lateral bending, and axial torsion. A motion was significantly reduced for implanted devices at both time points as compared with native segments. Radiographic assessments of fusion and bone formation were similar for both devices. PEEK-zeolite exhibited lower levels of IL-1ß ( P = 0.0003) and IL-6 ( P = 0.03). CONCLUSION: PEEK-zeolite interbody fusion devices provide initial fixation substantially equivalent to PEEK implants but exhibit a reduced pro-inflammatory response. PEEK-zeolite devices may reduce the chronic inflammation and fibrosis previously observed with PEEK devices.

Dental anxiety levels in British servicemen and women.

OBJECTIVES: The objectives of the study were to determine: 1, the level of dental anxiety in British Service personnel; 2 whether there was a difference in dental anxiety levels across the three Services; and, 3, the relationship between number of operational tours and level of dental anxiety. BASIC RESEARCH DESIGN: Cross sectional questionnaire survey of individuals attending 3 Armed Services dental treatment centres in the UK. The questionnaires were completed between February 2008 and April 2009. PARTICIPANTS: 50 patients each from the Royal Navy, Army and Royal Air Force, selected consecutively from those attending the centres for treatment. There was a 100% response rate. MAIN MEASURES: Dental fear as assessed by the Dental Fear Survey (DFS) and scores on a scale of fear of dental injections. RESULTS: 27% of the Armed Services experienced severe dental anxiety: a level similar to that found in the general population. There was no difference in the level of dental anxiety or fear of dental injections across the three Armed Services. There was no relationship between number of operational tours undertaken and level of dental anxiety. CONCLUSIONS: Dental anxiety is found amongst members of the British Armed Services at levels similar to that in the general population. This represents a challenge for service provision, particularly in operational settings.

Biomechanical Stability of Primary and Revision Sacroiliac Joint Fusion Devices: A Cadaveric Study.

STUDY DESIGN: An in vitro biomechanics study. OBJECTIVE: To evaluate the efficacy of triangular titanium implants in providing mechanical stabilization to a sacroiliac joint with primary and revision sized implants. METHODS: Ten lumbopelvic cadaveric specimens were tested in 4 stages: intact, pubic symphysis sectioned, primary, and simulated revision. Primary treatment was performed using 3 laterally placed triangular titanium implants. To simulate revision conditions before and after bone ingrowth and ongrowth on the implants, 7.5-mm and 10.75-mm implants were randomly assigned to one side of each specimen during the simulated revision stage. A 6 degrees of freedom spinal loading frame was used to load specimens in 4 directions: flexion extension, lateral bending, axial torsion, and axial compression. Biomechanical evaluation was based on measures of sacroiliac joint rotational and translational motion. RESULTS: Both primary and revision implants showed the ability to reduce translational motion to a level significantly lower than the intact condition when loaded in axial compression. Simulated revision conditions showed no statistically significant differences compared with the primary implant condition, with the exception of flexion-extension range of motion where motions associated with the revised condition were significantly lower. Comparison of rotational and translation motions associated with the 7.5- and 10.75-mm implants showed no significant differences between the treatment conditions. CONCLUSIONS: These results indicate that implantation of laterally placed triangular titanium implants significantly reduces the motion of a sacroiliac joint using either the primary and revision sized implants. No statistically significant differences were detected when comparing the efficacy of primary, 7.5-mm revision, or 10.75-mm revision implants.

A successful, cost-effective low back pain triage system: a pilot study.

BACKGROUND: Effective triage - directing patients with low back pain to appropriate treatment or correct referral - is fundamental to quality care. Without guidelines, a physician's initial decision may lead to unnecessary investigation, unneeded intervention or unwarranted consultation. Methods: To compare the functional outcomes of patients triaged by a classification based on clinical presentation with those of patients selected at the clinicians' discretion, an insurance-owned hospital network employed forty-seven specially-trained physical therapists, working within participating primary care practices, to classify low back pain patients into specific Patterns of Pain. Between October 2017 and April 2019, the primary care physicians used this classification, derived entirely from the patient's history and physical examination, to direct subsequent treatment for 260 consecutive low back pain patients. Patients with systemic symptoms, recent substantial trauma or non-mechanical diagnoses indicative of spinal infections or possible malignancy were excluded. Functional outcome measures were spinal imaging, opioid use, length of treatment and number of visits, back-related unplanned care, frequency of spinal surgery and back-related episode cost. These were compared with a control group of 256 propensity-matched patients and, for assessing the financial impact, with a historic cohort of 111 previously treated, non-classified patients. Results: Spinal imaging: study group 24.5%; controls 42.2% (P< .001). Narcotic use: study group 4.6%; controls 13.3% (P< .001). Treatment length: study group 62.2 days; controls 74.5 days (P=.10). Treatment visits: study group 1528 visits; controls 2,046 visits (P=.003). Unplanned care: study group 1.9%; controls 12.8% (P< .001). Spine surgery: study group 15.4%; controls 26.2% (P=.005). Episode cost: study group $1453; controls $2334 (P=.005). Conclusions: A well-defined clinically-based triage system produced meaningful reductions in imaging, opioid use, treatment duration, unplanned interventions, surgery and cost of care.

Grafting Polymer Brushes by ATRP from Functionalized Poly(ether ether ketone) Microparticles.

Poly(ether ether ketone) (PEEK) is a semi-crystalline thermoplastic with excellent mechanical and chemical properties. PEEK exhibits a high degree of resistance to thermal, chemical, and bio-degradation. PEEK is used as biomaterial in the field of orthopaedic and dental implants; however, due to its intrinsic hydrophobicity and inert surface, PEEK does not effectively support bone growth. Therefore, new methods to modify PEEK's surface to improve osseointegration are key to next generation polymer implant materials. Unfortunately, PEEK is a challenging material to both modify and subsequently characterize thus stymieing efforts to improve PEEK osseointegration. In this manuscript, we demonstrate how surface-initiated atom transfer radical polymerization (SI-ATRP) can be used to modify novel PEEK microparticles (PMP). The hard core-soft shell microparticles were synthesized and characterized by DLS, ATR-IR, XPS and TEM, indicating the grafted materials increased solubility and stability in a range of solvents. The discovered surface grafted PMP can be used as compatibilizers for the polymer-tissue interface.

A Deep Learning Model for Automated Classification of Intraoperative Continuous EMG.

OBJECTIVE: Intraoperative neurophysiological monitoring (IONM) is the use of electrophysiological methods during certain high-risk surgeries to assess the functional integrity of nerves in real time and alert the surgeon to prevent damage. However, the efficiency of IONM in current practice is limited by latency of verbal communications, inter-rater variability, and the subjective manner in which electrophysiological signals are described. METHODS: In an attempt to address these shortcomings, we investigate automated classification of free-running electromyogram (EMG) waveforms during IONM. We propose a hybrid model with a convolutional neural network (CNN) component and a long short-term memory (LSTM) component to better capture complicated EMG patterns under conditions of both electrical noise and movement artifacts. Moreover, a preprocessing pipeline based on data normalization is used to handle classification of data from multiple subjects. To investigate model robustness, we also analyze models under different methods for processing of artifacts. RESULTS: Compared with several benchmark modeling methods, CNN-LSTM performs best in classification, achieving accuracy of 89.54% and sensitivity of 94.23% in cross-patient evaluation. CONCLUSION: The CNN-LSTM model shows promise for automated classification of continuous EMG in IONM. SIGNIFICANCE: This technique has potential to improve surgical safety by reducing cognitive load and inter-rater variability.

Development of a model based method for investigating facet articulation.

Reported investigations of facet articulation in the human spine have often been conducted through the insertion of pressure sensitive film into the joint space, which requires incision of the facet capsule and may alter the characteristics of interaction between the facet surfaces. Load transmission through the facet has also been measured using strain gauges bonded to the articular processes. While this method allows for preservation of the facet capsule, it requires extensive instrumentation of the spine, as well as strain-gauge calibration, and is highly sensitive to placement and location of the strain gauges. The inherently invasive nature of these techniques makes it difficult to translate them into medical practice. A method has been developed to investigate facet articulation through the application of test kinematics to a specimen-specific rigid-body model of each vertebra within a lumbar spine segment. Rigid-body models of each vertebral body were developed from CT scans of each specimen. The distances between nearest-neighboring points on each facet surface were calculated for specific time frames of each specimen's flexion/extension test. A metric describing the proportion of each facet surface within a distance (2 mm) from the neighboring surface, the contact area ratio (CAR), was calculated at each of these time frames. A statistically significant difference (p<0.037) was found in the CAR between the time frames corresponding to full flexion and full extension in every level of the lumbar spine (L1-L5) using the data obtained from the seven specimens evaluated in this study. The finding that the contact area of the facet is greater in extension than flexion corresponds to other findings in the literature, as well as the generally accepted role of the facets in extension. Thus, a biomechanical method with a sufficiently sensitive metric is presented as a means to evaluate differences in facet articulation between intact and treated or between healthy and pathologic spines.

Stimulation of the globus pallidus internus in a patient with DYT1-positive primary generalized dystonia: a 10-year follow-up.

The authors report the case of DYT1-positive primary generalized dystonia refractory to medical management that was successfully treated with continuous deep brain stimulation of the internal segment of the globus pallidus. Prior studies have shown that neuromusculoskeletal deficits can remain permanent if early surgical intervention is not undertaken. The authors report prolonged efficacy and safety over a 10-year period in a 28-year-old man.

Modelling the effects of age-related morphological and mechanical skin changes on the stimulation of tactile mechanoreceptors.

Our sense of fine touch deteriorates as we age, a phenomenon typically associated with neurological changes to the skin. However, geometric and material changes to the skin may also play an important role on tactile perception and have not been studied in detail. Here, a finite element model is utilised to assess the extent to which age-related structural changes to the skin influence the tactile stimuli experienced by the mechanoreceptors. A numerical, hyperelastic, four-layered skin model was developed to simulate sliding of the finger against a rigid surface. The strain, deviatoric stress and strain energy density were recorded at the sites of the Merkel and Meissner receptors, whilst parameters of the model were systematically varied to simulate age-related geometric and material skin changes. The simulations comprise changes in skin layer stiffness, flattening of the dermal-epidermal junction and thinning of the dermis. It was found that the stiffness of the skin layers has a substantial effect on the stimulus magnitudes recorded at mechanoreceptors. Additionally, reducing the thickness of the dermis has a substantial effect on the Merkel disc whilst the Meissner corpuscle is particularly affected by flattening of the dermal epidermal junction. In order to represent aged skin, a model comprising a combination of ageing manifestations revealed a decrease in stimulus magnitudes at both mechanoreceptor sites. The result from the combined model differed from the sum of effects of the individually tested ageing manifestations, indicating that the individual effects of ageing cannot be linearly superimposed. Each manifestation of ageing results in a decreased stimulation intensity at the Meissner Corpuscle site, suggesting that ageing reduces the proportion of stimuli meeting the receptor amplitude detection threshold. This model therefore offers an additional biomechanical explanation for tactile perceptive degradation amongst the elderly. Applications of the developed model are in the evaluation of cosmetics products aimed at mitigating the effects of ageing, e.g. through skin hydration and administration of antioxidants, as well as in the design of products with improved tactile sensation, e.g. through the optimisation of materials and surface textures.