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The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

Background: Clubfoot occurs in up to 50% of patients with spina bifida (SB) and 90% with arthrogryposis (AR). Many of these patients with neuromuscular clubfoot deformity fail conservative casting and require surgery with posteromedial lateral release (PMLR). Limited data exist for the outcomes of PMLR in patients with SB and AR., Methods: Retrospective chart review was performed on PMLR in patients with SB and AR from January 2007 to June 2022, excluding those with follow-up <3 years or incomplete charts. Radiographic measurements were obtained pre-PMLR and post-PMLR when available., Results: In total, 51 patients with 79 cases of clubfeet treated with PMLR at a tertiary children's hospital were identified. Of those, 35 patients with 54 cases of clubfeet treated with PMLR were analyzed, including 22 patients (29 feet) with SB and 13 patients (25 feet) with AR. In the SB cohort, 41% of feet required reoperation at an average of 4.6 years, and 76% of AR feet required reoperation at an average of 4.7 years post-PMLR. In addition, 21% of SB feet and 8% of AR feet required 2 or more reoperations. Talectomy was required post-PMLR in 24% of SB feet and 40% of AR feet at an average of 4.9 and 5.9 years, respectively. Younger age at time of PMLR was associated with significantly increased reoperation rates in AR (P=0.01). Greater change in calcaneus-fifth metatarsal angle after PMLR was associated with a future need for reoperation (P=0.047). Greater talo-first metatarsal angle after PMLR was associated with a future need for reoperations of any kind (P=0.040) in SB., Conclusions: Although PMLR remains a safe and successful treatment in the short term, many neuromuscular clubfeet will require additional procedures. Younger age and greater preoperative versus postoperative changes in calcaneus-fifth metatarsal and postoperative talo-first metatarsal angles were associated with increased reoperation rate. These results help orthopaedic surgeons counsel families about the long-term prognosis of clubfoot treatment in SB and AR., Level of Evidence: Level IV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Radiation injury, either from radiotherapy or a mass-casualty event requires a health care system that can efficiently allocate resources to patients. We conducted a comprehensive transcriptome analysis of whole blood from a nonhuman primate model that received upper thoracic radiation (9.8-10.7 Gy). Blood samples were collected at multiple time points, extending up to 270 days post-irradiation with a minimum n = 6 for initial time points (Day 3-Day 40) and a total number of n = 28 primates. No males receiving the higher dose survived to Day 270. Using the Elastic Net model in R we found that pooling biomarkers from Day 3-21 increased our accuracy in discerning survival time, pleural effusion or dose compared to using biomarkers specific to a single day. For survival data, in predicting short term (less than 90 day), medium term (Day 91-269) or long-term survival (Day 270), prediction accuracy using only Day 3 data was 0.14 (95% Confidence Interval (CI) 0.1, 0.19) while pooled data for Male and Female was 0.76 (CI 0.69, 0.82). When pooled data was divided by biological sex, accuracy was 0.7 (CI 0.58, 0.8) for pooled data from Males and 0.84 (CI 0.76, 0.91) for Females. The development of RNA biomarkers as a tool to aid in clinical decision-making could significantly improve patient care in cases of radiation injury, whether from radiotherapy or mass-casualty events. Further validation and clinical translation of these findings could lead to improved patient care and management strategies in cases of radiation exposure., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Several toxic metabolites, such as aflatoxin M1 (AFM1), are known to contaminate dairy milk. However, as mentioned in an external EFSA report, there is a knowledge gap regarding the carry-over of certain emerging toxins such as microcystin-LR (MC-LR). Therefore, this work aimed to develop an LC-MS/MS method for MC-LR quantification in dairy milk. Also, the method included AFM1 as a common fungal metabolite and applied to analyze 113 dairy milk samples collected directly after the end of the summer peak. Both toxins were below their LODs, keeping the question on MC-LR carry-over still unanswered. Moreover, an in silico analysis, using a 3D molecular modeling was performed, pointing to a possible interaction between MC-LR and milk proteins, especially β-lactoglobulin. Since AFM1 and MC-LR are hepatotoxic, their interaction in inducing mitochondrial dysfunction in HepG2 cells was investigated at low (subcytotoxic) concentrations. Live cell imaging-based assays showed an inhibition in cell viability, without involvement of caspase-3/7, and a hyperpolarization in the mitochondrial membrane potential after the exposure to a mixture of 100 ng mL -1 AFM1 and 1000 ng mL -1 MC-LR for 48h. Extracellular flux analysis revealed inhibitions of several key parameters of mitochondrial function (basal respiration, ATP-linked respiration, and spare respiratory capacity)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Spatially Fractionated Radiation Therapy (SFRT) is an unconventional therapeutic approach with the potential to disrupt the classical paradigms of conventional radiation therapy. The high spatial dose modulation in SFRT is believed to activate distinct radiobiological mechanisms which lead to remarkable increases in normal tissue tolerance. To make optimal use of SFRT and its benefits, a deeper understanding of the biological response and its relationship with the complex dosimetric and geometric components of SFRT is essential., Method: A retrospective evaluation of preclinical studies was conducted to gain insight into the dosimetric and geometric parameters that are most correlated with normal tissue response. Current literature evaluates the response of tissue to MBRT and MRT according to various end points, e.g. the level of desquamation, degree of necrosis, or the amount of malcalcification. A set of metrics was developed to allow a quantitative comparison of these results., Results: The strongest correlations were observed with the doses in both the peaks and valleys as well as the ratio of the area covered by the peak over the total area. This emphasises the geometry of the beam. MBRT challenged previous uniform dose-distribution paradigms by highlighting the critical role of Peak Dose alongside Valley Dose in tissue sparing whereas MRT underscores the significant influence of geometric beam parameters on tissue preservation., Discussion: The data exhibits variability in the results obtained using different animal models and endpoints and additional research is warranted to explore the trends observed in this study under controlled conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 McGarrigle, Long and Prezado.)

Clinical studies have reported that increased epileptiform and subclinical epileptiform activity can be detected in many patients with an Alzheimer's disease (AD) diagnosis using electroencephalogram (EEG) and this may correlate with poorer cognition. Ascorbate may have a specific role as a neuromodulator in AD as it is released concomitantly with glutamate reuptake following excitatory neurotransmission. Insufficiency may therefore result in an exacerbated excitatory/inhibitory imbalance in neuronal signaling. Using a mouse model of AD that requires dietary ascorbate (Gulo -/- APP swe /PSEN1 dE9 ), EEG was recorded at baseline and during 4 weeks of ascorbate depletion in young (5-month-old) and aged (20-month-old) animals. Data were scored for changes in quantity of spike trains, individual spikes, sleep-wake rhythms, sleep fragmentation, and brainwave power bands during light periods each week. We found an early increase in neuronal spike discharges with age and following ascorbate depletion in AD model mice and not controls, which did not correlate with brain amyloid load. Our data also show more sleep fragmentation with age and with ascorbate depletion. Additionally, changes in brain wave activity were observed within different vigilance states in both young and aged mice, where Gulo -/- APP swe /PSEN1 dE9 mice had shifts towards higher frequency bands (alpha, beta, and gamma) and ascorbate depletion resulted in shifts towards lower frequency bands (delta and theta). Microarray data supported ascorbate insufficiency altering glutamatergic transmission through the decreased expression of glutamate related genes, however no changes in protein expression of glutamate reuptake transporters were observed. These data suggest that maintaining optimal brain ascorbate levels may support normal brain electrical activity and sleep patterns, particularly in AD patient populations where disruptions are observed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fiona Harrison reports financial support was provided by National Institutes of Health. James May reports financial support was provided by US Department of Veterans Affairs. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark.

Competing Interests: Competing interests: None declared.

Age-related vessel deterioration leads to changes in the structure and function of the heart and blood vessels, notably stiffening of vessel walls, increasing the risk of developing cardiovascular disease (CVD), which accounts for 17.9 million global deaths annually. This study describes the fabrication of custom-made silicon vessels with varying mechanical properties (arterial stiffness). The primary objective of this study was to explore how changes in silicone formulations influenced vessel properties and their correlation with features extracted from signals obtained from photoplethysmography (PPG) reflectance sensors in an in vitro setting. Through alterations in the silicone formulations, it was found that it is possible to create elastomers exhibiting an elasticity range of 0.2 MPa to 1.22 MPa. It was observed that altering vessel elasticity significantly impacted PPG signal morphology, particularly reducing amplitude with increasing vessel stiffness ( p < 0.001). A p -value of 5.176 × 10 -15 and 1.831 × 10 -14 was reported in the red and infrared signals, respectively. It has been concluded in this study that a femoral artery can be recreated using the silicone material, with the addition of a softener to achieve the required mechanical properties. This research lays the foundation for future studies to replicate healthy and unhealthy vascular systems. Additional pathologies can be introduced by carefully adjusting the elastomer materials or incorporating geometrical features consistent with various CVDs.

Objectives: Prompt HIV and STI diagnosis and treatment is a public health priority and relies on accessible testing. Technology-based approaches to distribute test kits have the potential to increase access to testing. We evaluated the acceptability and uptake of vending machines in publicly available settings in Brighton and Hove (BH) and Bristol, North Somerset and South Gloucestershire (BNSSG), to distribute HIV rapid self-test and STI self-sample kits., Methods: Seven machines were installed in BH and four in BNSSG. User characteristics, proportion of kits returned and test results, taken from the machine database and clinic records, combined with online questionnaires completed by self-recruited users and analysed using Stata and SPSS., Results: 2536 kits were dispensed over 12 months (April 2022 to March 2023). The STI self-sample kits were most popular (74% of vends). 78% of kits dispensed were among users aged 16-35 years and 56% identified as male. 68% and 59% of users had either not tested in the last 12 months or never tested for HIV and STIs, respectively. 51% of STI kits were returned via post, lower than the local online service (65%). 208 users completed questionnaires. Convenience, desire for instant access and increased confidentiality were the most common reasons for using machines. 92% of respondents thought the machines were user-friendly and 97% would recommend the service. Concerns about safety and privacy while using the machine were reported by 42% and 66% of respondents., Conclusions: This study demonstrates that vending machines are an acceptable and effective means of accessing infrequent or never testers in the general population and can act as a horizontal intervention to tackle HIV and STIs. Research is needed to understand optimal machine locations to assure privacy and safety along with the long-term impact on sexual health services., Competing Interests: Competing interests: JK and JH are partly funded by NIHR ARC West and NIHR Health Protection Research Unit (HPRU) in Behavioural Science and Evaluation. SDenford's time is supported by the NIHR HPRU in Behavioural Science and Evaluation., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, therefore understanding arterial stiffness is essential to developing innovative technologies to detect, monitor and treat them. The ubiquitous spread of photoplethysmography (PPG), a completely non-invasive blood-volume sensing technology suitable for all ages, highlights immense potential for arterial stiffness assessment in the wider healthcare setting outside specialist clinics, for example during routine visits to a General Practitioner or even at home with the use of mobile and wearable health devices. This study employs a custom-manufactured in vitro cardiovascular system with vessels of varying stiffness to test the hypothesis that PPG signals may be used to detect and assess the level of arterial stiffness under controlled conditions. Analysis of various morphological features demonstrated significant (p < 0.05) correlations with vessel stiffness. Particularly, area related features were closely linked to stiffness in red PPG signals, while for infrared PPG signals the most correlated features were related to pulse-width. This study demonstrates the utility of custom vessels and in vitro investigations to work towards non-invasive cardiovascular assessment using PPG, a valuable tool with applications in clinical healthcare, wearable health devices and beyond., (© 2024. The Author(s).)

Li 3 Fe 3 Te 2 O 12 adopts a crystal structure, described in space group Pnnm , related to that of LiSbO 3 , in which Te 6+ , Fe 3+ , and Li + cations reside in a partially ordered configuration within an hcp array of oxide ions. Chemical or electrochemical insertion of lithium is accompanied by a fully reversible migration of some of the Fe cations with an initial capacity of 120 mA h g -1 (2.85 Li per formula unit). Long-term cycling stability is limited by the facile reduction of Te 6+ to elemental Te, which leads to cathode decomposition. Partial substitution of Fe by In suppresses Te 6+ reduction, such that Li 3 Fe 2 InTe 2 O 12 shows no sign of this cathode decomposition pathway, even after 100 cycles. In contrast, Al-for-Fe substitution is chemically limited to Li 3 Fe 2.6 Al 0.4 Te 2 O 12 and appears to have almost no influence on cathode longevity. These features of the Li 3 Fe 3-x M x Te 2 O 12 system are discussed on the basis of a detailed structural analysis performed using neutron and synchrotron X-ray diffraction.

The incidence of concussions in football, and the ensuing media attention, has garnered scientific investigation, prompted technological advances in protective gear, and altered the rules of the game, including the National Football League's (NFL) "Targeting" rule, which began in 2018, but the impact of these changes is unclear. This study aims to describe the epidemiology of concussions that occurred in five NFL seasons from the 2017-2018 season through the 2021-2022 season and characterize positional differences in rate and games missed. There was a significant decrease (p = 0.02) in total concussions between the 2017-2018 season (102 concussions) and the remaining four seasons (average of 73.80 concussions per year), accounting for a 38% decrease. Offensive and defensive units had decreased concussion rates and average games missed per concussion. Defensive backs (10.46 per 1,000 athlete exposures (AEs)) and tight ends (10.69 per 1,000 AEs) had the highest concussion rates, and the defensive line had the highest average games missed per concussion at 3.97. The introduction of the "Targeting" rule and other rule changes in the NFL in 2018 correlated with a decrease in total concussions per year, total games missed due to concussion, and average games missed per concussion. Offense and defense experienced similar reductions in concussion incidence and severity. Overall, the updated epidemiology of NFL concussions suggests that the incidence of concussions has decreased; however, players continue to experience concussions that require them to miss multiple games., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, May et al.)

This review outlines the latest methods and innovations for assessing arterial stiffness, along with their respective advantages and disadvantages. Furthermore, we present compelling evidence indicating a recent growth in research focused on assessing arterial stiffness using photoplethysmography (PPG) and propose PPG as a potential tool for assessing vascular ageing in the future. Blood vessels deteriorate with age, losing elasticity and forming deposits. This raises the likelihood of developing cardiovascular disease (CVD), widely reported as the global leading cause of death. The ageing process induces structural modifications in the vascular system, such as increased arterial stiffness, which can cause various volumetric, mechanical, and haemodynamic alterations. Numerous techniques have been investigated to assess arterial stiffness, some of which are currently used in commercial medical devices and some, such as PPG, of which still remain in the research space.

Introduction: In April 2020, in response to government COVID-19 advice, changes were made to the way English drug services operated. Methadone and buprenorphine were typically dispensed in 1- to 2-week supplies, and key working was conducted by phone/online. Previous studies have examined the impact of these changes on people from urban settings. This study adds the experiences and perspectives of people receiving care from drug services in rural areas and makes suggestions for future emergency planning., Methods: Telephone semi-structured interviews were conducted with 15 people receiving care in Somerset, Wiltshire, and Suffolk, rural counties in England. Reflexive thematic analysis was used., Results: Three overarching themes were found. " Challenges of rural lockdown" (theme 1) describes how rural community challenges, especially reduced or no rural public transport, were experienced. This hampered some OST collections, with consequential drug use. It also impeded connections to loved ones, worsening isolation. For participants who were struggling pre-pandemic, the intersection between this and their experience of revised drug service operations is embodied in " Amplification of Social Disconnection: Cut off and unheard " (theme 2). They felt a lack of support, particularly from remote provision key working. Participants who had supportive relationships and time in the pandemic occupied in ways they found meaningful, and others who struggled with anxiety or depression, found pandemic changes " Fits better with my life" (theme 3). They experienced more freedom for other things, gained support by other means, such as family, or felt more comfortable with remote engagement. A cross-cutting sub-theme " Understandable Interruptions" showed acceptance of pandemic disruptions., Conclusion: National guidance and organizational policy impacted participants in different ways. Those who had supportive relationships and occupied time were better able to make positive use of newfound freedoms and engage with community-level support. In contrast, those who had less stability, including mental health struggles and social isolation, felt cut off and unheard, particularly from key workers. Reduced rural transport was a significant community-level issue, which impeded OST collection and social support. We suggest emergency response plans be created for individuals taking account of their pre-existing personal situations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Scott, Family, Kesten, Hines and Millar.)

Whole- or partial-body exposure to ionizing radiation damages major organ systems, leading to dysfunction on both acute and chronic timescales. Radiation medical countermeasures can mitigate acute damages and may delay chronic effects when delivered within days after exposure. However, in the event of widespread radiation exposure, there will inevitably be scarce resources with limited countermeasures to distribute among the affected population. Radiation biodosimetry is necessary to separate exposed from unexposed victims and determine those who requires the most urgent care. Blood-based, microRNA signatures have great potential for biodosimetry, but the affected population in such a situation will be genetically heterogeneous and have varying miRNA responses to radiation. Thus, there is a need to understand differences in radiation-induced miRNA expression across different genetic backgrounds to develop a robust signature. We used inbred mouse strains C3H/HeJ and BALB/c mice to determine how accurate miRNA in blood would be in developing markers for radiation vs. no radiation, low dose (1 Gy, 2 Gy) vs. high dose (4 Gy, 8 Gy), and high risk (8 Gy) vs. low risk (1 Gy, 2 Gy, 4 Gy). Mice were exposed to whole-body doses of 0 Gy, 1 Gy, 2 Gy, 4 Gy, or 8 Gy of X rays. MiRNA expression changes were identified using NanoString nCounter panels on blood RNA collected 1, 2, 3 or 7 days postirradiation. Overall, C3H/HeJ mice had more differentially expressed miRNAs across all doses and timepoints than BALB/c mice. The highest amount of differential expression occurred at days 2 and 3 postirradiation for both strains. Comparison of C3H/HeJ and BALB/c expression profiles to those previously identified in C57BL/6 mice revealed 12 miRNAs that were commonly expressed across all three strains, only one of which, miR-340-5p, displayed a consistent regulation pattern in all three miRNA data. Notably multiple Let-7 family members predicted high-dose and high-risk radiation exposure (Let-7a, Let-7f, Let-7e, Let-7g, and Let-7d). KEGG pathway analysis demonstrated involvement of these predicted miRNAs in pathways related to: Fatty acid metabolism, Lysine degradation and FoxO signaling. These findings indicate differences in the miRNA response to radiation across various genetic backgrounds, and highlights key similarities, which we exploited to discover miRNAs that predict radiation exposure. Our study demonstrates the need and the utility of including multiple animal strains in developing and validating biodosimetry diagnostic signatures. From this data, we developed highly accurate miRNA signatures capable of predicting exposed and unexposed subjects within a genetically heterogeneous population as quickly as 24 h of exposure to radiation., (© 2023 by Radiation Research Society.)

Background: Injury incidence is higher in the National Football League (NFL) than in other collision sports. Although previous research has identified that scheduling variations, including overseas games and bye week timing, does not affect concussion risk, data are currently lacking regarding the effects of scheduling variation on season-long musculoskeletal injury incidence., Purpose: To determine whether higher cumulative travel distance, overseas play, an early season bye week, and an expansion of the regular season is associated with higher injury rates in the NFL., Study Design: Descriptive epidemiology study., Methods: All 1275 injuries across 5 NFL seasons from 2017 to 2018 through 2021 to 2022 were reviewed retrospectively. Injury data and travel distances were extracted from publicly available sources, which were cross-referenced for validation. Injury rates were calculated per 1000 athletic-exposures (AEs). Cumulative team travel distances were compared statistically using a linear regression. Single factor analysis of variance was used to compare categorical variables., Results: Travel distance did not significantly predict injury rates ( P = .47), and there was no difference in injury rates between teams that played a game overseas versus teams that did not (19.3 injuries per 1000 AEs for both; P = .96). In addition, no difference was found in injury rates ( F [109,2100[ = 0.704; P = .73) or players placed on the injured reserve list ( F [99,778] = 1.70; P = .077) between various bye weeks ( P = .73). Injury rates did not differ between the new 17-game regular season (18.4 per 1000 AEs) versus the previous four 16-game regular seasons (19.7 per 1000 AEs; P = .12). However, teams that did not qualify for the playoffs had a significantly higher injury rate (19.9 per 1000 AEs) as well as players on injured reserve (8.0 per 1000 AEs) than playoff-qualifying teams (18.4 and 6.8 per 1000 AEs, respectively; P < .05 for both)., Conclusion: Over 5 NFL seasons, cumulative travel distance, overseas play, bye week timing, and adding 1 regular season game were not associated with increased injury rates in NFL players. However, a lack of regular season success was associated with higher injury rates and more players on injured reserve., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: V.K.T. has received education payments from Medwest Associates and consulting and nonconsulting fees from Smith & Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Background: Studies suggest that early-life gut microbiota composition and intestinal short-chain fatty acids (SCFAs) are linked to future asthma susceptibility. Furthermore, infancy offers a critical time window to modulate the microbiota and associated metabolites through diet-microbe interactions to promote infant health. Human milk oligosaccharides (HMOs), nondigestible carbohydrates abundant in breast milk, are prebiotics selectively metabolized by gut microbiota that consequently modify microbiome composition and SCFA production., Methods: Using a house dust mite mouse model of allergy, we investigated the impacts of early oral treatment of pups with biologically relevant doses of 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), two of the most abundant HMOs in human milk, in amelioration of allergic airway disease severity., Results: We found that administration of 2'-FL and 6'-SL during early life reduced lung histopathology scores, circulating IgE, cytokine levels, and inflammatory cell infiltration, all hallmark symptoms of allergic asthma. HMO supplementation also increased the relative abundance of intestinal Bacteroidetes and Clostridia , known SCFA producers within the gut. Indeed, we detected increased SCFA concentrations in both the intestine and blood of adult mice who received HMOs prior to weaning., Conclusion: We propose a model in which orally administered HMOs delivered during early life shift the microbiota toward increased production of SCFAs, which dampens the allergic immune responses behind allergy and asthma. Overall, these data suggest the potential for HMO supplementation to protect infants against asthma development later in life, with possible benefits against additional atopic diseases such as eczema and food allergies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Tahereh Bozorgmehr et al.)

Emotional disorders are common in childhood, and their prevalence sharply increases during adolescence. The Strengths and Difficulties Questionnaire (SDQ) is widely used for screening emotional and behavioural difficulties in children and young people, but little is known about the accuracy of the emotional subscale (SDQ-E) in detecting emotional disorders, and whether this changes over development. Such knowledge is important in determining whether symptom changes across age are due to developmental or measurement differences. This study assessed the validity of the SDQ-E and two individual items (low mood and general worry) in differentiating between cases and non-cases of Major Depressive Disorder (MDD), Generalised Anxiety Disorder (GAD), and other anxiety disorders across ages 7, 10, 13, 15, and 25 years in a UK population cohort. Analyses showed moderate accuracy of the subscale in discriminating cases of MDD (AUC = 0.67-0.85), and high accuracy for discriminating cases of GAD (AUC = 0.80-0.93) and any anxiety disorder (AUC = 0.74-0.83) compared to non-cases. The SDQ-E performed well across ages and sex, and generally performed better than the two individual items. Together our findings validate the SDQ-E as a screen for emotional disorders during childhood, adolescence, and early adulthood, and as a tool for longitudinal research on depression and anxiety disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Armitage et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Osteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no current treatments which can reverse the joint damage occurring during the pathogenesis of the disease. While many groups are investigating the use of stem cell therapies in the treatment of OA, we still don't have a clear understanding of the role of these cells in the body, including heterogeneity of tissue resident adult mesenchymal progenitor cells (MPCs)., Methods: In the current study, we examined MPCs from the synovium and individuals with or without a traumatic knee joint injury and explored the chondrogenic differentiation capacity of these MPCs in vitro and in vivo., Results: We found that there is heterogeneity of MPCs with the adult synovium and distinct sub-populations of MPCs and the abundancy of these sub-populations change with joint injury. Furthermore, only some of these sub-populations have the ability to effect cartilage repair in vivo. Using an unbiased proteomics approach, we were able to identify cell surface markers that identify this pro-chondrogenic MPC population in normal and injured joints, specifically CD82 Low CD59 + synovial MPCs have robust cartilage regenerative properties in vivo., Conclusions: The results of this study clearly show that cells within the adult human joint can impact cartilage repair and that these sub-populations exist within joints that have undergone a traumatic joint injury. Therefore, these populations can be exploited for the treatment of cartilage injuries and OA in future clinical trials., (© 2023. The Author(s).)

Background: Cardiac rehabilitation (CR) is underused in the United States and globally, with participation disparities across gender, socioeconomic status, race, and ethnicities. The pandemic led to greater adoption of telehealth CR and mobile app use., Objective: Our primary objective was to estimate the association between CR mobile app use and change in functional capacity from enrollment to completion in patients participating in a CR program that offered in-person, hybrid, and telehealth CR. Our secondary objectives were to study the association between mobile app use and changes in blood pressure (BP) or program completion., Methods: We conducted a retrospective cohort study of participants enrolled in CR at an urban CR program in the United States. Participants were English speaking, at least 18 years of age, participated in the program between May 22, 2020, and May 21, 2022, and downloaded the CR mobile app. Mobile app use was quantified by number of exercise logs, vitals logs, and education material views. The primary outcome was change in functional capacity, measured by change in 6-minute walk distance (6MWD) from enrollment to completion. The secondary outcome was change in BP from enrollment to completion. We estimated associations using multivariable linear or logistic regression models adjusted for age, sex, race, ethnicity, socioeconomic status by ZIP code, insurance, and primary diagnosis for CR referral., Results: A total of 107 participants (mean age 62.9, SD 13.02 years; 90/107, 84.1% male; and 57/105, 53.3% self-declared as White Caucasian) used the mobile app and completed the CR program. Participants had a mean 64.0 (SD 54.1) meter increase in 6MWD between enrollment and completion (P<.001). From enrollment to completion, participants with an elevated BP at baseline (≥130/80 mmHg) experienced a significant decrease in BP (systolic BP -11.5 mmHg; P=.002 and diastolic BP -7.7 mmHg; P=.003). We found no significant association between total app interactions and change in 6MWD (coefficient -0.03, 95% CI -0.1 to 0.07; P=.59) or change in BP (systolic coefficient 0.002, 95% CI -0.03 to 0.03; P=.87 and diastolic coefficient -0.005, 95% CI -0.03 to 0.02; P=.65). There was no significant association between total exercise logs and change in 6MWD (coefficient 0.1, 95% CI -0.3 to 0.4; P=.57) or total BP logs and change in BP (systolic coefficient -0.02, 95% CI -0.1 to 0.06; P=.63 and diastolic coefficient -0.02, 95% CI -0.09 to 0.04; P=.50). There was no significant association between total app interactions and completion of CR (adjusted odds ratio 1.00, 95% CI 0.99-1.01; P=.44)., Conclusions: CR mobile app use as part of an in-person, hybrid, or telehealth CR program was not associated with greater improvement in functional capacity or BP or with program completion., (©Janah May Oclaman, Michelle L Murray, Donald J Grandis, Alexis L Beatty. Originally published in JMIR Cardio (https://cardio.jmir.org), 15.05.2023.)

Abstract: An otherwise healthy 49-year-old man experienced a high-voltage electrical injury to the left shoulder resulting in total scapulectomy, partial calviculectomy, and a substantial soft tissue defect. The majority of the muscles around his shoulder were debrided because of necrosis, with only the pectoralis and latissimus dorsi muscles remaining attached to the humerus. Surprisingly, the patient's brachial plexus remained intact, and his left elbow, wrist, and hand function were preserved. A novel combination of 3 static and dynamic suspension techniques were used to stabilize his shoulder and prevent traction injury to the brachial plexus. Postoperative follow-up at 1 year demonstrated excellent stability of his reconstructed shoulder, which allowed him to ambulate independently and return to employment., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Responsive infant feeding occurs when a parent recognizes the infant's cues of hunger or satiety and responds promptly to these cues. It is known to promote healthy dietary patterns and infant weight gain and is recommended as part of the Dietary Guidelines for Americans. However, the use of responsive infant feeding can be challenging for many parents. Research is needed to assist caregivers recognize infant hunger or satiety cues and overcoming barriers to using responsive infant feeding., Objective: The Learning Early Infant Feeding Cues (LEIFc) intervention was designed to fill this gap by using a validated coaching approach, SS-OO-PP-RR ("super," Setting the Stage, Observation and Opportunities, Problem Solving and Planning, Reflection and Review), to promote responsive infant feeding. Guided by the Obesity-Related Behavioral Intervention Trials model, this study aims to test the feasibility and fidelity of the LEIFc intervention in a group of mother-infant dyads., Methods: This pre-post quasi-experimental study with no control group will recruit mothers (N=30) in their third trimester (28 weeks and beyond) of pregnancy from community settings. Study visit 1 will occur prenatally in which written and video material on infant feeding and infant hunger and satiety cues is provided. Demographic information and plans for infant feeding are also collected prenatally via self-report surveys. The use of responsive infant feeding via subjective (survey) and objective (video) measures is recorded before (study visit 2, 1 month post partum) and after (study visit 5, 4 months post partum) intervention. Coaching on responsive infant feeding during a feeding session is provided by a trained interventionist using the SS-OO-PP-RR approach at study visits 3 (2 months post partum) and 4 (3 months post partum). Infant feeding practices are recorded via survey, and infant weight and length are measured at each postpartum study visit. Qualitative data on the LEIFc intervention are provided by the interventionist and mother. Infant feeding videos will be coded and tabulated for instances of infant cues and maternal responses. Subjective measures of responsive infant feeding will also be tabulated. The use of responsive infant feeding pre-post intervention will be analyzed using matched t tests. Qualitative data will be examined to guide intervention refinement., Results: This study initially began in spring 2020 but was halted because of the COVID-10 pandemic. With new funding, recruitment, enrollment, and data collection began in April 2022 and will continue until April 2023., Conclusions: After refinement, the LEIFc intervention will be tested in a pilot randomized controlled trial. The long-term goal is to implement LEIFc in the curricula of federally funded maternal-child home visiting programs that serve vulnerable populations-those that often have infant feeding practices that do not align with recommendations and are less likely to use responsive infant feeding., International Registered Report Identifier (irrid): DERR1-10.2196/44329., (©Jessica Bahorski, Mollie Romano, Julie May McDougal, Edie Kiratzis, Kinsey Pocchio, Insu Paek. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.02.2023.)

A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro , and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.

Blood-brain barrier dysfunction (BBBD) and accumulation of senescent astrocytes occur during brain aging and contribute to neuroinflammation and disease. Here, we explored the relationship between these two age-related events, hypothesizing that chronic hippocampal exposure to the blood-borne protein serum albumin could induce stress-induced premature senescence (SIPS) in astrocytes via transforming growth factor beta 1 (TGFβ) signaling. We found that 1 week of albumin exposure significantly increased TGFβ signaling and senescence marker expression in cultured rat hippocampal astrocytes. These changes were preventable by pharmacological inhibition of the type I TGFβ receptor (TGFβR) ALK5. To study these effects in vivo, we utilized an animal model of BBBD in which albumin was continuously infused into the lateral ventricles of adult mice. Consistent with our in vitro results, 1 week of albumin infusion significantly increased TGFβ signaling activation and the burden of senescent astrocytes in hippocampal tissue. Pharmacological inhibition of ALK5 TGFβR or conditional genetic knockdown of astrocytic TGFβR prior to albumin infusion was sufficient to prevent albumin-induced astrocyte senescence. Together, these results establish a link between TGFβ signaling activation and astrocyte senescence and suggest that prolonged exposure to serum albumin due to BBBD can trigger these phenotypic changes., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: In Japan, responses to people with drug dependency problems and who frequently re-enter the criminal justice system have undergone significant change in recent years, resulting in a heavier emphasis placed on non-criminal justice interventions and greater diversification of practitioners. To better understand how different practitioners are negotiating and adapting to their changing environments, this paper examines the goals of practitioners who work with individuals who are on probation, parole or have received a suspended sentence for an illegal drug offence., Method: Q methodology was utilised, with participation of 89 practitioners from across the fields of criminal justice, health, social welfare, and local government. Participants ranked 64 goals in drug policy according to their perceived importance in a Q-sort activity, before reflecting on their decision-making during a post-sort questionnaire. Principal components analysis was conducted, along with an iterative and holistic approach that considered the Q-sort and questionnaire data as a whole, to extract and interpret groups of practitioners that shared similar perspectives., Results: Three groups of practitioner perspectives were identified, termed as recovery supporters, moral guardians, and crime bureaucrats. Overall, there are a number of commonalities which revolve around facilitating 'autonomous drug-free lives', but groups are distinguished in important ways, not least in terms of goals relating to the nature and role of criminal justice and treatment services., Conclusion: Although the notion of 'autonomous drug-free lives' binds together different perspectives, there are competing interpretations about why this matters and the preferred 'journey' to this social state. These findings show that the embracing of more welfare and health-based approaches in drug policy in Japan is also being largely reflected in practitioner perspectives, but the conflicts that exist have the potential to erode multi-agency co-operation and lead to variation in policy implementation., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Radiation injury from medical, accidental, or intentional sources can induce acute and long-term hepatic dysregulation, fibrosis, and cancer. This long-term hepatic dysregulation decreases quality of life and may lead to death. Our goal in this study is to determine acute changes in biological pathways and discover potential RNA biomarkers predictive of radiation injury. We performed whole transcriptome microarray analysis of mouse liver tissue (C57BL/6 J) 48 h after whole-body irradiation with 1, 2, 4, 8, and 12 Gray to identify significant expression changes in mRNAs, lncRNAs, and miRNAs, We also validated changes in specific RNAs through qRT-PCR. We used Ingenuity Pathway Analysis (IPA) to identify pathways associated with gene expression changes. We observed significant dysregulation of multiple mRNAs across all doses. In contrast, miRNA dysregulation was observed upwards of 2 Gray. The most significantly upregulated mRNAs function as tumor suppressors: Cdkn1a, Phlda3, and Eda2r. The most significantly downregulated mRNAs were involved in hemoglobin synthesis, inflammation, and mitochondrial function including multiple members of Hbb and Hba. The most significantly upregulated miRNA included: miR-34a-5p, miR-3102-5p, and miR-3960, while miR-342-3p, miR-142a-3p, and miR-223-3p were most significantly downregulated. IPA predicted activation of cell cycle checkpoint control pathways and inhibition of pathways relevant to inflammation and erythropoietin. Clarifying expression of mRNA, miRNA and lncRNA at a short time point (48 h) offers insight into potential biomarkers, including radiation markers shared across organs and animal models. This information, once validated in human models, can aid in development of bio-dosimetry biomarkers, and furthers our understanding of acute pathway dysregulation., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Previous research has highlighted the impact of radiation damage, with cancer patients developing acute disorders including radiation induced pneumonitis or chronic disorders including pulmonary fibrosis months after radiation therapy ends. We sought to discover biomarkers that predict these injuries and develop treatments that mitigate this damage and improve quality of life., Materials and Methods: Six- to eight-week-old female C57BL/6 mice received 1, 2, 4, 8, 12 Gy or sham whole body irradiation. Animals were euthanized 48 h post exposure and lungs removed, snap frozen and underwent RNA isolation. Microarray analysis was performed to determine dysregulation of messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA) after radiation injury., Results: We observed sustained dysregulation of specific RNA markers including: mRNAs, lncRNAs, and miRNAs across all doses. We also identified significantly upregulated genes that can indicate high dose exposure, including Cpt1c, Pdk4, Gdf15 , and Eda2r , which are markers of senescence and fibrosis. Only three miRNAs were significantly dysregulated across all radiation doses: miRNA-142-3p and miRNA-142-5p were downregulated and miRNA-34a-5p was upregulated. IPA analysis predicted inhibition of several molecular pathways with increasing doses of radiation, including: T cell development, Quantity of leukocytes, Quantity of lymphocytes, and Cell viability., Conclusions: These RNA biomarkers might be highly relevant in the development of treatments and in predicting normal tissue injury in patients undergoing radiation treatment. We are conducting further experiments in our laboratory, which includes a human lung-on-a-chip model, to develop a decision tree model using RNA biomarkers.

Maternal mortality in the United States is a public health crisis of preventable deaths among young women. The role of echocardiography in the evaluation of pregnant women with cardiovascular symptoms or risk factors without known heart disease is unclear. We retrospectively examined the clinical characteristics of consecutive pregnant patients without established heart disease who underwent echocardiography and evaluated associations between abnormal exam findings and obstetric outcomes. Among low-risk women undergoing echocardiography during pregnancy, older age, higher parity and a history of chronic hypertension are associated with a higher likelihood of echocardiographic abnormalities, which in turn are associated with a higher likelihood of adverse obstetric outcomes including caesarean section and preterm delivery.

Background: The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) is an advance care planning process designed to facilitate discussion and documentation of preferences for care in a medical emergency. Advance care planning is important in residential and nursing homes., Aim: To explore the views and experiences of GPs and care home staff of the role of ReSPECT in: (i) supporting, and documenting, conversations about care home residents' preferences for emergency care situations, and (ii) supporting decision-making in clinical emergencies., Setting/participants: Sixteen GPs providing clinical care for care home residents and 11 care home staff in the West of England., Methods: A qualitative research design using semi-structured interviews., Results: Participants' accounts described the ReSPECT process as facilitating person-centred conversations about residents' preferences for care in emergency situations. The creation of personalised scenarios supported residents to consider their preferences. However, using ReSPECT was complex, requiring interactional work to identify and incorporate resident or relative preferences. Subsequent translation of preferences into action during emergency situations also proved difficult in some cases. Care staff played an important role in facilitating and supporting ReSPECT conversations and in translating it into action., Conclusions: The ReSPECT process in care homes was positive for GPs and care home staff. We highlight challenges with the process, communication of preferences in emergency situations and the importance of balancing detail with clarity. This study highlights the potential for a multi-disciplinary approach engaging care staff more in the process., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Purpose: In context of changing patient demographics, this study explores what doctors and medical students believe being a 'good' doctor means and identifies implications for training., Method: Using Q-methodology, a purposive sample of 58 UK medical students and trainees sorted 40 responses to the prompt 'Being a "good" doctor means….' Participants explained their array choices in a post-sort questionnaire. Factor-groups, consensus and distinguishing statements were identified using Principal Components Analysis in R., Results: Three factor-groups best described shared and divergent perspectives, accounting for 61.64% of variance. The largest, 'patient-centred generalist' group valued patient wellbeing and empowerment, compassion and complex needs. They prioritised knowledge breadth and understanding other specialties. The 'efficient working doctors' group valued good work-life balance, pay and did not seek challenge. Some believed these made a stressful career sustainable. The 'specialist' group valued skills mastery, expertise, depth of knowledge and leadership. Participant-groups were distributed across these factor-groups, all agreeing early specialisation should be avoided., Conclusions: The largest factor-group's perceptions of holistic, patient-centred care align with Royal Colleges' curricula adaptions to equip doctors with generalist skills to manage multi-morbid patients. However, curriculum designers should acknowledge implications of generalist approaches for doctors' formulation of professional identities.

Mesenchymal progenitor cells (MPCs) have been recently identified in human and murine epidural fat and have been hypothesized to contribute to the maintenance/repair/regeneration of the dura mater. MPCs can secrete proteoglycan 4 (PRG4/lubricin), and this protein can regulate tissue homeostasis through bio-lubrication and immunomodulatory functions. MPC lineage tracing reporter mice (Hic1) and human epidural fat MPCs were used to determine if PRG4 is expressed by these cells in vivo. PRG4 expression co-localized with Hic1 + MPCs in the dura throughout skeletal maturity and was localized adjacent to sites of dural injury. When Hic1 + MPCs were ablated, PRG4 expression was retained in the dura, yet when Prx1 + MPCs were ablated, PRG4 expression was completely lost. A number of cellular processes were impacted in human epidural fat MPCs treated with rhPRG4, and human MPCs contributed to the formation of epidural fat, and dura tissues were xenotransplanted into mouse dural injuries. We have shown that human and mouse MPCs in the epidural/dura microenvironment produce PRG4 and can contribute to dura homeostasis/repair/regeneration. Overall, these results suggest that these MPCs have biological significance within the dural microenvironment and that the role of PRG4 needs to be further elucidated., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In a mass radiation exposure, the healthcare system may rely on differential expression of miRNA to determine exposure and effectively allocate resources. To this end, miRNome analysis was performed on non-human primate serum after whole thorax photon beam irradiation of 9.8 or 10.7 Gy with dose rate 600 cGy/min. Serum was collected up to 270 days after irradiation and sequenced to determine immediate and delayed effects on miRNA expression. Elastic net based GLM methods were used to develop models that predicted the dose vs. controls at 81% accuracy at Day 15. A three-group model at Day 9 achieved 71% accuracy in determining if an animal would die in less than 90 days, between 90 and 269 days, or survive the length of the study. At Day 21, we achieved 100% accuracy in determining whether an animal would later develop pleural effusion. These results demonstrate the potential ability of miRNAs to determine thorax partial-body irradiation dose and forecast survival or complications early following whole thorax irradiation in large animal models. Future experiments incorporating additional doses and independent animal cohorts are warranted to validate these results. Development of a serum miRNA assay will facilitate the administration of medical countermeasures to increase survival and limit normal tissue damage following a mass exposure., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Various studies have looked at the efficiency of artificial vessel and tissue networks in the study of photoplethysmography (PPG) in an effort to better understand the origin of various morphological features present in the signal. Whilst there are all reasonable attempts made to replicate geometrical features such as vessel depth, vessel wall thickness and diameter etc., not many studies have attempted to replicate the mechanical properties such as vessel elasticity and tissue compressibility. This study reports two methods for tissue mechanical testing for the analysis of vessel elasticity and tissue compressibility. A two-part polydimethylsiloxane (PDMS) was used as a base material for both tissue and vessel construction, and the properties altered by changing the curing component ratio. Tissue compression properties were investigated using an industrially calibrated materials testing device using the protocol from the ASTM 0575-91 testing method. Vessel elasticity was investigated using a custom method and apparatus to report vessel diameter and length change simultaneously. Tissue compressive properties proved reasonably easy to replicate through catalyst alteration, however the vessel elasticity properties were found to be higher than expected at all reasonable catalyst ratios. The property of hyper-elasticity was observed in the artificial vessels though, leading to the conclusion that alternative material recipes or construction methods may be needed to correctly replicate the expected mechanical characteristics. Clinical Relevance- The latest generation of health monitoring devices, especially those that are wearable and used widely by individuals wishing to monitor their health daily are becoming smarter and more sophisticated in their functionality. The majority of such devices use photoplethysmography (PPG) as their primary monitoring technique. Being able to replicate the PPG in a phantom allows the continued study and development of devices, and to improve their functionality without the continued need for extensive user-testing.