Assessing periparturient ewe characteristics and nemabiome composition to guide targeted selective treatment for sustainable gastrointestinal nematodes control in sheep.

Gastrointestinal nematodes (GINs) are a significant threat to the sustainability of global sheep production. Periparturient ewes play a key role in GIN epidemiology, with increased GIN faecal egg counts (FECs) in these ewes resulting in heavy pasture contamination that facilitates parasitic gastroenteritis in immunologically naïve lambs later during the grazing period. Traditionally, blanket anthelmintic treatment would suppress GIN egg outputs in these ewes and subsequent pasture contamination. However, farmers are now advised to implement targeted selective treatment (TST) to reduce anthelmintic use and subsequent anthelmintic resistance development, yet, there is currently limited evidence to determine optimal TST strategies in ewes. In this study, the characteristics of 226 ewes on seven Welsh farms were assessed postlambing to identify factors associated with their individual strongyle FECs using negative binomial mixed model analysis. Nemabiome analysis was conducted on 34 ewes across two study farms using the Oxford Nanopore MinIon platform with an aim of identifying factors associated with variations in ewe nemabiome composition within flocks. The best-fitted model of ewe FEC incorporated ewe body condition score, dag score, breed, and an interaction effect between ewe age and litter size as fixed factors. The addition of a mean FEC value for ewes of a specific litter size on each farm further improved model fit and reduced between-farm variance in the model. Nemabiome analysis revealed significant variation in within flock nemabiome diversity on individual farms, with significantly reduced nemabiome diversity recorded in ewes exhibiting dags and in twin-bearing ewes on respective farms, whilst T. circumcincta was present as a significantly higher proportion of the nemabiome in Suffolk ewes and twin bearing ewes (P < 0.05) in respective flocks. Our data demonstrate that commonly recorded ewe characteristics can be exploited to predict individual periparturient ewe FEC and subsequently may be used as a guide for TST strategies on sheep farms once specific TST thresholds are identified to deliver the optimal balance between minimal pasture contamination and maximal GIN refugia. This study is the first to utilise Oxford Nanopore MinIon sequencing to evaluate the nemabiome of sheep, and to molecularly assess the nemabiome of individual ruminants within a flock/herd, with results indicating that significant within flock variations in nemabiome composition which may have implications for TST and flock management strategies.

A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus.

BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Pilot study of a community pharmacist led program to treat hepatitis C virus among people who inject drugs.

Background: People who inject drugs (PWID) are a key population for treatment with direct-acting antiviral medications (DAAs) to eliminate hepatitis C virus (HCV). We developed a Pharmacist, Physician, and Patient Navigator Collaborative Care Model (PPP-CCM) for delivery of HCV treatment; this study describes clinical outcomes related to HCV treatment (initial evaluation, treatment initiation, completion, and cure), as well as patient satisfaction. Methods: We conducted a single-arm prospective pilot study of adult PWID living with HCV. Participants completed baseline and six-month follow-up surveys, and treatment and outcomes were abstracted from electronic health records. Primary outcome was linkage to pharmacist for HCV evaluation; secondary outcomes included DAA initiation, completion, and cure, as well as patient-reported satisfaction. Results: Of the 40 PWID enrolled, mean age was 43.6 years, 12 (30 %) were female, 20 (50 %) were non-white, and 15 (38 %) were unhoused. Thirty-eight (95 %) were successfully linked to the pharmacist for initial evaluation. Of those, 21/38 (55 %) initiated DAAs, and 16/21 (76 %) completed treatment. Among those completing treatment who had viral load data to document whether they achieved "sustained virologic response", i.e. cure, 10/11 (91 %) were found to be cured. There was high satisfaction with 100 % responding "agree or strongly agree" that they had a positive experience with the pharmacist. Conclusion: Nearly all participants in this pilot were successfully linked to the pharmacist for evaluation, and more than half were started on DAAs; results provide preliminary evidence of feasibility of pharmacist-led models of HCV treatment for PWID. Clinicaltrialsgov registration number: NCT04698629.

Polyglucosan body density in the aged mouse hippocampus is controlled by a novel modifier locus on chromosome 1.

Aging can be associated with the accumulation of hypobranched glycogen molecules (polyglucosan bodies, PGBs), particularly in astrocytes of the hippocampus. While PGBs have a detrimental effect on cognition in diseases such as adult polyglucosan body disease and Lafora disease, the underlying mechanism and clinical relevance of age-related PGB accumulation remains unknown. Here, we have investigated the genetic basis and functional impact of age-related PGB accumulation in 32 fully sequenced BXD-type strains of mice which exhibit a 400-fold variation in PGB burden in 16-18 month old females. We mapped a major locus controlling PGB density in the hippocampus to chromosome 1 at 72-75 Mb (linkage of 4.9 -logP), which we defined as the Pgb1 locus. To identify potentially causal gene variants within Pgb1, we generated extensive hippocampal transcriptome datasets and identified two strong candidate genes for which mRNA correlates with PGB density-Smarcal1 and Usp37. In addition, both Smarcal1 and Usp37 contain non-synonymous allele variations likely to impact protein function. A phenome-wide association analysis highlighted a trans-regulatory effect of the Pgb1 locus on expression of Hp1bp3, a gene known to play a role in age-related changes in learning and memory. To investigate the potential impact of PGBs on cognition, we performed conditioned fear memory testing on strains displaying varying degrees of PGB burden, and a phenome-wide association scan of ~12,000 traits. Importantly, we did not find any evidence suggesting a negative impact of PGB burden on cognitive capacity. Taken together, we have identified a major modifier locus controlling PGB burden in the hippocampus and shed light on the genetic architecture and clinical relevance of this strikingly heterogeneous hippocampal phenotype.

Should AMOC observations continue: how and why?

The Atlantic meridional overturning circulation (AMOC) is a large-scale circulation pattern responsible for northward heat transport in the Atlantic and is associated with climate variations on a wide range of time scales. Observing the time-varying AMOC has fundamentally changed our understanding of the large-scale ocean circulation and its interaction with the climate system, as well as identified shortcomings in numerical simulations. With a wide range of gains already achieved, some now ask whether AMOC observations should continue. A measured approach is required for a future observing system that addresses identified gaps in understanding, accounts for shortcomings in observing methods and maximizes the potential to guide improvements in ocean and climate models. Here, we outline a perspective on future AMOC observing and steps that the community should consider to move forward. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.

Development of a Mobile-First Registry to Recruit Healthy Volunteers and Members of Underrepresented Communities for Alzheimer's Disease Prevention Studies.

BACKGROUND: Web-based participant recruitment registries can be useful tools for accelerating enrollment into studies, but existing Alzheimer's disease (AD)-focused recruitment registries have had limited success enrolling individuals from underrepresented racial and ethnic groups. Designing these registries to meet the needs of individuals from these communities, including designing mobile-first, may facilitate improvement in the enrollment of underrepresented groups. OBJECTIVES: Evaluate the usability of a prototype mobile-first participant recruitment registry for AD prevention studies; assess users' perceptions of and willingness to sign up for the registry. DESIGN AND SETTING: Quantitative usability testing and an online survey; online setting. PARTICIPANTS: We recruited 1,358 adults ages 45-75 who self-reported not having a diagnosis of mild cognitive impairment, AD, or other forms of dementia (Study 1: n=589, Study 2: n=769). Black/African American and Hispanic/Latino participants were specifically recruited, including those with lower health literacy. METHODS AND MEASUREMENTS: Study 1 measures the prototype's usability through observed task success rates, task completion times, and responses to the System Usability Scale. Study 2 uses an online survey to collect data on perceptions of and willingness to sign up for the mobile-first registry. RESULTS: Study 1 findings show the prototype mobile-first recruitment registry website demonstrates high usability and is equally usable for Black / African American, Hispanic/Latino, and White user groups. Survey results from Study 2 indicate that users from underrepresented communities understand the registry's purpose and content and express willingness to sign up for the registry on a mobile device. CONCLUSIONS: Designing mobile-first participant recruitment registries based on feedback from underrepresented communities may result in more sign-ups by individuals from minoritized communities.

Transient dystonia correlates with parkinsonism after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in nonhuman primates.

Unilateral internal carotid artery 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion in non-human primates produces transient contralateral hemi-dystonia followed by stable contralateral hemi-parkinsonism; the relationship between dystonia and parkinsonism remains unclear. We hypothesized that transient dystonia severity following MPTP correlates with parkinsonism severity. In male Macaca nemestrina (n = 3) and M. fascicularis (n = 17) we administered unilateral intra-carotid MPTP, then correlated validated blinded ratings of transient peak dystonia and delayed parkinsonism. We also correlated dystonia severity with post-mortem measures of residual striatal dopamine and nigral neuron counts obtained a mean 53 ± 15 days following MPTP, after resolution of dystonia but during stable parkinsonism. Median latency to dystonia onset was 1 day, and peak severity 2.5 days after MPTP; total dystonia duration was 13.5 days. Parkinsonism peaked a median of 19.5 days after MPTP, remaining nearly constant thereafter. Peak dystonia severity highly correlated with parkinsonism severity (r[18] = 0.82, p < 0.001). Residual cell counts in lesioned nigra correlated linearly with peak dystonia scores (r[18] = -0.68, p=<0.001). Dystonia was not observed in monkeys without striatal dopamine depletion (n = 2); dystonia severity correlated with striatal dopamine depletion when residual nigral cell loss was less than 50% ([11] r = -0.83, p < 0.001) but spanned a broad range with near complete striatal dopamine depletion, when nigral cell loss was greater than 50%. Our data indicate that residual striatal dopamine may not reflect dystonia severity. We speculate on mechanisms of transient dystonia followed by parkinsonism that may be studied using this particular NHP MPTP model to better understand relationships of transient dystonia to nigrostriatal injury and parkinsonism.

Analytical variation concerning total 25-hydroxyvitamin D measurement, where are we now? A DEQAS review of current assay performance.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes serum samples globally, on a quarterly basis, to assess participants' performance of specific methods for 25-hydroxyvitamin D (25OHD) and other vitamin D metabolites. In this review an assessment of the state of the art in the performance of 25OHD methods is presented. This assessment is based on an analysis of data submitted by scheme participants for the 2021/22 distribution cycle, which comprised of four distributions each containing five DEQAS samples. These distributions enabled the assessment of performance across a wide concentration range and included samples containing endogenous 25OHD2. Overall analytical performance continues to improve, but there is still significant method variation and bias in some automated methods. These automated methods continue to be challenged in measuring 25OHD at the extremes of the measuring range and in the presence of 25OHD2. LC-MS/MS methods still show superior performance with regards to bias, but are out-performed by some automated methods in terms of assay variability. Through participating in an accuracy based EQA scheme, such as DEQAS, laboratories are able to assess the accuracy of their methods in comparison to a gold standard reference measurement procedure. It is crucial for all laboratories to be aware of the performance and limitations of their 25OHD assays and to educate their users accordingly in order to ensure reliable assessment of vitamin D status.

Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial.

BACKGROUND: Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months. METHODS: Resolvin (Rv) E1, 15-epi-lipoxin (LX) A4 and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants. RESULTS: Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15­epi-LXA4 were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21-1.95] ng/ml at baseline versus 0.95 [0.46-4.06] ng/ml at 6 months [P<0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (r = 0.82; P<0.001), but which do not predict polyp prevention efficacy by EPA or aspirin. CONCLUSION: Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15­epi-LXA4. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.

Spaceflight Maximum Allowable Concentrations for Ethyl Acetate.

INTRODUCTION: Ethyl acetate is a simple organic compound that occurs naturally and is used industrially as a solvent. It has been detected in the ISS atmosphere and is known to off-gas from building materials. As NASA astronauts have been and will be exposed to ethyl acetate during space missions, Spaceflight Maximum Allowable Concentrations (SMACs) were developed following an extensive review of the available literature.METHODS: Toxicological data relevant to SMAC development was collected from electronic databases using principles of systematic review, and from previous assessments and reviews of ethyl acetate.RESULTS: From an initial pool of over 35,000 studies, 10 were identified as studies appropriate to support SMAC development. The toxicological properties of ethyl acetate are relatively straightforward. Ethyl acetate is rapidly absorbed and converted by carboxyesterases to ethanol. At concentrations on the order of 400 ppm for 4-8 h, most volunteers experienced mild irritation but no lasting effects. In subchronic animal studies, mild sedative effects and changes in body weight and weight gain were observed at 750 ppm and above.DISCUSSION: Numerous studies were identified to support the development of both short- and long-duration SMACs. No chronic studies were available, but the high quality of the subchronic studies and the short half-life of ethyl acetate support extrapolation to longer durations.Williams ES, Ryder VE. Spaceflight maximum allowable concentrations for ethyl acetate. Aerosp Med Hum Perform. 2023; 94(1):25-33.

Growth with Commensal Streptococci Alters Streptococcus mutans Behaviors.

As oral bacteria grow and persist within biofilms attached to the tooth's surface, they interact with other species to form synergistic or antagonistic exchanges that govern homeostasis for the overall population. One example are the interactions between the cariogenic species Streptococcus mutans and oral commensal streptococci. Previously, we showed that the cell-cell signaling pathways of S. mutans were inhibited during coculture with other oral streptococci species, leading us to posit that the S. mutans transcriptome and behaviors are broadly altered during growth with these species. To test this hypothesis, we performed whole transcriptome sequencing (RNA-seq) on cocultures of S. mutans with either Streptococcus gordonii, Streptococcus sanguinis, or Streptococcus oralis and a quadculture containing all 4 species in comparison to S. mutans grown alone. Our results reveal that in addition to species-dependent changes to the S. mutans transcriptome, a conserved response to oral streptococci in general can be observed. We monitored the behavior of S. mutans by both microscopy imaging of biofilms and in a bacteriocin overlay assay and verified that S. mutans acts similarly with each of these species but noted divergences in phenotypes when cocultured with another cariogenic Streptococcus (Streptococcus sobrinus) or with oral nonstreptococci species. RNA-seq with oral nonstreptococci showed lack of a consistent gene expression profile and overlap of differentially expressed genes found with commensal streptococci. Finally, we investigated the role of upregulated S. mutans genes within our data sets to determine if they provided a fitness benefit during interspecies interactions. Eleven total genes were studied, and we found that a majority impacted the fitness of S. mutans in various assays, highlighted by increased biomass of commensal streptococci in mixed-species biofilms. These results confirm a common, species-independent modification of S. mutans behaviors with oral commensal streptococci that emphasizes the need to further evaluate oral bacteria within multispecies settings.

The 3D-printed miniplate-jig system: a new, rapid, precise, and user-friendly approach to miniplate fixation of free-tissue mandibular reconstructions.

Patient-specific, additively manufactured (printed) titanium reconstruction plates have been widely used to improve accuracy and efficiency of fibular flap reconstruction of the mandible. Miniplates possess some potential advantages over single-piece reconstruction plates, however multiple-miniplate fixation can be more technically demanding and may lengthen the duration of surgery. Furthermore, incremental angulation errors in screw placement for each miniplate could compromise overall dimensional accuracy of the neomandibular reconstruction. This preliminary article reports the first clinical use of a new patient-specific, printed titanium miniplate-jig system in a patient undergoing hemimandibulectomy for osteoradionecrosis of the mandible withfibular flap reconstruction. Our initial experience with the new deviceand technique demonstratesa quick, user friendly, and precise method for the placement and fixation of multiple miniplates in fibular-flap reconstruction of the mandible.

Dynamic ensemble prediction of cognitive performance in spaceflight.

During spaceflight, astronauts face a unique set of stressors, including microgravity, isolation, and confinement, as well as environmental and operational hazards. These factors can negatively impact sleep, alertness, and neurobehavioral performance, all of which are critical to mission success. In this paper, we predict neurobehavioral performance over the course of a 6-month mission aboard the International Space Station (ISS), using ISS environmental data as well as self-reported and cognitive data collected longitudinally from 24 astronauts. Neurobehavioral performance was repeatedly assessed via a 3-min Psychomotor Vigilance Test (PVT-B) that is highly sensitive to the effects of sleep deprivation. To relate PVT-B performance to time-varying and discordantly-measured environmental, operational, and psychological covariates, we propose an ensemble prediction model comprising of linear mixed effects, random forest, and functional concurrent models. An extensive cross-validation procedure reveals that this ensemble outperforms any one of its components alone. We also identify the most important predictors of PVT-B performance, which include an individual's previous PVT-B performance, reported fatigue and stress, and temperature and radiation dose. This method is broadly applicable to settings where the main goal is accurate, individualized prediction of human behavior involving a mixture of person-level traits and irregularly measured time series.

Impaired exercise outcomes with significant bronchodilator responsiveness in children with prematurity-associated obstructive lung disease.

INTRODUCTION: Preterm-born children have their normal in-utero lung development interrupted, thus are at risk of short- and long-term lung disease. Spirometry and exercise capacity impairments have been regularly reported in preterm-born children especially those who developed chronic lung disease of prematurity (CLD) in infancy. However, specific phenotypes may be differentially associated with exercise capacity. We investigated exercise capacity associated with prematurity-associated obstructive (POLD) or prematurity-associated preserved ratio of impaired spirometry (pPRISm) when compared to preterm- and term-controls with normal lung function. MATERIALS AND METHODS: Preterm- and term-born children identified through home screening underwent in-depth lung function and cardiorespiratory exercise testing, including administration of postexercise bronchodilator, as part of the Respiratory Health Outcomes in Neonates (RHiNO) study. RESULTS: From 241 invited children, aged 7-12 years, 202 underwent exercise testing including 18 children with POLD (percent predicted (%)FEV1 and FEV1 /FVC < LLN); 12 pPRISm (%FEV1 < LLN and FEV1 /FVC ≥ LLN), 106 preterm-controls (PTc , %FEV1 ≥ LLN) and 66 term-controls (Tc , %FEV1 > 90%). POLD children had reduced relative workload, peak O2 uptake, CO2 production, and minute ventilation compared to Tc , and used a greater proportion of their breathing reserve compared to both control groups. pPRISm and PTc children also had lower O2 uptake compared to Tc . POLD children had the greatest response to postexercise bronchodilator, improving their %FEV1 by 19.4% (vs 6.3%, 6% 6.3% in pPRISm PTc, Tc , respectively; p < .001). CONCLUSION: Preterm-born children with obstructive airway disease had the greatest impairment in exercise capacity, and significantly greater response to postexercise bronchodilators. These classifications can be used to guide treatment in children with POLD.

Dose adjustments of Elexacaftor/Tezacaftor/Ivacaftor in response to mental health side effects in adults with cystic fibrosis.

INTRODUCTION: Deterioration in mental health has been reported in a minority of individuals with cystic fibrosis starting elexacafor/tezacaftor/ivacaftor (ELX/TEZ/IVA). We report our experience of using sweat chloride and markers of clinical stability to titrate dose reduction with the aim of minimising adverse events and maintaining clinical stability. METHOD: Adults (n = 266) prescribed ELX/TEZ/IVA, were included. Adverse events, sweat chloride, lung function and clinical data were collected. RESULTS: Nineteen (7.1%) individuals reported anxiety, low mood, insomnia and "brain fog" with reduced attention and concentration span. Thirteen underwent dose reduction with sweat chloride remained normal (<30 mmol l-1) or borderline (30-60 mmol l-1) in six (46.2%) and seven (53.2%) cases respectively. Improvement or resolution of AEs occurring in 10 of the 13 cases. CONCLUSION: Dose adjustment of ELX/TEZ/IVA was associated with improvement in mental health AEs without significant clinical deterioration. Sweat chloride concentration may prove useful as a surrogate marker of CFTR function.

A molecular switch controls the impact of cholesterol on a Kir channel.

SignificanceCholesterol is one of the main components found in plasma membranes and is involved in lipid-dependent signaling enabled by integral membrane proteins such as inwardly rectifying potassium (Kir) channels. Similar to other ion channels, most of the Kir channels are down-regulated by cholesterol. One of the very few notable exceptions is Kir3.4, which is up-regulated by this important lipid. Here, we discovered and characterized a molecular switch that controls the impact (up-regulation vs. down-regulation) of cholesterol on Kir3.4. Our results provide a detailed molecular mechanism of tunable cholesterol regulation of a potassium channel.

A practical approach to continuous glucose monitoring (rtCGM) and FreeStyle Libre systems (isCGM) in children and young people with Type 1 diabetes.

Real-time continuous glucose monitoring (rtCGM) and FreeStyle Libre glucose monitoring systems (isCGM) are new evolving technologies used in the management of Type 1 diabetes. They offer potential to improve diabetes control and reduce hypoglycaemia. rtCGM can be linked to insulin pump providing hybrid closed loop therapy. Families of children and young people are keen to have the benefit from these technologies. These are relatively expensive so it is important that health care professionals, families of children and young people (CYP) with diabetes are adequately trained in the use of these devices. Health care professionals need to be able to make patient selection based on individual needs and preferences to achieve maximum benefit. Association of Children's Diabetes Clinicians (ACDC) developed a comprehensive guideline in 2017 to help identify which patients may be most likely to benefit and how these technologies may be practically implemented. Since then new technologies have been introduced and the use of GCM has expanded in routine clinical practice. This article, aims to provide a practical approach and help identify which patients may be most likely to benefit and how the technology may be implemented in order to maximise the clinical benefits.

Skin biomechanical properties and leg volume in aging healthy adults.

BACKGROUND: In adults ageing is accompanied by changes in limb volume and skin biomechanical properties. OBJECTIVES: To explore the relationship between body size, aging, skin biomechanics, and leg volume, VLeg and to define predictive equations linking leg volume with these properties. METHODS: Sixty-two healthy adults (Age 18-80 years, M:F 45:55) were recruited. Anthropomorphic measures were recorded along with VLeg (via circumferential method) and skin tone, stiffness, and elastance (via tonometry). Regression analysis was performed to define relationship between the measured parameters. RESULTS: In healthy adults bilateral VLeg were the same regardless of leg or sex, 5791 ± 1363 for females and 6151 ± 1203 mls for males. VLeg was positively correlated to body weight, where VLeg (mls) = 1058 + 69 × Wt (kg) for females and VLeg (mls) = 539 + 65 × Wt (Kg) of body weight for males. Skin surface biomechanical properties varied with sex, leg volume, and location on the leg with the malleolus exhibiting the stiffest surface. CONCLUSION: The study shows that anthropometric measures change with sex and leg size are multifactorial and body weight, sex, and skin condition as important determinant factors of leg volume.