Comparison of the Acinetobacter baumannii Reference Strains ATCC 17978 and ATCC 19606 in Antimicrobial Resistance Mediated by the AdeABC Efflux Pump.

The Acinetobacter baumannii RND efflux pump AdeABC is regulated by the 2-component regulator AdeRS. In this study, we compared the regulation and expression of AdeABC of the reference strains ATCC 17978 and ATCC 19606. A clearly stronger efflux activity was demonstrated for ATCC 19606. An amino acid substitution at residue 172 of adeS was identified as a potential cause for differential expression of the pump. Therefore, we recommend caution with exclusively using single reference strains for research.

Citrobacter rodentium Induces Tissue-Resident Memory CD4+ T Cells.

Tissue-resident memory T cells (TRM cells) are a novel population of tissue-restricted antigen-specific T cells. TRM cells are induced by pathogens and promote host defense against secondary infections. Although TRM cells cannot be detected in circulation, they are the major memory CD4+ and CD8+ T-cell population in tissues in mice and humans. Murine models of CD8+ TRM cells have shown that CD8+ TRM cells maintain tissue residency via CD69 and though tumor growth factor ß-dependent induction of CD103. In contrast to CD8+ TRM cells, there are few models of CD4+ TRM cells. Thus, much less is known about the factors regulating the induction, maintenance, and host defense functions of CD4+ TRM cells. Citrobacter rodentium is known to induce IL-17+ and IL-22+ CD4+ T cells (Th17 and Th22 cells, respectively). Moreover, data from IL-22 reporter mice show that most IL-22+ cells in the colon 3 months after C. rodentium infection are CD4+ T cells. This collectively suggests that C. rodentium may induce CD4+ TRM cells. Here, we demonstrate that C. rodentium induces a population of IL-17A+ CD4+ T cells that are tissue restricted and antigen specific, thus meeting the criteria of CD4+ TRM cells. These cells expand and are a major source of IL-22 during secondary C. rodentium infection, even before the T-cell phase of the host response in primary infection. Finally, using FTY 720, which depletes circulating naive and effector T cells but not tissue-restricted T cells, we show that these CD4+ TRM cells can promote host defense.

High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial.

OBJECTIVES: To investigate the molecular epidemiology, antimicrobial susceptibility and carbapenem resistance determinants of Acinetobacter baumannii isolates from respiratory tract samples of patients diagnosed with ventilator-associated pneumonia (VAP) who were enrolled in the MagicBullet clinical trial. METHODS: A. baumannii isolates were prospectively cultured from respiratory tract samples from 65 patients from 15 hospitals in Greece, Italy and Spain. Susceptibility testing was performed by broth microdilution. Carbapenem resistance determinants were identified by PCR and sequencing. Molecular epidemiology was investigated using rep-PCR (DiversiLab) and international clones (IC) were identified using our in-house database. RESULTS: Of 65 isolates, all but two isolates (97%) were resistant to imipenem and these were always associated with an acquired carbapenemase, OXA-23 (80%), OXA-40 (4.6%), OXA-58 (1.5%) or OXA-23/58 (1.5%). Resistance to colistin was 47.7%. Twenty-two isolates were XDR, and 20 isolates were pandrug-resistant (PDR). The majority of isolates clustered with IC2 (n = 54) with one major subtype comprising isolates from 12 hospitals in the three countries, which included 19 XDR and 16 PDR isolates. CONCLUSIONS: Carbapenem resistance rates were very high in A. baumannii recovered from patients with VAP. Almost half of the isolates were colistin resistant, and 42 (64.6%) isolates were XDR or PDR. Rep-PCR confirmed IC2 is the predominant clonal lineage in Europe and suggests the presence of an epidemic XDR/PDR A. baumannii clone that has spread in Greece, Italy and Spain. These data highlight the difficulty in empirical treatment of patients with A. baumannii VAP in centres with a high prevalence of carbapenem-resistant A. baumannii.

Erratum to: Frailty has a stronger association with inflammation than age in older veterans.

[This corrects the article DOI: 10.1186/s12979-016-0082-z.].

Frailty has a stronger association with inflammation than age in older veterans.

BACKGROUND: Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans. RESULTS: We analyzed 117 subjects (age range 62-95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty. Serum inflammatory markers were determined using commercially available ELISA kits. Frail and pre-frail (PF) subjects had higher levels than non-frail (NF) subjects of IL-6 (NF vs. PF: p = 0.002; NF vs. F: p < 0.001), TNFR1 (NF vs. F: p = 0.012), TNFRII (NF vs. F: 0.002; NF vs. PF: p = 0.005) and inflammatory index: = 0.333*log(IL-6) + 0.666*log(sTNFR1) (NF vs. F: p = 0.009; NF vs. PF: p < 0.001). Frailty status explained a greater percent of variability in markers of inflammation than age: IL-6 (12 % vs. 0.3 %), TNFR1 (5 % vs. 4 %), TNFR2 (11 % vs. 6 %), inflammatory index (16 % vs. 8 %). Aging was significantly associated with higher fibrinogen (p = 0.04) and D-dimer levels (p = 0.01) but only among NF subjects. CONCLUSION: In conclusion, these data suggest that among older veterans, frailty status has a stronger association with inflammation and the inflammatory index than age does. Larger studies, in more diverse populations are needed to confirm these findings.

Rates of neutropenia in adults with influenza A or B: a retrospective analysis of hospitalised patients in South East Queensland during 2015.

Neutropenia in adult patients is often attributed to intercurrent viral infections; however, there are limited data describing the frequency or natural history of this phenomenon. We examined all patients presenting to three large hospitals in the Metro South region of South East Queensland with laboratory-confirmed influenza A or B throughout the 2015 influenza season (January-October). Four hundred and thirty-six patients were studied and 15.3% of this cohort were neutropenic (absolute neutrophil count <2.0 × 109 /L) with no identifiable cause other than the influenza. Importantly, the majority of cases were mild, with absolute neutrophil count remaining >1.0 × 109 /L. The incidence of neutropenia was significantly higher in association with influenza B than influenza A (18.3% vs 10.3%). We conclude that mild, transient neutropenia is common among patients with influenza infection and advise that it should not cause alarm or invite specific investigation unless severe or prolonged.

MicroRNA regulation of islet and enteroendocrine peptides: Physiology and therapeutic implications for type 2 diabetes.

The pathogenesis of type 2 diabetes (T2D) is associated with dysregulation of glucoregulatory hormones, including both islet and enteroendocrine peptides. Microribonucleic acids (miRNAs) are short noncoding RNA sequences which post transcriptionally inhibit protein synthesis by binding to complementary messenger RNA (mRNA). Essential for normal cell activities, including proliferation and apoptosis, dysregulation of these noncoding RNA molecules have been linked to several diseases, including diabetes, where alterations in miRNA expression within pancreatic islets have been observed. This may occur as a compensatory mechanism to maintain beta-cell mass/function (e.g., downregulation of miR-7), or conversely, lead to further beta-cell demise and disease progression (e.g., upregulation of miR-187). Thus, targeting miRNAs has potential for novel diagnostic and therapeutic applications in T2D. This is reinforced by the success seen to date with miRNA-based therapeutics for other conditions currently in clinical trials. In this review, differential expression of miRNAs in human islets associated with T2D will be discussed along with further consideration of their effects on the production and secretion of islet and incretin hormones. This analysis further unravels the therapeutic potential of miRNAs and offers insights into novel strategies for T2D management.

Germline p16 mutations in familial melanoma.

The p16 gene is located in chromosome 9p21, a region that is linked to familial melanoma and homozygously deleted in many tumour cell lines. We describe eight p16 germline substitutions (one nonsense, one splice donor site and six missense) in 13/18 familial melanoma kindreds. Six of these mutations were identified in 33/36 melanoma cases in nine families, whereas two were detected in normal controls and are not disease-related. The melanoma-specific mutations were detected in 9p21-linked, but not in 1p36-linked, families, thereby confirming previous reports of genetic heterogeneity. Functional analyses of these mutations will confirm those causally related to the development of familial melanoma.

Characterization of MHC-II antigen presentation by B cells and monocytes from older individuals.

In this study we examine the effects of aging on antigen presentation of B cells and monocytes. We compared the antigen presentation function of peripheral blood B cells from young and old subjects using a system that specifically measures the B cell receptor (BCR)-mediated MHC-II antigen presentation. Monocytes were studied as well. Overall the mean magnitude of antigen presentation of soluble antigen and peptide was not different in older and younger subjects for both B cells and monocytes. Older subjects, however, showed increased heterogeneity of BCR-mediated antigen presentation by their B cells. The magnitude and variability of peptide presentation, which do not require uptake and processing, were the same between groups. Presentation by monocytes had similar variability between the older and younger subjects. These data suggest that poor B cell antigen processing, which results in diminished presentation in some older individuals may contribute to poor vaccine responses.

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study.

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the error in applied muscle forces is best judged against the magnitude of the effect that is being investigated.

Magnitude and associated factors of anti-retroviral therapy adherence among children attending HIV care and treatment clinics in Dar es Salaam, Tanzania.

INTRODUCTION: The HIV pandemic continues to contribute significantly towards childhood mortality and morbidity. The up-scaling of the Anti-retroviral therapy (ART) access has seen more children surviving and sanctions great effort be made on ensuring adherence. Adherence is a dynamic process that changes over time and is determined by variable factors. This necessitates the urgency to conduct studies to determine the potential factors affecting adherence in our setting and therefore achieve the 90-90-90 goal of sustainable viral suppression. OBJECTIVES: To assess the magnitude and associated factors of ART adherence among children (1-14 years) attending HIV care and treatment clinics during the months of July to November 2018 in Dar es Salaam. METHODS: A cross-sectional clinic-based study, conducted in three selected HIV care and treatment clinics in urban Dar es Salaam; Muhimbili National Hospital (MNH), Temeke Regional Referral Hospital (TRRH), Infectious Disease Centre- DarDar Paediatric Program (IDC-DPP) HIV clinics during the months of July to November 2018. HIV-infected children aged 1-14 years who had been on treatment for at least six months were consecutively enrolled until the sample size was achieved. A structured questionnaire was used for data collection. Four-day self-report, one-month self-recall report and missed clinic appointments were used to assess adherence. Frequencies and percentages were used to describe categorical data. The odds ratio was used to analyse the possible factors affecting ART adherence Logistic regression models were used to determine the factors associated with ART adherence. Analysis was conducted using SPSS version 20.0 and p-value <0.05 were considered statistically significant. RESULTS: 333 participants were recruited. The overall good adherence (≥95%) was approximated to be 60% (CI-54.3-65.1) when subjected to all three measures. On multivariable logistic regression, factors associated with higher odds of poor adherence were found to be caregivers aged 17-25 years [AOR = 3.5, 95%CI-(1.5-8.4)], children having an inter-current illness [AOR = 10.8, 95%CI-(2.3-50.4)], disbelief in ART effectiveness [AOR = 5.495; 95%CI-(1.669-18.182)] and advanced clinical stage [AOR = 1.972; 95% CI-(1.119-3.484)]. The major reasons reported by caregivers for missing medications included forgetfulness (41%), high pill burden (21%), busy schedule (11%) and long waiting hours at the clinic (9%). CONCLUSION AND RECOMMENDATIONS: In the urban setting of Dar es Salaam, ART adherence among children was found to be relatively low when combined adherence measures were used. Factors associated with poor ART adherence found were younger aged caregivers, and child intercurrent illness, while factors conferring good adherence were belief in ART effectiveness and lower HIV clinical stage. More attention and support should be given to younger aged caregivers, children with concomitant illness and advanced HIV clinical stages. Educating caregivers on ART effectiveness may also aid in improving adherence.

African genetic admixture is associated with body composition and fat distribution in a cross-sectional study of children.

OBJECTIVE: Although differences in body composition parameters among African American (AA), Hispanic American (HA) and European American (EA) children are well documented, the factors underlying these differences are not completely understood. Environmental and genetic contributors have been evaluated as contributors to observed differences. This study evaluated the extent to which African or European ancestral genetic background influenced body composition and fat distribution in 301 peripubertal AA (n = 107), HA (n = 79) and EA (n = 115) children aged 7-12. DESIGN: Estimates of African admixture (AFADM) and European admixture (EUADM) were obtained for every subject using 142 ancestry informative DNA markers. Dual energy X-ray absorptiometry and computed tomography scanning were used to determine body composition and abdominal fat distribution, respectively. Multiple regression models were conducted to evaluate the contribution of admixture estimates to body composition and fat distribution. RESULTS: Greater AFADM was associated with lower fat mass (P = 0.0163), lower total abdominal adipose tissue (P = 0.0006), lower intra-abdominal adipose tissue (P = 0.0035), lower subcutaneous abdominal adipose tissue (P = 0.0115) and higher bone mineral content (BMC) (P = 0.0253), after adjusting for socio-economic status, sex, age, height, race/ethnicity and pubertal status. Greater EUADM was associated with lower lean mass (LM) (P = 0.0056). CONCLUSION: These results demonstrate that ancestral genetic background contributes to racial/ethnic differences in body composition above and beyond the effects of racial/ethnic classification and suggest a genetic contribution to total body fat accumulation, abdominal adiposity, LM and BMC.

Validation of a morphometric reconstruction technique applied to a juvenile pelvis.

Three-dimensional reconstructions of bone geometry from microCT (computed tomography) data are frequently used in biomechanical and finite element analyses. Digitization of bone models is usually a simple process for specimens with a complete geometry, but in instances of damage or disarticulation it can be very challenging. Subsequent to digitization, further imaging techniques are often required to estimate the geometry of missing bone or connecting cartilage. This paper presents an innovative approach to the reconstruction of incomplete scan data, to reproduce proper anatomical arrangements of bones, including absent connecting cartilaginous elements. Utilizing geometric morphometric tools, the reconstruction technique is validated through comparison of a reconstructed 9 year old pelvis, to the original CT data. A principal component analysis and an overlay of the two pelves provide a measure of the accuracy of the reconstructed model. Future work aims to investigate the biomechanical effects of any minor positional error on the bone's predicted structural properties through the use of finite element analysis.

Characterization of Amino Acid Substitutions in the Two-Component Regulatory System AdeRS Identified in Multidrug-Resistant Acinetobacter baumannii.

In Acinetobacter baumannii, resistance-nodulation-cell division (RND)-type efflux is a resistance mechanism of great importance since it contributes to reduced susceptibility to multiple antimicrobial compounds. Some mutations within the genes encoding the two-component regulatory system AdeRS appear to play a major role in increased expression of the RND efflux pump AdeABC and, consequently, in reduced antimicrobial susceptibility, as they are commonly observed in multidrug-resistant (MDR) A. baumannii. In the present study, the impact of frequently identified amino acid substitutions, namely, D21V and D26N in AdeR and T156M in AdeS, on adeB expression, efflux activity, and antimicrobial susceptibility was investigated. Reverse transcription-quantitative PCR (qRT-PCR) studies revealed significantly increased adeB expression caused by D26N (AdeR) and T156M (AdeS). In addition, accumulation assays have shown that these mutations induce increased efflux activity. Subsequently, antimicrobial susceptibility testing via agar dilution and broth microdilution confirmed the importance of these substitutions for the MDR phenotype, as the MICs for various antimicrobials of different classes were increased. In contrast, the amino acid substitution D21V in AdeR did not lead to increased adeB expression and did not reduce antimicrobial susceptibility. This study demonstrates the impact of the D26N (AdeR) and T156M (AdeS) amino acid substitutions, highlighting that these regulators represent promising targets for interfering with efflux activity to restore antimicrobial susceptibility. IMPORTANCE The active efflux of antimicrobials by bacteria can lead to antimicrobial resistance and persistence and can affect multiple different classes of antimicrobials. Efflux pumps are tightly regulated, and their overexpression can be mediated by changes in their regulators. Identifying these changes is one step in the direction of resistance prediction, but it also opens the possibility of targeting efflux pump regulation as a strategy to overcome antimicrobial resistance. Here, we have investigated commonly found changes in the regulators of the main efflux pumps in Acinetobacter baumannii.

Outbreak of Pseudomonas aeruginosa infections after CT-guided spinal injections.

BACKGROUND: Meningitis and spinal infections with Gram-negative bacteria after local injections for treatment of chronic back pain are rare. This study investigated an outbreak of Pseudomonas aeruginosa infections following computed tomography (CT)-guided spinal injections (SI). METHODS: A case was defined as a spinal infection or meningitis with P. aeruginosa after SI between 10th January and 1st March 2019 in the same outpatient clinic. Patients without microbiological evidence of P. aeruginosa but with a favourable response to antimicrobial therapy active against P. aeruginosa were defined as probable cases. FINDINGS: Twenty-eight of 297 patients receiving CT-guided SI during the study period developed meningitis or spinal infections. Medical records were available for 19 patients. In 15 patients, there was microbiological evidence of P. aeruginosa, and four patients were defined as probable cases. Two of 19 patients developed meningitis, while the remaining 17 patients developed spinal infections. The median time from SI to hospital admission was 8 days (interquartile range 2-23 days). Patients mainly presented with back pain (N=18; 95%), and rarely developed fever (N=3; 16%). Most patients required surgery (N=16; 84%). Seven patients (37%) relapsed and one patient died. Although the source of infection was not identified microbiologically, documented failures in asepsis when performing SI probably contributed to these infections. CONCLUSIONS: SI is generally considered safe, but non-adherence to asepsis can lead to deleterious effects. Spinal infections caused by P. aeruginosa are difficult to treat and have a high relapse rate.

Three-dimensional geometric morphometrics applied to the study of children with cleft lip and/or palate from the North East of England.

This prospective cross-sectional, case-controlled morphometric study investigated three-dimensional facial morphological variation among and between 8- and 12-year-old children [40 with a unilateral cleft lip and palate (UCLP), 23 with a unilateral cleft lip and alveolus (UCLA), 19 with a bilateral cleft lip and palate (BCLP), and 21 with an isolated cleft palate (ICP)]. Eighty gender- and age-matched individuals comprised the control group. The mean shape of each group was computed using generalized Procrustes analysis (GPA). Differences in shape between group means were assessed using multivariate analysis of variance and permutation tests, and shape differences were visualized for interpretation using warpings of the grand mean shape and transformation grids computed using thin plate splines (TPA). Statistically significant differences between the mean facial shapes and forms (shape plus size) of all groups were found. The greatest difference was in the BCLP group and the second greatest in the UCLP group. The study of asymmetry indicated different degrees and differences in the nature of asymmetry that characterize different cleft lip and palate (CLP) deformities. Principal component analyses (PCA) of form space and of means, plus reflected means, were informative with respect to the differences in facial size and shape and asymmetry between these groups. The results highlight differences in the aetiology of ICP and CLP groups and underline the potential value of statistical shape analysis in assessing the outcomes of CLP treatment.

Modelling dysplasia detection in ulcerative colitis: clinical implications of surveillance intensity.

BACKGROUND: Endoscopic surveillance of chronic colitis uses random biopsies to find dysplastic fields. Enhanced endoscopic methods are more sensitive for dysplasia detection, but their specificity for colorectal cancer risk is unknown. AIMS: To develop a mathematical model of the sensitivity of random biopsy surveillance, and determine the implications of negative, a single positive, or multiple positive biopsies for dysplasia, and compare the detection threshold to that detectable by enhanced endoscopy. METHODS: Using mathematical modelling, we calculated the confidence level with which dysplasia can be excluded, the dysplastic field size detection threshold, the predicted area of a dysplastic field, and the number of biopsies needed for a given dysplasia detection threshold and confidence level. RESULTS: 32 random biopsies provide only 80% confidence that dysplasia involving > or =5% of the colon can be detected. When a single biopsy of 18 is dysplastic, this predicts a dysplastic area (89 cm(2)) several orders of magnitude greater than dysplastic fields that are readily detectable by enhanced endoscopy (1 cm diameter), and the predicted field size increases rapidly with multiple positive biopsies. CONCLUSIONS: Random biopsy surveillance is sufficiently sensitive to detect large dysplastic fields with significant colorectal cancer risk. Enhanced endoscopy can detect much smaller dysplastic fields, but these have unknown (perhaps much lower) colorectal cancer risk. Small dysplastic fields should not be assumed to indicate a high colorectal cancer risk that warrants colectomy. Prospective studies are needed to define the colorectal cancer risk and optimal management of small dysplastic lesions.

A bioenergetic model to predict habitability, biomass and biosignatures in astrobiology and extreme conditions.

In order to grow, reproduce and evolve life requires a supply of energy and nutrients. Astrobiology has the challenge of studying life on Earth in environments which are poorly characterized or extreme, usually both, and predicting the habitability of extraterrestrial environments. We have developed a general astrobiological model for assessing the energetic and nutrient availability of poorly characterized environments to predict their potential biological productivity. NutMEG (nutrients, maintenance, energy and growth) can be used to estimate how much biomass an environment could host, and how that life might affect the local chemistry. It requires only an overall catabolic reaction and some knowledge of the local environment to begin making estimations, with many more customizable parameters, such as microbial adaptation. In this study, the model was configured to replicate laboratory data on the growth of methanogens. It was used to predict the effect of temperature and energy/nutrient limitation on their microbial growth rates, total biomass levels, and total biosignature production in laboratory-like conditions to explore how it could be applied to astrobiological problems. As temperature rises from 280 to 330 K, NutMEG predicts exponential drops in final biomass ([Formula: see text]) and total methane production ([Formula: see text]) despite an increase in peak growth rates ([Formula: see text]) for a typical methanogen in ideal conditions. This is caused by the increasing cost of microbial maintenance diverting energy away from growth processes. Restricting energy and nutrients exacerbates this trend. With minimal assumptions NutMEG can reliably replicate microbial growth behaviour, but better understanding of the synthesis and maintenance costs life must overcome in different extremes is required to improve its results further. NutMEG can help us assess the theoretical habitability of extraterrestrial environments and predict potential biomass and biosignature production, for example on exoplanets using minimum input parameters to guide observations.

Reaction of monosaccharides with proteins: possible evolutionary significance.

Measurements were made of the rate of condensation of various monosaccharides with amino groups of hemoglobin to form Schiff base linkages. The reactivity of each sugar was dependent on the extent to which it exists in the open (carbonyl) structure rather than in the ring (hemiacetal or hemiketal) structure. Among the 15 monosaccharides tested, aldoses showed higher reactivities than ketoses. Glucose was the least reactive of the aldohexoses. The emergence of glucose as the primary metabolic fuel may be due in part to the high stability of its ring structure which limits potentially deleterious nonenzymatic glycosylation of proteins.

Masticatory loading and bone adaptation in the supraorbital torus of developing macaques.

Research on the evolution and adaptive significance of primate craniofacial morphologies has focused on adult, fully developed individuals. Here, we investigate the possible relationship between the local stress environment arising from masticatory loadings and the emergence of the supraorbital torus in the developing face of the crab-eating macaque Macaca fascicularis. By using finite element analysis (FEA), we are able to evaluate the hypothesis that strain energy density (SED) magnitudes are high in subadult individuals with resulting bone growth in the supraorbital torus. We developed three micro-CT-based FEA models of M. fascicularis skulls ranging in dental age from deciduous to permanent dentitions and validated them against published experimental data. Applied masticatory muscle forces were estimated from physiological cross-sectional areas of macaque cadaveric specimens. The models were sequentially constrained at each working side tooth to simulate the variation of the bite point applied during masticatory function. Custom FEA software was used to solve the voxel-based models and SED and principal strains were computed. A physiological superposition SED map throughout the face was created by allocating to each element the maximum SED value from each of the load cases. SED values were found to be low in the supraorbital torus region throughout ontogeny, while they were consistently high in the zygomatic arch and infraorbital region. Thus, if the supraorbital torus arises to resist masticatory loads, it is either already adapted in each of our subadult models so that we do not observe high SED or a lower site-specific bone deposition threshold must apply.