Refugee health and physiological profiles in transitional settlements in Serbia and Kenya: Comparative evidence for effects of gender and social support.

When armed conflict compels people to flee from their homelands, they embark on protracted journeys during which they experience wide ranging physical, social, and psychological challenges. Few studies have focused on refugee psychosocial and physiological profiles during the transitional phase of forced migration that often involves temporary sheltering. Transient refugees' experiences can vary substantially based on local socio-ecological conditions in temporary settlements, including the length of stay, living conditions, as well as the availability and accessibility of physical and social resources. In this study, we compared physiological and psychosocial data from refugees (N=365; 406 observations) in Serbia and Kenya, respectively, with divergent temporal (length of stay) and socio-ecological conditions. In Serbia, refugees resided in asylum centers (mean stay: 0.9 y); in Kenya they were living in Kakuma Refugee Camp (mean stay: 8.8 y), one of the world's largest camps at the time. We had limited ability to directly compare psychosocial measures and used meta-analytic techniques to evaluate predictors of refugee mental and physical health at the two sites, including based on perceived social support. Refugees in Serbia had higher fingernail cortisol (p < 0.001) and were less likely to have elevated C-reactive protein (CRP) levels (p < 0.01) than refugees in Kakuma. We found common gender differences in both settings; women had lower cortisol but higher EBV antibody titers and higher likelihood of having elevated CRP compared to men (all p < 0.01). Woman also reported poorer mental and physical health (p < 0.001). These physiological and health differences may reflect variation between men and women in their psychosocial and physical experiences of factors such as stress, violence, and trauma during their journeys and as transitional refugees. Finally, we also found that refugees with lower levels of perceived social support reported poorer physical and mental health (p < 0.001). Although our results are cross-sectional, they suggest that this intermittent phase of the refugee experience is a key window for helping enhance refugee well-being through an emphasis on interpersonal and community support systems.

Gender minority stress and diurnal cortisol profiles among transgender and gender diverse people in the United States.

The field of behavioral neuroendocrinology has only begun to explore the lived experiences of transgender and gender diverse (TGD) people exposed to stigma. In light of escalating attacks and legislation targeting TGD people in the United States, it is crucial to examine the physiological pathways through which gender minority stressors become embodied, impact health, and contribute to health inequities. The Trans Resilience and Health Study included baseline data collection from fall 2019 to spring 2020 from a sample of 124 TGD people, reflecting a diversity of gender identities (e.g., trans masculine, trans feminine, and nonbinary) and ages (range = 19-70 years old; M = 34.10), living in Michigan, Nebraska, Oregon, and Tennessee. These analyses examine experiences of gender-related enacted stigma in association with hypothalamic-pituitary-adrenal (HPA)-axis functioning. Among those experiencing the highest levels of enacted stigma, findings show a blunted cortisol awakening response and sluggish daily decline that resulted in elevated concentrations at bedtime compared to those experiencing less enacted stigma. These results of flattened diurnal activity are consistent with an emergent literature on discrimination as a social determinant of potential stress pathophysiology. In contrast, community connectedness was associated with a larger, more dynamic cortisol awakening response. These findings emphasize the importance of incorporating gender-minority stress and resilience measures when studying HPA-axis functioning among TGD people.

The utility of dried blood spot measurement of bone turnover markers in biological anthropology.

OBJECTIVES: Bone is a dynamic organ under continual turnover influenced by life history stage, energy dynamics, diet, climate, and disease. Bone turnover data have enormous potential in biological anthropology for testing evolutionary and biocultural hypotheses, yet few studies have integrated these biomarkers. In the present article we systematically review the current availability, future viability, and applicability of measuring bone turnover markers (BTMs) in dried blood spot (DBS) samples obtained from finger prick whole blood. METHODS: Our review considers clinical and public health relevance, biomarker stability in DBS, assay availability, and cost. We consider biomarkers of bone formation such as osteocalcin (bone matrix protein), PINP (N-terminal propeptide of type I collagen), and alkaline phosphatase (osteoblast enzyme), as well as biomarkers of bone resorption such as CTX (marker of collagen breakdown) and TRACP5b (tartrate-resistant acid phosphatase 5b; osteoclast enzyme). RESULTS: Two BTMs have been validated for DBS: osteocalcin (formation) and TRACP5b (resorption). Prime candidates for future development are CTX and PINP, the formation and resorption markers used for clinical monitoring of response to osteoporosis treatment. CONCLUSION: BTMs are a field-friendly technique for longitudinal monitoring of skeletal biology during growth, reproduction and aging, combining minimized risk to study participants with maximized ease of sample storage and transport. This combination allows new insights into the effects of energy availability, disease, and physical activity level on bone, and questions about bone gain and loss across life history and in response to environmental factors; these issues are important in human biology, paleoanthropology, bioarchaeology, and forensic anthropology.

Bringing the lab bench to the field: Point-of-care testing for enhancing health research and stakeholder engagement in rural/remote, indigenous, and resource-limited contexts.

Point-of-care testing (POCT) allows researchers and health-care providers to bring the lab bench to the field, providing essential health information that can be leveraged to improve health care, accessibility, and understanding across clinical and research settings. Gaps in health service access are most pronounced in what we term RIR settings-rural/remote regions, involving Indigenous peoples, and/or within resource-limited settings. In these contexts, morbidity and mortality from infectious and non-communicable diseases are disproportionately higher due to numerous geographic, economic, political, and sociohistorical factors. Human biologists and global health scholars are well-positioned to contribute on-the-ground-level insights that can serve to minimize global health inequities and POCT has the potential to augment such approaches. While the clinical benefits of POCT include increasing health service access by bringing testing, rapid diagnosis, and treatment to underserved communities with limited pathways to centralized laboratory testing, POCT also provides added benefits to both health-focused researchers and their participants. Through portable, minimally invasive devices, researchers can provide actionable health data to participants by coupling POCT with population-specific health education, discussing results and their implications, creating space for participants to voice concerns, and facilitating linkages to treatment. POCT can also strengthen human biology research by shedding light on questions of evolutionary and biocultural importance. Here, we expand on the epidemiological and research value, as well as practical and ethical challenges of POCT across stakeholders (i.e., participant, community, health researcher, and trainee). Finally, we emphasize the immense opportunities of POCT for fostering collaborative research and enhancing access to health delivery and information and, by extension, helping to mitigate persistent global health inequities.

Transient refugees' social support, mental health, and physiological markers: Evidence from Serbian asylum centers.

OBJECTIVES: Refugees seeking safety across international borders are often exposed to a wide breadth of psychosocially stressful experiences that may fracture existing sources of social support and impair the generation of new social relationships, with implications for their long-term health and resilience. Using data from recently settled refugees in two asylum centers in Serbia, we examined the associations between social support, mental health, and physiological markers. METHODS: In this mixed-method study of refugees (age 18-50 years, n = 76), we collected key socio-demographic information and conducted semi-structured interviews about refugees' journey and stay in Serbia, trauma/loss, and their sources of social support. We also collected self-reported measures of mental well-being as well as physiological markers relevant to repeated exposure to chronic psychosocial stress (fingernail cortisol and dried blood spots for analysis of Epstein-Barr virus [EBV] antibody titers). RESULTS: We found that refugees with longer journeys reported lower social support than those with shorter journeys. Refugees with lower social support reported poorer mental well-being, greater PTSD-related symptoms, and higher recent perceived stress than those with higher social support. We also observed that refugees with lower social support and higher recent stress, respectively, tended to exhibit higher fingernail cortisol levels. However, we did not observe comparable patterns linking EBV antibodies with psychosocial functioning. CONCLUSION: Our cross-sectional findings are consistent with the notion that social support is likely to be a critical component in effective interventions aimed at mitigating the adverse health effects of relocation-related illnesses and poor social functioning as they await resettlement.

Maternal hair cortisol concentrations across pregnancy and the early postpartum period in a Puerto Rican sample.

OBJECTIVE: Hair cortisol is a noninvasive, long-term biomarker of human stress. Strengths and weaknesses of this biomarker as a proxy measure of perinatal stress are not yet well understood. Hair cortisol data were collected from pregnant women in Puerto Rico to investigate maternal cortisol level variance across pregnancy. METHODS: In 2017, we recruited 86 pregnant women planning to birth at a large urban hospital. We aimed to collect four hair samples from each participant, one in each trimester and one in the postpartum period. RESULTS: Median cortisol in the first trimester (n = 82) was 5.7 picograms/milligram (pg/mg) (range: 1.0-62.4). In the second, third, and postpartum periods, the medians were 6.8 pg/mg (1.0-69.5), (n = 46), 20.1 pg/mg (5.6-89.0), (n = 30), and 14.1 pg/mg (1.7-39.8), (n = 9), respectively. These medians disguise a 10-fold and 50-fold variability for two participants. Our sample sizes declined sharply when Hurricane Maria caused major disruptions in services and participants' lives. CONCLUSION: Maternal hair cortisol concentrations were lower in the first and second trimester than the third trimester and early postpartum period. We also observed a wide range of variation in cortisol levels throughout pregnancy and in the postpartum period.

Age-related patterns of cytomegalovirus antibodies accompanying Epstein-Barr virus co-infection.

OBJECTIVE: Cytomegalovirus (CMV) infection is associated with age-related chronic disease, and co-infection with Epstein-Barr virus (EBV) may compound disease risk. We aimed to assess the frequency of CMV infection and its relationship with age among EBV seropositive individuals in an Indigenous Amazonian population. METHODS: We report concentrations of CMV and EBV antibodies in dried blood spot samples collected from 157 EBV positive Shuar participants aged 15-86 years (60.5% female) to assess CMV infection rate. We used logistic and linear regression models to examine associations among CMV, EBV, and age, adjusting for sex, geographic region, and body mass index. RESULTS: Nearly two-thirds (63.1%) of EBV seropositive participants were also CMV seropositive. A 1-year increase in age was associated with 3.4% higher odds of CMV infection (OR [95% CI]: 1.034 [1.009-1.064], p = .012), but CMV antibody concentration was not significantly associated with age or EBV antibody concentration among co-infected individuals. CONCLUSIONS: Herpesvirus-related immunosenescence may be important to understanding chronic disease risk among Shuar. Future studies should further explore the role of co-infection in shaping age-related changes in immune function.

After Theranos: Using point-of-care testing to advance measures of health biomarkers in human biology research.

OBJECTIVES: The rise and fall of the health technology startup Theranos is emblematic of the promise and peril of point-of-care testing (POCT). Instruments that deliver immediate results from minimally invasive samples at the location of collection can provide powerful tools to deliver health data in clinical and public health contexts. Yet, POCT availability is driven largely by market interests, which limits the development of inexpensive tests for diverse health conditions that can be used in resource-limited settings. These constraints, combined with complex regulatory hurdles and substantial ethical challenges, have contributed to the underutilization of POCT in human biology research. METHODS: We evaluate current POCT capabilities and limitations, discuss promising applications for POCT devices in resource-limited settings, and discuss the future of POCT. RESULTS: As evidenced by publication trends, POCT platforms have rapidly advanced in recent years, gaining traction among clinicians and health researchers. We highlight POCT devices of potential interest to population-based researchers and present specific examples of POCT applications in human biology research. CONCLUSIONS: Several barriers can limit POCT applications, including cost, lack of regulatory approval for non-clinical use, requirements for expensive equipment, and the dearth of validation in remote field conditions. Despite these issues, we see immense potential for emerging POCT technology capable of analyzing new sample types and used in conjunction with increasingly common technology (e.g., smart phones). We argue that the fallout from Theranos may ultimately provide an opportunity to advance POCT, leading to more ethical data collection and novel opportunities in human biology research.

Current and future applications of biomarkers in samples collected through minimally invasive methods for cancer medicine and population-based research.

Despite advances in cancer medicine and research, invasive and potentially risky procedures such as biopsies, venous blood tests, imaging, colonoscopy, and pap smear tests are still primarily used for screening, staging, and assessing response to therapy. The development and interdisciplinary use of biomarkers from urine, feces, saliva, scent, and capillary blood collected with minimally invasive methods represents a potential opportunity for integration with biomarker analysis for cancers, both in clinical practice (e.g., in screening, treatment, and disease monitoring, and improved quality of life for patients) and population-based research (e.g., in epidemiology/public health, studies of social and environmental determinants, and evolutionary medicine). In this article, we review the scientific rationale, benefits, challenges, and potential opportunities for measuring cancer-related biomarkers in samples collected through minimally invasive methods.

Pathogen disgust sensitivity protects against infection in a high pathogen environment.

Disgust is hypothesized to be an evolved emotion that functions to regulate the avoidance of pathogen-related stimuli and behaviors. Individuals with higher pathogen disgust sensitivity (PDS) are predicted to be exposed to and thus infected by fewer pathogens, though no studies have tested this directly. Furthermore, PDS is hypothesized to be locally calibrated to the types of pathogens normally encountered and the fitness-related costs and benefits of infection and avoidance. Market integration (the degree of production for and consumption from market-based economies) influences the relative costs/benefits of pathogen exposure and avoidance through sanitation, hygiene, and lifestyle changes, and is thus predicted to affect PDS. Here, we examine the function of PDS in disease avoidance, its environmental calibration, and its socioecological variation by examining associations among PDS, market-related lifestyle factors, and measures of bacterial, viral, and macroparasitic infection at the individual, household, and community levels. Data were collected among 75 participants (ages 5 to 59 y) from 28 households in three Ecuadorian Shuar communities characterized by subsistence-based lifestyles and high pathogen burden, but experiencing rapid market integration. As predicted, we found strong negative associations between PDS and biomarkers of immune response to viral/bacterial infection, and weaker associations between PDS and measures of macroparasite infection, apparently mediated by market integration-related differences. We provide support for the previously untested hypothesis that PDS is negatively associated with infection, and document variation in PDS indicative of calibration to local socioeconomic conditions. More broadly, findings highlight the importance of evolved psychological mechanisms in human health outcomes.

Motor Cortex Function in APOE4 Carriers and Noncarriers.

PURPOSE: The ε4 allele of the apolipoprotein-E gene has been associated with disease activity including Alzheimer disease, multiple sclerosis, and cardiovascular disease. Individuals who possess the ε4 variant of this gene (ε4 carriers) also demonstrate higher levels of cognitive impairment and lower motor scores compared with noncarriers. The purpose of this study was to establish whether there is a difference in motor cortex function between apoε4 carriers and noncarriers. We hypothesized that carriers would have lower levels of excitability and excitatory transmitter (glutamate) and similar levels of intracortical inhibition and inhibitory neurotransmitter (gamma-aminobutyric acid) than noncarriers. METHODS: Fifty-two participants provided saliva samples to determine apoε4 carrier status. Measures of motor cortex excitability and inhibition were obtained using transcranial magnetic stimulation, and measures of glutamate and gamma-aminobutyric acid concentrations were obtained using proton magnetic resonance spectroscopy. RESULTS: No significant differences in transcranial magnetic stimulation (P ≥ 0.19) or proton magnetic resonance spectroscopy measures (P ≥ 0.90) were found between carriers and noncarriers. CONCLUSIONS: The results from this study suggest that motor cortex function, as assessed by transcranial magnetic stimulation measures of excitability and inhibition, and MRS measures of excitatory and inhibitory neurotransmitter are similar in those who possess an apoε4 allele and those who do not.

Variability of C-reactive protein in first-generation Ecuadorian immigrants living in the United States.

OBJECTIVES: Establish the variability of C-reactive protein (CRP) within a population of first-generation immigrants living in the United States. Prior work has theorized that individuals with high levels of childhood pathogen exposure may have lower CRP levels in adulthood, and therefore that for these individuals, CRP may not be as accurate an index of chronic disease risk related to low-level inflammation as is presumed based on data from wealthy populations. This potentially has major implications for the interpretation of CRP as a biomarker of chronic inflammation. METHODS: This longitudinal study collected a total of 125 dried blood spot (DBS) samples from 31 participants (median 4 samples each) and CRP levels in these DBS were assayed by enzyme-linked immunosorbant assay. Surveys were administered to characterize childhood pathogen exposure, and current illness. Variance was estimated using mixed effects regression models. RESULTS: On average, participants were adults (mean = 41.9 years old) who had immigrated to the United States nearly 20 years prior to the study and had nearly universally experienced childhood helminth infection and other major pathogen exposures. Median serum-equivalent CRP was 0.77 mg/L. Individuals reliably differed in subacute CRP levels, and, depending on whether untransformed or log-transformed CRP was the outcome variable, 45% or 62% of variance in CRP was attributable to between-individual differences. CONCLUSIONS: The variability of CRP levels in individuals with relatively high childhood pathogen exposure is comparable to previously reported studies in North America and Europe. However, CRP values are relatively low. CRP is an appropriate measure of subacute inflammation in this sample.

Development and validation of an ELISA for a biomarker of thyroid dysfunction, thyroid peroxidase autoantibodies (TPO-Ab), in dried blood spots.

BACKGROUND: The prevalence of allergic and autoimmune conditions has been steadily increasing in wealthy nations over the past century. One hypothesis put forward to explain this is the Old Friends Hypothesis, which posits that increased hygiene, urbanization, and lifestyle changes have reduced our exposure to parasites and microbes that we co-evolved with, resulting in immune dysregulation. However, research in traditionally living populations, who are exposed to greater parasite and pathogen loads such as those encountered during our evolution, is limited, in part due to a lack of minimally invasive, field-friendly biomarkers of autoimmune disorders. We therefore developed an ELISA to assess positivity for thyroid peroxidase autoantibody (TPO-Ab), an indicator of autoimmune thyroid disease, based on dried blood spot (DBS) samples. RESULTS: We used the Accubind anti-thyroid peroxidase test system to screen our validation samples comprising matched fingerprick DBS, venous DBS, and plasma samples from 182 adults. After confirming that we had TPO-Ab-positive individuals in our validation sample (n = 12), we developed an indirect ELISA to measure TPO-Ab levels from one 3-mm DBS punch. The sensitivity and specificity of our assay for DBS samples ranged from 91.7-100% and 98.2-98.8%, respectively, using a cut-off value of ≥ 26 IU/mL. Intra-assay reliability for duplicate quality control DBS punches was 5.2%, while inter-assay reliability ranged from 11.5-24.4% for high, medium, and low DBS controls. Dilutional linearity ranged from 80 to 120%, and spike and recovery experiments indicated that the DBS matrix does not interfere with the detection of TPO-Ab. TPO-Ab levels remained stable in DBS samples stored at - 28 °C or - 80 °C, but decreased over time in DBS samples kept at 22 °C or at 37 °C. CONCLUSIONS: We developed an in-house, kit-independent indirect ELISA assay to determine individuals' TPO-Ab positivity based on dried blood spots, representing a cost-effective method with potential applications in a range of research settings.

Inflammation and central adiposity as mediators of depression and uncontrolled diabetes in the study on global AGEing and adult health (SAGE).

OBJECTIVES: Diabetes and depression are commonly present in the same individuals, suggesting the possibility of underlying shared physiological processes. Inflammation, as assessed with the biomarker C-reactive protein (CRP), has not consistently explained the observed relationship between diabetes and depression, although both are associated with inflammation and share proposed inflammatory mechanisms. Central adiposity has also been associated with both conditions, potentially by causing increased inflammation. This study uses the World Health Organization's Study on global AGEing and adult health (SAGE) Mexico Wave 1 biomarker data (n = 1831) to evaluate if inflammation and central adiposity mediate the relationship between depression and diabetes. METHODS: Depression was estimated using a behavior-based diagnostic algorithm, inflammation using venous dried blood spot (DBS) CRP, central adiposity using waist-to-height ratio (WHtR), and uncontrolled diabetes using venous DBS-glycated hemoglobin (HbA1c). RESULTS: The association between depression and uncontrolled diabetes was partially mediated by CRP before but not after WHtR was considered. When WHtR was added to the model, it partially mediated the relationship between diabetes and depression while fully mediating the relationship between depression and CRP. CONCLUSIONS: These findings suggest that central adiposity may be a more significant mediator between diabetes and depression than inflammation and account for the relationship between these disorders and inflammation. Depression may cause an increase in central adiposity, which then may lead to diabetes, but the increase in known systemic inflammatory pathways caused by central adiposity may not be the key pathological mechanism.

Validation of an enzyme-linked immunoassay assay for osteocalcin, a marker of bone formation, in dried blood spots.

OBJECTIVES: Investigating factors that contribute to bone loss and accretion across populations in remote settings is challenging, particularly where diagnostic tools are scarce. To mitigate this challenge, we describe validation of a commercial ELISA assay to measure osteocalcin, a biomarker of bone formation, from dried blood spots (DBS). METHODS: We validated the Osteocalcin Human SimpleStep ELISA kit from Abcam (ab1951214) using 158 matched plasma and DBS samples. Passing-Bablok regression analysis assessed the relationships between plasma and DBS osteocalcin concentrations. Dilutional linearity and spike and recovery experiments determined if the DBS matrix interfered with osteocalcin measurement, and intra- and inter-assay coefficients of variation (CVs) were calculated. Limit of detection, analyte stability, and specific forms of osteocalcin measured by the kit were also investigated. RESULTS: Mean plasma osteocalcin value was 218.2 ng/mL (range 64.6-618.1 ng/mL). Linear relationships existed between plasma and DBS concentrations of osteocalcin, with no apparent bias in plasma vs DBS concentrations. There was no apparent interference of the DBS matrix with measurement of osteocalcin in DBS. Intra-assay CV for DBS was ~8%, while average inter-assay CV was 14.8%. Limit of detection was 0.34 ng/mL. Osteocalcin concentrations were stable in DBS stored at -28°C and room temperature, but not those stored at 37°C. This ELISA kit detects total osteocalcin. CONCLUSIONS: Osteocalcin, a bone formation biomarker, can be measured from DBS. Combined with a previously validated DBS assay for TRACP-5b, a bone resorption biomarker, these assays have the potential to help researchers disentangle the many factors contributing to bone strength.

Epigenetic aging in children from a small-scale farming society in The Congo Basin: Associations with child growth and family conflict.

Developmental environments influence individuals' long-term health trajectories, and there is increasing emphasis on understanding the biological pathways through which this occurs. Epigenetic aging evaluates DNA methylation at a suite of distinct CpG sites in the genome, and epigenetic age acceleration (EAA) is linked to heightened chronic morbidity and mortality risks in adults. Consequently, EAA provides insights on trajectories of biological aging, which early life experiences may help shape. However, few studies have measured correlates of children's epigenetic aging, especially outside of the U.S. and Europe. In particular, little is known about how children's growth and development relate to EAA in ecologies in which energetic and pathogenic stressors are commonplace. We studied EAA from dried blood spots among Bondongo children (n = 54) residing in a small-scale, fisher-farmer society in a remote region of the Republic of the Congo. Here, infectious disease burdens and their resultant energy demands are high. Children who were heavier for height or taller for age, respectively, exhibited greater EAA, including intrinsic EAA, which is considered to measure EAA internal to cells. Furthermore, we found that children in families with more conflict between parents had greater intrinsic EAA. These results suggest that in contexts in which limited energy must be allocated to competing demands, more investment in growth may coincide with greater EAA, which parallels findings in European children who do not face similar energetic constraints. Our findings also indicate that associations between adverse family environments and greater intrinsic EAA were nonetheless observable but only after adjustment for covariates relevant to the energetically and immunologically demanding nature of the local ecology.

Functional Measures of Sarcopenia: Prevalence, and Associations with Functional Disability in 10,892 Adults Aged 65 Years and Over from Six Lower- and Middle-Income Countries.

Identification of sarcopenia in lower- and middle-income countries (LMICs) is limited by access to technologies that assess muscle mass. We investigated associations between two functional measures of sarcopenia, grip strength and gait speed (GS), with functional disability in adults from six LMICs. Data were extracted from the World Health Organization (WHO) Study on global AGEing and adult health Wave 1 (2007-2010) for adults (≥ 65 years) from China, Mexico, Ghana, India, Russia and South Africa (n = 10,892, 52.8% women). We calculated country-specific prevalence of low grip strength, slow GS (≤ 0.8 m/s), and both measures combined. Using multivariable negative binomial regression, we separately assessed associations between low grip strength, slow GS, and both measures combined, with the WHO Disability Assessment Schedule 2.0, accounting for selected socioeconomic factors. In women, low grip strength ranged from 7 in South Africa to 51% in India; in men, it ranged from 17 in Russia to 51% in Mexico. Country-specific proportions of slow GS ranged from 77 in Russia, to 33% in China. The concomitant presence of both was the lowest in South Africa and the highest in India (12.3% vs. 33%). Independent of age, those with both low grip strength and slow GS had between 1.2- and 1.5-fold worse functional disability scores, independent of comorbidities, low education, and low wealth (all country-dependent). Low grip strength, slow GS, and the combination of both, were all associated with higher levels of functional disability, thus indicating these objective measures offer a reasonably robust estimate for potential poor health outcomes.

Knee osteoarthritis risk in non-industrial societies undergoing an energy balance transition: evidence from the indigenous Tarahumara of Mexico.

Non-industrial societies with low energy balance levels are expected to be less vulnerable than industrial societies to diseases associated with obesity including knee osteoarthritis. However, as non-industrial societies undergo rapid lifestyle changes that promote positive energy balance, individuals whose metabolisms are adapted to energetic scarcity are encountering greater energy abundance, increasing their propensity to accumulate abdominal adipose tissue and thus potentially their sensitivity to obesity-related diseases. OBJECTIVES: Here, we propose that knee osteoarthritis is one such disease for which susceptibility is amplified by this energy balance transition. METHODS: Support for our hypothesis comes from comparisons of knee radiographs, knee pain and anthropometry among men aged ≥40 years in two populations: Tarahumara subsistence farmers in Mexico undergoing the energy balance transition and urban Americans from Framingham, Massachusetts. RESULTS: We show that despite having markedly lower obesity levels than the Americans, the Tarahumara appear predisposed to accrue greater abdominal adiposity (ie, larger abdomens) for a given body weight, and are more vulnerable to radiographic and symptomatic knee osteoarthritis at lower levels of body mass index. Also, proportionate increases in abdomen size in the two groups are associated with greater increases in radiographic knee osteoarthritis risk among the Tarahumara than the Americans, implying that the abdominal adipose tissue of the Tarahumara is a more potent stimulus for knee degeneration. CONCLUSIONS: Heightened vulnerability to knee osteoarthritis among non-industrial societies experiencing rapid lifestyle changes is a concern that warrants further investigation since such groups represent a large but understudied fraction of the global population.

Soil-transmitted helminth infection and intestinal inflammation among the Shuar of Amazonian Ecuador.

OBJECTIVES: Little research exists documenting levels of intestinal inflammation among indigenous populations where exposure to macroparasites, like soil-transmitted helminths (STHs), is common. Reduced STH exposure is hypothesized to contribute to increased prevalence of elevated intestinal inflammation in wealthy nations, likely due to coevolutionary histories between STHs and human immune systems that favored anti-inflammatory pathways. Here, we document levels of intestinal inflammation and test associations with STH infection among the Shuar of Ecuador, an indigenous population undergoing socioeconomic/lifestyle changes that influence their hygienic environment. We predict that fecal calprotectin (FC; a measure of intestinal inflammation) will be lower in STH infected individuals and that FC will be negatively associated with infection intensity. METHODS: Stool samples to analyze FC levels and STH infection were collected from 69 Shuar participants (ages 5-75 years). Children (<15 years) and adults (15+ years) were analyzed separately to understand the role of exposure in immune system development and the intestinal inflammatory response. RESULTS: Two species of STH were present: Ascaris lumbricoides and Trichuris trichiura. The relationships between infection and intestinal inflammation were age- and species-specific. While no significant relationships were found among adults, children who were singly infected with T. trichiura had lower FC levels than uninfected children. Infection intensity was not significantly associated with FC in children or adults. CONCLUSIONS: These preliminary results provide limited support for our hypotheses, documenting tentative age- and species-specific associations between FC and infection status. Findings may point to the importance of species-specific STH exposure during immune system development.

Genome-Wide Patterns of Gene Expression in a Wild Primate Indicate Species-Specific Mechanisms Associated with Tolerance to Natural Simian Immunodeficiency Virus Infection.

Over 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to human immunodeficiency virus in humans. Notably, an immunosuppressive gene, CD101, was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus.