RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma.

Hu Antigen R, also known as ELAVL1 (HuR), is a key posttranscriptional regulator in eukaryotic cells. HuR overexpression promotes several malignancies, including head and neck squamous cell carcinoma (HNSCC). However, its immune dysfunction-associated tumorigenesis pathways remain unknown. We examined HuR's effects on oral malignancies and immune cell function in vitro and in vivo using oral carcinoma cells and transgenic HuR knockout (KO) mice. CRISPR/Cas9-mediated HuR deletion in mice syngeneic oral cancer cells eliminated colony formation and tumor development. HuR-KO tumors had a lower tumor volume, fewer CD4+CD25+FoxP3+ regulatory T cells, and more CD8+ T cells, suggesting that HuR may suppress the immune response during oral cancer progression. In contrast, HuR KO oral epithelial tissues are resistant to 4NQO-induced oral malignancies compared to control tumor-bearing mice. HuR KO mice showed fewer Tregs and greater IFN levels than WT tumor-bearing mice, suggesting anticancer activity. Finally, the HuR inhibitor pyrvinium pamoate lowers tumor burden by enhancing CD8+ infiltration at the expense of CD4+, suggesting anticancer benefits. Thus, HuR-dependent oral neoplasia relies on immunological dysfunction, suggesting that decreasing HuR may boost antitumor potential and offer a novel HNSCC therapy.

SpaceANOVA: Spatial Co-occurrence Analysis of Cell Types in Multiplex Imaging Data Using Point Process and Functional ANOVA.

Multiplex imaging platforms have enabled the identification of the spatial organization of different types of cells in complex tissue or the tumor microenvironment. Exploring the potential variations in the spatial co-occurrence or colocalization of different cell types across distinct tissue or disease classes can provide significant pathological insights, paving the way for intervention strategies. However, the existing methods in this context either rely on stringent statistical assumptions or suffer from a lack of generalizability. We present a highly powerful method to study differential spatial co-occurrence of cell types across multiple tissue or disease groups, based on the theories of the Poisson point process and functional analysis of variance. Notably, the method accommodates multiple images per subject and addresses the problem of missing tissue regions, commonly encountered due to data-collection complexities. We demonstrate the superior statistical power and robustness of the method in comparison with existing approaches through realistic simulation studies. Furthermore, we apply the method to three real data sets on different diseases collected using different imaging platforms. In particular, one of these data sets reveals novel insights into the spatial characteristics of various types of colorectal adenoma.

SpaceANOVA: Spatial co-occurrence analysis of cell types in multiplex imaging data using point process and functional ANOVA.

Motivation: Multiplex imaging platforms have enabled the identification of the spatial organization of different types of cells in complex tissue or tumor microenvironment (TME). Exploring the potential variations in the spatial co-occurrence or co-localization of different cell types across distinct tissue or disease classes can provide significant pathological insights, paving the way for intervention strategies. However, the existing methods in this context either rely on stringent statistical assumptions or suffer from a lack of generalizability. Results: We present a highly powerful method to study differential spatial co-occurrence of cell types across multiple tissue or disease groups, based on the theories of the Poisson point process (PPP) and functional analysis of variance (FANOVA). Notably, the method accommodates multiple images per subject and addresses the problem of missing tissue regions, commonly encountered in such a context due to the complex nature of the data-collection procedure. We demonstrate the superior statistical power and robustness of the method in comparison to existing approaches through realistic simulation studies. Furthermore, we apply the method to three real datasets on different diseases collected using different imaging platforms. In particular, one of these datasets reveals novel insights into the spatial characteristics of various types of precursor lesions associated with colorectal cancer. Availability: The associated R package can be found here, https://github.com/sealx017/SpaceANOVA.

Maternal perceptions of human milk expression output: An experimental design using photographs of milk.

BACKGROUND: The widespread use of breast pumps in the United States is a recent phenomenon that is reshaping how individuals understand and perceive lactation. In the 1990s, adequacy of milk supply was primarily measured indirectly by infant weight gain and/or diapers; now >95% of all lactating persons in the United States use breast pumps and are seeing their milk regularly. How seeing milk impacts the perception of lactation sufficiency is an important area of research. Research aim/question: To understand personal and intersubjective influences of seeing expressed human milk on perceptions of milk supply among participants who express milk for their infants. METHODS: We surveyed 805 lactating participants from the United States about their pumping practices using an online survey. Participants described pumping practices, milk output, and beliefs. They were then randomized to view one of three photographs of expressed milk (<2 oz, 4 oz, >6oz) and asked to imagine they had just pumped that amount and provide a written response; this created 4 exposure groups (2 increase and 2 decrease) and a control group (no difference). RESULTS: Participants randomized to a higher volume reported more positive feelings and used the terms "good", "great", and "accomplished" to describe emotional responses to output. Participants randomized to lower milk volumes reported more feelings of "bad" or "depressed." A subset of participants reported feeling "annoyed" about small volumes of milk. CONCLUSIONS: Participants in this study were very conscious of the volume of milk pumped each session; both increases and decreases were associated with emotional responses that could contribute to decisions about pumping practices, perceived milk supply, and lactation duration.

Targeting TACC3 represents a novel vulnerability in highly aggressive breast cancers with centrosome amplification.

Centrosome amplification (CA) is a hallmark of cancer that is strongly associated with highly aggressive disease and worse clinical outcome. Clustering extra centrosomes is a major coping mechanism required for faithful mitosis of cancer cells with CA that would otherwise undergo mitotic catastrophe and cell death. However, its underlying molecular mechanisms have not been fully described. Furthermore, little is known about the processes and players triggering aggressiveness of cells with CA beyond mitosis. Here, we identified Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) to be overexpressed in tumors with CA, and its high expression is associated with dramatically worse clinical outcome. We demonstrated, for the first time, that TACC3 forms distinct functional interactomes regulating different processes in mitosis and interphase to ensure proliferation and survival of cancer cells with CA. Mitotic TACC3 interacts with the Kinesin Family Member C1 (KIFC1) to cluster extra centrosomes for mitotic progression, and inhibition of this interaction leads to mitotic cell death via multipolar spindle formation. Interphase TACC3 interacts with the nucleosome remodeling and deacetylase (NuRD) complex (HDAC2 and MBD2) in nucleus to inhibit the expression of key tumor suppressors (e.g., p21, p16 and APAF1) driving G1/S progression, and its inhibition blocks these interactions and causes p53-independent G1 arrest and apoptosis. Notably, inducing CA by p53 loss/mutation increases the expression of TACC3 and KIFC1 via FOXM1 and renders cancer cells highly sensitive to TACC3 inhibition. Targeting TACC3 by guide RNAs or small molecule inhibitors strongly inhibits growth of organoids and breast cancer cell line- and patient-derived xenografts with CA by induction of multipolar spindles, mitotic and G1 arrest. Altogether, our results show that TACC3 is a multifunctional driver of highly aggressive breast tumors with CA and that targeting TACC3 is a promising approach to tackle this disease.

Childhood growth and education migration among ethnic Tibetan children from Nepal.

BACKGROUND: Ethnographic work among high altitude populations has shown that children are highly mobile-the most recent expression of this is the educational migration of children born at high altitude to boarding schools at lower altitudes. The impact of these patterns of migration on size for age are unknown. AIM: We investigated the association between growth in weight and height and educational migration in ethnic Tibetan children living in and out of their natal communities. SUBJECTS AND METHODS: Five hundred and fifty eight children ages three to sixteen from the Nubri Valley, Nepal participated in this study. Three hundred children were living in natal villages and 258 were attending boarding schools in Kathmandu. Height, weight, and skinfold thicknesses were collected and matched to demographic data from the community. RESULTS: There was no association between altitude of family residence and size for age z-scores. Males had lower z-scores than females; z-scores for both groups declined with age. Differences in size for age among children in boarding schools were associated with two factors: sex and type of boarding school (individual sponsor or group funded). Individuals attending individually sponsored schools had greater size for age compared to children in group funded schools or in their natal villages; younger children in collectively funded schools were smaller than village peers. CONCLUSIONS: Despite popular perceptions, educational outmigration in Himalayan communities may not be associated with improved child growth outcomes and investment in community level schools may be a practical solution for improving child growth and physical and mental health.

Post-operative, inpatient rehabilitation after lung transplant evaluation (PIRATE): A feasibility randomized controlled trial.

BACKGROUND: Postoperative rehabilitation is crucial following lung transplantation (LTx); however, it is unclear whether intensive rehabilitation is feasible to deliver in the acute setting. We aimed to establish the feasibility and safety of intensive acute physiotherapy post-LTx. METHODS: This feasibility trial randomized 40 adults following bilateral sequential LTx to either standard (once-daily) or intensive (twice-daily) physiotherapy. Primary outcomes were feasibility (recruitment and delivery of intensive intervention) and safety. Secondary outcomes included six-minute walk test; 60-second sit-to-stand; grip strength; physical activity; pain; EQ-5D-5L; length of stay; and readmissions. Data were collected at baseline, week 3, and week 10 post-LTx. ClinicalTrials.gov #NCT03095859. RESULTS: Of 83 LTx completed during the trial, 49% were eligible and 48% provided consent. Median age was 61 years {range 18-70}; waitlist time 85 days [IQR 35-187]. Median time to first mobilization was 2 days [2-3]. Both groups received a median of 10 [7-14] standard interventions post-randomization. A median of 9 [6-18] individual intensive interventions were attempted (86% successful), the most common barrier being medical procedures/investigations (67%). No intervention-related adverse events or between-group differences in secondary outcomes were observed. CONCLUSIONS: Acute, intensive physiotherapy was feasible and safe post-LTx. This trial provides data to underpin definitive trials to establish efficacy.

Remote working during the COVID-19 pandemic: Computer-related musculoskeletal symptoms in university staff.

BACKGROUND: The COVID-19 pandemic resulted in mandatory remote working for workers in many sectors, including education. OBJECTIVE: This study aimed to investigate the physical characteristics of workspaces, computer use, and prevalence, associated factors, and reported impact of computer-related musculoskeletal symptoms (MSS) among university staff during the COVID-19 pandemic. METHODS: A cross-sectional study of staff in a university in Ireland was conducted in March 2021. An anonymous online survey of computer use, work practices and 3-month prevalence and the reported impact of computer-related MSS (modified Nordic Musculoskeletal Questionnaire) was conducted. Data analysis involved descriptive statistics and relationships were tested using chi-squared analysis. RESULTS: The analysis included 1045 responses. The majority (63%) worked solely from home, used a laptop more frequently than a desktop computer, and worked a greater number of hours. Almost half (48%) did not have a dedicated home workspace. More respondents reported their university workspace (72%) was more comfortable than their home workspace (51.2%) (p < 0.0001). Prevalence of computer-related MSS was 83% : neck (62%), shoulder (57%), lower back (47%). Laptop-related MSS was reported more frequently (82%) than desktop-related MSS (65%) (p < 0.05). Computer-related MSS was associated with workspace, equipment at home, laptop use, female gender, and righthandedness (p < 0.05). A reduction in non-work-related activities (35%), work activities (18%) and seeking medical attention (24%) was reported. CONCLUSION: The prevalence of computer-related MSS was high and associated with remote working. Further studies that aim to mitigate the risks of computer-related MSS in those working remotely or in hybrid models are required.

Utilizing multimodal mass spectrometry imaging for profiling immune cell composition and N-glycosylation across colorectal carcinoma disease progression.

Colorectal cancer (CRC) stands as a leading cause of death worldwide, often arising from specific genetic mutations, progressing from pre-cancerous adenomas to adenocarcinomas. Early detection through regular screening can result in a 90% 5-year survival rate for patients. However, unfortunately, only a fraction of CRC cases are identified at pre-invasive stages, allowing progression to occur silently over 10-15 years. The intricate interplay between the immune system and tumor cells within the tumor microenvironment plays a pivotal role in the progression of CRC. Immune cell clusters can either inhibit or facilitate tumor initiation, growth, and metastasis. To gain a better understanding of this relationship, we conducted N-glycomic profiling using matrix-assisted laser desorption-ionization mass spectrometry imaging (MALDI-MSI). We detected nearly 100 N-glycan species across all samples, revealing a shift in N-glycome profiles from normal to cancerous tissues, marked by a decrease in high mannose N-glycans. Further analysis of precancerous to invasive carcinomas showed an increase in pauci-mannose biantennary, and tetraantennary N-glycans with disease progression. Moreover, a distinct stratification in the N-glycome profile was observed between non-mucinous and mucinous CRC tissues, driven by pauci-mannose, high mannose, and bisecting N-glycans. Notably, we identified immune clusters of CD20+ B cells and CD3/CD44+ T cells distinctive and predictive with signature profiles of bisecting and branched N-glycans. These spatial N-glycan profiles offer potential biomarkers and therapeutic targets throughout the progression of CRC.

Elite female athletes' experiences of symptoms of pelvic floor dysfunction: A systematic review.

INTRODUCTION AND AIMS: Pelvic floor dysfunction (PFD) is a collection of signs, symptoms and conditions affecting the pelvic floor and urinary incontinence (UI) is the most common type of PFD. Recent systematic reviews have indicated a higher prevalence of UI among female athletes compared to their non-athletic counterparts. To date, no review has been undertaken to investigate female athletes' experiences of PFD. This review aims to offer insight and understanding, through aggregation, summary, synthesis and interpretation of findings from studies that report elite female athletes' experiences of symptoms of PFD. METHODS: The review protocol was registered in PROSPERO in August 2020. A systematic search was conducted in Embase, MEDLINE (OVID), Cochrane Library, CINAHL, PsycINFO and Web of Science for studies published in the English language reporting elite female athletes' experiences of symptoms of PFD. This review included primary research studies that involved elite female athletes of any age or ethnicity. RESULTS: Of the 1922 citations retrieved in the search, 32 studies met the methodological criteria for data extraction and analysis. Five main themes emerged: (1) triggers for symptoms of PFD; (2) strategies adopted by athletes to manage/mitigate symptoms of PFD; (3) impact on QOL/daily life; (4) impact on performance; (5) impact on emotions. CONCLUSIONS: The findings of this review suggest a need to further explore the experiences of PFD among elite female athletes and it is suggested that future research should adopt qualitative methods or incorporate a qualitative component.

Child dietary patterns in Homo sapiens evolution: A systematic review.

Dietary patterns spanning millennia could inform contemporary public health nutrition. Children are largely absent from evidence describing diets throughout human evolution, despite prevalent malnutrition today signaling a potential genome-environment divergence. This systematic review aimed to identify dietary patterns of children ages 6 months to 10 years consumed before the widespread adoption of agriculture. Metrics of mention frequency (counts of food types reported) and food groups (globally standardized categories) were applied to: compare diets across subsistence modes [gatherer-hunter-fisher (GHF), early agriculture (EA) groups]; examine diet quality and diversity; and characterize differences by life course phase and environmental context defined using Köppen-Geiger climate zones. The review yielded child diet information from 95 cultural groups (52 from GHF; 43 from EA/mixed subsistence groups). Animal foods (terrestrial and aquatic) were the most frequently mentioned food groups in dietary patterns across subsistence modes, though at higher frequencies in GHF than in EA. A broad range of fruits, vegetables, roots and tubers were more common in GHF, while children from EA groups consumed more cereals than GHF, associated with poor health consequences as reported in some studies. Forty-eight studies compared diets across life course phases: 28 showed differences and 20 demonstrated similarities in child versus adult diets. Climate zone was a driver of food patterns provisioned from local ecosystems. Evidence from Homo sapiens evolution points to the need for nutrient-dense foods with high quality proteins and greater variety within and across food groups. Public health solutions could integrate these findings into food-based dietary guidelines for children.

STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is associated with an incredibly dense stroma, which contributes to its recalcitrance to therapy. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types within the PDAC stroma and have context-dependent regulation of tumor progression in the tumor microenvironment (TME). Therefore, understanding tumor-promoting pathways in CAFs is essential for developing better stromal targeting therapies. Here, we show that disruption of the STAT3 signaling axis via genetic ablation of Stat3 in stromal fibroblasts in a Kras G12D PDAC mouse model not only slows tumor progression and increases survival, but re-shapes the characteristic immune-suppressive TME by decreasing M2 macrophages (F480+CD206+) and increasing CD8+ T cells. Mechanistically, we show that loss of the tumor suppressor PTEN in pancreatic CAFs leads to an increase in STAT3 phosphorylation. In addition, increased STAT3 phosphorylation in pancreatic CAFs promotes secretion of CXCL1. Inhibition of CXCL1 signaling inhibits M2 polarization in vitro. The results provide a potential mechanism by which CAFs promote an immune-suppressive TME and promote tumor progression in a spontaneous model of PDAC.

Repeatability of adaptive traits among ethnic Tibetan highlanders.

OBJECTIVES: Connecting traits to biological pathways and genes relies on stable observations. Researchers typically determine traits once, expecting careful study protocols to yield measurements free of noise. This report examines that expectation with test-retest repeatability analyses for traits used regularly in research on adaptation to high-altitude hypoxia, often in settings without climate control. METHODS: Two hundred ninety-one ethnic Tibetan women residing from 3500 to 4200 m in Upper Mustang District, Nepal, provided three observations of hemoglobin concentration, percent of oxygen saturation of hemoglobin, and pulse by noninvasive pulse oximetry under conditions designed to minimize environmental noise. RESULTS: High-intraclass correlation coefficients and low within-subject coefficients of variation reflected consistent measurements. Percent of oxygen saturation had the highest intraclass correlation coefficient and the smallest within-subject coefficient of variability; measurement noise occurred mainly in the lower values. Hemoglobin concentration and pulse presented slightly higher within-subject coefficients of variation; measurement noise occurred across the range of values. The women had performed the same measurements 7 years earlier using the same devices and protocol. The sample means and SD observed across 7 years differed little. Hemoglobin concentration increased substantially after menopause. CONCLUSIONS: Analyzing repeatability features of traits may improve our interpretation of statistical analyses and detection of variation from measurement or biology. The high levels of measurement repeatability and biological stability support the continued use of these robust traits for investigating human adaptation in this altitude range.

Social Determinants of Health Amplify the Association Between Ethnicity and COVID19: A Retrospective-Cohort study.

BACKGROUND: People in racial and ethnic minority groups have been shown to be at increased risk for a variety of diseases, including COVID-19. However, the role that social needs play in this increased risk has not yet been quantified. Investigating these roles can elicit a greater understanding of how social needs influence the manner in which this disease is contracted and spread. METHODS: A retrospective analysis was conducted of 1,969 Lynn Community Health Center patients. Patients that visited the center between February 1st and July 1st, 2020, tested for COVID-19, and screened for social determinants of health (SDOH) risk factors. Demographics were compared between COVID-19 positive and negative patients. Confounding by age on the association between ethnicity and COVID-19 status was evaluated. A stratified analysis was performed to evaluate the effect modification of SDOH on the relationship between race, ethnicity, and COVID-19 status. RESULTS: Hispanic patients had 2.93 times the odds of a positive COVID-19 test compared to non-Hispanics (95% CI: 2.37 - 3.64, p<0.0001). With at least one SDOH risk factor, Hispanics had 4.71 times the odds of a positive COVID-19 test relative to non-Hispanics (95% CI: 3.10 - 7.14). With no SDOH risk factors, Hispanics had 2.45 times the odds of a positive COVID-19 test relative to non-Hispanics (95% CI: 1.91 - 3.16). No significant associations were found for race. CONCLUSION: Ethnicity had a significant impact on COVID-19 status in our population, where the effect of ethnicity on COVID-19 status was amplified for those with SDOH risk factors.

Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma.

Neoadjuvant PD-1 blockade may be efficacious in some individuals with high-risk, resectable oral cavity head and neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 individuals displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, or JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T cell clones. A high ratio of regulatory T to T helper 17 cells in pretreatment blood predicts low T cell receptor repertoire diversity in pretreatment blood, a low cytolytic T cell signature in pretreatment tumors, and innate resistance. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for individuals with resectable head and neck cancer.

Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon's two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%-53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993).

Centering human milk composition as normal human biological variation.

OBJECTIVES: Human biological variation in the phenotype is the cornerstone of modern human biology, evolutionary anthropology, and related studies of human evolution. Minimal dialogue, however, has considered human milk to be part of this phenotypic variation. This may reflect researcher bias-mental models oriented around commercial infant formula and homogenized cow's milk, both of which present milk composition as static. A general lack of research outside primarily Western, well-nourished populations has also contributed to this underestimation of biological variation. METHODS: This review analyzes published research on breast milk composition, developmental metabolic programming, and maternal body composition to articulate the ways in which population-based studies of human milk outside the United Sates are necessary to better understanding biological variation in human milk phenotypes. RESULTS: This review discusses some of the common issues in current research on the biological variation in human milk composition and argues that anthropological inquiries that frame milk as part of an adaptive phenotype are necessary to better understand the biological significance of human milk composition in the production of human biological variation. CONCLUSIONS: Biological anthropology is uniquely positioned to investigate biological variation in human milk, using evolutionary theory, cutting edge biology, and anthropologically informed perspectives that challenge the biomedical framing of lactation and often act to privilege well nourished, primarily western populations and formula feeding as normatives for infant feeding research.

Navigating cross-cultural research: methodological and ethical considerations.

The intensifying pace of research based on cross-cultural studies in the social sciences necessitates a discussion of the unique challenges of multi-sited research. Given an increasing demand for social scientists to expand their data collection beyond WEIRD (Western, educated, industrialized, rich and democratic) populations, there is an urgent need for transdisciplinary conversations on the logistical, scientific and ethical considerations inherent to this type of scholarship. As a group of social scientists engaged in cross-cultural research in psychology and anthropology, we hope to guide prospective cross-cultural researchers through some of the complex scientific and ethical challenges involved in such work: (a) study site selection, (b) community involvement and (c) culturally appropriate research methods. We aim to shed light on some of the difficult ethical quandaries of this type of research. Our recommendation emphasizes a community-centred approach, in which the desires of the community regarding research approach and methodology, community involvement, results communication and distribution, and data sharing are held in the highest regard by the researchers. We argue that such considerations are central to scientific rigour and the foundation of the study of human behaviour.

Trekking and toddlers: Towards a biocultural analysis of growth among infants and young children in a rural region of the Himalayas.

OBJECTIVES: Rapid socioeconomic change, associated with development and a growing tourism industry is occurring across the Himalayas. The health impact of this rapid economic development is poorly understood, especially for infants and young children. This study investigated the associations between village level economic differences as indexed by economic development and tourism engagement on infant and young child growth and health in a population of ethnic Tibetans living in the western Himalayas of Nepal. METHODS: One hundred and fifty nine infants and young children (ages 1-24 months) were enrolled. Anthropometric data (height, weight, triceps skinfold thickness) were collected at a single time point. Village level measurements of tourism and market engagement were incorporated into a scale measuring tourism, healthcare, trail access, agriculture, and involvement in medicinal trade. Village level disease patterns were calculated from morbidity and mortality recalls collected since 2003. RESULTS: There were no significant associations between infant weight for age z-score (WAZ), length for age z-score (LAZ), or weight-for-length for age z-score (WLZ) and village altitude, village economic development score, or engagement in tourism. Males had significantly higher LAZ, WAZ, and WLZ compared to females; only females showed a decline in LAZ with age. Triceps skinfold thickness z-score (ZTSF) was inversely associated with village level economic development score in male but not female infants; females ZTSF was positively associated with IYC age. CONCLUSIONS: While overall size for age indices (WAZ, LAZ, WLZ) were not associated with altitude or village economic development in this population, ZTSF was inversely associated with village economic development in males but not females.