Mapping brain function in adults and young children during naturalistic viewing with high-density diffuse optical tomography.

Human studies of early brain development have been limited by extant neuroimaging methods. MRI scanners present logistical challenges for imaging young children, while alternative modalities like functional near-infrared spectroscopy have traditionally been limited by image quality due to sparse sampling. In addition, conventional tasks for brain mapping elicit low task engagement, high head motion, and considerable participant attrition in pediatric populations. As a result, typical and atypical developmental trajectories of processes such as language acquisition remain understudied during sensitive periods over the first years of life. We evaluate high-density diffuse optical tomography (HD-DOT) imaging combined with movie stimuli for high resolution optical neuroimaging in awake children ranging from 1 to 7 years of age. We built an HD-DOT system with design features geared towards enhancing both image quality and child comfort. Furthermore, we characterized a library of animated movie clips as a stimulus set for brain mapping and we optimized associated data analysis pipelines. Together, these tools could map cortical responses to movies and contained features such as speech in both adults and awake young children. This study lays the groundwork for future research to investigate response variability in larger pediatric samples and atypical trajectories of early brain development in clinical populations.

SLIM-Based High-Resolution Ion Mobility Reveals New Structural Insights into Isomeric Vitamin D Metabolites and their Isotopologues.

Testing for vitamin D deficiency remains a high-volume clinical assay, much of which is done using mass spectrometry-based methods to alleviate challenges in selectivity associated with immunoassays. Ion mobility-mass spectrometry (IM-MS) has been proposed as a rapid alternative to traditional LC-MS/MS methods, but understanding the structural ensemble that contributes to the ion mobility behavior of this molecular class is critical. Herein we demonstrate the first application of high-resolution Structures for Lossless Ion Manipulations (SLIM) IM separations of several groups of isomeric vitamin D metabolites. Despite previous IM studies of these molecules, the high resolving power of SLIM (Rp ∼ 200) has revealed additional conformations for several of the compounds. The highly similar collision cross sections (CCS), some differing by as little as 0.7%, precluded adequate characterization with low-resolution IM techniques where, in some cases, wider than expected peak widths and/or subtle shoulders may have hinted at their presence. Importantly, these newly resolved peaks often provided a unique mobility that could be used to separate isomers and provides potential for their use in quantification. Lastly, the contribution of isotopic labeling to arrival time distribution for commonly used 13C- and deuterium-labeled internal standards was explored. Minor shifts of ∼0.2-0.3% were observed, and in some instances these shifts were specific to the conformer being measured (i.e., "closed" vs "open"). Accounting for these shifts is important during raw data extraction to ensure reproducible peak area integration, which will be a critical consideration in future quantitative applications.

Multi-spectral photoacoustic imaging combined with acoustic radiation force impulse imaging for applications in tissue engineering.

Tissue engineering is a dynamic field focusing on the creation of advanced scaffolds for tissue and organ regeneration. These scaffolds are customized to their specific applications and are often designed to be complex, large structures to mimic tissues and organs. This study addresses the critical challenge of effectively characterizing these thick, optically opaque scaffolds that traditional imaging methods fail to fully image due to their optical limitations. We introduce a novel multi-modal imaging approach combining ultrasound, photoacoustic, and acoustic radiation force impulse imaging. This combination leverages its acoustic-based detection to overcome the limitations posed by optical imaging techniques. Ultrasound imaging is employed to monitor the scaffold structure, photoacoustic imaging is employed to monitor cell proliferation, and acoustic radiation force impulse imaging is employed to evaluate the homogeneity of scaffold stiffness. We applied this integrated imaging system to analyze melanoma cell growth within silk fibroin protein scaffolds with varying pore sizes and therefore stiffness over different cell incubation periods. Among various materials, silk fibroin was chosen for its unique combination of features including biocompatibility, tunable mechanical properties, and structural porosity which supports extensive cell proliferation. The results provide a detailed mesoscale view of the scaffolds' internal structure, including cell penetration depth and biomechanical properties. Our findings demonstrate that the developed multimodal imaging technique offers comprehensive insights into the physical and biological dynamics of tissue-engineered scaffolds. As the field of tissue engineering continues to advance, the importance of non-ionizing and non-invasive imaging systems becomes increasingly evident, and by facilitating a deeper understanding and better characterization of scaffold architectures, such imaging systems are pivotal in driving the success of future tissue-engineering solutions.

Imagery-Focused Therapy for Visual Hallucinations: A Case Series.

INTRODUCTION: Visual hallucinations (VH) are more common than previously thought and are linked to higher levels of distress and disability in people with a psychotic illness. Despite this, scant attention has been given to VHs in the clinical literature, and the few therapy case series of cognitive behavioural therapy (CBT) published to date have not demonstrated reliable change. In other areas of clinical research, problematic mental imagery has been found to be more strongly related to negative affect in psychological disorders than negative linguistic thinking, and imagery focused techniques have commonly been found to improve the outcomes in CBT trials. Given VHs have many similarities with visual mental imagery and many of the distressing beliefs associated with VHs targeted in CBT are maintained by accompanying mental imagery (i.e., imaging a hallucinated figure attacking them), it seems plausible that an imagery-focused approach to treating VHs may be most effective. METHODS: The current study is a multiple baseline case series (N = 11) of a 10-session imagery-focused therapy for VH in a transdiagnostic sample. RESULTS: The study had good attendance and feedback, no adverse events and only one [seemly unrelated] drop-out, suggesting good feasibility, safety and acceptability. The majority of clients reported reduction on both full-scale measures (administered at 3 baselines, midtherapy, posttherapy and 3-month follow-up) and weekly measures of VH severity and distress, ranging from medium to large effect sizes. CONCLUSIONS: The case series suggests that an imagery-focused approach to treating VHs may be beneficial, with a recommendation for more rigorous clinical trials to follow.

Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort.

AIMS: To determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. METHODS: Using UK Biobank data, we prospectively examined the relationship between non-invasive fibrosis markers [NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI)] and incident hospitalization/death from heart failure (n=413,860). Cox-regression estimated hazard ratios (HR) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype, and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. RESULTS: 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high risk NFS score HR 1.59 [1.47-1.76], p<0.0001; FIB-4 HR 1.69 [1.55-1.84], p<0.0001; APRI HR 1.85 [1.56-2.19], p<0.0001; combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD) and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3 a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score and heart failure. CONCLUSION: In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

The relationship of trust and dependence.

The concepts of automation trust and dependence have often been viewed as closely related and on occasion, have been conflated in the research community. Yet, trust is a cognitive attitude and dependence is a behavioural measure, so it is unsurprising that different factors can affect the two. Here, we review the literature on the correlation between trust and dependence. On average, this correlation across people was quite low, suggesting that people who are more trusting of automation do not necessarily depend upon it more. Separately, we examined experiments that explicitly manipulated the reliability of automation, finding that higher automation reliability increased trust ratings twice as fast as dependence behaviours. This review provides novel quantitative evidence that the two constructs are not strongly correlated. Implications of this work, including potential moderating variables, contexts where trust is still relevant, and considerations of trust measurement, are discussed.

Trust in automation is a cognitive attitude, and dependence on automation is a physical behaviour. Therefore, it is important to understand the differences between the two, especially as they have been conflated in the literature. This review highlights the small average correlation in the literature between subjective trust and objective dependence, which suggests that measuring trust as dependence (or vice versa) may not be valid. This suggests, then, that practitioners should carefully consider how trust and dependence are being measured in a given context so as not to incorrectly conflate the two.

Secondary production of the central rangeland region of the United States.

Rangelands are the dominant land use across a broad swath of central North America where they span a wide gradient, from <350 to >900 mm, in mean annual precipitation. Substantial efforts have examined temporal and spatial variation in aboveground net primary production (ANPP) to precipitation (PPT) across this gradient. In contrast, net secondary productivity (NSP, e.g., primary consumer production) has not been evaluated analogously. However, livestock production, which is a form of NSP or primary consumer production supported by primary production, is the dominant non-cultivated land use and an integral economic driver in these regions. Here, we used long-term (mean length = 19 years) ANPP and NSP data from six research sites across the Central Great Plains with a history of a conservative stocking to determine resource (i.e., PPT)-productivity relationships, NSP sensitivities to dry-year precipitation, and regional trophic efficiencies (e.g., NSP:ANPP ratio). PPT-ANPP relationships were linear for both temporal (site-based) and spatial (among site) gradients. The spatial PPT-NSP model revealed that PPT mediated a saturating relationship for NSP as sites became more mesic, a finding that contrasts with many plant-based PPT-ANPP relationships. A saturating response to high growing-season precipitation suggests biogeochemical rather than vegetation growth constraints may govern NSP (i.e., large herbivore production). Differential sensitivity in NSP to dry years demonstrated that the primary consumer production response heightened as sites became more xeric. Although sensitivity generally decreased with increasing precipitation as predicted from known PPT-ANPP relationships, evidence suggests that the dominant species' identity and traits influenced secondary production efficiency. Non-native northern mixed-grass prairie was outperformed by native Central Great Plains rangeland in sensitivity to dry years and efficiency in converting ANPP to NSP. A more comprehensive understanding of the mechanisms leading to differences in producer and consumer responses will require multisite experiments to assess biotic and abiotic determinants of multi-trophic level efficiency and sensitivity.

Myxoid Inflammatory Myofibroblastic Sarcoma: Clinicopathologic Analysis of 25 Cases of a Distinctive Sarcoma With Deceptively Bland Morphology and Aggressive Clinical Behavior.

The number of recognized sarcoma types harboring targetable molecular alterations continues to increase. Here we present 25 examples of a distinctive myofibroblastic tumor, provisionally termed "myxoid inflammatory myofibroblastic sarcoma," which might be related to inflammatory myofibroblastic tumor, and which occurred in 13 males (52%) and 12 females at a median age of 37 years (range: 7 to 79 years). Primary tumor sites were peritoneum (18 patients; 72%), paratesticular (2; 8%), chest wall (1), upper extremity (1), esophagus (1), retroperitoneum (1), and uterus (1). Nine peritoneal tumors (50%) were multifocal at presentation; all other tumors were unifocal. Tumors showed bland-to-mildly-atypical neoplastic myofibroblasts in a myxoid stroma, with prominent inflammatory infiltrates in 22 cases (88%). Most tumors showed delicate branching stromal vessels like those of myxoid liposarcoma, and most showed infiltrative growth through non-neoplastic tissue. Immunohistochemistry demonstrated expression of SMA (19/25 tumors; 76%), desmin (13/22; 59%), and CD30 (5/11; 45%), while ALK was expressed in 1 tumor (of 25; 4%) that was negative for ALK rearrangement. Sequencing of 11 tumors showed seven to harbor tyrosine kinase fusions (4 PDGFRB, 2 PML::JAK1, 1 SEC31A::PDGFRA). Two instead harbored hot spot KRAS mutations (G12V and Q61H), and 2 were negative for known driving alterations. Clinical follow-up was available for 18 patients (72%; median: 2.7 years; range: 4 mo-12.3 years). Nine patients (50%) were alive with no evidence of disease, 5 (28%) died of disease, and 4 (22%) were alive with disease. Seven patients (39%) experienced peritoneal relapse or distant metastasis. Two patients showed disease progression on conventional, nontargeted chemotherapy. The patient whose tumor harbored SEC31A::PDGFRA was treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.

Preoperative laboratory measurements as a predictor for nasal steroid irrigations after sinus surgery for chronic rhinosinusitis with nasal polyps.

PURPOSE: To assess whether preoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunoglobulin E (IgE), and blood eosinophil percentage (EOS) can predict need for steroid irrigations after FESS. MATERIALS AND METHODS: Adult patients at BIDMC from inception until September 8, 2023 with chronic rhinosinusitis with nasal polyps who underwent FESS and had preoperative CRP (n = 129), ESR (n = 79), IgE (n = 107), or EOS (n = 125) were included. Labs were divided into normal (CRP: 0-5.0 mg/L; ESR: 0-15 mm/h; IgE: 150-300Ul/mL; EOS: 1-7 %) and high groups (CRP: >5.0 mg/L; ESR: >15 mm/h; IgE: >300Ul/mL; EOS: >7 %). The primary outcome was need for intranasal steroid irrigations after FESS (≤4 weeks, 4-12 weeks, 12-26 weeks, 26-52 weeks, 1-3 years, 3-5 years, and > 5 years). Receiver operating characteristic curves were created to determine thresholds for predicting postoperative steroid irrigations. RESULTS: Elevated IgE required intranasal steroid irrigation at 1-3 years (normal 34 %, high 62 %, p = 0.02), 3-5 years (normal 24 %, high 48 %, p = 0.04), and > 5 years (normal 19 %, high 43 %, p = 0.02). Elevated EOS required intranasal steroid irrigation at 26-52 weeks (normal 7 %, high 25 %, p = 0.009) and > 5 years (normal 19 %, high 46 %, p = 0.005). The area under the curve for IgE at 1-3 years was 0.696 (95 % CI: 0.597-0.795) with cutoff at 144-148 Ul/mL. CRP and ESR were not predictive of postoperative intranasal steroid treatment. CONCLUSIONS: Elevated IgE and EOS (but not CRP or ESR) may predict need for intranasal steroid treatment after FESS.

Behavioral control through the direct, focal silencing of neuronal activity.

The ability to optically stimulate and inhibit neurons has revolutionized neuroscience research. Here, we present a direct, potent, user-friendly chemical approach for optically silencing neurons. We have rendered saxitoxin (STX), a naturally occurring paralytic agent, transiently inert through chemical protection with a previously undisclosed nitrobenzyl-derived photocleavable group. Exposing the caged toxin, STX-bpc, to a brief (5 ms) pulse of light effects rapid release of a potent STX derivative and transient, spatially precise blockade of voltage-gated sodium channels (NaVs). We demonstrate the efficacy of STX-bpc for parametrically manipulating action potentials in mammalian neurons and brain slice. Additionally, we show the effectiveness of this reagent for silencing neural activity by dissecting sensory-evoked swimming in larval zebrafish. Photo-uncaging of STX-bpc is a straightforward method for non-invasive, reversible, spatiotemporally precise neural silencing without the need for genetic access, thus removing barriers for comparative research.

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice increased their responding for liquid protein rewards, but not carbohydrate, fat, or sweet rewards. The protein restriction-induced increase in operant responding for protein was absent in Fgf21 -KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho ( Klb Cam2ka ) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation of dopamine neurons as compared to casein in control-fed mice, while casein produced a larger response in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21 -KO mice. These data demonstrate that FGF21 acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

The mutagenic forces shaping the genomic landscape of lung cancer in never smokers.

Lung cancer in never smokers (LCINS) accounts for up to 25% of all lung cancers and has been associated with exposure to secondhand tobacco smoke and air pollution in observational studies. Here, we evaluate the mutagenic exposures in LCINS by examining deep whole-genome sequencing data from a large international cohort of 871 treatment-naïve LCINS recruited from 28 geographical locations within the Sherlock- Lung study. KRAS mutations were 3.8-fold more common in adenocarcinomas of never smokers from North America and Europe, while a 1.6-fold higher prevalence of EGFR and TP53 mutations was observed in adenocarcinomas from East Asia. Signature SBS40a, with unknown cause, was found in most samples and accounted for the largest proportion of single base substitutions in adenocarcinomas, being enriched in EGFR -mutated cases. Conversely, the aristolochic acid signature SBS22a was almost exclusively observed in patients from Taipei. Even though LCINS exposed to secondhand smoke had an 8.3% higher mutational burden and 5.4% shorter telomeres, passive smoking was not associated with driver mutations in cancer driver genes or the activities of individual mutational signatures. In contrast, patients from regions with high levels of air pollution were more likely to have TP53 mutations while exhibiting shorter telomeres and an increase in most types of somatic mutations, including a 3.9-fold elevation of signature SBS4 (q-value=3.1 × 10 -5 ), previously linked mainly to tobacco smoking, and a 76% increase of clock-like signature SBS5 (q-value=5.0 × 10 -5 ). A positive dose-response effect was observed with air pollution levels, which correlated with both a decrease in telomere length and an elevation in somatic mutations, notably attributed to signatures SBS4 and SBS5. Our results elucidate the diversity of mutational processes shaping the genomic landscape of lung cancer in never smokers.

Hypertension control after intracerebral hemorrhage among varying small vessel disease etiologies.

INTRODUCTION: Intracerebral hemorrhage (ICH) is attributable to cerebral small vessel disease (cSVD), which includes cerebral amyloid angiopathy (CAA) and hypertensive-cSVD (HTN-cSVD). HTN-cSVD includes patients with strictly deep ICH/microbleeds and mixed location ICH/microbleeds, the latter representing a more severe form of HTN-cSVD. We test the hypothesis that more severe forms of HTN-cSVD are related to worse hypertension control in long-term follow-up after ICH. METHODS: From consecutive non-traumatic ICH patients admitted to a tertiary care center, we classified the ICH as CAA, strictly deep ICH/microbleeds, and mixed-location ICH/microbleeds. CSVD burden was quantified using a validated MRI-based score (range: 0-6 points). We created a multivariable (linear mixed effects) model adjusting for age, sex, race, year of inclusion, hypertension, and antihypertensive medication usage to investigate the association of average systolic blood pressure (SBP) during follow-up with cSVD etiology/severity. RESULTS: 796 ICH survivors were followed for a median of 48.8 months (IQR 41.5-60.4). CAA-related ICH survivors (n = 373) displayed a lower median SBP (138 mmHg, IQR 133-142 mmHg) compared to those of strictly deep ICH (n = 222, 141 mmHg, IQR 136-143 mmHg, p = 0.04), and mixed location ICH/microbleeds (n = 201, 142 mmHg, IQR 135-144 mmHg, p = 0.02). In the multivariable analysis, mixed location ICH/microbleeds (effect: + 3.8 mmHg, SE: 1.3 mmHg, p = 0.01) and increasing cSVD severity (+ 1.8 mmHg per score point, SE: 0.8 mmHg, p = 0.03) were associated with higher SBP in follow-up. CONCLUSION: CSVD severity and subtype predicts long-term hypertension control in ICH patients.

Is it time to reduce the length of postgraduate training for physician-scientists in internal medicine?

Physician-scientists play a crucial role in advancing medical knowledge and patient care, yet the long periods of time required to complete training may impede expansion of this workforce. We examined the relationship between postgraduate training and time to receipt of NIH or Veterans Affairs career development awards (CDAs) for physician-scientists in internal medicine. Data from NIH RePORTER were analyzed for internal medicine residency graduates who received specific CDAs (K08, K23, K99, or IK2) in 2022. Additionally, information on degrees and training duration was collected. Internal medicine residency graduates constituted 19% of K awardees and 28% of IK2 awardees. Of MD-PhD internal medicine-trained graduates who received a K award, 92% received a K08 award; of MD-only graduates who received a K award, a majority received a K23 award. The median time from medical school graduation to CDA was 9.6 years for K awardees and 10.2 years for IK2 awardees. The time from medical school graduation to K or IK2 award was shorter for US MD-PhD graduates than US MD-only graduates. We propose that the time from medical school graduation to receipt of CDAs must be shortened to accelerate training and retention of physician-scientists.

Proceedings of the Clinical Microbiology Open 2023: discussions about pandemic preparedness.

The 4th Clinical Microbiology Open (CMO) took place in Carlsbad, California, on 10 and 11 February 2023. This event facilitated discussion between clinical and public health laboratory directors, government agencies, and industry representatives from the companies that make up ASM's Corporate Council. While many topics were discussed, much of the discussion focused on pandemic preparedness. There were four major questions addressed: (i) When is the perfect the enemy of good in pandemic testing? (ii) What other types of pathogens might cause another pandemic and how would this affect laboratory response? (iii) What research is needed to better understand the effectiveness of the pandemic response? (iv) What have we learned about the utility of self and at-home testing in future pandemics? This review serves as a summary of these discussions.

Novel CRTC1::MRTFB(MKL2) Gene Fusion detected in Myxoid Mesenchymal Neoplasms with Myogenic Differentiation involving Bone and Soft Tissue.

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present three cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 2 female and 1 male patient with a median age of 72 (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). While one tumor presented as an incidental finding, the other two tumors were noted given their persistent growth. At the time of last follow-up, one patient was alive with unresected disease at 6 months, one patient was alive without evidence of disease at 12 months after surgery and one patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.

Why religion and spirituality are important in human biological research.

The study of human biology includes exploration of all the genetic and environmental influences on human variation and life history, including impacts of sociocultural and physical environments. Religious practice and spirituality may be one of these influences. There are more than 5.8 billion religiously affiliated adults and children, accounting for 84% of the world's 6.9 billion people. Furthermore, 70% of Americans consider themselves spiritual in some way, including 22% who do not consider themselves religious, and the numbers for Europe are lower but proportionally similar. Such a high rate of religious affiliation and spiritual belief suggests that religion and spirituality could be sociocultural influences on human variation, but human biologists have scarcely attended to their impacts, as indicated by the limited numbers of relevant articles in the two flagship human biology journals. In this article, we discuss why human biologists may have overlooked this important force for human variability and highlight foundational work from human biology and other disciplines that can give our colleagues directions forward. We review the impacts of religion and spirituality at population and individual levels and call for human biologists to attend to the many aspects of religion and spirituality that can impact human biology and are much more than simply influences of denominational affiliation.