Structural Determinants Research Articles

A structural determinant of the behavior of water at hydration and nanoconfinement conditions.

The molecular nature of the phases that conform the two-liquid scenario is elucidated in this work in the light of a molecular principle governing water structuring, which unveils the relevance of the contraction and reorientation of the second molecular shell to allow for the existence of coordination defects in water's hydrogen bond network. In turn, such principle is shown to also determine the behavior of hydration and nanoconfined water while enabling to define conditions for wettability (quantifying hydrophobicity and predicting drying transitions), thus opening the possibility to unravel the active role of water in central fields of research.

Health Disparities Curricula in General Surgery Residency Programs: A Critical Scoping Review

IntroductionIn 2021, the structural determinants of health (SDOH) were added to the Accreditation Council of Graduate Medical Education common program requirements for all accredited residency programs, including general surgery. In this study, we sought to explore the current scope of, and concepts used in, health disparities curricula for general surgery residents, specifically investigating how general surgery residents learn about health disparities and the SDOH. MethodsWe searched PubMed, EMBASE, Education Research Complete (EBSCOhost), and Web of Science Core Collection using keywords related to health disparities and the SDOH. Inclusion criteria consisted of all studies published after 2005 that discussed health disparities curricula for Accreditation Council of Graduate Medical Education–accredited general surgery residency programs. Five thousand three hundred seventeen articles were screened using a two-phase process. Data extraction and analysis was performed using critical review methods. ResultsSeventeen articles were identified. Within these articles, seven unique health disparities curricula were found. All seven of the identified curricula employed cultural frameworks as methods to mitigate health disparities. Three curricula, all published after 2011, included education on the SDOH. A wide variety of educational methods were utilized; in-person didactics was the most common. ConclusionsIn the current literature, culture continues to play a large role in health disparities training for general surgery residents. Though further efforts are needed to understand the methods used in programs that have not published scholarly work, it is imperative to ensure that residents are provided with the sociopolitical perspective needed to understand the SDOH and serve all patients, including those affected by health disparities.

Enhancing the Integration of Race and Health Discussion in Physician Assistant Curriculum.

This article offers a unique perspective on integrating historical and contemporary issues of racism and public health within physician assistant (PA) education, specifically through the lens of personal experience as a public health data analyst during the COVID-19 pandemic. By highlighting the intersection of race, health equity, and education, this article underscores the need for PA programs to incorporate and enhance comprehensive training on the structural determinants of health and the impact of systemic racism on patient care.

Molecular recognition of an odorant by the murine trace amine-associated receptor TAAR7f

There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin, dopamine and histamine. To elucidate the structural determinants of ligand recognition by TAARs, we have determined the cryo-EM structure of a murine receptor, mTAAR7f, coupled to the heterotrimeric G protein Gs and bound to the odorant N,N-dimethylcyclohexylamine (DMCHA) to an overall resolution of 2.9 Å. DMCHA is bound in a hydrophobic orthosteric binding site primarily through van der Waals interactions and a strong charge-charge interaction between the tertiary amine of the ligand and an aspartic acid residue. This site is distinct and non-overlapping with the binding site for the odorant propionate in the odorant receptor OR51E2. The structure, in combination with mutagenesis data and molecular dynamics simulations suggests that the activation of the receptor follows a similar pathway to that of the β-adrenoceptors, with the significant difference that DMCHA interacts directly with one of the main activation microswitch residues, Trp6.48.

Nonpharmacological treatment for older adults with mild cognitive impairment: Considerations for culturally informed clinical practice and research.

Numerous nonpharmacological treatments (NPTs) have been developed for older adults with mild cognitive impairment (MCI). Two forms of cognition-focused NPTs, cognitive rehabilitation (CR) and cognitive training (CT), demonstrate cognitive benefit, but limitations remain regarding the contribution of cultural and demographic factors to study outcome heterogeneity, generalizability to diverse populations, and feasibility. This article aimed to review demographic and culturally informed NPTs and provides recommendations for culturally informed clinical practice and research. We conducted a PubMed review to identify CR and CT interventions that incorporated cultural adaptations. Results from the review, combined with the authors' clinical expertise, were used to identify methodological, demographic, social, cultural, and systemic variables relevant to NPTs. Existing CR and CT studies that included cultural adaptations adopted modifications to language, measures (cognition, function), and lifestyle factors (diet, physical activity) among others. In addition, provider, patient, and group-level factors were then raised to promote inclusivity and increase NPT generalizability. Nevertheless, there is a paucity of research considering cultural and demographic factors when delivering cognition-focused NPTs. Recommendations were generated that incorporated current literature as well as the authors' clinical and research experiences. Culturally informed NPTs are understudied. Social, demographic, and cultural factors may contribute to the heterogeneity of outcomes, lack of generalizability of findings to diverse groups, and application of intervention to said groups. Several tools are available and can focus on broadening collection of information regarding patients' identities, social network, adapting to literacy level and linguistic diversity needs, and responding to social and structural determinants of health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Exploring the role of the residues into catalytic cavity of inulosucrase from Leuconostoc citreum CW28

Inulosucrases are enzymes capable of synthesizing inulin polymers using sucrose as the main substrate. The enzymatic activity relies on the catalytic triad within the active site and residues responsible for substrate recognition and orientation, termed carbohydrate-binding subsites. This study investigates the role of specific residues within the catalytic cavity of a truncated version of IslA4 in enzymatic catalysis. Mutants at residues S425, L499, A602, R618, F619, Y676, Y692, and R696 were constructed and characterized. Characterization results, and in silico structural comparison with other fructansucrases, reveal these residues' functional significance in catalysis. Residue S425 belongs to subsite −1; residues R618 and Y692 are part of subsite +1, and residue R696 belongs to subsites +1 and +2. Residues L499 and A602 are support residues; the former favors the formation of the fructosyl-enzyme intermediate, while the latter stabilizes the acid/base catalyst during catalysis. Residues Y676 and F619 may participate in stabilizing residues at −1/+1 subsites. This study represents the first comprehensive exploration of the structural determinants essential for enzymatic function in the inulosucrase of Leuconostoc citreum, and proposes the identity of residues involved in the −1 to +2 subsites.

Structural Barriers to Primary Care Among Sex Workers: Findings from a Community- Based Cohort in Vancouver, Canada (2014-2021).

Due to structural marginalization, sex workers experience health inequities including a high prevalence of sexually transmitted and blood-borne infections, mental health disorders, trauma, and substance use, alongside a multitude of barriers to HIV and substance use services. Given limited evidence on sex workers' broader primary healthcare access, we aimed to examine structural factors associated with primary care access among sex workers over a 7-year period. Data were derived from An Evaluation of Sex Workers Health Access (AESHA), a community-based open prospective cohort of women (cis and trans) sex workers in Metro Vancouver, from 2014 to 2021. Descriptive statistics were used to summarize the proportion of primary care use in the past six months and to assess primary care trends over time from 2014-2021. We used multivariate logistic regression with generalized estimating equations (GEE) to identify structural factors associated with primary care access (seeing a family doctor in the last six months), after adjusting for confounders. Amongst 646 participants, most (87.4%) accessed primary care at some point during the study period, and primary care use in the in the last 6 months was relatively stable (ranging from 60-78%) across each follow-up period. At first available observation, participants faced a high burden of sexually transmitted and blood-borne infections (STBBIs) (48.0%, 11.5%, and 10.4% were HCV, HIV, or STI seropositive, respectively), 56.8% were diagnosed with a mental health disorder, 8.1% had recently overdosed, and 14.7% were recently hospitalized. In multivariable GEE analysis, exposure to intimate partner violence was associated with reduced access to primary care (Adjusted odds ratios (AOR) 0.63, 95% Confidence interval (CI): 0.49 - 0.82), and limited English fluency was marginally associated (AOR 0.76 CI: 0.51 - 1.14). This study characterized primary care access and its structural determinants among sex workers over 7-years. Participants faced a high burden of STBBIs and other health disparities, and a proportion faced gaps in primary care access. Scale-up of trauma-informed, culturally and linguistically tailored, sex worker-friendly primary care models are needed, alongside structural interventions to decriminalize and destigmatize sex work and substance use.

The Study of Environmental Exposure of Mothers and Infants Impacted by Large-Scale Agriculture (SEMILLA): Description of the Aims and Methods of a Community-Based Birth Cohort Study.

Women of childbearing age not only reside in agricultural communities but also form an integral part of the agricultural labor force. Limited research investigates the impact of prenatal fungicide exposure on infant health, specifically ethylenebisdithiocarbamates and their toxic by-product, ethylenethiourea (ETU), particularly in occupational settings. This paper describes the background, aims, protocol, and baseline sample characteristics for the SEMILLA study, which investigates prenatal ETU exposure, neonatal thyroid function, infant growth, and neurobehavioral development in an agricultural region of Ecuador. This cohort study follows pregnant women and their infants up to 18 months of age, incorporating urinary biomarkers and survey data on ETU exposure and infant growth and neurodevelopmental measures. Data collection includes detailed questionnaires, scales, and physical examinations on maternal and infant health and development, as well as environmental factors. Descriptive statistics on key characteristics of the study population at baseline are presented. SEMILLA enrolled 409 participants (72% enrollment rate): 111 agricultural workers (mostly floricultural), 149 non-agricultural workers, and 149 non-workers. Baseline characteristics show comparability between work sector groups, with some economic differences. SEMILLA will provide key evidence on prenatal fungicide exposure and infant development and encompass comprehensive multistage data collection procedures in pregnancy and infancy, focusing on structural and social determinants of health as well as individual-level chemical exposures. The community-based approach has proven essential, even amid challenges like the COVID-19 pandemic. The medium-term objective is to inform sustainable interventions promoting maternal and child health, with a long-term goal to reduce community exposures and improve worker health policies, particularly for women and pregnant workers.

Why Do Chinese and Indian Positions on Climate Differ? Labor Surplus Absorption as a Key Factor

During international negotiations for the Rio Earth Summit of 1992, coalitions made up of countries from the Global South took shape, only to break up gradually over time. The climate positions of two leading emerging powers, the People’s Republic of China and India, have increasingly drifted apart from each other since 2010. This paper seeks to account for this drift by relying on structural factors. The analytical framework proposed here relies on three structural determinants of development: factor endowments, sector specialization, and labor surplus absorption potential. These determinants are complemented by a carbon variable to account for sustainability. This framework reveals a triangle of incompatibility between development, labor surplus absorption, and sustainability that highlights how the People’s Republic of China now has sufficient leeway to engage in more ambitious sustainable policies, while India still faces the mutual incompatibility of either pushing forward with economic development or committing to a sustainable agenda.

Addressing Racial Disparities in the Hypertensive Disorders in Pregnancy: A Plan for Action from the Preeclampsia Foundation's Racial Disparities Task Force.

Hypertensive disorders of pregnancy (HDP) are among the leading causes of maternal mortality in the United States, with Black women and birthing people disproportionately having higher HDP-related deaths and morbidity. In 2020, the Preeclampsia Foundation formed a national Racial Disparities Task Force (RDTF) to identify key recommendations to address issues of racial disparities related to HDP. Recommendations are centered around the Foundation's three pillars: Community, Healthcare Practice, and Research. Healthcare practices include adequate treatment of chronic hypertension in Black women and birthing people, re-branding low-dose aspirin to prenatal aspirin to facilitate uptake, and innovative models of care that especially focus on postpartum follow-up. A research agenda that examines the influence of social and structural determinants of health (ssDOH) on HDP care, access, and outcomes is essential to addressing disparities. One specific area that requires attention is the development of metrics to evaluate the quality of obstetrical care as it relates to racial disparities in Black women and birthing people with HDP. The recommendations generated by the Preeclampsia Foundation's RDTF highlight the strategic priorities and are a call to action that requires listening to the voices and experiences of Black women and birthing people, engaging their communities, and multi-sectoral collaboration to improve healthcare practices and drive needed research.

Anti-enterovirus 71 activity of native fucosylated chondroitin sulfates and their derivatives

Enterovirus 71 (EV71) is recognized as a major causative agent of hand, foot, and mouth disease (HFMD), posing a significant global public health concern due to its widespread impact and resulting in a major public health issue worldwide. Despite its prevalence, current clinical therapy lacks effective antiviral agents. Fucosylated chondroitin sulfates (FCS) derived from sea cucumber exhibits a range of biological activities including potent antiviral effects. This study provides compelling evidence of the potent antiviral efficacy of FCS against EV71. To further elucidate the impact of structural variations on the anti-EV71 activity, native FCSs with diverse sulfation patterns and a varity of FCS derivatives were prepared and analyzed. Notably, this study presents the detailed structural characterization of FCSs from the sea cucumbers Holothuria scabra Jaege and Holothuria fuscopunctata. Analysis of the structure-activity relationships revealed that molecular weight, sulfated fucose branches, and sulfation pattern were all crucial factors contributing to the potent inhibitory effects of FCS against EV71. Interestingly, molecular weight emerged as the most significant structural determinant of the antiviral potency. These findings suggest the promising potential of utilizing FCS as an innovative EV71 entry inhibitor for the treatment of HFMD.

Structural and functional analysis of plant ELO-like elongase for fatty acid elongation.

ELO-like elongase is a condensing enzyme elongating long chain fatty acids in eukaryotes. Eranthis hyemalis ELO-like elongase (EhELO1) is the first higher plant ELO-type elongase that is highly active in elongating a wide range of polyunsaturated fatty acids (PUFAs) and some monounsaturated fatty acids (MUFAs). This study attempted using domain swapping and site-directed mutagenesis of EhELO1 and EhELO2, a close homologue of EhELO1 but with no apparent elongase activity, to elucidate the structural determinants critical for catalytic activity and substrate specificity. Domain swapping analysis of the two showed that subdomain B in the C-terminal half of EhELO1 is essential for MUFA elongation while subdomain C in the C-terminal half of EhELO1 is essential for both PUFA and MUFA elongations, implying these regions are critical in defining the architecture of the substrate tunnel for substrate specificity. Site-directed mutagenesis showed that the glycine at position 220 in the subdomain C plays a key role in differentiating the function of the two elongases. In addition, valine at 161 and cysteine at 165 in subdomain A also play critical roles in defining the architecture of the deep substrate tunnel, thereby contributing significantly to the acceptance of, and interaction with primer substrates.

General High School or Vocational High School: School Choice for Students Near the High School Entrance Examination Score Line

The study focuses on exploring the Chinese students’ school choice decisions. In particular, it explores why some students prefer vocational schools over general high schools, even when eligible for the latter. The research also examines how pupils make sense of these dual purposes at the time of choosing. According to this study’s results which were based on in-depth interviews with eight vocational school students, most of them chose these schools because they considered the courses offered there as more important than attending prestigious general high schools. Students choose their schools according to personal feelings and understandings about educational equality and achievement in society. Students' choices reflect their subjective experiences and individual interpretations of social signals regarding educational equity and success. The findings emphasized psychological and structural determinants in selecting schools so as to foster equal learning opportunities among all children regardless of their backgrounds. This study contributes to the understanding of how students navigate the complex landscape of educational options, and how their choices are influenced by broader societal forces.

Determinants of Capital Structure: A Case of Nepalese Non-Financial Firms

This study examines the determinants of capital structure in the context of Nepalese non-financial firms. Short term debt ratio and long term debt ratio are selected as the dependent variables. The selected independent variables are assets tangibility, liquidity, non-debt tax shields, firm size, profitability, Tobin’s q and firm’s age. The study is based on secondary data with 105 observations from 7 hydro power firms, 3 hotel industries and 4 manufacturing firms listed in Nepal Stock Exchange (NEPSE). The data were collected from annual reports of the selected non-financial firms. The correlation coefficients and regression models are estimated to test the significance and importance of determinants of capital structure in the context of Nepalese non-financial firms. The study showed that assets tangibility has a positive impact on long-term debt ratio and short-term debt ratio. It indicates that higher the assets tangibility, higher would be the long-term debt ratio and short-term debt ratio. Similarly, liquidity has a positive impact on long-term debt ratio and short-term debt ratio. It indicates that increase in liquidity leads to increase in long-term debt ratio and short-term debt ratio. Likewise, non-debt tax shields has a positive impact on long-term debt ratio and short-term debt ratio. It indicates that increase in non-debt tax shields leads to increase in long-term debt ratio and short-term debt ratio. Further, firm size has a positive impact on long-term debt ratio and short-term debt ratio. It indicates that increase in firm size leads to increase in long-term debt ratio and short-term debt ratio. In addition, profitability has a positive impact on long-term debt ratio and short-term debt ratio. It indicates that increase in profitability leads to increase in long-term debt ratio and short-term debt ratio. Likewise, Tobin’s q has a positive impact on long-term debt ratio and short-term debt ratio. It indicates that higher the Tobin’s q, higher would be the long-term debt ratio and short-term debt ratio. Moreover, firm’s age has a negative impact on long-term debt ratio and short-term debt ratio. It indicates that higher the firm’s age, higher would be the long-term debt ratio and short-term debt ratio.

Introducing the “Nursing Education Integrating Social Change for Health Equity (NISCHE)” framework for nursing education

BackgroundA need exists for a unified curriculum framework for nurse educators, recognizing racism as a central driver of health inequities. PurposeThis paper provides nurse educators with a unifying curriculum framework that centers racism as a root cause of health inequity shaping SSDH. MethodsA critical examination of the social and structural determinants of health (SSDH) and Yob’s (2018) Framework for a Curriculum in Social Change was conducted, to develop a curriculum framework tailored to the intersection of SSDH and social change within nursing education. DiscussionThe “Nursing Education Integrating Social Change for Health Equity (NISCHE)” framework was developed as a comprehensive curriculum framework for SSDH and social change specifically tailored for nursing education. Practical examples of curricular activities across various settings are offered, thus illustrating implementation and potential impact. ConclusionBy centering racism in the curriculum framework and emphasizing its role in perpetuating health inequities, this paper advances a crucial agenda in nursing education.

Structural determinants of spike infectivity in bat SARS-like coronaviruses RsSHC014 and WIV1.

The bat SARS-like CoVs RsSHC014 and WIV1 can use hACE2 for cell entry without further adaptation, indicating their potential risk of emergence in human populations. The S glycoprotein, responsible for receptor recognition and membrane fusion, plays a crucial role in cross-species transmission and infection. In this study, we determined the cryo-EM structures of the S glycoproteins of RsSHC014 and WIV1. Detailed comparisons revealed dynamic structural variations within spike proteins. We also elucidated the complex structure of WIV1 S-hACE2, providing structural evidence for the potential emergence of WIV1 in humans. Although RsSHC014 and WIV1 had similar hACE2-binding affinities, they exhibited distinct pseudovirus cell entry behavior. Through mutagenesis and cryo-EM analysis, we revealed that besides the structural variations, the 623 site in the SD2 region is another important structural determinant of spike infectivity.

Claudin-4 polymerizes after a small extracellular claudin-3-like substitution

Tight junctions play a pivotal role in the functional integrity of the human body by forming barriers that compartmentalize tissues and protect the body from external threats. Essential components of tight junctions are the transmembrane claudin proteins, which can polymerize into tight junction strands and meshworks. This study delves into the structural determinants of claudin polymerization, utilizing the close homology yet strong difference in polymerization capacity between claudin-3 and claudin-4. Through a combination of sequence alignment and structural modeling, critical residues in the second extracellular segment are pinpointed. Molecular dynamics simulations provide insights into the interactions of and the conformational changes induced by the identified extracellular segment 2 residues. Live-STED imaging demonstrates that introduction of these residues from claudin-3 into claudin-4 significantly enhances polymerization in non-epithelial cells. In tight junction-deficient epithelial cells, mutated claudin-4 not only influences tight junction morphology but also partially restores barrier function. Understanding the structural basis of claudin polymerization is crucial, as it offers insights into the dynamic nature of tight junctions. This knowledge could be applied to targeted therapeutic interventions, offering insight to repair or prevent barrier defects associated with pathological conditions, or introduce temporary barrier openings during drug delivery.

Alzheimer's disease risk gene CD2AP is a dose-sensitive determinant of synaptic structure and plasticity.

CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity. Moreover, in mice harboring either one or two copies of a germline Cd2ap null allele, we noted increased paired-pulse facilitation at hippocampal Schaffer-collateral synapses, consistent with a haploinsufficient requirement for pre-synaptic release. Whereas conditional Cd2ap knockout in the brain revealed no gross behavioral deficits in either 3.5- or 12-month-old mice, Cd2ap heterozygous mice demonstrated subtle impairments in discrimination learning using a touchscreen task. Based on unbiased proteomics, partial or complete loss of Cd2ap triggered perturbation of proteins with roles in protein folding, lipid metabolism, proteostasis, and synaptic function. Overall, our results reveal conserved, dose-sensitive requirements for CD2AP in the maintenance of neuronal structure and function, including synaptic homeostasis and plasticity, and inform our understanding of possible cell-type specific mechanisms in Alzheimer's Disease.

Effect of precursor amino acids for carnosine synthesis on breast fiber microstructures and myofiber differentiation-related gene expression in slow-growing chicken.

: The effects of carnosine synthesis on the structural and microstructural determinants of meat quality have not been studied to date. Therefore, this study aimed to investigate the effect of supplementation with carnosine synthesis precursors on the characteristics and microstructure of breast muscle fibers in slow-growing Korat chickens (KR). : Slow-growing KR were fed a non-supplemented commercial diet (control group) or a commercial diet supplemented with 1.0% β-alanine, 0.5% L-histidine, or a combination of both 1.0% β-alanine and 0.5% L-histidine. At 10 weeks, KR were slaughtered, and the breast muscle was collected. Samples were fixed and extracted to study the microstructure, fat level, and porosity of the meat using X-ray and scanning electron microscopy, and real-time polymerase chain reaction was performed to analyze the expression of genes related to myofiber differentiation. : L-histidine supplementation significantly altered myofiber diameter and muscle fiber density and compactness by regulating muscle fiber-type differentiation via carnosine synthase (CARNS1) and myocyte enhancer factor 2C (MEF2C) expression, as well as myogenic differentiation antigen (MyoD) and myogenic regulatory factor 5 (Myf5) expression. While excess L-histidine potentially stimulated CARNS1 to modify muscle fiber arrangement and tenderness in breast meat, dietary β-alanine supplementation alone or in combination with L-histidine supplementation induced a relatively less remarkable but not significant (p<0.05) effect on the breast meat characteristics studied. : Interestingly, the combination of β-alanine and L-histidine supplementation had no effect on meat microstructure, meat porosity, and fat content in comparison with the control group. Thus, this combination had the best selectivity for improving meat quality. However, further studies are required to clarify the effects of carnosine levels on meat processing.

The microfoundations of strategy: empirical explorations under conditions of environmental uncertainty

PurposeStrategy scholars have argued that microlevel behavioral decisions by firms play a disproportionate role in making a firm nimble. Central to this issue is the interplay among several factors, such as actions by individual actors, firm-level decisions and broader changes in the economic environment that lead to a firm being successful in a competitive environment. The purpose of this paper is to offer a theoretical exploration of microfoundations research and subject the idea to empirical analysis using the constructs of customer orientation, competitor orientation and technology orientation as microfoundations of strategy.Design/methodology/approachData collected through a key informant survey of executives were tested through a hierarchical regression analysis.FindingsThe results of the study suggest that the microfoundations of strategy are located more in a firm’s customer and competitor focus, rather than a technological orientation. The findings also suggest that that customer orientation is a significant component of firm-level strategy and needs to be incorporated into decision-making in firms.Originality/valueThis study provides a framework that integrates the structural determinants of firm performance with microfoundations theory to refine our understanding of market knowledge capability.