Corrigendum: miR-31-3p functions as a tumor suppressor by directly targeting GABBR2 in prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2022.945057.].

Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.

Contraceptive Method Use Among a Population-Based Cohort During the South Carolina Choose Well Initiative.

Importance: Evaluating the impact of statewide contraceptive access initiatives is necessary for informing health policy and practice. Objective: To examine changes in contraceptive method use among a cohort of women of reproductive age in South Carolina during the Choose Well contraceptive access initiative. Design, Setting, and Participants: In this cohort study, baseline data from the initial Statewide Survey of Women administered from October 1, 2017, to April 30, 2018, to a probability-based sample of women of reproductive age in South Carolina and a peer state (Alabama) were linked with 3 follow-up surveys given in 2019, 2020, and 2021. Responses about contraception use from the initial survey were compared with responses across follow-up surveys using the regression-based differences-in-differences method. Data analysis was performed from October 2023 to February 2024. Exposure: The South Carolina Choose Well contraceptive access initiative seeks to fill contraceptive access gaps and increase provision of a full range of contraceptive methods through engagement with a wide range of health care organizations across the state. Main Outcomes and Measures: Changes in contraceptive method use, including long-acting reversible contraception (LARC), intrauterine devices (IUDs), implants, short-acting hormonal injection, and barrier or other methods between the baseline survey (2017-2018) and 3 subsequent surveys (2019-2021). Results: A total of 1344 female participants (mean [SD] age, 34 [7] years) completed the first survey (667 in Alabama and 677 in South Carolina). Use of LARC significantly increased in South Carolina (119 [17.6%] to 138 [21.1%]) compared with Alabama (120 [18.0%] to 116 [18.1%]; P = .004). Use of IUDs increased in South Carolina (95 [14.0%] to 114 [17.4%]) compared with Alabama (92 [13.8%] to 102 [15.9%]; P = .003). These associations persisted in the adjusted analysis, with a significant increase in the odds of LARC (adjusted odds ratio, 1.24; 95% CI, 1.06-1.44) and IUD (adjusted odds ratio, 1.19; 95% CI, 1.06-1.32) use at follow-up in South Carolina compared with Alabama. Conclusions and Relevance: In this cohort study of 1344 participants, increases in the use of IUDs in South Carolina were noted after the implementation of the South Carolina Choose Well initiative that were not observed in a peer state with no intervention. Our findings may provide support in favor of statewide contraceptive access initiatives and their role in promoting access to reproductive health services.

Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons.

LAR-RPTPs are evolutionarily conserved presynaptic cell-adhesion molecules that orchestrate multifarious synaptic adhesion pathways. Extensive alternative splicing of LAR-RPTP mRNAs may produce innumerable LAR-RPTP isoforms that act as regulatory "codes" for determining the identity and strength of specific synapse signaling. However, no direct evidence for this hypothesis exists. Here, using targeted RNA sequencing, we detected LAR-RPTP mRNAs in diverse cell types across adult male mouse brain areas. We found pronounced cell-type-specific patterns of two microexons, meA and meB, in Ptprd mRNAs. Moreover, diverse neural circuits targeting the same neuronal populations were dictated by the expression of different Ptprd variants with distinct inclusion patterns of microexons. Furthermore, conditional ablation of Ptprd meA+ variants at presynaptic loci of distinct hippocampal circuits impaired distinct modes of synaptic transmission and objection-location memory. Activity-triggered alterations of the presynaptic Ptprd meA code in subicular neurons mediates NMDA receptor-mediated postsynaptic responses in CA1 neurons and objection-location memory. Our data provide the evidence of cell-type- and/or circuit-specific expression patterns in vivo and physiological functions of LAR-RPTP microexons that are dynamically regulated.

Baf-mediated transcriptional regulation of teashirt is essential for the development of neural progenitor cell lineages.

Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system. Through single-cell RNA sequencing, we demonstrated that Baf knockdown induces prominent transcriptomic changes, particularly in type I neuroblasts. Among the differentially expressed genes, our genetic analyses identified teashirt (tsh), a transcription factor that interacts with beta-catenin, to be closely associated with Baf knockdown-induced phenotypes that were suppressed by the overexpression of tsh or beta-catenin. We also found that Baf and tsh colocalized in a region adjacent to heterochromatin in type I NBs. Notably, the subnuclear localization pattern remained unchanged when one of these two proteins was knocked down, indicating that both proteins contribute to the anchoring of heterochromatin to the inner nuclear membrane. Overall, this study reveals that the Baf-mediated transcriptional regulation of teashirt is a novel molecular mechanism that regulates the development of neural progenitor cell lineages.

Adoption of virtual prenatal visits linked to recurrent virtual or forgone visits for postpartum care.

BACKGROUND: To investigate the association between prenatal and postpartum visits, with a specific focus on the modality of these visits, and to assess whether barriers to virtual visits experienced during the prenatal period are linked to types of postpartum visits. METHODS: The repeated cross-sectional study used the Pregnancy Risk Assessment Monitoring System from 2020 through 2021. Women who had prenatal visits and who also reported their postpartum visits were included (n = 11,258). The outcome was the modality of postpartum visits, and the key independent variable was virtual prenatal visit experience. Multinomial logistic regression analysis was performed to examine the relationship of postpartum visits with virtual prenatal visit experience. RESULTS: Among those who had virtual prenatal visits, about one-third used virtual visits again for postpartum care. Individuals who had virtual prenatal visits showed greater odds of utilizing virtual visits (OR 8.54, 95%CI 7.05-10.35, p=<0.001) or no office visits (OR 1.61, 95%CI 1.25-2.07, p=<0.001) compared to in-person visits during the postpartum period. Women who reported a lack of virtual appointment availability (OR 0.58, 95%CI 0.40-0.86, P = 0.006) or cellular data (OR 0.18, 95%CI 0.05-0.68, p = 0.012) in their prenatal care had lower odds of virtual postpartum visits. CONCLUSIONS: While virtual prenatal visits are linked to greater virtual visits for postpartum care, they are also associated with increased forgone care. The unavailability of virtual appointments and cellular data is a significant barrier to virtual visits. The findings provide practical implications for advancing equitable and sustainable care in a rapidly changing healthcare landscape.

A longitudinal molecular and cellular lung atlas of lethal SARS-CoV-2 infection in K18-hACE2 transgenic mice.

BACKGROUND: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research. METHODS: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue. FINDINGS: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor-ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFß signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes. INTERPRETATION: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFß signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19. FUNDING: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501).

Beyond Being Insured: Insurance Coverage Denial as a Major Barrier to Accessing Care During Pregnancy and Postpartum.

This study investigates the association between insurance coverage denial and delays in care during pregnancy and postpartum. An online survey was administered in March and April 2022 to women who were either pregnant or within 1 year postpartum (n = 1,113). The outcome was delayed care, measured at four time points: during pregnancy and 1 week, 2 to 6 weeks, and after 7 weeks postpartum. The key covariate was insurance coverage denial by providers during pregnancy. Delayed care due to having an unaccepted insurance and being "out-of-network" was more pronounced at 1 week postpartum with 3.37 times and 3.47 times greater odds and in 2 to 6 weeks postpartum with 5.74 times and 2.97 times greater odds, respectively. The association between insurance denial and delays in care encapsulated transportation, rural residency, time issues, and financial constraints. The findings suggest that coverage denial is associated with significant delays in care, providing practical implications for effective perinatal care.

Correlates of and Disparities in Cancellations or Delays of Prenatal Visits During the Covid-19 Pandemic: Emphasis on Racial/Ethnic Minorities and Persons with Low Socioeconomic Status.

OBJECTIVES: To investigate barriers and disparities in prenatal visits across population subgroups. METHODS: This pooled cross-sectional study was conducted using Pregnancy Risk Assessment Monitoring System for 2020 through 2021. Women who reported their experiences of cancellation or delay in prenatal visits were included. A multivariable regression analysis estimated adjusted prevalence ratios (aPR) for cancellations or delays in prenatal care. RESULTS: Of a total of 11,427, one-third had cancelled or delayed care. Hispanics, compared to their white counterparts, were 22% likelier to have cancelled or delayed care. Women covered by Medicaid and those with depression had 17% and 34% greater likelihoods of cancellation or delay, respectively. Cancellations or delays were comparable for the years 2020 and 2021 across reasons, except for facility closures, which were more common in 2020 than in 2021. Hispanics tended to cancel or delay prenatal visits more often than whites for reasons, such as facility closures, COVID-19-related reasons, a lack of transportation, and loss of insurance, while transportation and insurance issues were greater barriers for blacks. Women with less than a high school diploma were more likely to report cancellations or delays due to transportation issues (aPR 2.86, 95%CI 1.47-5.57; p = 0.002) and loss of insurance (aPR 4.82, 95%CI 1.64-14.23; P = 0.004). CONCLUSIONS: While a large proportion of women experienced disruptions in prenatal care, subsets of the population, including racial/ethnic minorities and the low socioeconomically disadvantaged, faced disproportionate challenges. The current findings provide practical implications for a tailored approach to reducing barriers and disparities in prenatal care.

Infectious Spondylitis Caused by Streptococcus gordonii.

Infectious spondylitis is a rare but severe disease of the spine caused by bacteria or other pathogens. Particularly in immunocompromised patients, a definitive source of infection often remains uncertain. Among many pathogens, Streptococcus gordonii, a normal oral flora, is a very rare pathogen in infectious spondylitis. Only a few articles have reported infectious spondylitis caused by Streptococcus gordonii. To the best of our knowledge, there have been no reports of surgically treated infectious spondylitis caused by Streptococcus gordonii. Hence, in the current report, we present the case of a 76-year-old woman with known type 2 diabetes who was transferred to our medical center due to infectious spondylitis caused by Streptococcus gordonii following an L1 compression fracture and underwent an operation for treatment.

Association of Health Insurance with Contraceptive Use and Interpersonal Quality of Contraceptive Care in the Southeast United States.

OBJECTIVES: Health insurance remains an important dimension of contraceptive access. This study investigated the role of insurance in contraceptive use, access, and quality in South Carolina and Alabama. METHODS: The study used a cross-sectional statewide representative survey that assessed reproductive health experiences and contraceptive use among reproductive-age women in South Carolina and Alabama. The primary outcomes were current contraceptive method use, barriers to access (inability to afford wanted method, delay/trouble obtaining wanted method), receipt of any contraceptive care in the past 12 months, and perceived quality of care. The independent variable was insurance type. Generalized linear models were applied to estimate prevalence ratios for each outcome's association with insurance type while adjusting for potentially confounding variables. RESULTS: Nearly 1 in 5 women (17.6%) was uninsured, and 1 in 4 women (25.3%) reported not using a contraceptive method at the time of the survey. Compared with women with private insurance, women with no insurance had a lower likelihood of current method use (adjusted prevalence ratio 0.75; 95% confidence interval 0.60-0.92) and receipt of contraceptive care in the past 12 months (adjusted prevalence ratio 0.61; 95% confidence interval 0.45-0.82). These women also were more likely to experience cost barriers to access care. The insurance type was not significantly associated with the interpersonal quality of contraceptive care. CONCLUSIONS: Findings highlight the need for expanding Medicaid in states that did not do so under the Patient Protection and Affordable Care Act, interventions to increase the number of providers who accept Medicaid patients, and protections to Title X funding as key elements for enhancing contraceptive access and population health outcomes.

Reasons for Not Pursuing Virtual Prenatal Care in 2020 Through 2021 and Policy Implications.

Aim: To investigate patterns of virtual prenatal visits and examine reasons for not pursuing virtual visits for prenatal care. Methods: A pooled cross-sectional study used Pregnancy Risk Assessment Monitoring System from October 2020 through June 2021, a nationally representative surveillance system targeted at women who recently gave live birth. Individuals (n = 11,829) who reported their prenatal care experiences were included. A modified poison regression estimated prevalence ratios for virtual prenatal visits and reasons for not using virtual services. Results: One-third of participants used virtual prenatal care. Hispanics were more likely to use virtual prenatal care than whites. Compared with college graduates, those with high school graduation (Prevalence Ratios [PR] 0.87, 95% confidence interval [CI] 0.76-0.99; p = 0.033) or some college education (PR 0.86, 95% CI 0.77-0.96; p = 0.009) were less likely to use virtual visits. A preference for in-person was the most common reason for not pursuing virtual visits (77.1%), followed by no available virtual appointments (29.5%), technology barriers (6.1%), and no private space (1.7%). Individuals with less than or with high school graduation had 4.16 times (95% CI 2.32-7.46; p ≤ 0.001) and 2.72 times (95% CI 1.67-4.43; p ≤ 0.001) greater technology barriers, and 10.03 times (95% CI 3.42-29.46; p ≤ 0.001) and 4.29 times (95% CI 1.56-11.80; p = 0.005) greater likelihood of lacking private space, respectively, while they had a lesser in-person preference. Conclusions: In a disrupted health care landscape, barriers to accessing virtual prenatal care may have further exacerbated access to care and effective management of pregnancy among those underserved. The findings provide practical implications for safe and effective prenatal care.

Delayed or Forgone Care and Virtual Care in a Public Health Crisis Using Nationally Representative Population Data.

Aim: To investigate factors influencing delayed or forgone care due to the coronavirus pandemic and examine patterns in overall virtual care use and virtual care related to the coronavirus pandemic. Methods: The cross-sectional study used the 2020 National Center for Health Statistics, National Health Interview Survey. Individuals (17,586) who responded to delayed or forgone care questions were included. A generalized linear model estimated prevalence ratios (PRs) for delayed care, forgone care, and virtual care. Results: Approximately 26.5% of participants reported either having delayed (23.6%) or forgone care (15.7%). Females showed 1.29 (95% confidence interval [CI] 1.20-1.38; p ≤ 0.000) and 1.29 (95% CI 1.17-1.48; p ≤ 0.000) times greater risk of delayed and forgone care than males, respectively. Being insured and having chronic conditions were associated with more delayed and forgone care. About 32.5% of adults reported 1 year of virtual care, and of these, 83.6% were related to the coronavirus pandemic. Patterns of virtual care use of 1 year and the one related to the coronavirus pandemic varied. In the coronavirus pandemic-related virtual care, adults of 85 years old or above had a lower likelihood (PR 0.87, 95% CI 0.77-1.00; p = 0.043) of receiving virtual care. Low education attainment and nonmetro areas showed less virtual care usage. Conclusions: The coronavirus pandemic greatly affected health care. While virtual care significantly increased, historically underserved populations, such as older adults, rural residents, and those with low education attainment, experienced disparities in virtual care use. The findings provide important implications for sustained health care in a rapidly changing public health landscape.

Increased Self-Reported Mental Health Problems Among Asian-Americans During the COVID-19 Pandemic in the United States: Evidence from a Nationally Representative Database.

BACKGROUND: To investigate changes in mental health outcomes among racial groups between 2019 and 2020. METHODS: A retrospective cohort study was conducted using the third through fourth quarters of 2019-2020 longitudinal data from the National Health Interview Survey. Self-reports of diagnosed depression and anxiety disorder were key outcomes. We calculated the percentage of depression and anxiety disorder across baseline sample characteristics. Discrete-time hazard models stratified by race/ethnicity were conducted, with hazard ratios (HRs), 95% confidence intervals (CIs), and p-values reported. RESULTS: Of a total 10,415 individuals, 16.3 and 14.1% reported that they were diagnosed with depression and anxiety disorder in 2019, respectively. In the multivariable model, only Asian-Americans experienced a significant increase in the probability of receiving a diagnosis of depression by 104% between 2019 and 2020 (HR 2.04, 95%CI 1.19-3.52; p = 0.010). Also, Asian-Americans had a 97% (HR 1.97, 95%CI 1.23-3.15; p = 0.005) greater probability of being diagnosed with anxiety disorder in 2020 than in the previous year, while Hispanics and Whites had a relatively moderate increase of 40% (HR 1.40, 95%CI 1.01-1.76; p = 0.040) and 11% (HR 1.11, 95%CI 1.03-1.20; p = 0.007), respectively. CONCLUSIONS: Asian-Americans experienced a disproportionate increase in mental health conditions during the COVID-19 pandemic. Discriminatory behaviors against Asian-Americans may be important contributors. The study findings suggest the need for serious actions to address this issue.

Differentiation of Isomeric, Nonseparable Carbohydrates Using Tandem-Trapped Ion Mobility Spectrometry-Mass Spectrometry.

Carbohydrates play important roles in biological processes, but their identification remains a significant analytical problem. While mass spectrometry has increasingly enabled the elucidation of carbohydrates, current approaches are limited in their abilities to differentiate isomeric carbohydrates when these are not separated prior to tandem-mass spectrometry analysis. This analytical challenge takes on increased relevance because of the pervasive presence of isomeric carbohydrates in biological systems. Here, we demonstrate that TIMS2-MS2 workflows enabled by tandem-trapped ion mobility spectrometry-mass spectrometry (tTIMS/MS) provide a general approach to differentiate isomeric, nonseparated carbohydrates. Our analysis shows that (1) cross sections measured by TIMS are sufficiently precise and robust for ion identification; (2) fragment ion cross sections from TIMS2 analysis can be analytically exploited to identify carbohydrate precursors even if the precursor ions are not separated by TIMS; (3) low-abundant fragment ions can be exploited to identify carbohydrate precursors even if the precursor ions are not separated by IMS. (4) MS2 analysis of fragment ions produced by TIMS2 can be used to validate and/or further characterize carbohydrate structures. Taken together, our analysis underlines the opportunities that tandem-ion mobility spectrometry/MS methods offer for the characterization of mixtures of isomeric carbohydrates.

Dissemination or participation? Exploring scientists' definitions and science communication goals in the Netherlands.

The field of science communication has grown considerably over the past decade, and so have the number of scientific writings on what science communication is and how it should be practiced. The multitude of theoretisations and models has led to a lack of clarity in defining science communication, and to a highly popularised-and theorised-rhetorical shift from deficit to dialogue and participation. With this study, we aim to remediate the absence of research into what science communication is, for scientists themselves. We also investigate whether the transition towards dialogue and participation is reflected in the goals scientists identify as important to their science communication efforts, both in a general and a social media context. For this, we analyse survey data collected from scientists in the Netherlands using thematic qualitative analysis and statistical analysis. Our results reveal six main dimensions of science communication as defined by our respondents. The 584 definitions we analyse demonstrate a focus on a one-way process of transmission and translation of scientific results and their impacts towards a lay audience, via mostly traditional media channels, with the goals of making science more accessible, of educating audiences, and of raising awareness about science. In terms of the goals identified as most important by scientists in the Netherlands, we find goals aligned with the deficit and dialogue models of science communication to be the most important. Overall, our findings suggest we should be cautious in the face of recent claims that we live in a new era of dialogue, transparency, and participation in the realm of science communication.

Dynamic landscape of long noncoding RNAs during leaf aging in Arabidopsis.

Leaf senescence, the last stage of leaf development, is essential for whole-plant fitness as it marks the relocation of nutrients from senescing leaves to reproductive or other developing organs. Temporally coordinated physiological and functional changes along leaf aging are fine-tuned by a highly regulated genetic program involving multi-layered regulatory mechanisms. Long noncoding RNAs (lncRNAs) are newly emerging as hidden players in many biological processes; however, their contribution to leaf senescence has been largely unknown. Here, we performed comprehensive analyses of RNA-seq data representing all developmental stages of leaves to determine the genome-wide lncRNA landscape along leaf aging. A total of 771 lncRNAs, including 232 unannotated lncRNAs, were identified. Time-course analysis revealed 446 among 771 developmental age-related lncRNAs (AR-lncRNAs). Intriguingly, the expression of AR-lncRNAs was regulated more dynamically in senescing leaves than in growing leaves, revealing the relevant contribution of these lncRNAs to leaf senescence. Further analyses enabled us to infer the function of lncRNAs, based on their interacting miRNA or mRNA partners. We considered functionally diverse lncRNAs including antisense lncRNAs (which regulate overlapping protein-coding genes), competitive endogenous RNAs (ceRNAs; which regulate paired mRNAs using miRNAs as anchors), and mRNA-interacting lncRNAs (which affect the stability of mRNAs). Furthermore, we experimentally validated the senescence regulatory function of three novel AR-lncRNAs including one antisense lncRNA and two mRNA-interacting lncRNAs through molecular and phenotypic analyses. Our study provides a valuable resource of AR-lncRNAs and potential regulatory networks that link the function of coding mRNA and AR-lncRNAs. Together, our results reveal AR-lncRNAs as important elements in the leaf senescence process.

Adversity in Infancy and Childhood Cognitive Development: Evidence From Four Developing Countries.

Objectives: We investigated whether adverse experiences at age 1 (AE-1) affect the level of and change in cognition during childhood using harmonized data from four developing countries. Methods: Data included children born in 2001/2002 and were followed longitudinally in 2006/2007 and in 2009/2010 by Young Lives study in Ethiopia, India, Peru, and Vietnam. Childhood cognition was measured using the Peabody Picture Vocabulary Test (PPVT) at ages 5 (PPVT-5) and 8 (PPVT-8). We also examined the effect on a change in cognition between age 5-8 (PPVT-Change). The AE-1 scores were constructed using survey responses at age 1. The ordinary least squares regression was used for estimation. Results: We found that children with higher adversities as infants had lower cognition scores at ages 5 and 8. The change in cognition between the two ages was also generally smaller for those with severe adversities at infancy. The negative association between adversities and childhood cognition was strongest for India. Conclusion: The results provide policy relevant information for mitigation of undesirable consequences of early life adversities through timely interventions.

Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy.

BACKGROUND: The substance P-neurokinin 1 receptor pathway has been proposed as a therapeutic target for tendinopathy. However, there is a lack of evidence regarding its practical applications. PURPOSE: To investigate the therapeutic effects of substance P inhibitor (SPI) on inflamed tenocytes in vitro and in a collagenase-induced rat model of tendinopathy in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: We analyzed the mRNA levels of inflammatory (cyclooxygenase [COX]-2 and interleukin [IL]-6) and tenogenic (Mohawk and scleraxis [SCX]) markers using reverse transcription quantitative polymerase chain reaction to demonstrate the effects of SPI on lipopolysaccharide-treated (inflamed) tenocytes. A collagenase-induced rat model of tendinopathy was created by injecting 20 µL of collagenase into the Achilles tendon. A behavior test using an incapacitance apparatus was performed to detect changes in postural equilibrium. The tendon specimens were obtained, and their gross findings were examined. The tensile strength was measured, and histopathological evaluation was performed (hematoxylin and eosin, alcian blue, and immunohistochemical staining). RESULTS: The mRNA levels of COX-2, IL-6, Mohawk, and SCX differed significantly between inflamed tenocytes and those treated with SPI. SPI improved the weight burden in a rat model of tendinopathy in a behavioral test. The specimens of the SPI group showed a normal tendon-like appearance. In the biomechanical test, the tensile strength of the SPI group was significantly greater than that of the tendinopathy group. In the histopathological evaluation, the degree of collagen matrix breakdown was mild in the SPI group. In alcian blue staining, only small focal depositions of proteoglycans and glycosaminoglycans were observed in the SPI group. The SPI group showed decreased expression of IL-6 and neurokinin 1 receptor. CONCLUSION: This study suggests that SPI has therapeutic effects on tendon healing and restoration in a collagenase-induced rat model of tendinopathy. CLINICAL RELEVANCE: SPI is a promising agent for tendinopathy in humans.