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Inner dynein arms (IDAs) are formed from a protein complex that is essential for appropriate flagellar bending and beating. IDA defects have previously been linked to the incidence of asthenozoospermia (AZS) and male infertility. The testes-enriched ZMYND12 protein is homologous with an IDA component identified in Chlamydomonas. ZMYND12 deficiency has previously been tied to infertility in males, yet the underlying mechanism remains uncertain. Here, a CRISPR/Cas9 approach was employed to generate Zmynd12 knockout (Zmynd12-/-) mice. These Zmynd12-/- mice exhibited significant male subfertility, reduced sperm motile velocity, and impaired capacitation. Through a combination of co-immunoprecipitation and mass spectrometry, ZMYND12 was found to interact with TTC29 and PRKACA. Decreases in the levels of PRKACA were evident in the sperm of these Zmynd12-/- mice, suggesting that this change may account for the observed drop in male fertility. Moreover, in a cohort of patients with AZS, one patient carrying a ZMYND12 variant was identified, expanding the known AZS-related variant spectrum. Together, these findings demonstrate that ZMYND12 is essential for flagellar beating, capacitation, and male fertility.
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Infertilidad Masculina , Ratones Noqueados , Motilidad Espermática , Animales , Humanos , Masculino , Ratones , Astenozoospermia/genética , Astenozoospermia/metabolismo , Astenozoospermia/patología , Sistemas CRISPR-Cas , Dineínas/metabolismo , Dineínas/genética , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Infertilidad Masculina/patología , Ratones Endogámicos C57BL , Capacitación Espermática/genética , Motilidad Espermática/genética , Espermatozoides/metabolismo , Contactina 2/genética , Contactina 2/metabolismoRESUMEN
Plants shed organs such as leaves, petals, or fruits through the process of abscission. Monitoring cues such as age, resource availability, and biotic and abiotic stresses allow plants to abscise organs in a timely manner. How these signals are integrated into the molecular pathways that drive abscission is largely unknown. The INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) gene is one of the main drivers of floral organ abscission in Arabidopsis and is known to transcriptionally respond to most abscission-regulating cues. By interrogating the IDA promoter in silico and in vitro, we identified transcription factors that could potentially modulate IDA expression. We probed the importance of ERF- and WRKY-binding sites for IDA expression during floral organ abscission, with WRKYs being of special relevance to mediate IDA up-regulation in response to biotic stress in tissues destined for separation. We further characterized WRKY57 as a positive regulator of IDA and IDA-like gene expression in abscission zones. Our findings highlight the promise of promoter element-targeted approaches to modulate the responsiveness of the IDA signaling pathway to harness controlled abscission timing for improved crop productivity.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Flores/metabolismo , Regiones Promotoras Genéticas/genética , Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Statistical regression models are used for predicting outcomes based on the values of some predictor variables or for describing the association of an outcome with predictors. With a data set at hand, a regression model can be easily fit with standard software packages. This bears the risk that data analysts may rush to perform sophisticated analyses without sufficient knowledge of basic properties, associations in and errors of their data, leading to wrong interpretation and presentation of the modeling results that lacks clarity. Ignorance about special features of the data such as redundancies or particular distributions may even invalidate the chosen analysis strategy. Initial data analysis (IDA) is prerequisite to regression analyses as it provides knowledge about the data needed to confirm the appropriateness of or to refine a chosen model building strategy, to interpret the modeling results correctly, and to guide the presentation of modeling results. In order to facilitate reproducibility, IDA needs to be preplanned, an IDA plan should be included in the general statistical analysis plan of a research project, and results should be well documented. Biased statistical inference of the final regression model can be minimized if IDA abstains from evaluating associations of outcome and predictors, a key principle of IDA. We give advice on which aspects to consider in an IDA plan for data screening in the context of regression modeling to supplement the statistical analysis plan. We illustrate this IDA plan for data screening in an example of a typical diagnostic modeling project and give recommendations for data visualizations.
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Modelos Estadísticos , Humanos , Análisis de Regresión , Interpretación Estadística de Datos , Análisis Multivariante , Reproducibilidad de los Resultados , Programas Informáticos , Análisis de DatosRESUMEN
BACKGROUND: Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA. METHODS: In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0 g/dL; and serum ferritin < 50 ng/mL [CKD]; < 12 ng/mL [non-CKD]) were randomized 1:1 to FC-low (500 mg: approximately 120 mg elemental iron/day) or FC-high (1000 mg: approximately 240 mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued. RESULTS: Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were -58.00 RU/mL in CKD and -725.00 RU/mL in non-CKD; in FC-high group, the median changes were -66.00 RU/mL in CKD and -649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 104/µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD). CONCLUSION: Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA. CLINICAL TRIAL REGISTRATION NUMBER: jRCT2080223943.
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Anemia Ferropénica , Compuestos Férricos , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Insuficiencia Renal Crónica , Humanos , Factores de Crecimiento de Fibroblastos/sangre , Compuestos Férricos/uso terapéutico , Compuestos Férricos/administración & dosificación , Masculino , Femenino , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/sangre , Persona de Mediana Edad , Anciano , Recuento de Plaquetas , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Ferritinas/sangre , Hematínicos/uso terapéutico , Resultado del Tratamiento , AdultoRESUMEN
Ida B. Wells (1862-1931) led an extraordinary life as a journalist, educator, and activist while navigating the intersecting social realities of race, gender, and class. She embodied courage, advocating for the civil rights of Black Americans in an uncompromising fashion.Building on decades of research in social psychology, sociologist Cecilia L. Ridgeway presents (2019) a cultural schema theory of status. She contends that issues of status in interpersonal contexts are an unavoidable aspect of the human condition. Despite the ubiquity of status as a sociocultural force, Ridgeway believes that status hierarchies may be undermined.The present study is a psychobiographical exploration of Wells through the lens of Ridgeway's status theory. It explores: the development of Wells' cultural schemas; how Wells navigated her own status; the inter-relationship between Wells and her sociocultural context; and how Wells undermined and overcame status hierarchies.
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OBJECTIVE: To explore the clinical use of 'My Hearing Explained for Children' (MHEfC) with children aged 8-11 years, from the perspectives of the child, parents and audiologist. DESIGN: A mixed methods randomised control trial. Participants completed evaluation questionnaires after their appointment. Statistical and thematic analyses were used to examine the rating scale and open response elements of the questionnaires respectively. STUDY SAMPLE: 45 families participated, 24 randomised to MHEfC and 21 to standard care. RESULTS: Use of MHEfC increased the appointment duration by 8.2 minutes (95% CI 4.1 to 14.2 minutes), which was acceptable to parents (96%) and audiologists (67%). It promoted conversation around 'behavioural and communication tactics', 'specific listening situations' and 'listening effort' at the expense of 'anatomy/physiology/aetiology'. MHEfC positively impacted the discussion of test results (54%); ease of finding joint solutions to problems (71%); and the nature of issues and management options discussed (54%). Parental satisfaction with discussion was high on both pathways, so some parents and audiologists questioned MHEfC necessity and recommended targeted use in future. CONCLUSIONS: MHEfC was acceptable to children (70%) and parents (86%). It successfully promoted child-centred topics of discussion and can positively impact discussion outcomes.
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OBJECTIVE: Explore the impact of Ida's "My Hearing Explained" (MHE) tool on audiologists' language and patients' understanding/interpretation of hearing test results. DESIGN: Audiologists were video-recorded in two sequential conditions: 1) giving standard audiogram explanations to 13 patients and, 2) following discretionary self-training, giving explanations using the MHE tool (nine patients). Outcomes of interest were audiologists' language complexity, use of jargon, and audiologist-patient interactivity. Semi-structured patient interviews, conducted 1-7 days after appointments, were analysed using inductive qualitative content analysis. Patient recall was verified. STUDY SAMPLE: Four audiologists from one United Kingdom audiology service, and 22 patients (mean age 63.5 yrs) participated. RESULTS: In comparison to standard audiogram explanations, audiologists' language was simpler and audiologist-patient interactivity greater with the MHE tool. Interview data analysis revealed differences between explanation types within the themes of "Understanding" and "Interpretation." 54% (standard audiogram) and 22% (MHE tool) of patients expressed a desire for takeaway information. 31% (standard audiogram) and 67% (MHE tool) of patients reported their explanation helped them relay their results to others. Four patients (one receiving the MHE tool) incorrectly recalled information, suggesting inadequate understanding in these cases. CONCLUSIONS: The MHE tool has potential for improving the accessibility and comprehensibility of hearing test results.
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At the physiological level, the interplay between auxin and ethylene has long been recognized as crucial for the regulation of organ abscission in plants. However, the underlying molecular mechanisms remain unknown. Here, we identified transcription factors involved in indoleacetic acid (IAA) and ethylene (ET) signaling that directly regulate the expression of INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) and its receptor HAESA (HAE), which are key components initiating abscission. Specifically, litchi IDA-like 1 (LcIDL1) interacts with the receptor HAESA-like 2 (LcHSL2). Through in vitro and in vivo experiments, we determined that the auxin response factor LcARF5 directly binds and activates both LcIDL1 and LcHSL2. Furthermore, we found that the ETHYLENE INSENSITIVE 3-like transcription factor LcEIL3 directly binds and activates LcIDL1. The expression of IDA and HSL2 homologs was enhanced in LcARF5 and LcEIL3 transgenic Arabidopsis plants, but reduced in ein3 eil1 mutants. Consistently, the expressions of LcIDL1 and LcHSL2 were significantly decreased in LcARF5- and LcEIL3-silenced fruitlet abscission zones (FAZ), which correlated with a lower rate of fruitlet abscission. Depletion of auxin led to an increase in 1-aminocyclopropane-1-carboxylic acid (the precursor of ethylene) levels in the litchi FAZ, followed by abscission activation. Throughout this process, LcARF5 and LcEIL3 were induced in the FAZ. Collectively, our findings suggest that the molecular interactions between litchi AUXIN RESPONSE FACTOR 5 (LcARF5)-LcIDL1/LcHSL2 and LcEIL3-LcIDL1 signaling modules play a role in regulating fruitlet abscission in litchi and provide a long-sought mechanistic explanation for how the interplay between auxin and ethylene is translated into the molecular events that initiate abscission.
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Etilenos , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Litchi , Proteínas de Plantas , Transducción de Señal , Ácidos Indolacéticos/metabolismo , Etilenos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Transducción de Señal/genética , Litchi/metabolismo , Litchi/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiología , Plantas Modificadas Genéticamente , Frutas/metabolismo , Frutas/genética , Frutas/crecimiento & desarrolloRESUMEN
Objective: To evaluate vitamin D deficiency in children with iron-deficiency anaemia, and to identify the risk factors for such deficiency. METHODS: The cross-sectional study was conducted at the Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from October 2021 to March 2022, and comprised children aged 1-5 years who had been diagnosed with iron-deficiency anaemia. Quantitative variables, like age, height, weight, gender, socioeconomic status and sibling status, were controlled by stratification. Data was compared to assess the risk factors of vitamin D deficiency among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 236 children with iron-deficiency anaemia, 159(67.5%) also had vitamin D deficiency; 95(59%) girls and 65(41%) boys. Overall, 104(65.4%) subjects were aged 4-5 years and 55(34.6%) were aged 1-3 years. Vitamin D deficiency had significant association with female gender, older age, height and weight <5th centiles, educated parents, low to middle socioeconomic status, urban residence and higher number of siblings (p<0.05). CONCLUSIONS: The prevalence of vitamin D deficiency among children with iron-deficiency anaemia was found to be high.
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Anemia Ferropénica , Deficiencia de Vitamina D , Humanos , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/complicaciones , Anemia Ferropénica/epidemiología , Femenino , Masculino , Preescolar , Pakistán/epidemiología , Estudios Transversales , Lactante , Factores de Riesgo , Prevalencia , Factores Sexuales , Estatura , Factores de Edad , Peso Corporal , Escolaridad , Clase Social , HermanosRESUMEN
In severe acute malnutrition, micronutrient deficiency as well as protein energy malnutrition is a major obstacle to growth & development. Iron deficiency dominates the spectrum of nutritional anemia. After taking informed consent, 211 SAM children and 211 age-and sex-matched healthy children with normal nutritional status were enrolled for the study. MUAC was used to diagnose SAM. A 5-part automated hematoanalyzer was used to measure the complete blood count and red cell indices, and the peripheral smear method to determine the red cell morphology. We measured serum ferritin, Vitamin B12, and folic acid using the ELISA method. Compared to controls, children with SAM had significantly lower red cell indices, platelet counts, and white cell counts. The most common clinical symptoms seen in SAM children were diarrhea, pneumonia, acute gastroenteritis, and acute respiratory infection. Children with SAM are more likely to suffer from iron deficiency and B12 deficiency. Severe vitamin B12 deficiency was more frequently associated with severe anemia. The severe anemia in SAM children constantly changes the body's defense mechanism, affecting the haematopoiesis. In this study, haematological indices are recommended for predicting severity of anemia, and hematopoietic changes are described, in order to improve anticipatory care and outcome in children with SAM.
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KEY MESSAGE: RbIDL1 and RbIDL4 are up-regulated in an ethylene-responsive manner during rose petal abscission and restored the Arabidopsis ida-2 mutant abscission defect suggesting functional conservation of the IDA pathway in rose. Abscission is an ethylene-regulated developmental process wherein plants shed unwanted organs in a controlled manner. The INFLORESCENCE DEFICIENT IN ABSCISSION family has been identified as a key regulator of abscission in Arabidopsis, encoding peptides that interact with receptor-like kinases to activate abscission. Loss of function ida mutants show abscission deficiency in Arabidopsis. Functional conservation of the IDA pathway in other plant abscission processes is a matter of interest given the discovery of these genes in several plants. We have identified four members of the INFLORESCENCE DEFICIENT IN ABSCISSION-LIKE family from the ethylene-sensitive, early-abscising fragrant rose, Rosa bourboniana. All four are conserved in sequence and possess well-defined PIP, mIDa and EPIP motifs. Three of these, RbIDL1, RbIDL2 and RbIDL4 show a three-fourfold increase in transcript levels in petal abscission zones (AZ) during ethylene-induced petal abscission as well as natural abscission. The genes are also expressed in other floral tissues but respond differently to ethylene in these tissues. RbIDL1 and RbIDL4, the more prominently expressed IDL genes in rose, can complement the abscission defect of the Arabidopsis ida-2 mutant; while, promoters of both genes can drive AZ-specific expression in an ethylene-responsive manner even in Arabidopsis silique AZs indicating recognition of AZ-specific and ethylene-responsive cis elements in their promoters by the abscission machinery of rose as well as Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Inflorescencia/metabolismo , Flores/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Etilenos/farmacología , Etilenos/metabolismo , Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas/genéticaRESUMEN
Huangqi Guizhi Wuwu decoction (HGWD) is an effective traditional Chinese medicine prescription, which is used for treating blood arthralgia in the clinic. However, its material basis has not been studied yet. Herein, a new and highly sensitive ultra-high-performance liquid chromatography-quadrupole-time of flight-MS (UHPLC-Q-TOF-MS) technique is proposed and used for the high-resolution and accurate identification of the material basis of HGWD. Seventy-eight compounds have been identified in HGWD. The advantages of information-dependent acquisition (IDA), sequential window acquisition of all theoretical fragment-ion spectra (SWATH), and MSALL in the quantitative and qualitative analyses of compounds were compared. For the identification of compounds, the best mode with the highest accuracy is the IDA. For the quantification of compounds, MSALL shows the best repeatability and linearity. This research provides a theoretical basis for the study of quality control of traditional Chinese medicine preparations.
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Fármacos Neuroprotectores , Cromatografía Líquida de Alta Presión , Medicina Tradicional China , Control de Calidad , Espectrometría de Masas en TándemRESUMEN
There has been increasing interest in applying integrative data analysis (IDA) to analyze data across multiple studies to increase sample size and statistical power. Measures of a construct are frequently not consistent across studies. This article provides a tutorial on the complex decisions that occur when conducting harmonization of measures for an IDA, including item selection, response coding, and modeling decisions. We analyzed caregivers' self-reported data from the ADHD Teen Integrative Data Analysis Longitudinal (ADHD TIDAL) dataset; data from 621 of 854 caregivers were available. We used moderated nonlinear factor analysis (MNLFA) to harmonize items reflecting depressive symptoms. Items were drawn from the Symptom Checklist 90-Revised, the Patient Health Questionnaire-9, and the World Health Organization Quality of Life questionnaire. Conducting IDA often requires more programming skills (e.g., Mplus), statistical knowledge (e.g., IRT framework), and complex decision-making processes than single-study analyses and meta-analyses. Through this paper, we described how we evaluated item characteristics, determined differences across studies, and created a single harmonized factor score that can be used to analyze data across all four studies. We also presented our questions, challenges, and decision-making processes; for example, we explained the thought process and course of actions when models did not converge. This tutorial provides a resource to support prevention scientists to generate harmonized variables accounting for sample and study differences.
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Depresión , Calidad de Vida , Adolescente , Humanos , Encuestas y Cuestionarios , Autoinforme , Análisis FactorialRESUMEN
Despite decades of concern about disparities in educational outcomes for low SES students and students of color, there has been limited rigorous study of programmatic approaches for reducing these disparities in elementary or middle schools. We conducted integrative data analysis (IDA) of the combined data from eight Institute of Education Sciences funded cluster randomized trials to address the research gaps on social and behavioral outcome disparities. The final analytic sample includes 90,880 students in varying grade levels from kindergarten to grade 8 in 387 schools in 4 states (Maryland, Missouri, Virginia, and Texas). Two-level hierarchical linear modeling was used for multilevel moderation analysis. This study provided empirical evidence that there were significant gender, racial, and socioeconomic disparities on social and behavioral outcome measures for elementary and middle school students, the disparities significantly varied across schools, and the disparities could be reduced by interventions. We discussed our findings, implications for interpreting effect sizes of interventions using disparities as empirical benchmarks, and study limitations. We concluded with suggestions for future research.
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Grupos Raciales , Disparidades Socioeconómicas en Salud , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudiantes , EscolaridadRESUMEN
Integrative data analysis (IDA) was used to derive developmental models of depression, externalizing problems, and self-regulatory processes in three prevention trials of the Family Check-Up and one longitudinal, community-based study of girls over a 10-year span covering early to late adolescence (N = 4,773; 74.9% female, 41.7% white). We used moderated nonlinear factor analysis to create harmonized scores based on all available items for a given participant in the pooled dataset while accounting for potential differences in both the latent factor and the individual items as a function of observed covariates. We also conducted latent growth model analyses to examine developmental trajectories of risk. Results indicated a bidirectional relationship between depression and externalizing problems, with greater baseline externalizing problems and depression predicting growth in inhibitory control difficulties. Furthermore, initial level of inhibitory control difficulties was associated with growth in depression. We did not, however, find a relationship between early inhibitory control difficulties and growth in externalizing problems. This work illustrates the utility of IDA techniques to harmonize data across multiple studies to identify risk factors for the development of depression and externalizing problems that can be targeted by prevention efforts.
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Depresión , Humanos , Femenino , Adolescente , Masculino , Estudios Longitudinales , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the perceived satisfaction and understanding of hearing assessment feedback, using the Ida My Hearing Explained Tool (IMHET), compared to the standard audiogram reported by adult clients and audiologists. DESIGN: This study is a mixed-method design comparing clients and audiologists' perceptions through a single-blinded, randomised control trial and focus group discussions. After using either the audiogram or IMHET for feedback, clients and audiologists completed the adapted Patient Satisfaction Questionnaire (PSQ). STUDY SAMPLE: During client's initial audiological consultations, audiologists provided hearing assessment feedback (Total = 51) using the IMHET or audiogram. Twenty-seven clients and seven audiologists participated in focus groups, and/or open-ended questions. RESULTS: Satisfaction was not significantly different (p > 0.05) between the IMHET (76.18; SD: 2.66) or audiogram (75.63; SD: 4.73) for the overall PSQ scores reported by clients and audiologists. Two shared main themes, understanding and satisfaction, were identified for both tools from the focus groups and open-ended questions. A third main theme, recommendations, was identified only for the IMHET. CONCLUSIONS: The IMHET is a valuable resource for clients during hearing assessment feedback. Audiologists recommend that the audiogram be used as a supplement when using the IMHET to provide feedback.
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Audiólogos , Audiología , Adulto , Humanos , Retroalimentación , Audición , Audiología/métodos , Pruebas AuditivasRESUMEN
Meta-analysis using individual participant data (IPD) is an important methodology in intervention research because it (a) increases accuracy and precision of estimates, (b) allows researchers to investigate mediators and moderators of treatment effects, and (c) makes use of extant data. IPD meta-analysis can be conducted either via a one-step approach that uses data from all studies simultaneously, or a two-step approach, which aggregates data for each study and then combines them in a traditional meta-analysis model. Unfortunately, there are no evidence-based guidelines for how best to approach IPD meta-analysis for count outcomes with many zeroes, such as alcohol use. We used simulation to compare the performance of four hurdle models (3 one-step and 1 two-step models) for zero-inflated count IPD, under realistic data conditions. Overall, all models yielded adequate coverage and bias for the treatment effect in the count portion of the model, across all data conditions. However, in the zero portion, the treatment effect was underestimated in most models and data conditions, especially when there were fewer studies. The performance of both one- and two-step approaches depended on the formulation of the treatment effects, suggesting a need to carefully consider model assumptions and specifications when using IPD.
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Modelos Estadísticos , Humanos , Simulación por Computador , SesgoRESUMEN
EBV and Helicobacter pylori (H. pylori) cause highly prevalent persistent infections as early as in childhood. Both pathogens are associated with gastric carcinogenesis. H. pylori interferes with iron metabolism, enhancing the synthesis of acute-phase proteins hepcidin, C-reactive protein (CRP), and α-1 glycoprotein (AGP), but we do not know whether EBV does the same. In this study, we correlated the EBV antibody levels and the serum levels of hepcidin, CRP, and AGP in 145 children from boarding schools in Mexico City. We found that children IgG positive to EBV antigens (VCA, EBNA1, and EA) presented hepcidin, AGP, and CRP levels higher than uninfected children. Hepcidin and AGP remained high in children solely infected with EBV, while CRP was only significantly high in coinfected children. We observed positive correlations between hepcidin and EBV IgG antibodies (p < 0.5). Using the TCGA gastric cancer database, we also observed an association between EBV and hepcidin upregulation. The TCGA database also allowed us to analyze the two important pathways controlling hepcidin expression, BMP−SMAD and IL-1ß/IL-6. We observed only the IL-1ß/IL-6-dependent inflammatory pathway being significantly associated with EBV infection. We showed here for the first time an association between EBV and enhanced levels of hepcidin. Further studies should consider EBV when evaluating iron metabolism and anemia, and whether in the long run this is an important mechanism of undernourishment and EBV gastric carcinogenesis.
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Infecciones por Virus de Epstein-Barr , Helicobacter pylori , Neoplasias Gástricas , Niño , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/metabolismo , Helicobacter pylori/metabolismo , Hepcidinas/metabolismo , Herpesvirus Humano 4 , Inmunoglobulina G/metabolismo , Interleucina-6/metabolismo , Hierro/metabolismo , Neoplasias Gástricas/etiologíaRESUMEN
The pH-dependent binding strengths and modes of the organometallic [(η6-p-cym)M(H2O)3]2+ (MII = Ru, Os; p-cym = 1-methyl-4-isopropylbenzene) or [(η5-Cp*)M(H2O)3]2+ (MIII = Rh, Ir; Cp* = pentamethylcyclopentadienyl anion) cations towards iminodiacetic acid (H2Ida) and its biorelevant mono- and diphosphonate derivatives N-(phosphonomethyl)-glycine (H3IdaP) and iminodi(methylphosphonic acid) (H4Ida2P) was studied in an aqueous solution. The results showed that all three of the ligands form 1:1 complexes via the tridentate (O,N,O) donor set, for which the binding mode was further corroborated by the DFT method. Although with IdaP3- and Ida2P4- in mono- and bis-protonated species, where H+ might also be located at the non-coordinating N atom, the theoretical calculations revealed the protonation of the phosphonate group(s) and the tridentate coordination of the phosphonate ligands. The replacement of one carboxylate in Ida2- by a phosphonate group (IdaP3-) resulted in a significant increase in the stability of the metal complexes; however, this increase vanished with Ida2P4-, which was most likely due to some steric hindrance upon the coordination of the second large phosphonate group to form (5 + 5) joined chelates. In the phosphonate-containing systems, the neutral 1:1 complexes are the major species at pH 7.4 in the millimolar concentration range that is supported by both NMR and ESI-TOF-MS.
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Introduction: To evaluate the efficacy of ferric carboxy maltose (FCM) in the treatment of iron deficiency/iron deficiency anaemia (ID/IDA) during pregnancy. Material and methods: Pregnant women ≥ 20 years old diagnosed with ID (serum ferritin < 15 µg/l) and moderate IDA were included in this study for correction of their ID/IDA. The participants received an FCM infusion for correction of their ID/IDA. The pre-treatment ferritin, haemoglobin (Hb), and red blood cell (RBC) indices were compared with the 6- and 12-week post-treatment values to evaluate the efficacy of FCM in the treatment of ID/IDA during pregnancy. Results: The pre-treatment ferritin and Hb significantly increased from 10.3 ±2.3 µg/l and 7.99 ±0.6 g/dl, respectively, to 139.5 ±1.9 and 14.04 ±0.45, respectively, 6-weeks after FCM infusion (p = 0.02 and 0.001, respectively), and to 128.9 ±1.7 and 13.02 ±0.5, respectively, 12-weeks after FCM infusion (p = 0.0008 and 0.02, respectively). In addition, the pre-treatment RBCs mean corpuscular volume and RBCs mean corpuscular haemoglobin (MCH) significantly increased from 72.02 ±3.5 fl and 23.9 ±1.9 pg, respectively, to 90.6 ± 2.8 fl and 29.98 ±1.5 pg, respectively, 6 weeks after FCM infusion (p = 0.01 and p = 0.007, respectively), and to 89.5 ±2.9 fl and 30.2 ±1.5 pg, respectively, 12 weeks after FCM infusion (p = 0.02 and 0.007 respectively). Conclusions: The ferric carboxy maltose was safe and effective for the treatment of ID/IDA during pregnancy within 6 weeks. The serum ferritin and Hb levels and the RBC indices remained significantly high 12 weeks after FCM infusion compared to the pre-treatment values.