Combining non-canonical amino acid mutagenesis and native chemical ligation for multiply modifying proteins: A case study of α-synuclein post-translational modifications.

The Parkinson's disease associated protein α-synuclein (αS) has been found to contain numerous post-translational modifications (PTMs), in both physiological and pathological states. One PTM site of particular interest is serine 87, which is subject to both O-linked ß-N-acetylglucosamine (gS) modification and phosphorylation (pS), with αS-pS87 enriched in Parkinson's disease. An often-overlooked aspect of these PTMs is their effect on the membrane-binding properties of αS, which are important to its role in regulating neurotransmitter release. Here, we show how one can study these effects by synthesizing αS constructs containing authentic PTMs and labels for single molecule fluorescence correlation spectroscopy measurements. We synthesize αS-gS87 and αS-pS87 by combining native chemical ligation with genetic code expansion approaches. We introduce the fluorophore by a click reaction with a non-canonical amino acid. Beyond the specific problem of PTM effects on αS, our studies highlight the value of this combination of methods for multiply modifying proteins.

Imagining Her Future: Diversity in Mothers' Socialization Goals for Their Adolescent Daughters.

According to developmental niche theory, members of different cultural and ethnic groups often have distinct ideas about what children need to become well-adapted adults. These beliefs are reflected in parents' long-term socialization goals for their children. In this study, we test whether specific themes that have been deemed important in literature on diverse families in the United States (e.g., Strong Black Woman [SBW], marianismo, familismo) are evident in mothers' long-term socialization goals. Participants included 192 mothers of teenage daughters from a low-income city in the United States (58% Latina, 22% African American, and 20% European American [EA]/White). Socialization goals were assessed through a q-sort task on important traits for a woman to possess and content analysis of open-ended responses about what values mothers hoped they would transmit to their daughters as they become adults. Results from ANCOVAs and logistic regression indicate significant racial/ethnic differences on both tasks consistent with hypotheses. On the q-sort task, African American mothers put more importance on women possessing traits such as independence than mothers from other racial/ethnic groups. Similarly, they were more likely to emphasize self-confidence and strength in what they hoped to transmit to their daughters. Contrary to expectation, Latina mothers did not emphasize social traits on the q-sort; however, in open-ended responses, they were more likely to focus on the importance of motherhood, one aspect of marianismo and familismo. Overall, results suggest that these mothers' long-term socialization goals incorporate culturally relevant values considered important for African American and Latino families.

Evaluating Fmoc-amino acids as selective inhibitors of butyrylcholinesterase.

Cholinesterases are involved in neuronal signal transduction, and perturbation of function has been implicated in diseases, such as Alzheimer's and Huntington's disease. For the two major classes of cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), previous studies reported BChE activity is elevated in patients with Alzheimer's disease, while AChE levels remain the same or decrease. Thus, the development of potent and specific inhibitors of BChE have received much attention as a potential therapeutic in the alleviation of neurodegenerative diseases. In this study, we evaluated amino acid analogs as selective inhibitors of BChE. Amino acid analogs bearing a 9-fluorenylmethyloxycarbonyl (Fmoc) group were tested, as the Fmoc group has structural resemblance to previously described inhibitors. We identified leucine, lysine, and tryptophan analogs bearing the Fmoc group as selective inhibitors of BChE. The Fmoc group contributed to inhibition, as analogs bearing a carboxybenzyl group showed ~tenfold higher values for the inhibition constant (K I value). Inclusion of a t-butoxycarbonyl on the side chain of Fmoc tryptophan led to an eightfold lower K I value compared to Fmoc tryptophan alone suggesting that modifications of the amino acid side chains may be designed to create inhibitors with higher affinity. Our results identify Fmoc-amino acids as a scaffold upon which to design BChE-specific inhibitors and provide the foundation for further experimental and computational studies to dissect the interactions that contribute to inhibitor binding.

Myocardial infarction during treatment of Crotalinae envenomation: A case report.

While myocardial infarction is a rare, but known, potential side effect of snakebite envenomation, snake antivenom has thus far not been associated with any cardiovascular adverse events. We report the case of a 71-year-old man who developed an anterolateral MI during administration of Crotalidae immune F(ab')2 (equine) (ANAVIP), given as treatment for Crotalidae envenomation. The patient required cardiac catheterization with stenting of the left anterior descending artery and was discharged two days later on long-term clopidogrel and aspirin. Treatment of MI in the setting of envenomation should mirror typical management, with consideration of additional antivenom if the ischemia is determined to be venom-induced. Clinicians should have a high index of suspicion for patients with chest pain after snake envenomation or administration of antivenom.

Evaluation of the International Society on Thrombosis and Haemostasis definition of major bleeding in Arizona rattlesnake bites.

INTRODUCTION: In 2023, a group of experts proposed that a definition of major bleeding in pharmaceutically anticoagulated patients be used in all snakebite trials. This includes bleeding that results in death, is life-threatening, causes chronic sequelae, or consumes major healthcare resources, including bleeding into a major area or hemoglobin concentration decrease ≥20 g/L. We hypothesized that a decline in hemoglobin concentration ≥20 g/L is common but rarely clinically significant in our population of Arizona rattlesnake bite patients. METHODS: Poison center records of rattlesnake bites in humans from 2018 through 2022 were retrospectively reviewed and assessed for major bleeding by the above criteria. RESULTS: Four hundred and eighty-one patients met the inclusion criteria, of whom 265 (55.1%) had a hemoglobin concentration decrease ≥20 g/L. No patients died, and there was no evidence of bleeding into a critical organ. Three patients (1.1%) received blood transfusions. A decrease in hemoglobin concentration ≥20 g/L was 100% sensitive for identifying the major bleeding-associated outcomes; however, specificity was only 45.2%. Measures of healthcare utilization and chronic sequelae were somewhat higher in patients with a decrease in hemoglobin concentration ≥20 g/L. DISCUSSION: Laboratory manifestations of hemotoxicity were common in this population, but hemorrhage was rare. While over half of patients met the major bleeding criterion of a decline in hemoglobin concentration ≥20 g/L, only 1.1% had bleeding that was potentially life-threatening as measured by receipt of a red blood cell transfusion. None died or had bleeding into a critical area. While nonspecific for major bleeding, a drop in hemoglobin concentration correlated with worse envenomation severity: these patients received more vials of antivenom, had a higher medical bill, a longer hospital stay, and were less likely to report full recovery at 90 days. CONCLUSIONS: A decrease in hemoglobin concentration ≥20 g/L should not be used as evidence of major bleeding for Arizona rattlesnake envenomation studies, but it may have a role as an indirect marker of envenomation severity.

Twenty-five years of suspected rattlesnake encounters in Arizona.

INTRODUCTION: Rattlesnake (Crotalus spp., Sistrurus spp.) bites in the southwestern United States are associated with significant morbidity. This study aims to describe 25 years of rattlesnake encounters reported to the Arizona Poison and Drug Information Center to identify vulnerable populations and circumstances where encounters occur to create public education to reduce future bites. METHODS: Cases of suspected rattlesnake encounters in Arizona reported to the Arizona Poison and Drug Information Center between 1999 and 2023 were analyzed to identify populations and circumstances associated with encounters. RESULTS: A total of 3,808 cases were analyzed overall and by age subgroups. Most encounters occurred in men (69.9%), during the evening (16:00-21:59; 49.2%), in summer (41.9%), and close to home (38.2%). Most bites occurred to the lower extremity (51%). Children 0 to 12-years-old have more encounters than those 13-years-old and older in rural zip codes (27.7% versus 14.8%; P = 0.005), during spring (31.8% versus 22.3%; P = 0.0005), and during the evening (64.4% versus 48.1%; P < 0.001). DISCUSSION: Rattlesnakes are encountered when rattlesnake and human behavior patterns overlap. Many people spend time outside during evening hours in the summer, and valuable resources like food, water, and shelter can be found near houses where humans spend much of their time. Most age groups have similar encounter circumstances but encounters among children 0 to 12-years-old differ in time of day, season, and urbanization level than encounters of those 13-years-old and older. Limitations of this study include underreporting of encounters, incomplete case details, potential reporting bias, potential snake misidentification, and geographic coverage of the poison center. CONCLUSION: Prevention of rattlesnake bites by reducing encounters is the most effective way to reduce suffering and healthcare costs. Future steps include creating and disseminating targeted public health education using the data collected.

Multivalency drives interactions of alpha-synuclein fibrils with tau.

Age-related neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by deposits of protein aggregates, or amyloid, in various regions of the brain. Historically, aggregation of a single protein was observed to be correlated with these different pathologies: tau in AD and α-synuclein (αS) in PD. However, there is increasing evidence that the pathologies of these two diseases overlap, and the individual proteins may even promote each other's aggregation. Both tau and αS are intrinsically disordered proteins (IDPs), lacking stable secondary and tertiary structure under physiological conditions. In this study we used a combination of biochemical and biophysical techniques to interrogate the interaction of tau with both soluble and fibrillar αS. Fluorescence correlation spectroscopy (FCS) was used to assess the interactions of specific domains of fluorescently labeled tau with full length and C-terminally truncated αS in both monomer and fibrillar forms. We found that full-length tau as well as individual tau domains interact with monomer αS weakly, but this interaction is much more pronounced with αS aggregates. αS aggregates also mildly slow the rate of tau aggregation, although not the final degree of aggregation. Our findings suggest that co-occurrence of tau and αS in disease are more likely to occur through monomer-fiber binding interactions, rather than monomer-monomer or co-aggregation.

Perceived worsening of obsessive-compulsive disorder symptoms after childbirth in women and men: An understudied phenomenon.

The aim of this study was to examine worsening of OCD symptoms after childbirth in individuals seeking assessment or treatment of OCD. The postpartum period may make parents biologically and psychologically vulnerable to OCD symptoms. Participants included 222 parents with OCD who completed surveys through a self-help website. Most women and almost half of men with self-reported OCD reported an increase in OCD symptoms following childbirth. Retrospective report of perceived worsening of OCD symptoms after childbirth was associated with more aggressive obsessions for both men and women, in comparison to individuals whose OCD symptoms did not worsen around childbirth. Women whose OCD symptoms worsened after childbirth reported more impairment in social functioning than individuals whose symptoms did not worsen. These results highlight the need to develop a better understanding of aggressive obsessions in parents, and improve education about prevalence, content, assessment, and intervention for aggression-focused intrusive thoughts.

The Effects of Lipids on α-Synuclein Aggregation In Vitro.

The small neuronal protein α-synuclein (αS) is found in pre-synaptic terminals and plays a role in vesicle recycling and neurotransmission. Fibrillar aggregates of αS are the hallmark of Parkinson's disease and related neurodegenerative disorders. In both health and disease, interactions with lipids influence αS's structure and function, prompting much study of the effects of lipids on αS aggregation. A comprehensive collection (126 examples) of aggregation rate data for various αS/lipid combinations was presented, including combinations of lipid variations and mutations or post-translational modifications of αS. These data were interpreted in terms of lipid structure to identify general trends. These tabulated data serve as a resource for the community to help in the interpretation of aggregation experiments with lipids and to be potentially used as inputs for computational models of lipid effects on aggregation.

Large-scale releases and establishment of wMel Wolbachia in Aedes aegypti mosquitoes throughout the Cities of Bello, Medellín and Itagüí, Colombia.

BACKGROUND: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and has been shown to reduce the transmission of dengue and other Aedes-borne viruses. Here we report the entomological results from phased, large-scale releases of Wolbachia infected Ae. aegypti mosquitoes throughout three contiguous cities located in the Aburrá Valley, Colombia. METHODOLOGY/PRINCIPAL FINDINGS: Local wMel Wolbachia-infected Ae. aegypti mosquitoes were generated and then released in an initial release pilot area in 2015-2016, which resulted in the establishment of Wolbachia in the local mosquito populations. Subsequent large-scale releases, mainly involving vehicle-based releases of adult mosquitoes along publicly accessible roads and streets, were undertaken across 29 comunas throughout Bello, Medellín and Itagüí Colombia between 2017-2022. In 9 comunas these were supplemented by egg releases that were undertaken by staff or community members. By the most recent monitoring, Wolbachia was found to be stable and established at consistent levels in local mosquito populations (>60% prevalence) in the majority (67%) of areas. CONCLUSION: These results, from the largest contiguous releases of wMel Wolbachia mosquitoes to date, highlight the operational feasibility of implementing the method in large urban settings. Based on results from previous studies, we expect that Wolbachia establishment will be sustained long term. Ongoing monitoring will confirm Wolbachia persistence in local mosquito populations and track its establishment in the remaining areas.

Symptom Prevalence in Spanish and Colombian Oncology Patients Measured with the MSAS.

Cancer patients experience several symptoms throughout their illness and the treatments they receive. While this pathology represents a worldwide health problem, knowing the symptom prevalence in oncology patients remains a challenge; validated tools to obtain this information are essential. Furthermore, this prevalence information would help health professionals to establish appropriate treatments. The objective of this study was to ascertain the symptom prevalence in cancer patients from Spain and Colombia to improve future approaches. The frequency, severity, and distress of 32 symptoms from a validated scale experienced by cancer patients from Spain and Colombia were measured. Two hundred and forty-six patients (49.7%) who attended the Day University Hospital of Salamanca (Spain) and two hundred and forty-nine outpatients (50.3%) of the San Diego Cancer Center (Colombia) between 2016 and 2019 participated in the study. All patients filled in the Assessment Scale only once. Four hundred and ninety-five patients (333 women (67.3%) and 162 men (32.7%)) completed the Memorial Symptom Assessment Scale (Spanish version). The most frequent symptom for both samples (Spanish and Colombian) was "lack of energy" (38.4% and 13.7%, respectively). The most severe symptoms for the Spanish and Colombian samples were "problems with sexual interest or activity" (38.4%) and "dry mouth" (13.7%), respectively, and both samples agreed on the most distressing symptom: "hair loss" (Spanish, 38%; Colombian, 10.1%). The Spanish version of the MSAS has proven to be a valid and reliable tool in Spanish-speaking countries to obtain the most prevalent, severe, and distressing symptoms in Spanish and Colombian oncology patients. The prevalence of symptoms was demonstrated to be similar across both countries, and the results will help to design and adapt treatments for cancer patients, targeting these symptoms to reduce or avoid them and thus improving their quality of life.

Quantitative confocal Raman microscopy study of ion-interaction retention at reversed-phase chromatographic interfaces.

Ion-interaction chromatography utilizes the addition of amphiphilic (surfactant) molecules to the mobile-phase solution in order to bring about the retention and separation of hydrophilic ionic analytes on reversed-phase liquid chromatographic stationary phases. The mechanism by which retention and separation in ion-interaction chromatography is accomplished remains unclear, although two primary mechanisms of this phenomenon have been proposed: preadsorption of the hydrophobic counterions to the hydrophobic stationary phase followed by interaction with the ionic analyte or adsorption of ion-paired species to the hydrophobic surface. There is evidence that both mechanisms contribute to ionic retention and separations. In this work, ion interactions at a C(18) stationary-phase interface are investigated by confocal Raman microscopy of individual stationary-phase particles, which is capable of quantifying surface concentrations of surfactants and model solutes. Raman spectra taken within the interior of the particle indicate that preadsorption of the hydrophobic surfactant cetylpyridinium to the stationary-phase interface is sensitive to ionic strength and concentration of organic modifier in the mobile phase. It was also determined that the presence of low concentrations of a model, ionic solute, nitrobenzenesulfonate, leads to greater adsorption of cetylpyridinium ion at the hydrophobic interface. As the concentration of nitrobenzenesulfonate is increased, the 1:1 increase in the cetylpyridinium ion interfacial concentration provides evidence of ion pairs forming at the stationary-phase surface.

Structural Characterization of Tau in Fuzzy Tau:Tubulin Complexes.

Tau is a neuronal microtubule (MT)-associated protein of significant interest due to its association with several neurodegenerative disorders. Tau's intrinsic disorder and the dynamic nature of its interactions with tubulin and MTs make its structural characterization challenging. Here, we use an environmentally sensitive fluorophore as a site-specific probe of tau bound to soluble tubulin. Comparison of our results with a recently published tau:MT cryoelectron microscopy model reveals structural similarities between tubulin- and MT-bound tau. Analysis of residues across the repeat regions reveals a hierarchy in tubulin occupancy, which may be relevant to tau's ability to differentiate between tubulin and MTs. As binding to soluble tubulin is a critical first step in MT polymerization, our characterization of the structural features of tau in dynamic, fuzzy tau:tubulin assemblies advances our understanding of how tau functions in the cell and how function may be disrupted in disease.

Confocal Raman microscopy investigation of the wetting of reversed-phase liquid chromatographic stationary phase particles.

Wetting phenomena in reversed-phase liquid chromatographic (RPLC) stationary phase particles strongly influence the retention of solutes with high water-content mobile phases. To better understand these phenomena, this work reports the spectroscopic observation of the wetting of the interior of individual C(18)-silica stationary phase particles with acetonitrile-water mobile phase solutions by confocal Raman microscopy. It was found that the pores of dry C(18) silica do not wet when the concentration of acetonitrile is below 0.12 mol fraction (28% by volume). It was also found that there is a wetting hysteresis, where particles that had been previously exposed to acetonitrile solutions above the wetting transition remain filled with solution even at much lower concentrations of acetonitrile in the surrounding solution. Contact angles of acetonitrile-water solutions were measured at a planar C(18)-modified silica surface and used to predict the capillary wetting of the particles based on the Young-Laplace equation. The solution composition at the wetting transition detected by Raman microscopy is higher in acetonitrile concentration than predicted by the Young-Laplace equation, which may be due to the presence of a vapor or air gap at the interface between the hydrophobic pores and aqueous solution. Further evidence of this behavior is found in water porosimetry results, which show wetting pressures approximately 5 times greater than predicted by the Young-Laplace equation and are consistent with only 50% of a water interface being in contact with the C(18) surface. This fraction increases to 80% at an acetonitrile concentration of 0.12 mol fraction, leading to spontaneous and irreversible wetting of the hydrophobic pores.

Confocal Raman microscopy of the interfacial regions of liquid chromatographic stationary-phase materials.

The influence of organic modifiers on the structure of reversed-phase liquid chromatographic (RPLC) stationary phases has been a topic of considerable investigation. Retention of organic modifiers in the stationary phase has previously been determined by chromatographic measurements, and the polarity and heterogeneity of the resulting solvation environment has been studied using solvatochromic, fluorescent, and spin probes. In the present work, the composition and solvation environment of a stationary phase is investigated using confocal Raman microscopy, which allows the in situ examination of the solvation environment within individual chromatographic stationary phase particles without the use of probe molecules. The accumulation of organic modifiers in the stationary phase can be quantified, and the environment of the modifier in the stationary phase can be determined. Specifically, we have investigated the interactions of acetonitrile with C(18)-functionalized silica particles using confocal Raman microscopy, which enables the sampling of small (approximately 1 fL) volumes within individual 10 microm particles. Bare chromatographic silica was also studied in order to investigate the interactions of acetonitrile with surface silanols. The nitrile-stretching (nu(CN)) frequency of acetonitrile responds sensitively to the dipolarity of its local microenvironment. The populations of solution-phase and interfacial acetonitrile are thus spectroscopically distinguishable. Scattering from nu(CN) shows contributions from three different environments within a single RPLC chromatographic particle: acetonitrile in the interparticle mobile phase, C(18)-chain associated acetonitrile, and acetonitrile that is interacting with residual surface silanols. Data are presented quantifying these populations and characterizing their environments within single stationary phase particles.

Escala de evaluación de síntomas Memorial 10-18: Adaptación cultural y validez para oncología pediátrica Colombia / Memorial symptom assessment scale 10-18: Cultural adaptation and validity for pediatric oncology Colombia

Objetivo principal: Adaptar culturalmente y validar en el componente de validez facial y de contenido la escala de evaluación de síntomas Memorial 10-18 años en pediatría oncológica en Colombia. Metodología: Estudio de validación de escalas en dos fases: 1. Adaptación cultural al contexto colombiano 2. Validación facial y de contenido. Los participantes eran adolescentes sanos y con diagnóstico oncológico entre 10 a 18 años de edad. Resultados principales: Se obtuvo versión adaptada de la MSAS 10-18 al contexto colombiano para escenarios de oncología pediátrica, con comprensibilidad global de ítems mayor al 85 % e índice de validez de contenido de 0.71. Conclusión principal: La escala de evaluación de síntomas Memorial 10-18 años proporciona cumple con propiedades psicométricas para su aplicación en la práctica, contribuyendo a mejorar la calidad de vida al niño con cáncer y su familia.(AU)

Objective: Culturally adapt and validate in the component of facial validity and content the Memorial Symptom Assessment Scale 10-18 years in oncological pediatrics in Colombia. Methods: Scale validation study in two phases: 1. Cultural adaptation of the MSAS 10-18 to the Colombian, 2. Facial and content validation with experts in the phenomenon and children with cancer between the ages described. Participants were healthy adolescents and with oncological diagnosis between 10 and 18 years of age. Results: An adapted version of the Memorial Symptom Assessment Scale 10-18 was obtained for the Colombian context for pediatric oncology scenarios, with an overall comprehensibility of the items greater than 85 % and a content validity index of 0.71. Conclusions: Having specific scales adapted to the age group and the context in which they are applied, provides theoretical and disciplinary knowledge to guide the practice, contributing to improve the quality of life and comprehensive care for children with cancer and their family.(AU)

Seeing through your daughter's eyes: Factors associated with maternal meta-accuracy.

Dyadic meta-accuracy reflects the ability to judge how one is viewed by a relationship partner. Drawing from the attachment literature on parental mentalization, it is tested whether maternal meta-accuracy is associated with (a) mothers' history of maltreatment or maternal absence during her childhood and (b) observed relational behaviors during an interaction task. Participants included 182 low-income mother-daughter dyads (adolescent mean age = 15.1). Mothers were modestly accurate in judging how daughters rated their warmth and hostility. Mothers with histories of maltreatment or maternal absence showed less meta-accuracy, but the nature of their inaccuracies (e.g., self-enhancement) differed. Differences in maternal meta-accuracy were also associated with relationship quality as rated by independent observers. The relevance of meta-accuracy for mentalization-based interventions with families is discussed.

Depressive Symptoms in Mothers and Daughters: Attachment Style Moderates Reporter Agreement.

Parents and adolescents show only modest agreement when reporting on depressive symptoms. Drawing from attachment theory and previous research on informant discrepancies, we tested hypotheses about how adolescent attachment style may impact reporting agreement in a sample of 184 low-income mother-adolescent daughter dyads (adolescent mean age = 15.4 (SD = 1.05), maternal mean age = 41.4 (SD = 7.60); 58 % Latina, 26 % African-American/Black, 16 % as non-Hispanic, White). Mothers and adolescents reported on their own and each others' depressive symptoms and adolescents reported on attachment style. Using a moderated Actor Partner Interdependence Model (APIM) to calculate reporter bias and accuracy estimates, we tested whether attachment style moderated maternal and adolescent accuracy in theoretically consistent ways. Mothers and adolescents showed similar levels of accuracy and bias when reporting on each other. Consistent with hypotheses, we found that adolescents who reported high levels of preoccupation were less accurate when reporting on their mothers because they tended to observe symptoms that their mothers did not endorse. Conversely, mothers were the most accurate in these dyads, potentially because preoccupied adolescents tend to elevate displays of emotional distress. Reporting accuracy was not affected by a dismissive style. These results add to literature indicating that parent-child reporting discrepancies often reflect meaningful information about relationships, and highlight the need to consider different sources of reporting bias and accuracy in assessment and treatment.

Childhood Sexual Abuse Moderates the Relationship Between Obesity and Mental Health in Low-Income Women.

We examined whether a history of self-reported childhood sexual abuse (CSA) moderates the relationship between obesity and mental health symptoms (depression, anxiety, and posttraumatic stress disorder) in an ethnically diverse sample of low-income women. A community sample of 186 women completed self-report measures and had their weight and height measured. Body mass index and CSA had an interactive effect on all mental health measures, such that obese women with a CSA history reported substantially higher levels of all symptoms. These results give greater specificity to the obesity-mental health link reported in previous studies and provide possible directions for targeted intervention.

Protecting Texas children: evidence-based recommendations for improving childhood vaccination rates.

Currently, Texas ranks in the bottom quintile of states for childhood vaccinations. Approximately, one fourth of Texas children younger than age 3 years have not received the recommended full schedule of vaccinations. Such a low rate can produce serious health consequences by reducing "community immunity." We review the current literature on barriers to high immunization rates and on effective, evidence-based strategies and programs. In addition, we report the results of interviews with public health officials responsible for implementing immunization programs in Texas and in a sample of high-ranking states for their assessment of the most effective strategies. We suggest legislative and administrative changes for Texas on the basis of the literature review and interview results. These recommendations involve improving the public health network, strengthening financial and administrative incentives to providers, enhancing incentives for parents, and encouraging federal program modifications.