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.

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.

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.

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.

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.

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.

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.

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.

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)

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.

Evaluación de síntomas en niños y adolescentes con cáncer: revisión integrativa / Evaluation of symptoms in children and adolescents with cancer: comprehensive review / Avaliação dos sintomas em crianças e adolescentes com câncer: uma revisão integrativaJennifer

Los niños y adolescentes diagnosticados con cáncer se enfrentan a una serie de cam-bios en los diferentes aspectos de su vida, y experimentan múltiples síntomas físicos y psicosociales a causa de la enfermedad y su tratamiento, lo que afecta su calidad de vida y la de sus cuidadores. Objetivo: Indagar el estado del aspecto investigativo relacionado con la temática sobre evaluación de síntomas en niños y adolescentes con cáncer. Método: Revisión integrativa de la producción científica generada entre 2007 y 2018 en las bases de datos Embase, Ovid, Medline, Pubmed, Science Direct y Scie-lo en inglés, español y portugués. Se incluyeron 50 artículos que aportan información sobre evaluación de síntomas en población pediátrica con diagnóstico de cáncer. Re-sultados: Las investigaciones sobre herramientas que evalúan la manifestación de síntomas, adaptadas y validadas a población pediátrica son limitadas. Conclusiones: Los niños y adolescentes con cáncer presentan síntomas durante las distintas fases de la enfermedad y el tratamiento. Son escasos los estudios sobre estos síntomas en el contexto local, por tanto se requiere validar escalas específicas para esta población, describir los síntomas incluyendo variables clínicas y de calidad de vida percibidas que sirvan para orientar intervenciones oportunas en el manejo de los mismos.

Children and adolescents diagnosed with cancer face a number of changes in diffe-rent aspects of their lives, and experience multiple physical and psychosocial symp-toms from the disease and its treatment, affecting their quality of life and that of their caregivers. Objective: To investigate the state of the research aspect related to the subject of symptom assessment in children and adolescents with cancer. Methods: Integrative review of the scientific production generated between 2007 and 2018 in the databases Embase, Ovid, Medline, Pubmed, Science Direct and Scielo in English, Spanish and Portuguese. It included 50 articles that provide information on symptom assessment in pediatric population with cancer diagnosis. Results: Research on tools that evaluate the manifestation of symptoms, adapted and validated to paediatric population are limited. Con-clusions: Children and adolescents with cancer present with symptoms during the different stages of the disease and treatment. Studies on these symptoms in the local context are scarce, therefore it is necessary to validate specific scales for this population, to describe the symptoms including clinical variables and perceived quality of life that serve to guide opportune interventions in their management.

As crianças e adolescentes diagnosticadas com câncer enfrentam-se a uma série de mudanças nos diferentes aspectos das suas vidas, experimentam sintomas físicos e psicossociais a causa da doença e o tratamento, afetando a sua qualidade de vida e a dos seus cuidadores. Objetivo: Indagar o estado das pesquisas relacionadas com a temática sobre a avalição dos sintomas de crianças e adolescentes com câncer. Métodos: Revisão integrativa da produção científica gerada entre 2007 e 2018 dispo-nível em recursos bibliográficos na internet como Embase, Ovid, Medline, Pubmed, Science Direct e Scielo em inglês, espanhol e português. Incluíram-se 50 artigos que contribuíram com informação sobre avaliação de sintomas em população pediátrica com diagnostico de câncer Resultados: As investigações sobre as ferramentas que avaliaram manifestações dos sintomas, adaptadas e vali-dadas na população pediátrica são limitadas. Conclusões: As crianças e adolescentes com câncer presentam sintomas durante as diferentes etapas da doença e o tratamento. São poucos os estudos sobre estes sintomas no contexto local, portanto, requerem-se instrumentos validados na população pediátrica, descrevendo os sintomas incluindo variáveis clínicas e de qualidade de vida percebidas que orientem intervenções oportunas para o acompanhamento dos mesmos.

Adaptación cultural y validez de la "Memorial Symptom Assessment Scale (MSAS) 10­18" para Pediatría Oncológica en Colombia / Cultural adaptation and validity of the "Memorial Symptom Assessment Scale (MSAS) 10­18" for Pediatric Oncology in Colombia

Los niños y adolescentes con cáncer se enfrentan a una serie de cambios en su dinámica familiar, actividad social, experimentan síntomas físicos y psicoemocionales como consecuencia de la enfermedad y el tratamiento. La comprensión de la prevalencia y características de los síntomas en niños con cáncer se ha visto obstaculizada por la falta de herramientas de evaluación validadas en esta población. Para los enfermeros de la práctica en oncología pediátrica es determinante reconocer y manejar los síntomas, en tanto que tienen contacto directo con su sujeto de cuidado. Objetivo: Adaptar culturalmente y validar la escala de evaluación de síntomas Memorial para adolescentes entre 10- 18 años de edad en pediatría oncológica en el contexto colombiano en el año 2018. Método: Estudio de validación de escalas que se desarrolló en dos fases; la primera fue la adaptación cultural del MSAS 10-18 al contexto colombiano en donde participaron adolescentes sanos y la segunda fase de validación facial y de contenido con participantes expertos en el fenómeno, adolescentes con cáncer entre las edades descritas. Resultados: Se obtuvo versión adaptada de la Memorial Symptom Assessment Scale 10-18 al contexto colombiano para escenarios de oncología pediátrica, con una comprensibilidad global de los ítems mayores al 85% y un índice de validez de contenido de 0.71.

Children and adolescents with cancer face a series of changes in their family dynamics, social activity, they experience physical and psycho-emotional symptoms as a result of the disease and treatment. Understanding the prevalence and characteristics of symptoms in children with cancer has been hampered by the lack of validated assessment tools in this population. For nurses practice in pediatric oncology, it is crucial to recognize and manage the symptoms, as long as they have direct contact with the patients. Objective: To adapt culturally and validate the Memorial symptom assessment scale for children between 10-18 years of age in pediatric oncology in the Colombian context in 2018. Method: Study of validation scale that was developed in two phases; the first was the cultural adaptation of MSAS 10-18 to the Colombian context and the second phase of facial and content validation with expert in the phenomenon and adolescents with cancer between the ages described. Results: An adapted version of the Memorial Symptom Assessment Scale 10-18 was obtained in the Colombian context for pediatric oncology with a global comprehensibility of the items greater than 85% and a content validity index of 0.71

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.

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.

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.

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.

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.

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.

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.