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Norberto C Chavez-Tapia,1,2 Sofía Murúa-Beltrán Gall,1 Ana Luisa Ordoñez-Vázquez,1 Natalia Nuño-Lambarri,2 Paulina Vidal-Cevallos,1 Misael Uribe1 1Gastroenterology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico; 2Transational Research Department, Medica Sur Clinic & Foundation, Mexico City, MexicoCorrespondence: Norberto C Chavez-Tapia, Gastroenterology Department, Medica Sur Clinic & Foundation, Puente de Piedra 150. Col. Toriello Guerra, Tlalpan, Mexico City, CP 14050, Mexico, Email nchavezt@medicasur.org.mxAbstract: Hepatocellular carcinoma (HCC) and metabolic syndrome (MetS) have a rising prevalence worldwide. The relationship between these two entities has long been studied and understanding it has become a public health and clinical priority. This association follows, in most patients, the path through non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis and finally HCC. Nonetheless, increasing evidence has been found, that shows MetS as an independent risk factor for the development of HCC. This review brings together the clinical evidence of the relationship between these highly prevalent diseases, with a particular interest in the impact of each component of MetS on HCC; It aims to summarize the complex physiopathological pathways that explain this relationship, and to shed light on the different clinical scenarios of this association, the impact of treating the different components of MetS on the risk of HCC and what is known about screening for HCC in patients with MetS. By doing so, it hopes to improve awareness on this topic.Keywords: metabolic syndrome, hepatocellular carcinoma, excess body weight, diabetes mellitus, non-alcoholic fatty liver disease

This paper presents a teaching sequence explicitly designed to improve the understanding of Nature of Science and support Secondary School students to acquire adequate understanding about scientific hypothesis, theories and laws. The instructional intervention engages students in an inquiry process where they have to formulate hypothesis, analyse data and draw conclusions based on evidence. It is a student-centred methodology where teachers act as facilitators and guides, promoting the development of scientific competences and the meaningful understanding of the terms hypothesis, law and theory.

En este estudio se presenta la aplicación del Cuestionario de Opiniones de Ciencia,Tecnología y Sociedad (COCTS) con una nueva metodología de respuesta múltiple para la evaluación más válida y significativa de las actitudes relacionadas con los temas Ciencia, Tecnología y Sociedad (CTS) de una muestra de estudiantes, así como la eficacia de un curso correspondiente a la asignatura “Ciencia, Tecnología y Sociedad” de bachillerato para modificar las creencias y actitudes iniciales del alumnado. Se analiza esta metodología, su validez para el contraste estadístico de hipótesis y su capacidad para evaluar de manera más precisa, cualitativa y cuantitativamente, las creencias y actitudes CTS del alumnado con el objeto de dar cuenta de los cambios que se producen después de su participación en el curso CTS.

OBJETIVO: Describir los resultados de la vigilancia de tuberculosis en trabajadores de la salud en un centro hospitalario de tercer nivel. MATERIAL Y MÉTODOS: Se revisaron los registros de vigilancia de trabajadores durante 1992-1998, analizando variables demográficas, laborales, antecedentes clínicos, así como pruebas previas, prueba de la tuberculina (PPD), refuerzos y seguimiento. Como medida de asociación se utilizó la razón de momios (RM) con su respectiva significancia y los intervalos de confianza; la comparación entre diferentes subgrupos se realizó con la prueba ji², y se determinó tiempo de conversión con análisis de Kaplan Meier. RESULTADOS: Se vigilaron 1 617 trabajadores, 68%, mujeres y 32%, hombres. La edad promedio fue 26.9±7.6 (15-68) años. Del total, 30.5% eran enfermeras; 14.6%, médicos residentes, y 14.1%, internos. Un 65.8% provenía del Distrito Federal. El 71.6% tenía BCG, y 15.1%, PPD previo. El PPD al ingreso fue positivo en 39.6% de los casos; negativo, en el 48.3%, y sin lectura, en el 12.1% restante. Se aplicaron 483 refuerzos (booster) en aquellos inicialmente negativos, y se encontraron 49 positivos. Se vigiló la conversión a PPD+ por aplicaciones periódicas en 231 trabajadores, y se encontró dicha conversión en 100 de ellos (43.3%). El tiempo promedio para detectar la conversión fue de 22.8±12.4 meses. La tasa de conversión a los 12 meses fue de 20%. Únicamente 50 trabajadores (50%) recibieron y aceptaron profilaxis con isoniazida. CONCLUSIONES: Un alto porcentaje de trabajadores son PPD+ al ingreso. Los refuerzos detectan 10% más de casos. La tasa de conversión enfatiza la necesidad de organizar estos programas en México.

Abstract Background The creation of a coherent genomic map of recent selection is one of the greatest challenges towards a better understanding of human evolution and the identification of functional genetic variants. Several methods have been proposed to detect linkage disequilibrium (LD), which is indicative of natural selection, from genome-wide profiles of common genetic variations but are designed for large regions. Results To find population-specific LD within small regions, we have devised an entropy-based method that utilizes differences in haplotype frequency between populations. The method has the advantages of incorporating multilocus association, conciliation with low allele frequencies, and independence from allele polarity, which are ideal for short haplotype analysis. The comparison of HapMap SNPs data from African and Caucasian populations with a median resolution size of ~23 kb gave us novel candidates as well as known selection targets. Enrichment analysis for the yielded genes showed associations with diverse diseases such as cardiovascular, immunological, neurological, and skeletal and muscular diseases. A possible scenario for a selective force is discussed. In addition, we have developed a web interface (ENIGMA, available at http://gibk21.bse.kyutech.ac.jp/ENIGMA/index.html), which allows researchers to query their regions of interest for population-specific LD. Conclusion The haplotype entropy method is powerful for detecting population-specific LD embedded in short regions and should contribute to further studies aiming to decipher the evolutionary histories of modern humans.

Abstract Background The Rio Grande River is the natural boundary between U.S. and Mexico from El Paso, TX to Brownsville, TX. and is one of the major water resources of the area. Agriculture, farming, maquiladora industry, domestic activities, as well as differences in disposal regulations and enforcement increase the contamination potential of water supplies along the border region. Therefore, continuous and accurate assessment of the quality of water supplies is of paramount importance. The objectives of this study were to monitor water quality of the Rio Grande and to determine if any correlations exist between fecal coliforms, E. coli, chemical toxicity as determined by Botsford's assay, H. pylori presence, and environmental parameters. Seven sites along a 112-Km segment of the Rio Grande from Sunland Park, NM to Fort Hancock, TX were sampled on a monthly basis between January 2000 and December 2002. Results The results showed great variability in the number of fecal coliforms, and E. coli on a month-to-month basis. Fecal coliforms ranged between 0–106 CFU/100 ml while E. coli ranged between 6 to > 2419 MPN. H. pylori showed positive detection for all the sites at different times. Toxicity ranged between 0 to 94% of inhibition capacity (IC). Since values above 50% are considered to be toxic, most of the sites displayed significant chemical toxicity at different times of the year. No significant correlations were observed between microbial indicators and chemical toxicity. Conclusion The results of the present study indicate that the 112-Km segment of the Rio Grande river from Sunland Park, NM to Fort Hancock, TX exceeds the standards for contact recreation water on a continuous basis. In addition, the presence of chemical toxicity in most sites along the 112-Km segment indicates that water quality is an area of concern for the bi-national region. The presence of H. pylori adds to the potential health hazards of the Rio Grande. Since no significant correlation was observed between the presence of H. pylori antigens and the two indicators of fecal contamination, we can conclude that fecal indicators cannot be used to detect the presence of H. pylori reliably in surface water.

Parental support is crucial in the well-being of transgender and gender diverse (TGD) youth. Research shows that parents of TGD youth often experience stigma and negative mental health outcomes as a result of being exposed to cissexist settings as they advocate and seek services for their child. Yet, there is a lack of research on the experiences of parents of TGD youth in the United States. This study explores the reported hopes of 990 parents ( M age = 48.6 years; SD = 6.7; 88.1% White; 67.3% heterosexual; 89.4% cisgender women) of TGD youth for their children (youth ages 3-18 years) in the United States. Radical hope framework is applied to unpack narratives of hopes by parents of TGD youth as a critical component of resistance and motivation toward healing from oppression. For this study, the following open-ended question was analyzed using thematic analysis: What is your greatest hope for your child ? Four main themes and 11 subthemes of parental hopes emerged: (1) living authentically (freely expressing themselves, developing self-love, living a happy and normal life), (2) interpersonal connections (finding community, building social networks and friendships, developing romantic relationships, building their own family, and loved by others), (3) meeting life milestones (career and employment, achieving goals and dreams, and becoming an advocate), and (4) acceptance by society. We provide clinical recommendations grounded on the tenets of radical hope such as collective ways in which parents of TGD youth can engage in both resisting systemic oppression and building strong loving relationships with their child. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary In this case, authors describe a successful endoscopic papillectomy for the management of ampullary neuroendocrine tumor (NET). Duodenal NETs are uncommon. with a prevalence of 2.6% of all NETs. Ampullary NETs are exceedingly rare, with a <0.3% incidence of all GI NETs. Ampullary NET has an aggressive nature by default, with a higher tendency for metastasis regardless of tumor size. As such, it is essential to thoroughly assess patients with ampullary NETs for local and distant metastasis before endoscopic resection. Patients with ampullary NETs that are well differentiated and low grade, without involvement of the pancreatic or bile duct, and without peritoneal lymphadenopathy or distant metastasis, are ideal candidates for endoscopic resection. Although endoscopic papillectomy is an excellent alternative for pancreaticoduodenectomy, it is associated with a higher risk of pancreatitis. The risk of postprocedure pancreatitis is substantial, ranging between 6% and 58% in published reports. This risk can be potentially decreased with prophylactic placement of biliary and pancreatic stents. In consideration of the aggressive naure of these tumors, close surveillance after resection with serial endoscopy and radiologic imaging is recommended. Tara Keihanian, MD, MPH, Assistant Professor, Division of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA. Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Caregiver strain or stress directly related to caring for a youth with emotional and/or behavioral problems may be an important and understudied cultural factor associated with mental health disparities among Latinx families. Caregiver strain is a highly relevant construct for research questions focused on the identification of youth's mental health needs, family-level impacts of youth mental health problems, and utilization of youth mental health services. Unfortunately, there is a dearth of research on measures of caregiver strain and the psychometric properties of existing measures in Latinx samples. This study examined the structural and construct validity of the English version of the Caregiver Strain Questionnaire (CGSQ) with a sample of United States-based Latinx caregivers of youths ages 6-18 (N = 598). Confirmatory factor analysis showed that the original three-factor model of caregiver strain was evidenced in this sample. Internal consistency analyses and a poor factor loading led to the elimination of one item. The factor structure held after item removal. Significant associations between each dimension of caregiver strain with youth internalizing/externalizing symptom severity and utilization of youth mental health services provided evidence of construct validity (i.e., psychological counseling, telepsychology, parenting classes). Results provide important evidence of the psychometric properties of the English CGSQ in a Latinx sample and support its use in future research aimed at unpacking mental health disparities among Latinx youth and families. Researchers should translate and validate the CGSQ in Spanish to increase the utility of this measure for research with Latinx families., (© 2024 Family Process Institute.)

Latinx families face unique barriers to accessing traditional youth mental health services and may instead rely on a wide range of supports to meet youth emotional or behavioral concerns. Previous studies have typically focused on patterns of utilization for discrete services, classified by setting, specialization, or level of care (e.g., specialty outpatient, inpatient, informal supports), yet little is known about how youth support services might be accessed in tandem. This analysis used data from the Pathways to Latinx Mental Health study - a national sample of Latinx caregivers (N = 598) from across the United States collected at the start of the coronavirus pandemic (i.e., May-June 2020) - to describe the broad network of available supports that are used by Latinx caregivers. Using exploratory network analysis, we found that the use of youth psychological counseling, telepsychology, and online support groups was highly influential on support service utilization in the broader network. Specifically, Latinx caregivers who used one or more of these services for their child were more likely to report utilizing other related sources of support. We also identified five support clusters within the larger network that were interconnected through specific sources of support (i.e., outpatient counseling, crisis, religious, informal, and non-specialty). Findings offer a foundational look at the complex system of youth supports available to Latinx caregivers, highlighting areas for future study, opportunities to advance the implementation of evidence-based interventions, and channels through which to disseminate information about available services., (© 2023 Family Process Institute.)

Whether Latinx families use youth mental health services (MHS) depends on complex influences of barriers and facilitators within and outside of the home. This research sought to shed light on caregiver strain as part of the equation focused on parental identification and responses to youth mental health needs. We examined multiple dimensions of caregiver strain as potential mediators between youth mental health symptom severity and psychological counseling utilization. The present sample consisted of 598 Latinx caregivers to youths ages 6-18 who provided information on youth internalizing and externalizing problems, caregiver strain, and youth psychological counseling service utilization within the last year. Our findings suggest that youth symptom severity (internalizing and externalizing problems) was generally positively associated with dimensions of caregiver strain. Youth symptom severity through objective and subjective internalized strain pathways were associated with greater odds of youth MHS utilization. In contrast, youth symptom severity through subjective externalized strain reduced the odds that Latinx caregivers would report utilizing youth MHS. These models only partially mediated the relationship between youth problems and service use. Findings suggest that Latinx caregivers may navigate conflicting sources of strain related to their child's mental health problem severity in ways that may differentially impact the odds that they access youth MHS. Along with addressing structural and systemic barriers to care, utilization of psychological counseling services may also be improved through interventions that help Latinx caregivers view youth services as avenues for addressing caregiver strain and providing psychoeducation that frames externalized strain within a mental health lens., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (Copyright: © 2024 Vázquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The COVID-19 pandemic led countries' governments to rapidly establish lockdowns and social distancing, which altered family routines and the quality of family relationships worldwide., Objectives: This exploratory cross-sectional study aimed to identify the impacts of the social distancing and lockdown in parenting practices of caregivers from Brazil, Mexico, and the USA, and to analyze the continuity of parenting intervention support for children and their families at the beginning of the pandemic in these countries., Methods: The sample consisted of 704 caregivers of children (286 from Brazil, 225 from Mexico, and 193 from the USA) who answered an online survey about parenting practices before/after quarantine, caregiver/child routines, feelings related to quarantine, changes in everyday life since the beginning of the COVID-19 pandemic, contact with health professionals, and sources of parenting information., Results: Data indicate that caregivers from the three countries experienced similar parenting practices during this time, and did not report significant changes before and after the lockdown. They sought information about parenting predominantly via social media. Those receiving previous mental health care perceived the transition from in-person to telehealth services during the pandemic as feasible and acceptable., Conclusion: This study will be helpful for clinicians and parents to contextualize their practices amid long-standing effects that the COVID-19 pandemic can have on children and their families during and post-pandemic from multiple cultural backgrounds., (© 2024. The Author(s).)

Youth exposed to natural disasters are at risk of developing trauma-related symptoms as well as engaging in substance use. Although previous research has established associations between disaster-related stressors and substance use in youth, less has focused on how symptoms of posttraumatic stress disorder (PTSD) may underpin this association. The current study used network analysis to identify specific PTSD symptoms associated with substance use following a natural disaster. Participants were 91,732 youths (Grades 3-12) from across Puerto Rico who completed a needs assessment 5-9 months after Hurricane Maria made landfall in September 2017. We examined associations between PTSD symptoms and substance use, identified clusters of symptoms and bridges between them, and explored age- and binary gender-related differences in associations between specific PTSD symptoms and substance use. Analyses identified two symptom communities: (a) arousal and reactivity, negative alterations in cognition and mood, and substance use, and (b) avoidance and intrusion. Broader findings suggested that substance use was most strongly associated with PTSD-related irritability and angry outbursts among youths. Surrounding nodes explained only 4.1% of the variance in substance use, but this was higher among youths who reported not having a supportive adult, R 2 = 8.5; friend, R 2 = 7.9; or teacher/counselor, R 2 = 7.7, in their life. The bridge symptoms of sleep disruption and physiological reactivity were identified as potentially critical intervention targets for disrupting PTSD symptom networks after a natural disaster. Implications for triaged mental health care following natural disasters and directions for future research are discussed., (© 2024 International Society for Traumatic Stress Studies.)

Hamelia patens (Rubiaceae), known as firebush, is a source of bioactive monoterpenoid oxindole alkaloids (MOAs) derived from monoterpenoid indole alkaloids (MIAs). With the aim of understanding the regulation of the biosynthesis of these specialized metabolites, micropropagated plants were elicited with jasmonic acid (JA) and salicylic acid (SA). The MOA production and MIA biosynthetic-related gene expression were evaluated over time. The production of MOAs was increased compared to the control up to 2-fold (41.3 mg g DW -1 ) at 72 h in JA-elicited plants and 2.5-fold (42.4 mg g DW -1 ) at 120 h in plants elicited with SA. The increment concurs with the increase in the expression levels of the genes HpaLAMT , HpaTDC , HpaSTR , HpaNPF2.9 , HpaTHAS1 , and HpaTHAS2. Interestingly, it was found that HpaSGD was downregulated in both treatments after 24 h but in the SA treatment at 120 h only was upregulated to 8-fold compared to the control. In this work, we present the results of MOA production in H. patens and discuss how JA and SA might be regulating the central biosynthetic steps that involve HpaSGD and HpaTHAS genes.

E-cigarette use among adolescents is a national health epidemic spreading faster than researchers can amass evidence for risk and protective factors and long-term consequences associated with use. New technologies, such as machine learning, may assist prevention programs in identifying at risk youth and potential targets for intervention before adolescents enter developmental periods where e-cigarette use escalates. The present study utilized machine learning algorithms to explore a wide array of individual and socioecological variables in relation to patterns of lifetime e-cigarette use during early adolescence (i.e., exclusive, or with tobacco cigarettes). Extant data was used from 14,346 middle school students (Mage = 12.5, SD = 1.1; 6th and 8th grades) who participated in the Utah Prevention Needs Assessment. Students self-reported their substance use behaviors and related risk and protective factors. Machine learning algorithms examined 112 individual and socioecological factors as potential classifiers of lifetime e-cigarette use outcomes. The elastic net algorithm achieved outstanding classification for lifetime exclusive (AUC = .926) and dual use (AUC = .944) on a validation test set. Six high value classifiers were identified that varied in importance by outcome: Lifetime alcohol or marijuana use, perception of e-cigarette availability and risk, school suspension(s), and perceived risk of smoking marijuana regularly. Specific classifiers were important for lifetime exclusive (parent's attitudes regarding student vaping, best friend[s] tried alcohol or marijuana) and dual use (best friend[s] smoked cigarettes, lifetime inhalant use). Our findings provide specific targets for the adaptation of existing substance use prevention programs to address early adolescent e-cigarette use., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vázquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A lack of validated measures to examine barriers to youth telepsychology services among Latinx families limits research that could identify targets for reducing mental health disparities. We developed and validated the Latinx Barriers to Accessing Telepsychology Services (Latinx BATS) questionnaire, a brief multidimensional measure for caregivers of youths. Participants included 511 Latinx caregivers of youths Ages 6-18 (English n = 275, Spanish n = 236) who completed the Latinx BATS and reported on telepsychology service utilization and youth mental health problems. Caregivers whose youths had clinically elevated mental health problems were more likely to report barriers to accessing youth telepsychology services compared to nonclinical youths. Commonly endorsed barriers included concerns that the child would be distracted and not get much benefit, and that providers would be unfamiliar with the family's culture or would not pick up on nuances and emotions. Loadings from an exploratory graph analysis returned four-factors: relational, acceptability, quality, and access concerns. Network centrality measures identified provider knowledge regarding community resources and Latinx culture as important targets for reducing barriers to youth telepsychology services. Confirmatory factor analyses were then conducted and found that the four-factor structure outperformed a single-factor solution. The four-factor structure was similar for the English and Spanish versions of the Latinx BATS, but the strength of item loadings varied across languages. Implications for the use of the Latinx BATS in research and clinical practice are discussed including specific strategies for reducing these obstacles to care among Latinx families. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: A disproportionate number of COVID-19 cases and deaths have been reported among Latinxs in the U.S. Among those most affected by the pandemic are marginalized families, including those that are undocumented and mixed-status, in which some, but not all members are undocumented. Undocumented and mixed-status families face multiple and chronic daily stressors that compromised their health and wellbeing. Salient stressors faced by undocumented Latinx families include poverty, social disadvantage, discrimination, dangerous living and working conditions, and limited access to healthcare. These stressors are frequently compounded with trauma, fear of detention, deportation, and family separation., Purpose: Informed by the literature and insights from our community-based work to address the health needs of undocumented and mixed status Latinx families during the pandemic, this paper uses a social determinants of health lens to present a narrative summary that highlights four primary psychosocial stressors faced by these families and their implications for mental health., Discussion: These include stressors pertaining to (a) anti-immigrant rhetoric and actions; (b) family stressors and disruptions in family dynamics; (c) economic changes and financial losses; and (c) limited access to healthcare. Implications of the aforesaid stressors on the mental health of undocumented families and youth are also discussed. In addition, recommendations are provided for the provision of mental health services, best practices, and resources from a strengths-based approach.

Cholestasis is a condition characterized by decrease in bile flow due to progressive pathological states that lead to chronic cholestatic liver diseases which affect the biliary tree at the intrahepatic level and extrahepatic level. They induce complications such as cirrhosis, liver failure, malignancies, bone disease and nutritional deficiencies that merit close follow-up and specific interventions. Furthermore, as those conditions progress to liver cirrhosis, there will be an increase in mortality but also an important impact in quality of life and economic burden due to comorbidities related with liver failure. Therefore, it is important that clinicians understand the treatment options for cholestatic liver diseases. With a general view of therapeutic options and their molecular targets, this review addresses the pathophysiology of cholangiopathies. The objective is to provide clinicians with an overview of the safety and efficacy of the treatment of cholangiopathies based on the current evidence.

Research examining the effects of traumatic events on undocumented Latinx immigrants often focuses on assessing posttraumatic stress disorder or general psychological distress, which may obscure the field's understanding of how trauma exposure impacts other common mental health disorders (e.g., anxiety, depression). This study sought to assess the cumulative, individual, and timing effects of immigration-related traumatic events on anxiety and depressive symptoms among undocumented Latinx immigrants. Participants were 253 undocumented Latinx immigrants recruited using respondent-driven sampling who reported their history of immigration-related trauma exposure and symptoms of depression and anxiety. Results suggest that cumulative immigration-related trauma was significantly associated with increases in anxiety and depressive symptoms, τ = .26. Significant positive correlations were found for cumulative trauma at each point in the immigration process (i.e., before immigration, while in transit to the United States, and while living in the United States) such that increases in the number of events were associated with higher anxiety and depressive symptom levels, τ = .11-.29. Trauma frequency differed throughout the immigration process such that some events more commonly occurred before immigration or during transit to the United States, whereas others occurred while an individual resided in the United States. Random forest algorithms uncovered differences in the relative importance of individual traumatic events in explaining the variance of depressive, R 2 = .13, and anxiety symptoms, R 2 = .14. The findings highlight the importance of providing trauma-informed care when treating anxiety and depression among undocumented Latinx immigrants and considering multidimensional epidemiological approaches in assessing immigration-related trauma., (© 2023 International Society for Traumatic Stress Studies.)

Sleep-related problems often precede escalating anxiety in early adolescence. Pushing beyond broad sleep-mental health associations and toward mechanistic theories of their interplay can inform etiological models of psychopathology. Recent studies suggest that sleep depotentiates neural (e.g., amygdala) reactivity during reexposure to negative emotional stimuli in adults. Persistent amygdala reactivity to negative experiences and poor sleep characterize anxiety, particularly at the transition to adolescence. We propose that sleep depotentiates amygdala reactivity in youth but fails to do so among youth with anxiety. Participants (n = 34; 18 males; age, mean [M] = 11.35, standard deviation [SD] = 2.00) recruited from the community and specialty anxiety clinics viewed valenced images (positive, negative, and neutral) across two fMRI sessions (Study, Test), separated by a 10-12-hour retention period of sleep or wake (randomized). Mixed linear models regressed basolateral amygdala (BLA) activation and BLA-medial prefrontal cortex (mPFC) functional connectivity to negative images on Time, Condition, and Anxiety Severity. There were greater reductions in BLA activations to negative target images from Study to Test in the Sleep Condition, which was blunted with higher anxiety (b = -0.065, z = -2.355, p = 0.019). No such sleep- or anxiety-related effects were observed for BLA-mPFC functional connectivity (ps > 0.05). Sleep supports depotentiation of amygdala reactivity to negative stimuli in youth, but this effect is blunted at higher levels of anxiety. Disruptions in sleep-related affective habituation may be a critical, modifiable driver of anxiety., (© 2023. The Psychonomic Society, Inc.)

Neither the Pseudomonas aeruginosa aldehyde dehydrogenase encoded by the PA4189 gene nor its ortholog proteins have been biochemically or structurally characterized and their physiological function is unknown. We cloned the PA4189 gene, obtained the PA4189 recombinant protein, and studied its structure-function relationships. PA4189 is an NAD+-dependent aminoaldehyde dehydrogenase highly efficient with protonated aminoacetaldehyde and 3-aminopropionaldehyde, which are much more preferred to the non-protonated species as indicated by pH studies. Based on the higher activity with aminoacetaldehyde than with 3-aminopropionaldehyde, we propose that aminoacetaldehyde might be the PA4189 physiological substrate. Even though at the physiological pH of P. aeruginosa cells the non-protonated aminoacetaldehyde species will be predominant, and despite the competition of these species with the protonated ones, PA4189 would very efficiently oxidize ACTAL in vivo, producing glycine. To our knowledge, PA4189 is the first reported enzyme that might metabolize ACTAL, which is considered a dead-end metabolite because its consuming reactions are unknown. The PA4189 crystal structure reported here suggested that the charge and size of the active-site residue Glu457, which narrows the aldehyde-entrance tunnel, greatly define the specificity for small positively charged aldehydes, as confirmed by the kinetics of the E457G and E457Q variants. Glu457 and the residues that determine Glu457 conformation inside the active site are conserved in the PA4189 orthologs, which we only found in proteobacteria species. Also is conserved the PA4189 genomic neighborhood, which suggests that PA4189 participates in an uncharacterized metabolic pathway. Our results open the door to future efforts to characterize this pathway., (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

A critical step to reduce the spread of COVID-19 is vaccination. We conducted a mixed methods project that used online surveys and focus groups with 64 Community Health Workers and Promotor/as (CHW/Ps) located near the U.S.-Mexico border to identify barriers and facilitators to COVID-19 vaccination among Latino communities that have been historically underrepresented and medically underserved. Overall, personal barriers to vaccination included mistrust of manufacturers and administrators as well as fear of: becoming infected from the vaccine, discrimination/stigmatization from healthcare professionals administering the vaccine, exploitation/manipulation by the government or health authorities, and having personal information mishandled. Environmental and community barriers included being undocumented and fear-inducing myths and beliefs. Additional barriers included limited information and logistics pertaining to vaccination access. Targeted efforts are needed to overcome barriers in a culturally and contextually sensitive manner to prevent harm and reduce risk of infection among communities that have been historically underrepresented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garcini, Ambriz, Vázquez, Abraham, Sarabu, Abraham, Lucas-Marinelli, Lill and Tsevat.)

Background: Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Recently, the term metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed and adapted to body mass index (BMI). This study describes the impact on prevalence of the application of both criteria in overweight and lean patients., Methods: Patients who were evaluated for liver steatosis by transient elastography were included and divided according to BMI (≥25 kg/m 2 and <25 kg/m 2 ) and classified as NAFLD or MAFLD, according to metabolic abnormalities. Differences in prevalence were evaluated applying both criteria. A multivariate analysis was performed to evaluate independent associations of metabolic abnormalities and liver steatosis in lean patients., Results: 3847 patients were included. In overweight patients (61%), the prevalence NAFLD was 63.6% and 65.3% for MAFLD ( p = 0.22). In contrast, the prevalence of MAFLD was lower (7.9% vs. 18.3%, p ≤ 0.001) in lean patients. In this group, higher age, fasting glucose, triglycerides, and waist circumference showed independent association with liver steatosis., Conclusion: The application of NAFLD/MAFLD criteria did not show prevalence differences in overweight patients. With MAFLD criteria, the prevalence is lower in lean patients, but patients with high risk of progression of liver disease for steatosis were identified, according to their metabolic abnormalities.

Measuring cultural competence has been difficult for conceptual and practical reasons. Yet, professional guidelines and stated values call for training to improve cultural competence. To develop a strong evidence-base for training and improving cultural competence, professionals need reliable and valid measures to capture meaningful changes in cultural competence training. We developed a measure for cultural competence that could be used in a general population to measure changes in awareness, knowledge, and skills in interacting with culturally diverse others. We built an 81-item scale with items conceptually categorized into awareness, knowledge, and skills and was presented to an expert panel for feedback. For evaluation, a national panel of 204 adults responded to the new scale and other measures associated with cultural competence. Factor analysis revealed four factors with strong reliabilities: Awareness of Self, Awareness of Others, Proactive Skills Development, and Knowledge (as = .87 - .92). The final overall scale, Awareness, Knowledge, Skills-General (ASK-G) had 37 items and strong reliability (a = .94). The ASK-G was then compared to validated scales to provide evidence of concurrent, convergent, and divergent validity. Strong evidence emerged for these. The ASK-G is a promising tool to measure cultural competence in a general population., Competing Interests: The authors have declared that no competing interests exist.

The current study (1) characterizes patterns of mental health service utilization over 8 years among youth who received psychotherapy in the context of a community implementation of multiple evidence-based practices (EBPs), and (2) examined youth-, provider- and service-level predictors of service use patterns. Latent profile analyses were performed on 5,663,930 administrative claims data furnished by the county department of mental health. Multinomial logistic regression with Vermunt's method was used to examine predictors of care patterns. Based on frequency, course, cost, and type of services, three distinct patterns of care were identified: (1) Standard EBP Care (86.3%), (2) Less EBP Care (8.5%), and (3) Repeated/Chronic Care (5.2%). Youth age, ethnicity, primary language, primary diagnosis and secondary diagnosis, provider language and provider type, and caregiver involvement and service setting were significant predictors of utilization patterns. Although the majority of youth received care aligned with common child EBP protocols, a significant portion of youth (13.7%) received no evidence-based care or repeated, costly episodes of care. Findings highlight opportunities to improve and optimize services, particularly for youth who are adolescents or transition-aged, Asian-American/Pacific Islander, Spanish-speaking, or presenting with comorbidities., (© 2021. The Author(s).)

Background: Few existing evidence-based parent interventions (EBPIs) for prevention and treatment of child and youth mental health disorders are implemented in low-middle-income countries. This study aimed to translate and confirm the factor structure of the Evidence-Based Practice Attitude Scale (EBPAS-15) survey in Brazilian Portuguese with the goal of examining providers' perspective about EBPIs., Methods: We translated and back translated the EBPAS-15 from English to Brazilian Portuguese. Participants were recruited via snowball sampling and data were collected using an online survey from July of 2018 through January of 2020. A confirmatory factor analysis was conducted to determine if the scale retained its original structure. Open-ended questions about providers' perspectives of their own clinical practice were coded using the Theoretical Domains Framework (TDF). Analyses included data from 362 clinicians (318 women, 41 men) from 20 of the 27 states of Brazil. Participants on average were 26.7 years old, held specialist degrees in the field of psychology, actively worked as therapists, and practiced in private clinics., Results: The translation of the EBPAS to Brazilian Portuguese retained the same four-factor structure as the English version except for dropping one item from the Divergence domain. When asked about the challenges in their practices, providers generally referred to parents as clients with little skills to discipline their children and lacking knowledge about child development., Discussion: The Brazilian version of the EBPAS-15 is promising, but future research should consider using quantitative data alongside qualitative information to better understand providers' attitudes about evidence-based interventions to inform implementation efforts., Trial Registration: N/A., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Knowledge regarding barriers faced by Latina/o/x caregivers in accessing youth mental health services (MHS) have largely depended on resource intensive interview-based assessments., Objective: We evaluated a questionnaire for Latina/o/x caregivers of youths that presents a briefer and more feasible alternative., Method: We conducted a psychometric evaluation of the Barriers to Treatment Questionnaire - Latina/o/x Caregivers (BTQ-LC) with a sample of 598 Latina/o/x caregivers from across the United States. Descriptive statistics and confirmatory factor analyses were used to identify common barriers to services, confirm the factor structure of the scale, and establish construct validity., Results: Descriptive statistics suggest that not knowing where and how to access services, and normalization of youth psychopathology were the most frequently reported barriers among caregivers of youth with clinically elevated problems on the CBCL. Confirmatory factor analysis suggests that the BTQ-LC was best represented by a three-factor structure: (1) structural, (2) perceptions regarding mental health problems, and (3) services. Our finding suggest that the BTQ-LC could also be used as a single factor as fit indices ranged from acceptable to poor. BTQ-LC scales were all negatively correlated with the utilization of common youth MHS (i.e., psychological counseling, medical doctors, school professionals)., Conclusions: The BTQ-LC represents an important step towards improving our understanding and assessment of barriers to services contributing to mental health disparities among Latina/o/x youths., Competing Interests: Conflicts of interest/Competing interestsThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Adolescents with a history of child maltreatment experience increased risk for psychopathology that sets them on a trajectory towards a range of difficulties in adulthood. Various factors influence caregivers' decisions to seek mental health services (MHS) that could improve developmental outcomes. The present study applied a machine learning algorithm, elastic net, to a sample of 878 adolescent-caregiver dyads from the Longitudinal Studies of Child Abuse and Neglect. Analyses simultaneously examined a large number of factors to determine their ability to discriminate between caregivers who perceived a need for MHS and those who did not, as well as caregivers who utilized MHS and those who did not. Results highlight family demographics, chronic parental stressors, youth psychopathology, and exposure to recent adversities as good classifiers of caregiver perceived need for (77.6%; sensitivity = .77; specificity = .78) and utilization of (71%; sensitivity = .71; specificity = .71) adolescent MHS. Elastic net identified adolescent clinical externalizing and internalizing problems, and parental stress related to child(ren)'s behavior as high value classifiers of both outcomes. Youth living with non-kin caregivers were also significantly more likely to utilize MHS. Findings highlight the importance of assessing clinical need, stress related to child(ren)'s behavior, and caregiver kinship in understanding the likelihood that at-risk families will seek adolescent MHS., Competing Interests: The authors have declared that no competing interests exist.

The registered incidence of nonalcoholic fatty liver disease (NAFLD) in primary healthcare centers is lower than expected, suggesting a lack of awareness by primary care healthcare professionals. The implementation of educational tools for healthcare workers has been found to increase timely referral and treatment of patients. We aimed to determine healthcare workers' knowledge of NAFLD to identify their educational needs in one marginalized region. We performed a cross-sectional survey of 261 healthcare professionals in Tlapa de Comonfort, Guerrero, Mexico from October 2019 to December 2019. We created a questionnaire that assessed domains most relevant to NAFLD knowledge. Two hundred and forty-six questionnaires were completed. Of the respondents, 38.3% were nurses and 63.4% were women. Most nurses identified NAFLD as a prevalent (89%) and preventable (93%) disease. Hypertension (33%) and obesity (84%) were recognized as risk factors. The associations between NAFLD and cancer, cirrhosis and cardiovascular disease were identified by 53%, 67% and 72% of respondents, respectively. The largest gaps were found in diagnostic workup, therapeutic approach and the current treatments. We identify modifiable knowledge gaps in NAFLD. Educational strategies for primary care workers could enhance the identification of patients with NAFLD and prevent complications.

Background: Youth who are victimized by violence are at heightened risk for substance use (SU) during adolescence, a period characterized by elevated impulsivity and risk-taking behavior. This risk may be magnified by attention-deficit/hyperactivity disorder (ADHD)., Objective: To examine risk/protective factors for adolescent SU among adolescents at-risk for victimization and whether ADHD moderates these associations., Participants and Setting: Participants were 1058 caregiver-adolescent dyads in the U.S. who participated in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN)., Method: Binary logistic regression analyses were conducted for each SU type. First-order effects of all variables were tested first and for each SU outcome, followed by tests of two-way interactions between ADHD group and each predictor, after controlling for first-order effects., Results: More externalizing behavior (odds ratio [OR] = 1.38; 95 % confidence interval [CI]:1.12, 1.71) and less parental knowledge (OR = .75; 95 %CI: .60, .95) were associated with greater risk for subsequent tobacco use. Less positive peer affiliation was associated with greater risk for subsequent illicit SU (OR = .59; 95 %CI: .36, .96). More deviant peer affiliation were associated with greater risk for all forms of SU. ADHD moderated the association between deviant peer affiliation and marijuana use [b = .9, p < .05, 95 %CI: .03, 1.77), such that deviant peer affiliation was a significantly stronger predictor of marijuana use among adolescents with ADHD than those without., Conclusions: Findings suggest risk and protective factors for SU are largely consistent for adolescents at-risk for victimization with and without ADHD, but at-risk adolescents with ADHD may be more susceptible to deviant peer influences., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Antecedentes: La patología de la próstata más frecuente es la hiperplasia prostática benigna. A los 50 años, el 50% de los hombres son diagnosticados y a los 80 años aumenta hasta al 90%. La prevalencia de disfunción eréctil en conjunto con hiperplasia prostática benigna es del 5.2-40%, y los pacientes con hiperplasia prostática benigna es 1.33-6.24 veces más frecuente que tengan disfunción eréctil que aquellos sin hiperplasia prostática benigna. Ambas afecciones repercuten en la calidad de vida., Objetivo: Identificar la calidad de vida y el grado de disfunción eréctil en pacientes con hiperplasia prostática benigna., Método: Estudio transversal, descriptivo, en pacientes con crecimiento prostático benigno a los cuales se les aplicaron dos cuestionarios: SF-12 para calidad de vida e Índice Internacional de Función Eréctil versión 5 para disfunción eréctil., Resultados: Fueron 101 pacientes, edad media de 66.5 ± 8.5 años, promedio físico de 38.68, promedio mental de 43.35, 14 de ellos sin disfunción eréctil y 38 con disfunción eréctil leve, 33 leve a moderada, 15 moderada y 1 grave., Conclusiones: Los pacientes con hiperplasia prostática benigna tienen una salud física mala y una salud mental buena. El 70.3% de los pacientes muestran grado leve o leve-moderado de disfunción eréctil., Background: The most frequent prostatic pathology is benign prostatic hyperplasia. By the age of 50, 50% are diagnosed with it and by the age of 80, it increases to 90%. The erectile dysfunction prevalence along benign prostatic hyperplasia is 5.2%-40%. Patients with benign prostatic hyperplasia are 1.33-6.24 times more likely to have erectile dysfunction tan without benign prostatic hyperplasia., Objective: To identify quality of life and to grade erectile dysfunction in patients with benign prostatic hyperplasia., Method: A transversal, descriptive study was conducted in patients with benign prostatic hyperplasia. Two questionnaires were applied: SF-12 for quality of life and IIEF-5 for erectile dysfunction., Results: 101 patients, mean age 66.5 ± 8.5 years, mean physical aspect 38.68, mean mental aspect 43.35, 14 without erectile dysfunction, 38 mild grade, 33 mild to moderate, 15 moderate and 1 severe., Conclusions: Benign prostatic hyperplasia patients have poor physical health and good mental health. 70.3% of patients have a grade of erectile dysfunction between mild and mild-moderate., (Copyright: © 2021 Permanyer.)

Machine learning provides a method of identifying factors that discriminate between substance users and non-users potentially improving our ability to match need with available prevention services within context with limited resources. Our aim was to utilize machine learning to identify high impact factors that best discriminate between substance users and non-users among a national sample (N = 52,171) of Mexican children (i.e., 5th, 6th grade; M age  = 10.40, SD age  = 0.82). Participants reported information on individual factors (e.g., gender, grade, religiosity, sensation seeking, self-esteem, perceived risk of substance use), socioecological factors (e.g., neighborhood quality, community type, peer influences, parenting), and lifetime substance use (i.e., alcohol, tobacco, marijuana, inhalant). Findings suggest that best friend and father illicit substance use (i.e., drugs other than tobacco or alcohol) and respondent sex (i.e., boys) were consistent and important discriminators between children who tried substances and those that did not. Friend cigarette use was a strong predictor of lifetime use of alcohol, tobacco, and marijuana. Friend alcohol use was specifically predictive of lifetime alcohol and tobacco use. Perceived danger of engaging in frequent alcohol and inhalant use predicted lifetime alcohol and inhalant use. Overall, findings suggest that best friend and father illicit substance use and respondent's sex appear to be high impact screening questions associated with substance initiation during childhood for Mexican youths. These data help practitioners narrow prevention efforts by helping identify youth at highest risk.

Objective: The objective of the study was to compare lower urinary tract symptoms and prostatic anatomic characteristic with prostatic enlargement in obese patients., Materials and Methods: A comparative and cross-sectional study was conducted from October 2018 to November 2018. Lower urinary tract symptoms were compared in patients with body mass index (BMI) 30-34.9 and BMI 35-39. To evaluate these symptoms, the International Prostatic Symptom Score (IPSS) was used on 537 patients. The variables were age, weight and size, BMI, prostatic volume measurement by ultrasound, prostate-specific antigen (PSA), and finasteride treatment. Descriptive statistic was used, Cronbach's alpha, Fisher's exact test, and Chi-square., Results: One hundred fulfilled inclusion criteria. Mean values were age 68.73 years, weight 84.98 kg, size 1.61 m, BMI 32.62, ultrasonographic prostatic size was 69.09 cm 3 , and PSA 1.94 ng/dl. The IPSS was severe in 3.6% (Group 1), 17.6% (Group 2); moderate 72% (Group 1), 70.5% (Group 2); and mild 33.3% (Group 1), 11.7% (Group 2), with significant differences between both groups (p = 0.05). Differences between values of prostatic volume and BMI did not show statistical significance (p ≥ 0.05)., Conclusion: Statistical association between obesity and severe obesity and lower urinary tract symptoms is positive., (Copyright: © 2020 Permanyer.)

Parents shape their children's behaviors and impact their developmental trajectories. Despite this, few studies have examined the potential relationship between child reported parenting factors and lifetime substance use and use intentions. The current study examined the potential impact of parenting factors (i.e., positive parenting, supervision, parental illicit substance use, substance-specific communication) on early substance use and intentions among Latinx children. Data for the present study utilized a representative sample of Mexican children (n = 52,171; 5th and 6th grades) who participated in a national survey on substance use. Children reported their demographics, lifetime substance use/intentions, and perceived parenting characteristic and practices. Child reported parental (i.e., individual or both parents) illicit substance use was associated with the largest increases in risk for reporting lifetime use of all substances examined. Higher levels of positive parenting were consistently associated with reductions in risk for reporting intentions for and use of all substances examined. Parent-child substance specific communication was not significantly related to child reported lifetime use or use intentions, with the exception of a minor decrease in the odds of reporting lifetime inhalant use. Supervision was associated with small to modest increase in risk. Substance use prevention efforts targeting Latinx populations may benefit from promoting positive parenting and direct supervision during childhood. Targeted prevention efforts may be needed for Latinx children exposed to parental illicit substance use, as they may be especially at risk for early substance initiation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Black caregivers may be more likely to have negative experiences with mental health services/providers and lack knowledge of psychopathology and mental health services relative to White caregivers. These perceptual and informational barriers could influence the likelihood that Black caregivers utilize psychological counseling and support services for their adolescents compared to White caregivers. The current study examined differences between Black and White caregivers in the associations between their adolescents' internalizing and externalizing problems and their perceptions of need for and utilization of psychological counseling and support services., Method: Data for the present study were collected from 741 diverse caregivers (63% Black, 37% non-Hispanic White) about their adolescents. Caregivers reported their adolescent's psychopathology and their perceptions of their adolescent's need for and utilization of psychological counseling, parenting classes, and youth mentoring programs., Results: Caregivers who reported that their adolescents had clinically elevated psychopathology were more likely to report a need for psychological counseling or support services in general. However, they were only more likely to report that their adolescents received psychological counseling services. Black caregivers were significantly less likely than White caregivers to report that their adolescent needed psychological counseling and were more likely than White caregivers to report that their adolescents needed a youth mentoring program if they had clinically elevated externalizing problems., Conclusions: Black caregivers may perceive mentoring programs as a less stigmatizing and more culturally congruent support service for addressing externalizing problems. Integration and dissemination of evidence-based intervention strategies to underserved populations using culturally acceptable intervention modalities is needed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A new, rapid, simple and specific method to determine 5-chloro 8-hydroxyquinoline (5-HQ) and 5,7-dichloro 8-hydroxyquinoline (5,7-HQ) stability in swine feed was optimized and validated. A system consisting of an ACQUITY UPLC BEH C 18 column (1.7 μm, 2.1 mm × 100 mm), a mobile phase of acetonitrile-0.1% o-phosphoric acid (55:45 v/v) with a 0.5 mL/min flow rate, and a PDA detector (247 nm) were used. The retention times of 5-HQ and 5,7-HQ, were 0.77 min and 1.6 min, respectively. The pure drug was subjected to acid and alkali hydrolysis, chemical oxidation and UV light degradation to perform forced degradation studies. 5,7-HQ was more susceptible to degradation than 5-HQ. The figures of merit of the method (linearity, accuracy, precision, and robustness) were determined. The method was successfully applied to estimate the stability of both analytes in medicated feed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.

Background: Current sequence-based approaches to identify enzyme functional shifts, such as enzyme promiscuity, have proven to be highly dependent on a priori functional knowledge, hampering our ability to reconstruct evolutionary history behind these mechanisms. Hidden Markov Model (HMM) profiles, broadly used to classify enzyme families, can be useful to distinguish between closely related enzyme families with different specificities. The (βα)8-isomerase HisA/PriA enzyme family, involved in L-histidine (HisA, mono-substrate) biosynthesis in most bacteria and plants, but also in L-tryptophan (HisA/TrpF or PriA, dual-substrate) biosynthesis in most Actinobacteria, has been used as model system to explore evolutionary hypotheses and therefore has a considerable amount of evolutionary, functional and structural knowledge available. We searched for functional evolutionary intermediates between the HisA and PriA enzyme families in order to understand the functional divergence between these families., Results: We constructed a HMM profile that correctly classifies sequences of unknown function into the HisA and PriA enzyme sub-families. Using this HMM profile, we mined a large metagenome to identify plausible evolutionary intermediate sequences between HisA and PriA. These sequences were used to perform phylogenetic reconstructions and to identify functionally conserved amino acids. Biochemical characterization of one selected enzyme (CAM1) with a mutation within the functionally essential N-terminus phosphate-binding site, namely, an alanine instead of a glycine in HisA or a serine in PriA, showed that this evolutionary intermediate has dual-substrate specificity. Moreover, site-directed mutagenesis of this alanine residue, either backwards into a glycine or forward into a serine, revealed the robustness of this enzyme. None of these mutations, presumably upon functionally essential amino acids, significantly abolished its enzyme activities. A truncated version of this enzyme (CAM2) predicted to adopt a (βα)6-fold, and thus entirely lacking a C-terminus phosphate-binding site, was identified and shown to have HisA activity., Conclusion: As expected, reconstruction of the evolution of PriA from HisA with HMM profiles suggest that functional shifts involve mutations in evolutionarily intermediate enzymes of otherwise functionally essential residues or motifs. These results are in agreement with a link between promiscuous enzymes and intragenic epistasis. HMM provides a convenient approach for gaining insights into these evolutionary processes.

Folates are tripartite molecules comprising pterin, para-aminobenzoate (PABA), and glutamate moieties, which are essential cofactors involved in DNA and amino acid synthesis. The obligately intracellular Chlamydia species have lost several biosynthetic pathways for essential nutrients which they can obtain from their host but have retained the capacity to synthesize folate. In most bacteria, synthesis of the pterin moiety of folate requires the FolEQBK enzymes, while synthesis of the PABA moiety is carried out by the PabABC enzymes. Bioinformatic analyses reveal that while members of Chlamydia are missing the genes for FolE (GTP cyclohydrolase) and FolQ, which catalyze the initial steps in de novo synthesis of the pterin moiety, they have genes for the rest of the pterin pathway. We screened a chlamydial genomic library in deletion mutants of Escherichia coli to identify the "missing genes" and identified a novel enzyme, TrpFCtL2, which has broad substrate specificity. TrpFCtL2, in combination with GTP cyclohydrolase II (RibA), the first enzyme of riboflavin synthesis, provides a bypass of the first two canonical steps in folate synthesis catalyzed by FolE and FolQ. Notably, TrpFCtL2 retains the phosphoribosyl anthranilate isomerase activity of the original annotation. Additionally, we independently confirmed the recent discovery of a novel enzyme, CT610, which uses an unknown precursor to synthesize PABA and complements E. coli mutants with deletions of pabA, pabB, or pabC. Thus, Chlamydia species have evolved a variant folate synthesis pathway that employs a patchwork of promiscuous and adaptable enzymes recruited from other biosynthetic pathways. Importance: Collectively, the involvement of TrpFCtL2 and CT610 in the tetrahydrofolate pathway completes our understanding of folate biosynthesis in Chlamydia. Moreover, the novel roles for TrpFCtL2 and CT610 in the tetrahydrofolate pathway are sophisticated examples of how enzyme evolution plays a vital role in the adaptation of obligately intracellular organisms to host-specific niches. Enzymes like TrpFCtL2 which possess an enzyme fold common to many other enzymes are highly versatile and possess the capacity to evolve to catalyze related reactions in two different metabolic pathways. The continued identification of unique enzymes such as these in bacterial pathogens is important for development of antimicrobial compounds, as drugs that inhibit such enzymes would likely not have any targets in the host or the host's normal microbial flora., (Copyright © 2014 Adams et al.)

Self-assembly, the process by which objects initially distributed at random arrange into well-defined patterns exclusively due to their local mutual interactions without external intervention, is generally accepted to be the most promising method for large-scale fabrication of functional nanostructures. In particular, the ordering of molecular building-blocks deposited at solid surfaces is relevant for the performance of many organic electronic and optoelectronic devices, such as organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs) or photovoltaic solar cells. However, the fundamental knowledge on the nature and strength of the intermolecular and molecule-substrate interactions that govern the ordering of molecular adsorbates is, in many cases, rather scarce. In most cases, the structure and morphology of the organic-metal interface is not known and it is just assumed to be the same as in the bulk, thereby implicitly neglecting the role of the surface on the assembly. However, this approximation is usually not correct, and the evidence gathered over the last decades points towards an active role of the surface in the assembly, leading to self-assembled structures that only in a few occasions can be understood by considering just intermolecular interactions in solid or gas phases. In this work we review several examples from our recent research demonstrating the apparently endless variety of ways in which the surface might affect the assembly of organic adsorbates., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery. Microneedles have been fabricated with a range of sizes, shapes, and materials. Most in vitro drug delivery studies have shown these needles to increase skin permeability to a broad range of drugs that differ in molecular size and weight. In vivo studies have demonstrated satisfactory release of oligonucleotides and insulin and the induction of immune responses from protein and DNA vaccines. Microneedles inserted into the skin of human subjects were reported to be painless. For all these reasons, microneedles are a promising technology to deliver drugs into the skin. This review presents the main findings concerning the use of microneedles in transdermal drug delivery. It also covers types of microneedles, their advantages and disadvantages, enhancement mechanisms, and trends in transdermal drug delivery.

Introduction: Rivastigmine transdermal patches for the treatment of Alzheimer's disease (AD) have potential benefits compared to capsules because of their sustained absorption through the skin, good local tolerability and reduction of gastrointestinal problems., Purpose: To assess gastrointestinal and skin tolerability and the need for optimal dose titration of rivastigmine transdermal patches in Alzheimer's disease patients previously treated with oral rivastigmine., Patients and Methods: A multicenter, randomized, open-label study including patients with mild to moderate AD (DSM-IV) previously treated with rivastigmine capsules (6-12 mg/day) was conducted. Patients were randomized to: continue with capsules for 3 months (n=49) or switch to rivastigmine patch without titration (9.5mg/day for 3 months; n=48), or switch to rivastigmine patch with titration (4.6 mg/day for 1 month followed by 9.5mg/day for 2 months, n=43)., Results: Incidence of gastrointestinal adverse events was 6.1% in the group treated orally and 4.2% in the group treated with non-titrated patches (P=.908). Skin tolerability was good (n=15, 16.7%) without any serious adverse events registered. Patch treatment was considered very easy to use by 72% of patients compared with 30% in the group with oral treatment (P=.0005). 60% of patients were satisfied with the patch, while only 14% were satisfied with capsules (P<.0001)., Conclusions: Rivastigmine patches have a tolerability profile similar to that shown by capsules, but are associated with greater patient satisfaction., (Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Candida spp. is a component of the endogenous flora of the digestive tract and can consequently form part of the etiology of almost any type of abdominal infection. Candida spp. is therefore frequently isolated in polymicrobial secondary peritonitis due to intestinal suture dehiscence. In these cases, there is no clear consensus on when Candida spp. isolation in peritoneal drainage fluid represents infection rather than colonization. The general recommendation is to interpret that there is infection when the sample containing the pathogen is intraoperative or has been obtained directly from the intraabdominal collection. When Candida spp. is cultured in samples from subsequently obtained drainage fluid, colonization is a possibility. However, when these cultures are accompanied by signs of sepsis, the patient shows severity criteria or Candida spp. is repeatedly isolated, most intensivists decide to begin antifungal therapy. This treatment is similar for candidemias, disseminated invasive candidiasis and Candida peritonitis., (Copyright © 2010 Elsevier España S.L. All rights reserved.)

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of high-voltage pulses to the skin increases its permeability (electroporation) and enables the delivery of various substances into and through the skin. The application of electroporation to the skin has been shown to increase transdermal drug delivery. Moreover, electroporation, used alone or in combination with other enhancement methods, expands the range of drugs (small to macromolecules, lipophilic or hydrophilic, charged or neutral molecules) that can be delivered transdermally. The efficacy of transport depends on the electrical parameters and the physicochemical properties of drugs. The in vivo application of high-voltage pulses is well tolerated, but muscle contractions are usually induced. The electrode and patch design is an important issue to reduce the discomfort of the electrical treatment in humans. This review presents the main findings in the field of electroporation-namely, transdermal drug delivery. Particular attention is paid to proposed enhancement mechanisms and trends in the field of topical and transdermal delivery.

In this work we have investigated the influence of NaCl on the adsorption of the antimicrobial cationic peptide bactenecin in the monolayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at the air-water interface, as a function of NaCl concentrations in the subphase. We show that the effect of the salt concentration on DPPC monolayers is a monotonic decrease of the liquid-condensed-liquid-expanded (LC-LE) coexistence region. By contrast, the effect of the bactenecin adsorption at the DPPC monolayer not only removed the LC-LE coexistence region plateau, but also shifted the DPPC isotherms to higher pressures and increased the compressibility of the DPPC/bactenecin monolayers with respect to the pure DPPC monolayer around the LC phase. Analysis of the domain structure, obtained by Brewster angle and atomic force microscopes, indicates that the salt concentration in the subphase builds an electrostatic barrier, increasing the rigidity of DPPC monolayers and limiting the bactenecin adsorption at the LC-LE phase coexistence.

Objectives: Caregivers of patients with Alzheimer's disease (AD) experience physical and psychological stress due to the caring experience. This study evaluated the benefits of a Psychoeducational Intervention Program (PIP) on caregiver burden in southern Europe., Methods: A multicentre, prospective, randomised study was conducted. One hundred and fifteen caregivers of patients with clinical diagnosis of AD (DSM-IV-TR criteria, mini-mental score = 10-26) and functional impairment (Lawton and Brody Scale and Katz Index) were recruited. Caregivers were randomised to receive either PIP (IG: intervention group, n = 60) or standard care (CG: control group, n = 55). PIP consisted of eight individual sessions over 4 months for teaching strategies for confronting problems of AD patient care. Caregivers' stress, quality of life and perceived health were measured using validated scales (Zarit, SF-36, GHQ-28, respectively) at baseline and after 4 and 10-months follow-up., Results: Mean change in caregiver burden (Zarit baseline-Zarit final scores) was statistically significant (p = 0.0083) showing an improvement in the IG (-8.09 points) and a worsening in the CG (2.08 points). The IG showed significant improvements in all the well-being perception areas measured by the SF-36 and a significantly lower score in the GHQ-28 (p = 0.0004). 97.7% of caregivers and 88.6% of therapists considered PIP 'useful/very useful' at 4 months (the end of PIP) whereas at 10 months the estimates were 93.2% and 86.3%, respectively., Conclusions: Psychosocial training of caregivers can minimise caregiver distress and help them to develop problem-solving strategies. A PIP improves quality of life and the perceived health of caregivers of patients with AD., ((c) 2008 John Wiley & Sons, Ltd.)

By means of variable-temperature scanning tunneling microscopy and spectroscopy we studied the thickness-dependent roughening temperature of Pb films grown on Cu(111), whose electronic structure and total energy is controlled by quantum well states created by the spatial confinement of electrons. Large scale STM images are employed to quantify the layer population, i.e., the fraction of the surface area covered by different Pb thicknesses, directly in the real space as a function of temperature. The roughening temperature oscillates repeatedly with bilayer periodicity plus a longer beating period, mirroring the thickness dependence of surface energy calculations. Conditions have been found to stabilize at 300 K Pb films of particular magic thicknesses, atomically flat over microns.