Intersectionality in Intervention Development: Insights From Formative Work on a Tailored Tobacco Cessation Program for LGBTQIA+ Young Adults.

Tailored tobacco cessation interventions focusing on minoritized communities are proliferating, but the extent to which these interventions address the needs of individuals with multiple minoritized social identities is unclear. We developed Empowered, Queer, Quitting, and Living (EQQUAL), an avatar-led digital smoking cessation intervention tailored for lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and more (LGBTQIA+) young adults based on acceptance and commitment therapy (ACT), via a multistage user-centered design process. The purpose was to evaluate feedback from EQQUAL development activities using an intersectional lens. Intersectionality is a paradigm created by Kimberlé Crenshaw illustrating the multiple social identities each person possesses along with the marginalization of these different social identities. We conducted a rapid deductive content analysis focused on intersectional design gaps using interviewer notes from user testing (n = 7), a diary study (n = 8), and treatment satisfaction responses from a single-arm trial of the EQQUAL intervention (n = 22). Feedback related to intersectional design fell under three broad themes: (a) inadequate representativeness of the avatar, (2) inadequate representativeness within the program broadly, and (3) non-inclusive ACT intervention content. Feedback on inclusiveness included reference to socioeconomic status, race/ethnicity, religious/cultural affiliation, and ability/disability. Although we previously found that EQQUAL was highly acceptable and showed promise in terms of efficacy in a single-arm pilot trial, we identified several gaps in intersectional design as the iterative intervention development proceeded. Because intersectional design is a critical part of developing interventions with a health equity focus, applying standardized procedures for intersectional design and analysis could improve intervention design and better address tobacco cessation treatment needs of individuals who may experience multiple forms of marginalization.

"I Felt Defeated. I Felt Helpless": Social Determinants of Health Influencing the Cancer Survivorship of a Young Latina Mother.

Social determinants of health (SDOH) contribute to cancer disparities among young Latina women (<50 years) residing in the counties along the US-Mexico border. These SDOH are particularly burdensome to young Latina mothers diagnosed with cancer while they are raising school-age children. Conexiones, a culturally adapted program designed to improve mother and child adjustment to maternal cancer, was piloted with diagnosed Latina mothers residing in border counties in New Mexico and Texas. The purpose of this case analysis was to highlight the SDOH affecting a young Latina mother's cancer survivorship in the U.S.-Mexico border region. The participant's Conexiones education sessions were recorded, transcribed, translated to English, back translated to Spanish to establish accuracy, and inductively coded. The participant's baseline survey indicated she was a young (<50 years), married, Spanish-speaking Latina mother diagnosed with breast cancer while raising a teenage daughter. Seventeen SDOH themes affecting the participant's cancer experience were identified in the cancer-related emotional triggers she reported across five Conexiones sessions. These themes were organized using Yanez's conceptual model of determinants of cancer outcomes in Hispanics (i.e., socioeconomic, healthcare, cultural context, and psychosocial). Findings provide direction for cultural adaptations of evidence-based programs.

A Latina Community's Evaluation of the Culturally Adapted Conexiones Program.

BACKGROUND: Enhancing Connections (EC) is an evidence-based intervention that promotes communication between cancer-diagnosed mothers and their school-age children. EC was validated with college-educated non-Latina White mothers of privileged socioeconomic status. Latina researchers culturally adapted EC for Latina mothers diagnosed with cancer and renamed it Conexiones. Following cultural adaptation guidelines, the next recommended step was to engage the new consumer group (Latina mothers) in evaluating the newly adapted educational materials. PURPOSE: The purpose of this study was to evaluate the cognitive and cultural fit of the newly adapted Conexiones educational materials for use with Latina mothers diagnosed with cancer. METHOD: Eighteen Latina mothers participated in focus groups evaluating the Conexiones educational materials. An inductive approach was used to identify problem areas and recommendations for corrections to the Conexiones program content. RESULTS: Within the cognitive-informational dimension, recommendations were made to improve the ease of comprehension in the Spanish version of the program. Recommendations within the affective-motivational dimension described the cultural adjustments needed to more effectively engage cancer-diagnosed Latina mothers in the Conexiones program. Implications for Practice. Engagement of the new consumer group in evaluating the initial adaptation of Conexiones served to identify additional cognitive-informational and affective-motivational corrections needed to further refine the cultural adaptation of the Conexiones program. This study reinforced the importance of community engagement in evaluating and refining newly adapted evidence-based interventions.

Administration of low doses of the 5-HT1A receptor agonist 8-OH-DPAT attenuates the discriminative signal of amphetamine in the conditioned taste aversion procedure.

Several studies have reported that low doses of the 5-HT1A receptor agonist 8-OH-DPAT reduce cocaine-induced locomotor activity. However, it has also been reported that high doses of 8-OH-DPAT do not substitute for or alter the discriminative signal of cocaine (COC) or amphetamine (AMPH). This study aimed to evaluate the effects of low and high doses of the 5-HT1A agonist 8-OH-DPAT on the discriminative signal of AMPH using conditioned taste aversion as a drug discrimination procedure. Additionally, to establish a correlation between the behavioral effects in drug discrimination and changes in dopamine (DA) and gamma-aminobutyric acid (GABA) concentrations, we evaluated the effect of systemic administration of low or high doses of the 5-HT1A receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist WAY100135 on DA and GABA extracellular concentrations in the nucleus accumbens (nAcc) and ventral tegmental area (VTA), respectively, using cerebral microdialysis. The behavioral results showed that low but not high doses of 8-OH-DPAT produced a reduction in the AMPH-induced discriminative signal, while WAY100135 administration prevented such effects. The microdialysis results showed that a low dose of 8-OH-DPAT decreased extracellular DA concentrations in the nAcc and increased GABA concentrations in the VTA. Pretreatment with WAY100135 prevented these effects. These data support the hypothesis that 5-HT1A receptors modulate the behavioral effects of psychostimulant drugs, such as AMPH, through somatodendritic 5-HT1A autoreceptors in the raphe nucleus indicating that 5-HT1A receptors may be an important target for the development of pharmacological treatments for psychostimulant addiction.

Oregano (Lippia graveolens) essential oil added within pectin edible coatings prevents fungal decay and increases the antioxidant capacity of treated tomatoes.

BACKGROUND: Tomato is a fruit widely consumed due to its flavor and nutritional value; however, it is susceptible to fungi contamination. Oregano essential oil (OEO) is a fungicide whose constituents are volatile; therefore, their incorporation within edible coatings can protect them and maintain their efficacy. In this context, this study evaluated the effect of OEO applied within pectin coatings on the inhibition of Alternaria alternata growth, antioxidant content and sensorial acceptability of tomatoes. RESULTS: The major volatile compounds of OEO were carvacrol (47.41%), p-cymene (26.44%) and thymol (3.02%). All the applied OEO concentrations (15.7, 25.9 and 36.1 g L(-1) ) inhibited the in vitro growth of A. alternata, whereas the in vivo effective concentrations were 25.9 and 36.1 g L(-1) . Additionally, there was an increment of total phenols and antioxidant activity in coated tomatoes compared to controls. Aroma acceptability of tomatoes was not affected by the pectin-OEO coating; additionally, the pectin, pectin-OEO 15.7 g L(-1) treatments and control tomatoes showed higher flavor acceptability than those coated with pectin-OEO 25.9 and 36.1 g L(-1) . CONCLUSION: Pectin-OEO coatings showed antifungal effect and increased the antioxidant activity without negative effects on the sensorial acceptability of tomatoes. © 2015 Society of Chemical Industry.

N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA): A potential cognitive enhancer with MAO inhibitor properties.

BACKGROUND: A considerable body of human and animal experimental evidence links monoaminergic systems and cognition. Monoamine oxidase inhibitors (MAOIs), being able to enhance monoaminergic transmission and having neuroprotective properties, might represent a promising therapeutic strategy in cognitive impairment in Alzheimer's disease (AD) and other dementias. METHODS: The MAO-A and MAO-B inhibition profile of N-(furan-2-ylmethyl)-N-prop-2-yn-1-amine derivates (compounds 1-3) were evaluated by fluorimetric method and their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties estimated. The effects of the selected compound 1, N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA), were evaluated on the basic synaptic transmission, long-term potentiation (LTP), and excitability in the dentate gyrus (DG) of the hippocampus of anesthetized rats. RESULTS: F2MPA is a partially reversible inhibitor of hMAO-B, with moderate to good ADMET properties and drug-likeness. Intraperitoneal administration of 1 mg/kg F2MPA greatly enhanced basic synaptic transmission, induced LTP, and potentiated electrically induced LTP in the dentate gyrus. Moreover, F2MPA did not modify seizure threshold of pilocarpine-induced convulsion in CD1 mice. CONCLUSION: Our findings suggest that, the MAO-B inhibitor, F2MPA improves DG synaptic transmission without triggering pathological hyperexcitability. Therefore, F2MPA shows promise as a potential cognition-enhancing therapeutic drug.

Potential of medicinal plants as antimicrobial and antioxidant agents in food industry: a hypothesis.

Many food preservation strategies can be used for the control of microbial spoilage and oxidation; however, these quality problems are not yet controlled adequately. Although synthetic antimicrobial and antioxidant agents are approved in many countries, the use of natural safe and effective preservatives is a demand of food consumers and producers. This paper proposes medicinal plants, traditionally used to treat health disorders and prevent diseases, as a source of bioactive compounds having food additive properties. Medicinal plants are rich in terpenes and phenolic compounds that present antimicrobial and antioxidant properties; in addition, the literature revealed that these bioactive compounds extracted from other plants have been effective in food systems. In this context, the present hypothesis paper states that bioactive molecules extracted from medicinal plants can be used as antimicrobial and antioxidant additives in the food industry.

Oregano essential oil-pectin edible films as anti-quorum sensing and food antimicrobial agents.

Edible films can be used as carriers for antimicrobial compounds to assure food safety and quality; in addition, pathogenesis of food bacteria is related to a cell to cell communication mechanism called quorum sensing (QS). Oregano essential oil (OEO) has proved to be useful as food antimicrobial; however, its food applications can be compromised by the volatile character of its active constituents. Therefore, formulation of edible films containing OEO can be an alternative to improve its food usages. QS inhibitory activity of OEO and pectin-OEO films was evaluated using Chromobacterium violaceum as bacterial model. Additionally, antibacterial activity was tested against Escherichia coli O157:H7, Salmonella Choleraesuis, Staphylococcus aureus, and Listeria monocytogenes. OEO was effective to inhibit bacterial growth at MIC of 0.24 mg/mL for all tested bacteria and MBC of 0.24, 0.24, 0.48, and 0.24 mg/mL against E. coli O157:H7, S. Choleraesuis, S. aureus, and L. monocytogenes, respectively. Pectin-films incorporated with 36.1 and 25.9 mg/mL of OEO showed inhibition diameters of 16.3 and 15.2 mm for E. coli O157:H7; 18.1 and 24.2 mm for S. Choleraesuis; 20.8 and 20.3 mm for S. aureus; 21.3 and 19.3 mm for L. monocytogenes, respectively. Pectin-OEO film (15.7 mg/mL) was effective against E. coli O157:H7 (9.3 mm), S. aureus (9.7 mm), and L. monocytogenes (9.2 mm), but not for S. Choleraesuis. All concentrations of OEO (0.0156, 0.0312, 0.0625 and 0.125 mg/mL) and pectin-OEO films (15.7, 25.9 and 36.1 mg/mL) showed a significant anti-QS activity expressed as inhibition of violacein production by C. violaceum. Additionally, the application of pectin-OEO films was effective reducing total coliforms, yeast, and molds of shrimp and cucumber slices stored at 4°C during 15 d. These results demonstrated the potential of pectin films enriched with OEO as food related microorganisms and QS inhibitors.

Review of synthesis, biological assay, and QSAR studies of HMGR inhibitors.

Effective as statin drugs or acids are inhibitors mevinic limiting enzyme in cholesterol biosynthesis, 3-hydroxy- 3-methyl-glutaryl coenzyme A-3-hydroxy-3-reductase (HMGR), an enzyme responsible for the reduction the double methyl-glutaryl coenzyme A. These compounds promoted the synthesis and evaluation of new inhibitors of HMGR, called HMGRIs. The high number of potential candidates need to create models of quantitative structure-activity relationship in order to guide the HMGRI (3-hydroxy-3-methyl-glutarylcoenzyme A inhibitor) synthesis. In this work, we revised different computational studies for a very large and heterogeneous series of HMGRIs. First, we revised QSAR studies with conceptual parameters how flexibility of rotation, probability of availability, etc; Next, using method of regression analysis; and QSAR studies in order to understand the essential structural requirement for binding with receptor. Next, we review 3D QSAR, CoMFA and CoMSIA with different compound to find out the structural requirements for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitory activity.

Review of QSAR for DNA polymerase inhibitors and new models for heterogeneous series of compounds.

DNA polymerases are essential enzymes for DNA replication, repair and recombination. The high number of possible candidates creates the necessity of Quantitative Structure-Activity Relationship models in order to guide the DNA polymerase inhibitors. In this work, we revised different computational studies for a very large and heterogeneous series of DNA polymerase inhibitors. First, we reviewed QSAR methods with different compounds to find out the structural requirements for DNA polymerase inhibitory activity. Last, we report a new LDA analysis with the different molecular descriptors calculated with DRAGON software.

Theoretical study of GSK-3α: neural networks QSAR studies for the design of new inhibitors using 2D descriptors.

Glycogen synthase kinase-3 (GSK-3) targets encompass proteins implicated in AD and neurological disorders. The functions of GSK-3 and its implication in various human diseases have triggered an active search for potent and selective GSK-3 inhibitors. In this sense, QSAR could play an important role in studying these GSK-3 inhibitors. For this reason, we developed QSAR models for GSK-3α, linear discriminant analysis (LDA), and artificial neural networks (ANNs) from nearly 50,000 cases with more than 700 different GSK-3α inhibitors obtained from ChEMBL database server; in total we used more than 20,000 different molecules to develop the QSAR models. The model correctly classified 237 out of 275 active compounds (86.2%) and 14,870 out of 15,970 non-active compounds (93.2%) in the training series. The overall training performance was 93.0%. Validation of the model was carried out using an external predicting series. In these series, the model classified correctly 458 out of 549 (83.4%) compounds and 29,637 out of 31,927 non-active compounds (83.4%). The overall predictability performance was 92.7%. In this study, we propose three types of non-linear ANN as alternative to already existing models, such as LDA. Linear neural network: LNN: 236:236-1-1:1 which had an overall training performance of 96% proved to be the best model. In addition, we did a study of the different fragments of the molecules of the database to see which fragments had more influence in the activity. This can help design new inhibitors of GSK-3α. This study reports the attempts to calculate, within a unified framework probabilities of GSK-3α inhibitors against different molecules found in the literature.

First computational chemistry multi-target model for anti-Alzheimer, anti-parasitic, anti-fungi, and anti-bacterial activity of GSK-3 inhibitors in vitro, in vivo, and in different cellular lines.

In the work described here, we developed the first multi-target quantitative structure-activity relationship (QSAR) model able to predict the results of 42 different experimental tests for GSK-3 inhibitors with heterogeneous structural patterns. GSK-3ß inhibitors are interesting candidates for developing anti-Alzheimer compounds. GSK-3ß are also of interest as anti-parasitic compounds active against Plasmodium falciparum, Trypanosoma brucei, and Leishmania donovani; the causative agents for Malaria, African Trypanosomiasis and Leishmaniosis. The MARCH-INSIDE technique was used to quickly calculate total and local polarizability, n-octanol/water partition coefficients, refractivity, van der Waals area and electronegativity values to 4,508 active/non-active compounds as well as the average values of these indexes for active compounds in 42 different biological assays. Both the individual molecular descriptors and the average values for each test were used as input for a linear discriminant analysis (LDA). We discovered a classification function which used in training series correctly classifies 873 out of 1,218 GSK-3 cases of inhibitors (97.4%) and 2,140 out of 2,163 cases of non-active compounds (86.1%) in the 42 different tests. In addition, the model correctly classifies 285 out of 406 GSK-3 inhibitors (96.3%) and 710 out of 721 cases of non-active compounds (85.4%) in external validation series. The result is important because, for the first time, we can use a single equation to predict the results of heterogeneous series of organic compounds in 42 different experimental tests instead of developing, validating, and using 42 different QSAR models. Lastly, a double ordinate Cartesian plot of cross-validated residuals (first ordinate), standard residuals (second ordinate), and leverages (abscissa) defined the domain of applicability of the model as a squared area within ± 2 band for residuals and a leverage threshold of h = 0.0044.

Using topological indices to predict anti-Alzheimer and anti-parasitic GSK-3 inhibitors by multi-target QSAR in silico screening.

Plasmodium falciparum, Leishmania, Trypanosomes, are the causers of diseases such as malaria, leishmaniasis and African trypanosomiasis that nowadays are the most serious parasitic health problems worldwide. The great number of deaths and the few drugs available against these parasites, make necessary the search for new drugs. Some of these antiparasitic drugs also are GSK-3 inhibitors. GSKI-3 are candidates to develop drugs for the treatment of Alzheimer's disease. In this work topological descriptors for a large series of 3,370 active/non-active compounds were initially calculated with the ModesLab software. Linear Discriminant Analysis was used to fit the classification function and it predicts heterogeneous series of compounds like paullones, indirubins, meridians, etc. This study thus provided a general evaluation of these types of molecules.

QSAR, docking, and CoMFA studies of GSK3 inhibitors.

GSK-3 inhibitors are interesting candidates to develop Anti-Alzheimer compounds. GSK-3ß are also interesting as Anti-parasitic compounds active against Plasmodium falciparum, Trypanosoma brucei, and Leishmania donovani; the causative agents for Malaria, African Trypanosomiasis and Leishmaniosis. The high number of possible candidates creates the necessity of Quantitative Structure-Activity Relationship models in order to guide the GSK3 (glycogen synthase kinase 3 inhibitor) synthesis. In this work, we revised different computational studies for a very large and heterogeneous series of GSK-3Is. First, we revised QSAR studies with conceptual parameters such as flexibility of rotation, probability of availability, etc. we then used the method of regression analysis and QSAR studies in order to understand the essential structural requirement for binding with receptor. Next, we reviewed 3D-QSAR, CoMFA and CoMSIA with different compounds to find out the structural requirements for GSK-3 inhibitory activity.

QSAR & complex network study of the HMGR inhibitors structural diversity.

Efficient drugs such as statins or mevinic acids are inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR), an enzyme responsible for the double reduction of 3-hydroxy-3-methyl-glutaryl coenzyme A. These compounds promoted the synthesis and evaluation of new inhibitors for HMGR, named HMGRIs. The high number of possible candidates creates the necessity of Quantitative Structure-Activity Relationship models in order to guide the HMGRI (3-hydroxy-3-methyl-glutaryl coenzyme A inhibitor) synthesis. In this work, we revised different computational studies for a very large and heterogeneous series of HMGRIs. First, we revised QSAR studies with conceptual parameters such as flexibility of rotation, probability of availability, etc; we then used the method of regression analysis; and QSAR studies in order to understand the essential structural requirement for binding with receptor. Next, we reviewed 3D QSAR, CoMFA and CoMSIA with different compounds to find out the structural requirements for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitory activity.

QSAR and complex network study of the chiral HMGR inhibitor structural diversity.

Efficient drugs such as statins or mevinic acids are inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR), an enzyme responsible for the double reduction of 3-hydroxy-3-methyl-glutaryl coenzyme A into mevalonic acid. These compounds promoted the synthesis and evaluation of new inhibitors for HMGR, named HMGRIs. The high number of possible candidates creates the necessity of Quantitative Structure-Activity Relationship models in order to guide the HMGRI synthesis. There are two main problems of the reported QSAR models: the homogeneous series of the compounds and the chirality of many candidates. In this work, we propose for the first time a QSAR model for a very large and heterogeneous series of HMGRIs. The model is based on the Topological Indices (TIs) of molecular structures. Using the predictions of this model as input, we construct the first complex network that describes the drug-drug similarity relationships for more than 1600 experimentally non-explored chiral HMGRIs isomers. We also presented a reduced version of this network (Giant Component) that contains the most representative set of chiral HMGRI candidates. The work suggests a new mixed application in the QSAR study of relevant aspects of structural diversity by using chiral/non-chiral TIs, combined with complex networks.