Neurocognitive, Sociocultural, and Psychological Factors Impacting Medication Beliefs Among HIV-Seropositive Latinx Adults.

Among Latinx people living with HIV (PLWH), neurocognitive (NC) function, culture, and mental health impact medication adherence. Similarly, health beliefs and attitudes play a role in health care barriers and health behaviors. Research has not examined the effect that compromised neurocognition, sociocultural factors, and mental health have on health beliefs and attitudes. This is especially relevant for Latinx PLWH who are disproportionately impacted by HIV, given that sociocultural factors may uniquely impact HIV-related NC and psychological sequelae. This study investigated the associations between neurocognition, sociocultural factors, mental health, health beliefs, and health attitudes among Latinx HIV-seropositive adults. Within a sample of 100 Latinx PLWH, better verbal learning and executive functioning abilities were associated with more positive attitudes about the benefits of medications and memory for medications. In terms of sociocultural factors, higher English language competence was related to better self-reported memory for medications, and overall, higher US acculturation was associated with more positive attitudes toward health professionals. Depressive symptomatology was negatively associated with attitudes toward medications and health professionals, as well as with self-reported memory for medications. These findings highlight the important interplay between NC, sociocultural, psychological factors, and health beliefs among Latinx PLWH. Adherence intervention strategies and suggestions for dispensing medical information are presented for clinicians and health care practitioners.

Prevalence, stability, and predictive utility of the Multidimensional Assessment of Preschoolers Scales clinically optimized irritability score: Pragmatic early assessment of mental disorder risk.

OBJECTIVES: Characterizing the scope and import of early childhood irritability is essential for real-world actualization of this reliable indicator of transdiagnostic mental health risk. Thus, we utilize pragmatic assessment to establish prevalence, stability, and predictive utility of clinically significant early childhood irritability. METHODS: Data included two independent, diverse community samples of preschool age children (N = 1857; N = 1490), with a subset enriched for risk (N = 425) assessed longitudinally from early childhood through preadolescence (∼4-9 years old). A validated, brief (2-item) scale pragmatically assessed clinically significant irritability. In the longitudinal subsample, clinical interviews assessed internalizing/externalizing disorders. RESULTS: One in five preschool-age children had clinically significant irritability, which was independently replicated. Irritability was highly stable through preadolescence. Children with versus without clinically significant early childhood irritability had greater odds of early onset, persistent internalizing/externalizing disorders. The pragmatic assessment effectively screened out low-risk children and identified 2/3 of children with early-onset, persistent psychopathology. CONCLUSIONS: Clinically significant early childhood irritability prevalence is akin to the pediatric obesity epidemic and may warrant similar universal screening/intervention. Also, irritability's stability demonstrates the common guidance "they'll grow out of it" to be false. Finally, pragmatic irritability assessment has transdiagnostic predictive power and addresses a need for feasible measures to flag risk.

Advancing earlier transdiagnostic identification of mental health risk: A pragmatic approach at the transition to toddlerhood.

OBJECTIVES: In light of the youth mental health crisis, as 1 in 5 children have a mental disorder diagnosis by age 3, identification of transdiagnostic behavioral vulnerability prior to impairing psychopathology must occur at an earlier phase of the clinical sequence. Here, we lay the groundwork for a pragmatic irritability measure to identify at-risk infant-toddlers. METHODS: Data comprised N = 350 diverse infant-toddlers and their mothers assessed at ∼14 months old for irritability (Multidimensional Assessment Profiles- Temper Loss-Infant/Toddler (MAPS-TL-IT) and impairment (Early Childhood Irritability-Related Impairment Interview, E-CRI; and Family Life Impairment Scale (FLIS). Bimonthly follow-up surveys assessed impairment (FLIS) over the following year. RESULTS: Stepwise logistic regression indicated that 5 MAPS-TL-IT items were most informative for differentiating concurrent impairment on the FLIS: "frustrated about small things"; "hit, bite, or kick during tantrums"; "trouble cheering up when grumpy"; "grumpy during fun activities" and "tantrums in public". With this summed score, Receiver Operating Characteristics analysis differentiating concurrent impairment on the E-CRI indicated good classification accuracy for (Area under the curve = 0.755, p < 0.05), with a cutoff of 5 maximizing sensitivity (71.4%) and specificity (70.6%). Elevated irritability on this MAPS-TL-IT clinically optimized screener increased likelihood of persistently elevated FLIS impairment trajectories over the following year more than fourfold (OR = 4.37; Confidence intervals = 2.40-7.97, p < 0.001). CONCLUSIONS: Our findings represent the first step toward a pragmatic tool for screening for transdiagnostic mental health risk in toddlers, optimized for feasibility in clinical care. This has potential to strengthen resilience pathways via earlier identification of mental health risk and corollary prevention in toddlers.

How consumer digital signals are reshaping the customer journey.

Marketers are adopting increasingly sophisticated ways to engage with customers throughout their journeys. We extend prior perspectives on the customer journey by introducing the role of digital signals that consumers emit throughout their activities. We argue that the ability to detect and act on consumer digital signals is a source of competitive advantage for firms. Technology enables firms to collect, interpret, and act on these signals to better manage the customer journey. While some consumers' desire for privacy can restrict the opportunities technology provides marketers, other consumers' desire for personalization can encourage the use of technology to inform marketing efforts. We posit that this difference in consumers' willingness to emit observable signals may hinge on the strength of their relationship with the firm. We next discuss factors that may shift consumer preferences and consequently affect the technology-enabled opportunities available to firms. We conclude with a research agenda that focuses on consumers, firms, and regulators.

Cryo-EM structure of arabinosyltransferase EmbB from Mycobacterium smegmatis.

Arabinosyltransferase B (EmbB) belongs to a family of membrane-bound glycosyltransferases that build the lipidated polysaccharides of the mycobacterial cell envelope, and are targets of anti-tuberculosis drug ethambutol. We present the 3.3 Å resolution single-particle cryo-electron microscopy structure of Mycobacterium smegmatis EmbB, providing insights on substrate binding and reaction mechanism. Mutations that confer ethambutol resistance map mostly around the putative active site, suggesting this to be the location of drug binding.

Cryo-EM Structures and Regulation of Arabinofuranosyltransferase AftD from Mycobacteria.

Mycobacterium tuberculosis causes tuberculosis, a disease that kills over 1 million people each year. Its cell envelope is a common antibiotic target and has a unique structure due, in part, to two lipidated polysaccharides-arabinogalactan and lipoarabinomannan. Arabinofuranosyltransferase D (AftD) is an essential enzyme involved in assembling these glycolipids. We present the 2.9-Å resolution structure of M. abscessus AftD, determined by single-particle cryo-electron microscopy. AftD has a conserved GT-C glycosyltransferase fold and three carbohydrate-binding modules. Glycan array analysis shows that AftD binds complex arabinose glycans. Additionally, AftD is non-covalently complexed with an acyl carrier protein (ACP). 3.4- and 3.5-Å structures of a mutant with impaired ACP binding reveal a conformational change, suggesting that ACP may regulate AftD function. Mutagenesis experiments using a conditional knockout constructed in M. smegmatis confirm the essentiality of the putative active site and the ACP binding for AftD function.

Survey of 138 Conjunctival Tumors in the Dominican Republic.

PURPOSE: To report the frequency of conjunctival tumors in the Dominican Republic. METHODS: Retrospective noninterventional case series. One hundred thirty-eight consecutive patients with a conjunctival mass evaluated at two tertiary referral centers from 2010 to 2018. Main outcome measures were frequency of tumors by diagnosis and distribution of tumors relative to patients' age and gender. RESULTS: The mean age at presentation was 41.2 years (median, 42 years; range 10 days - 91 years). There were 83 male patients (60%) and 55 female patients (40%). The three most common specific diagnoses were junctional, compound, and subepithelial naevi (47 [34%]), squamous cell carcinoma (SCC) (26 [19%]) and conjunctival squamous intraepithelial neoplasia (CIN) (17 [12%]). The mean age at detection was 36.5 years for non-malignant tumors and 56.3 years for malignant tumors (p < .001), with a mean difference of 19.8 years at time of diagnosis (95% CI, 10.7-28.8). Benign tumors were more common in children and young adults; malignant and premalignant tumors were more common in mid and older adults (p = .009). Malignant tumors were more common in males (73%) than in females (27%) (p = .04). CONCLUSION: In the Dominican Republic, conjunctival tumors are benign (63%), premalignant (13%) and malignant (24%). Malignant tumors are more common in older adults and men.

Physical Activity, Exercise, and Physiotherapy in Parkinson's Disease: Defining the Concepts.

BACKGROUND: Exercise is gaining extreme relevancy as a new therapeutic intervention for Parkinson's disease (PD). However, the frequent misuse of the concepts exercise, physiotherapy, and physical activity limits the possibility of summarizing research findings. This review aims to clarify these concepts and summarize the evidence on exercise in PD. METHODS: We critically appraised physical activity-related concepts and conducted a systematic review of clinical trials evaluating exercise interventions in PD. Additionally, we discussed the implications for PD clinical practice and research. RESULTS: Exercise is a subset of physical activity, and a major component of physiotherapy for PD management, having as the main goal to improve physical fitness. The appraisal of the 83 identified clinical trials found high variability in exercise interventions. Multimodal exercise was the most studied, and 60 minutes, two times/week for 12 weeks, the most reported prescription parameters. CONCLUSION: The best available evidence recommends increasing physical activity levels in PD. Exercise and physiotherapy programs seem the most efficacious strategies to achieve this goal. As a result of the heterogeneity in the type and manner exercise is prescribed, it is not possible to propose strong recommendations for exercise in PD. We believe that, in addition to the clarification of concepts here presented, a collaborative and rigorous work of different areas of knowledge is needed.

Neurocognitive intra-individual variability within HIV+ adults with and without current substance use.

OBJECTIVE: HIV infection and current substance use (SU) are linked to cognitive and functional deficits, yet findings on their combined effects are mixed. Neurocognitive intraindividual variability, measured as dispersion of scores across a neuropsychological battery, is associated with worse cognitive outcomes and functional deficits among HIV+ adults but has not been studied in the context of HIV+ adults with current SU. We hypothesized that, among HIV+ adults, current SU would be associated with greater dispersion, that greater dispersion would be associated with worse medication adherence, and that this relationship would be worse among substance users. METHOD: Forty HIV+ adults completed neuropsychological, psychiatric, SU, and medical evaluations and an electronic medication adherence measure. General linear models evaluated the main effect of SU status on neurocognitive dispersion, and models stratified by SU status evaluated the effect of dispersion on medication adherence, adjusting for relevant covariates. RESULTS: The SU+ group showed greater dispersion than did the SU- group, t(38) = 2.74, p = .049, d = 0.81, but this association did not survive multiple comparisons. Stratified analyses indicated a negative relationship between dispersion and medication adherence among the SU+ group but not in the SU- group; however, this effect was reduced after accounting for depressive symptoms. CONCLUSIONS: We found preliminary evidence that current SU is associated with greater neurocognitive dispersion among HIV+ adults. SU and neurocognitive dispersion may have a synergistic effect on medication adherence; however, this effect is largely accounted for by depressive symptoms. Future research should examine progression of dispersion in HIV and consequent neurocognitive and functional deficits in those with current SU. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Gremlin-1 potentiates the dedifferentiation of VSMC in early stages of atherosclerosis.

Vascular smooth muscle cells (VSMC) are highly specialized, and exhibit a contractile phenotype when mature and fully differentiated, being responsible for vessel homeostasis and blood pressure control. In response to pro-atherogenic stimuli VSMC alter their state of differentiation, increase proliferation and migration, resulting in SMC phenotypes ranging from contractile to synthetic. This variability is observed in cell morphology and expression level of marker genes for differentiation status. There is growing evidence that bone morphogenetic protein (BMP) signaling is involved in vascular diseases, including atherosclerosis. Here, we evaluated in vitro the role of specific agonists/antagonists belonging to the BMP pathway on dedifferentiation of VSMC harvested during early stages of atherosclerosis. RESULTS: Comparing primary VSMC isolated from aortas of susceptible ApoE-/- animals fed 8 weeks of western diet with their littermate controls fed usual diet, we observed that recombinant BMP4 was able to reduce SM22-alpha and alpha actin gene expression indicating dedifferentiation was under way. Unexpectedly, treatment with recombinant Gremlin-1, a known BMP antagonist, also reduced 4-6.5 folds gene expression of SM22-alpha, alpha-actin and, calponin, exclusively in VSMC from ApoE-/- animals, independently on the diet consumed. CONCLUSION: Our data show that BMP4 is capable of modulating of SM22-alpha and alpha actin gene expression, indicative of cell dedifferentiation in VSMC. Additionally, we report for first time that Gremlin-1 acts independently of the BMP pathway and selectively on VSMC from susceptible animals, reducing the expression of all genes evaluated.

Onicomicosis por alga sin clorofila / Onychomycosis caused by algae without chlorophyll

No disponible

Molecular modeling of inhibitors against fructose bisphosphate aldolase from Candida albicans.

Candida albicans is an opportunistic pathogen that causes from vulvovaginal and oropharyngeal candidiasis to systemic infections. The enzyme 1,6-fructose bisphosphate aldolase class II (FBA II), is a macromolecule existing only in lower organisms, being essential for the survival of the pathogen due to its function of maintaining the glycolysis process. The aim of this paper was to evaluate the inhibitors of FBA II regarding their physicochemical, pharmacokinetic and toxicological properties and apply concepts of rational drug development to propose new compounds for the treatment of fungal infections of C. albicans. Physicochemical (HyperChem software and the webserver cactus) and ADME/Tox (PreADMET webserver) properties were calculated to four inhibitors described in the literature and three analogues. None of the compounds presented in this study violated RO5, however all inhibitors demonstrated low or moderate human intestinal absorption (HIA), as well as low or moderate permeability in Caco-2 and MDCK, poor plasma proteins binding (PPB) and low permeability of the blood-brain barrier (BBB); however, Compound 4 is the exception for BBB permeability, being also the only non-mutagenic compound, and therefore, used as a lead compound. Analogues B and C presented high HIA, weak PPB and low BBB permeability, as well as a positive prediction for carcinogenicity in rats and mouse and non-mutagenicity in the Ames test. Through the evaluations carried out, it was concluded that the analogues B and C have proved to be promising candidates for oral administration drugs in the treatment of fungal infections of the genus Candida.

T Cell-Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing ∼1.5 million deaths annually. CD4+ T cells and several cytokines, such as the Th1 cytokine IFN-γ, are critical in the control of this infection. Conversely, the immunosuppressive cytokine IL-10 has been shown to dampen Th1 cell responses to M. tuberculosis infection impairing bacterial clearance. However, the critical cellular source of IL-10 during M. tuberculosis infection is still unknown. Using IL-10 reporter mice, we show in this article that during the first 14 d of M. tuberculosis infection, the predominant cells expressing IL-10 in the lung were Ly6C+ monocytes. However, after day 21 postinfection, IL-10-expressing T cells were also highly represented. Notably, mice deficient in T cell-derived IL-10, but not mice deficient in monocyte-derived IL-10, showed a significant reduction in lung bacterial loads during chronic M. tuberculosis infection compared with fully IL-10-competent mice, indicating a major role for T cell-derived IL-10 in TB susceptibility. IL-10-expressing cells were detected among both CD4+ and CD8+ T cells, expressed high levels of CD44 and Tbet, and were able to coproduce IFN-γ and IL-10 upon ex vivo stimulation. Furthermore, during M. tuberculosis infection, Il10 expression in CD4+ T cells was partially regulated by both IL-27 and type I IFN signaling. Together, our data reveal that, despite the multiple immune sources of IL-10 during M. tuberculosis infection, activated effector T cells are the major source accounting for IL-10-induced TB susceptibility.

[Formula: see text]The Relative Utility of Three English Language Dominance Measures in Predicting the Neuropsychological Performance of HIV+ Bilingual Latino/a Adults.

OBJECTIVE: Given the disproportionate impact of neurologic disorders such as HIV on racial/ethnic minorities, neuropsychologists are increasingly evaluating individuals of diverse linguistic backgrounds. This study compares the utility of two brief and one comprehensive language measure to account for variation in English neuropsychological performance within a bilingual population. METHOD: Sixty-two HIV+ English/Spanish bilingual Latino adults completed three language measures in English and Spanish: Self-Reported Language Ability; Verbal Fluency (FAS/PMR); and the Woodcock Munoz Language Survey-Revised (WMLS-R). All participants also completed an English language neuropsychological (NP) battery. RESULTS: It was hypothesized that the comprehensive English/Spanish WMLS-R language dominance index (LDI) would be significantly correlated with NP performance, as well as the best predictor of NP performance over and above the two brief language measures. Contrary to our hypothesis, the WMLS-R LDI was not significantly correlated to NP performance, whereas the easily administered Verbal Fluency and Self-Report LDIs were each correlated with global NP performance and multiple NP domains. After accounting for Verbal Fluency and Self-Report LDI in a multivariate regression predicting NP performance, the WMLS-R LDI did not provide a unique contribution to the model. CONCLUSIONS: These findings suggest that the more comprehensive WMLS-R does not improve understanding of the effects of language on NP performance in an HIV+ bilingual Latino population.

Secular trends and predictors of mortality in acute lymphoblastic leukemia for children of low socioeconomic level in Northeast Brazil.

BACKGROUND: The treatment for ALL has evolved in recent decades and as a result survival rates are now close to 90% in many developed countries. However, this is not the case in developing countries where survival rates are often below 35%. More than 80% of children who are affected by ALL worldwide live in developing countries. The objective of this study was to evaluate the secular trend in mortality for children with ALL living in Sergipe, a state in northeastern Brazil, and to investigate any association with variables that relate to socioeconomic status. METHOD: This study evaluated ALL patients who were less than 20 years of age and who were treated at the Dr. Osvaldo Leite Oncology Center in the capital city, Aracaju. The sample comprised two cohorts of patients from the public health service: patients treated from 1980 to 2004 (cohort A) and from 2005 to 2014 (cohort B). The findings were compared to those of patients treated in the one private service for pediatric cancer treatment available in the region, from 2005 to 2014 (cohort C). Two categories of variables were considered in this study: biological and socioeconomic. RESULTS: We analyzed 412 patients who were divided into three cohorts (cohort A: 287 patients, cohort B: 106 patients and cohort C: 19 patients). The mortality rates for the three cohorts were significantly different: 57.5% in cohort A, 45.3% in cohort B and 26.3% in cohort C (p=0.006). Mortality during induction in cohort B was 22.6%, while in cohort C no deaths occurred during this phase (p=0.041). Patients living in rural areas had higher mortality rates (p=0.036). CONCLUSIONS: The reduction in deaths from infection during induction seems to be the starting point for improving the chances for children and adolescents with ALL anywhere in the world.

Expression, purification, crystallization and preliminary X-ray diffraction analysis of a type II NADH:quinone oxidoreductase from the human pathogen Staphylococcus aureus.

In recent years, type II NADH dehydrogenases (NDH-IIs) have emerged as potential drug targets for a wide range of human disease causative agents. In this work, the NDH-II enzyme from the Gram-positive human pathogen Staphylococcus aureus was recombinantly expressed in Escherichia coli, purified, crystallized and a crystallographic data set was collected at a wavelength of 0.873 Å. The crystals belonged to the orthorhombic space group P212121, with unit-cell parameters a = 81.8, b = 86.0, c = 269.9 Å, contained four monomers per asymmetric unit and diffracted to a resolution of 3.32 Å. A molecular-replacement solution was obtained and model building and refinement are currently under way.