Examining the Interplay Between Preexposure Prophylaxis (PrEP) and Gender-Related Stigmas as Barriers for PrEP Uptake Among Transgender Women in Tijuana, Mexico: A Mixed-Methods Study.

HIV prevalence among transgender women (TW) in Tijuana, Mexico is estimated at 22%. Pre-exposure prophylaxis (PrEP) reduces the risk of HIV acquisition by > 90%, though uptake in Tijuana has been low due to limited availability. The interplay between PrEP and gender stigmas may also serve as a barrier to PrEP uptake among TW in Tijuana. Experiences of gender- and PrEP- stigmas were assessed quantitatively (Quan) among 110 HIV-negative TW and qualitatively (Qual) among 17 TW through semi-structured interviews guide by the Health Stigma and Discrimination Framework. Qual findings were triangulated with Quant data to identify factors that may support gender affirmation and reduce PrEP stigma in an explanatory sequential Quan → Qual fashion. Most participants were < 40 years of age (80%), while approximately half had at least a high school education (48.2%) and were accessing gender-affirming hormone therapy (56.4%). Mean expectations of gender stigma were greatest for endorsing negative future expectations from others (M = 17.69; possible range 0-36). PrEP stigma was prominent among those who associated negative stereotypes with PrEP users, such as poor judgment (M = 45.91; possible range 14-70) and high personal risk attributes (M = 28.61; possible range 12-60). While PrEP knowledge was low among the qualitative sample, participants identified gender-, PrEP-, and intersectional- stigmas as potential barriers to PrEP uptake. Participants suggested that resilience strategies used to combat gender stigma could also mitigate PrEP stigma. Enhancing resilience skills at the intersection of gender and PrEP stigma may reduce these barriers, facilitating greater PrEP uptake as it becomes more available in Mexico.

Behavior and Use of Quaternary Ammonium-Based Disinfectants in Biosafety Protocols Against Fusarium oxysporum f. sp. cubense Race 1 and Tropical Race 4.

The banana is one of Colombia's main export products. However, production is seriously affected by Fusarium wilt of banana, which is the most destructive disease caused by the fungus Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4). Currently, management strategies focus on containment and biosecurity protocols to prevent its spread to territories that are free of this disease. This study aimed to evaluate nine quaternary ammonium-based disinfectants (i.e., quaternary ammonium compounds [QACs]) in vitro in Colombia on reproductive (microconidia and macroconidia) and resistance structures (chlamydospores) of Foc race 1 (R1) and tropical race 4 (TR4), with and without soil, to determine the influence of organic matter and soil texture on the action of QACs. A method for inhibiting the action of QACs was standardized and evaluated at 1,200 ppm with a contact time of ≤30 s while evaluating the soil-inoculum and soil-disinfectant interactions. In the soil-inoculum interaction, the efficacy of QACs was 100% in the reproductive and resistance structures of Foc R1 and TR4 without soil. However, in the soil-disinfectant interaction, only QAC4 controlled the pathogen at 100%. The presence of organic matter influenced the biocidal action of the QACs, and fine textures had a greater reducing effect on the concentration. The soil decreased the efficacy of the QACs and, therefore, must be removed from contaminated boots before treatments are applied.

Incidence, and natural history of inflammatory bowel disease in Castilla y León: Prospective and multicenter epidemiological study. / Incidencia e historia natural de la enfermedad inflamatoria intestinal en Castilla y León: estudio prospectivo, multicéntrico y poblacional.

INTRODUCTION: The incidence of inflammatory bowel disease (IBD) is increasing worldwide. OBJECTIVES: To evaluate the incidence of IBD in Castilla y León describing clinical characteristics of the patients at diagnosis, the type of treatment received and their clinical course during the first year. MATERIALS AND METHODS: Prospective, multicenter and population-based incidence cohort study. Patients aged >18 years diagnosed during 2017 with IBD (Crohn's disease [CD], ulcerative colitis [UC] and indeterminate colitis [IC]) were included from 8 hospitals in Castilla y León. Epidemiological, clinical, and therapeutic variables were registered. The global incidence and disease incidence were calculated. RESULTS: 290 patients were diagnosed with IBD (54.5% UC, 45.2% CD, and 0.3% IC), with a median follow-up of 9 months (range 8-11). The incidence rate of IBD in Castilla y Leon in 2017 was 16.6 cases per 10,000 inhabitants-year (9/105 UC cases and 7.5/105 CD cases), with a UC/CD ratio of 1.2:1. Use of systemic corticosteroids (47% vs 30%; P=.002), immunomodulatory therapy (81% vs 19%; P=.000), biological therapy (29% vs 8%; P=.000), and surgery (11% vs 2%; p=.000) were significatively higher among patients with CD comparing with those with UC. CONCLUSIONS: The incidence of patients with UC in our population increases while the incidence of patients with CD remains stable. Patients with CD present a worse natural history of the disease (use of corticosteroids, immunomodulatory therapy, biological therapy and surgery) compared to patients with UC in the first year of follow-up.

Regularized continuous-time Markov Model via elastic net.

Continuous-time Markov models are commonly used to analyze longitudinal transitions between multiple disease states in panel data, where participants' disease states are only observed at multiple time points, and the exact state paths between observations are unknown. However, when covariate effects are incorporated and allowed to vary for different transitions, the number of potential parameters to estimate can become large even when the number of covariates is moderate, and traditional maximum likelihood estimation and subset model selection procedures can easily become unstable due to overfitting. We propose a novel regularized continuous-time Markov model with the elastic net penalty, which is capable of simultaneous variable selection and estimation for large number of parameters. We derive an efficient coordinate descent algorithm to solve the penalized optimization problem, which is fully automatic and data driven. We further consider an extension where one of the states is death, and time of death is exactly known but the state path leading to death is unknown. The proposed method is extensively evaluated in a simulation study, and demonstrated in an application to real-world data on airflow limitation state transitions.

Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers.

BACKGROUND: The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. OBJECTIVE: We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. METHODS: We used the Methylated CpG Island Recovery Assay chip to survey DNA methylation in cord blood mononuclear cells from 36 children (18 nonasthmatic and 18 asthmatic subjects by age 9 years) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n = 60) and in 2 replication cohorts (the Manchester Asthma and Allergy Study [n = 30] and the Childhood Origins of Asthma Study [n = 28]) was analyzed by using bisulfite sequencing or Illumina 450K arrays. Cord blood mononuclear cell-derived IL-1ß levels were measured by means of ELISA. RESULTS: Neonatal immune cells harbored 589 differentially methylated regions that distinguished IIS children who did and did not have asthma by age 9 years. In all 3 cohorts methylation in SMAD3, the most connected node within the network of asthma-associated, differentially methylated regions, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1ß, an innate inflammatory mediator. CONCLUSIONS: The trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and proinflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory.

Least absolute shrinkage and selection operator type methods for the identification of serum biomarkers of overweight and obesity: simulation and application.

BACKGROUND: The study of circulating biomarkers and their association with disease outcomes has become progressively complex due to advances in the measurement of these biomarkers through multiplex technologies. The Least Absolute Shrinkage and Selection Operator (LASSO) is a data analysis method that may be utilized for biomarker selection in these high dimensional data. However, it is unclear which LASSO-type method is preferable when considering data scenarios that may be present in serum biomarker research, such as high correlation between biomarkers, weak associations with the outcome, and sparse number of true signals. The goal of this study was to compare the LASSO to five LASSO-type methods given these scenarios. METHODS: A simulation study was performed to compare the LASSO, Adaptive LASSO, Elastic Net, Iterated LASSO, Bootstrap-Enhanced LASSO, and Weighted Fusion for the binary logistic regression model. The simulation study was designed to reflect the data structure of the population-based Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD), specifically the sample size (N = 1000 for total population, 500 for sub-analyses), correlation of biomarkers (0.20, 0.50, 0.80), prevalence of overweight (40%) and obese (12%) outcomes, and the association of outcomes with standardized serum biomarker concentrations (log-odds ratio = 0.05-1.75). Each LASSO-type method was then applied to the TESAOD data of 306 overweight, 66 obese, and 463 normal-weight subjects with a panel of 86 serum biomarkers. RESULTS: Based on the simulation study, no method had an overall superior performance. The Weighted Fusion correctly identified more true signals, but incorrectly included more noise variables. The LASSO and Elastic Net correctly identified many true signals and excluded more noise variables. In the application study, biomarkers of overweight and obesity selected by all methods were Adiponectin, Apolipoprotein H, Calcitonin, CD14, Complement 3, C-reactive protein, Ferritin, Growth Hormone, Immunoglobulin M, Interleukin-18, Leptin, Monocyte Chemotactic Protein-1, Myoglobin, Sex Hormone Binding Globulin, Surfactant Protein D, and YKL-40. CONCLUSIONS: For the data scenarios examined, choice of optimal LASSO-type method was data structure dependent and should be guided by the research objective. The LASSO-type methods identified biomarkers that have known associations with obesity and obesity related conditions.

Asthma, airflow limitation and mortality risk in the general population.

Asthma and chronic obstructive pulmonary disease co-exist in a significant proportion of patients. Whether asthma increases mortality risk among subjects with airflow limitation remains controversial. We used data from 2121 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease cohort. At enrolment (1972-1973), participants completed questionnaires and lung function tests. Participants were categorised into four groups based on the combination of airflow limitation (AL; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <70%) and physician-confirmed asthma at baseline. Vital status as of January 2011 was assessed through the National Death Index. Cox proportional hazards models were used to test differences in mortality risk across the four airflow limitation/asthma groups. In multivariate Cox models, the AL+/asthma+ group had a 114% increased mortality risk during follow-up compared with the AL-/asthma- group (adjusted HR 2.14; 95% CI 1.64-2.79). The corresponding hazard ratios were 1.09 (95% CI 0.89-1.34) and 1.34 (95% CI 1.14-1.57) for the AL-/asthma+ and AL+/asthma- groups, respectively. Among subjects with airflow limitation, asthma was associated with increased mortality risk (HR 1.58, 95% CI 1.17-2.12). However, this increased risk was substantially reduced and no longer significant after further adjustment for baseline FEV1 levels. Similar results were obtained when airflow limitation was defined as FEV1/FVC less than the lower limit of normal. In a population-based cohort, subjects with concomitant airflow limitation and asthma had an increased risk of dying, which was mainly related to their baseline lung function deficits.

Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes.

Radical trachelectomy is the treatment of choice in women with early-stage cervical cancer wishing to preserve fertility. Radical trachelectomy can be performed with a vaginal, abdominal, or laparoscopic/robotic approach. Vaginal radical trachelectomy (VRT) is generally not offered to patients with tumors 2cm or larger because of a high recurrence rate. There are no conclusive recommendations regarding the safety of abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) in such patients. Several investigators have used neoadjuvant chemotherapy in patients with tumors 2 to 4cm to reduce tumor size so that fertility preservation may be offered. However, to our knowledge, no published study has compared outcomes between patients with cervical tumors 2cm or larger who underwent immediate radical trachelectomy and those who underwent neoadjuvant chemotherapy followed by radical trachelectomy. We conducted a literature review to compare outcomes with these 2 approaches. Our main endpoints for evaluation were oncological and obstetrical outcomes. The fertility preservation rate was 82.7%, 85.1%, 89%; and 91.1% for ART (tumors larger than >2cm), ART (all sizes), NACT followed by surgery and VRT (all sizes); respectively. The global pregnancy rate was 16.2%, 24% and 30.7% for ART, VRT, and NACT followed by surgery; respectively. The recurrence rate was 3.8%, 4.2%, 6%, 7.6% and 17% for ART (all sizes), VRT (all sizes), ART (tumors>2cm), NACT followed by surgery, and VRT (tumors>2cm). These outcomes must be considered when offering a fertility sparing technique to patients with a tumor larger than 2cm.

The Gender Minority Stress and Resilience Measure: Psychometric Validity for Use in Spanish.

Purpose: Stigma is a fundamental driver of HIV disparities among transgender women (TW). The gender minority stress and resilience (GMSR) measure has not been validated in Spanish-speaking, resource-limited settings. We examined the psychometric properties of a translated and abbreviated GMSR among TW in Tijuana, Mexico. Methods: From 2020 to 2021, 152 participants were recruited through social media and venue-based sampling. We collected information on the abbreviated GMSR, psychosocial factors (e.g., depressive symptoms), and sociodemographics. The abbreviated GMSR assessed 7 factors (Discrimination, Rejection, Internalized Transphobia, Negative Expectations, Nondisclosure, Pride, and Community Connectedness). Confirmatory factor analysis, Cronbach's alphas, and McDonald's omegas assessed structural validity. Pearson's partial correlations assessed criterion, convergent, and discriminant validities. Results: The 7-factor structure solution had acceptable fit (root mean square error of approximation [95% confidence interval]=0.05 [0.05-0.06]; comparative fit index/Tucker-Lewis index=0.92/0.91); and internal reliability (α=0.62-0.89; ω=0.62-0.89). Depressive (r=0.22-0.43; p<0.001-0.007), post-traumatic stress disorder (PTSD; r=0.20-0.34; p<0.001-0.017) symptoms, and perceived stress (r=0.19-0.41; p≤0.001-0.030) were all positively associated with all stress factors (e.g., Discrimination, Rejection, Internalized Transphobia, Negative Expectations, and Nondisclosure). The resilience factor Pride was associated with fewer PTSD symptoms (r=-0.18; p=0.027), lower perceived life stress (r=-0.21; p=0.012), and greater general resilience (r=0.26; p=0.002). The Community Connectedness resilience factor was associated with fewer depressive symptoms (r=-0.22; p=0.007). Constructs were conceptually distinct with factor correlations below 0.60. Conclusion: Findings suggest that the Spanish-translated, abbreviated GMSR is a reliable and valid measure. These data expand the usability of the GMSR to TW in a Latin American, Spanish-speaking context.

Microbial-Based Biofungicides Mitigate the Damage Caused by Fusarium oxysporum f. sp. cubense Race 1 and Improve the Physiological Performance in Banana.

Fusarium wilt of banana (FWB) is the most limiting disease in this crop. The phytosanitary emergency caused by FWB since 2019 in Colombia has required the development of ecofriendly control methods. The aim of this study was to test the effectiveness of microbial-based biofungicides against FWB caused by Fusarium oxysporum f. sp. cubense race 1 (Foc R1) and correlate such effect with plant physiological parameters. Five Trichoderma (T1 to T4 and T9) and four Bacillus (T5 to T8)-based biofungicides were evaluated in pot experiments. In vitro, dual confrontation tests were also carried out to test whether the in vitro effects on Foc growth were consistent with the in vivo effects. While Trichoderma-based T3, T4, and T9, and Bacillus-based T8, significantly reduced the growth of Foc R1 in vitro, Trichoderma-based T1, T3, T4, and T9 temporarily reduced the Foc population in the soil. However, the incidence progress of FWB was significantly reduced by Bacterial-based T7 (74% efficacy) and Trichoderma-based T2 (50% efficacy). The molecular analysis showed that T7 prevented the inner tissue colonization by Foc R1 in 80% of inoculated plants. The T2, T4, T7, and T9 treatments mitigated the negative effects caused by Foc R1 on plant physiology and growth. Our data allowed us to identify three promising treatments to control FWB, reducing the progress of the disease, delaying the colonization of inner tissue, and mitigating physiological damages. Further studies should be addressed to determine the modes of action of the biocontrol agents against Foc and validate the utilization in the field.

Vertical Immobilization Method for Time-Lapse Microscopy Analysis in Filamentous Cyanobacteria.

A main event in bacterial cell division is the septation process, where the protein FtsZ is the key element. FtsZ polymerizes forming a ring-like structure (Z-ring) in the middle of the cell that serves as a scaffold for other division proteins. Super-resolution microscopy in bacterial models Escherichia coli and Bacillus subtilis showed that the Z-ring is discontinuous, while live cell imaging studies demonstrated that FtsZ moves along the ring by a mechanism known as treadmilling. To study the dynamics of FtsZ in vivo, a special cell placement in a vertical position is necessary for imaging the complete structure of the ring in the XY plane. In the case of FtsZ imaging in multicellular cyanobacteria, such as Anabaena sp. PCC7120, maintaining the filaments in a vertical position is challenging because of the size of the cells and the filaments' length. In this article, we describe a method that allows the vertical immobilization of Anabaena sp. PCC 7120 filaments using low melting point agarose and syringes, to record the Z-ring in a mutant that expresses a FtsZ-sfGFP fusion protein. This method is a rapid and inexpensive way to register protein dynamics at the division site using confocal microscopy.

Suicide prevention programming across ecological levels: Recommendations from Latinx immigrant origin youth and their parents.

INTRODUCTION: Latinx immigrant-origin youth (IOY) have unique risks for suicidal thoughts and behaviors. It has been suggested that these risks should be addressed from an ecological perspective, addressing cultural and family context as well as structural and systemic barriers to prevention. This study sought to explore perspectives of immigrant-origin Latinx adolescents and their caregivers on suicide and its prevention, including the potential impact of stressors specific to immigrant status. METHOD: Focus groups were conducted in 2018-2019 with Latinx immigrant-origin caregivers (N = 41, 97.5% female) and adolescents (ages = 14-19, N = 56, 50% female). Participants were recruited from community-based organizations in two different cities. A codebook approach to thematic analysis was used to identify themes, which were subsequently mapped onto levels of the Center for Disease Control's Social-Ecological Framework for Violence Prevention. RESULTS: Participants identified both contributors to suicidal behavior and potential components of prevention programming across ecological levels. Specific recommendations for suicide prevention included engaging in recreation, parenting education and support, enhancing academic supports for adolescents, and enhancing school-family communication. Structural barriers (e.g., caregiver work schedules) to implementing recommendations were described. DISCUSSION: Our results highlight the potential role of access to school and community-based supports as public health-oriented suicide prevention strategies and suggest a need to address barriers faced by immigrant families in accessing these supports alongside addressing barriers to mental health treatment. Policies impacting immigrant families' financial stability and increasing the availability of recreational and academic opportunities may promote mental health and prevent suicidal thoughts and behavior among IOY. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of sleep patterns and obesity on increases in blood pressure in a 5-year period: report from the Tucson Children's Assessment of Sleep Apnea Study.

OBJECTIVES: To determine associations between body mass index and sleep on blood pressure in a 5-year period from childhood to adolescence. STUDY DESIGN: Study consisted of a longitudinal, community-based sample of 334 children recruited at ages 6 through 11 years. Each participant underwent in-home polysomnography initially and then 5 years later. Individual systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated at both points during wake periods and classified as hypertensive when SBP or DBP was ≥ 95th standardized percentiles for height and weight. RESULTS: Hypertension was present in 3.6% of the sample at time one and increased to 4.2% 5 years later. Obesity prevalence increased from 15.0% to 19.5%. Normal changes in sleep architecture were observed in the sample. With random effects modeling, which controlled for age, sex, and ethnicity, change in obesity status and decrease in total sleep time were indicated to be associated with increases in SBP. Change in obesity status was also associated with increases in DBP in the 5-year period. A trend for sleep-disordered breathing to increase SBP was noted. CONCLUSIONS: Increases in SBP and DBP were associated with increasing body mass index and decreased total sleep time in a 5-year period from childhood to adolescence.

Club cell secretory protein and lung function in children with cystic fibrosis.

BACKGROUND: Club cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF). METHODS: We used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEV1 levels in adolescence (LLF and HLF groups, respectively; N = 130-per-group). Single nucleotide variants (SNVs) in the SCGB1A1, EHF-APIP loci were tested for association with circulating CC16 and with decline of FEV1 and FEV1/FVC% predicted levels between ages 7-16 using mixed models. RESULTS: Compared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p = 0.0002) and higher levels of the normalized inflammatory score (-0.21 vs 0.21, p = 0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p<0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEV1/FVC and, marginally, FEV1 (p = 0.003 and 0.025, respectively; N = 611 participants, 20,801 lung function observations). CONCLUSIONS: Serum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240 A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.

Incidence and remission of sleep-disordered breathing and related symptoms in 6- to 17-year old children--the Tucson Children's Assessment of Sleep Apnea Study.

OBJECTIVE: To determine the incidence and remission of sleep-disordered breathing in adolescent children. STUDY DESIGN: A total of 319 children completed 2 home polysomnograms approximately 5 years apart. Sleep-disordered breathing (SDB) was determined to be present if a child had a respiratory disturbance index>or=1 event per hour associated with >or=3% oxygen desaturation. Subjective symptoms such as witnessed apnea, excessive daytime sleepiness, difficulty initiating and maintaining sleep, and habitual loud snoring were considered present if they occurred frequently or almost always. Body mass index percentiles were calculated with childhood growth charts from the Centers for Disease Control and Prevention adjusted for sex and age. RESULTS: The mean age at assessment was 8.5 years at baseline and 13.7 years at follow-up, respectively. Incident SDB was more common in boys (odds ratio [OR]=3.93, P=.008, confidence interval [CI]=1.41-10.90). Children with prevalent SDB were more likely to be boys (OR=2.48, P=.006) and had a greater increase in body mass index percentile change (OR 1.01, P=.034). Children with prevalent SDB also had 3.41 greater odds for development of obesity from baseline to follow-up in comparison with children with prevalent NoSDB. CONCLUSIONS: Adolescent boys are more likely to have persistent and incident SDB than girls. Children with prevalent SDB are more likely to have development of obesity. These risks are similar to those observed in adults.