Exploring the potential of omics technologies in medicinal plant research: a review in Colombia / Explorando el potencial de las tecnologías ómicas en la investigación de plantas medicinales: una revisión en Colombia

This review presents advances in the implementation of high - throughput se quencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (versi on 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine t hem widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcr iptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics ( e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce. (185)

El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria se evaluaron para determinar su actividad antiproliferativa in vitro contra 10 líneas ce lulares tumorales humanas [leucemia (K - 562), mama (MCF - 7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR - RES), melanoma (UACC - 62), pulmón (NCI - H460), próstata (PC - 3), colon (HT29), ovario (OVCAR - 3), glioma (U251) y riñón (786 - 0)]. CE presentó actividad antiproliferativa débil a moderada (log GI 50 medio 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent - pimara - 8 (14), ácido 15 - dien - 19 - oico y ent - 8(14),15 - pimaradien - 3 ß - ol], presentaron activid ad moderada a potente para la mayoría de las líneas celulares, con un log GI 50 medio de 0.62 y 0.59, respectivamente. Los resultados mostraron una acción antiproliferativa in vitro prometedora de las muestras obtenidas de A. arenaria , con los mejores resul tados para NCI/ADR - RES, HT29 y OVCAR - 3, y valores de TGI que van desde 5.95 a 28.71 µg.mL - 1, demostrando que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos

Therapeutic inhibition of monocyte recruitment prevents checkpoint inhibitor-induced hepatitis.

BACKGROUND: Checkpoint inhibitor-induced hepatitis (CPI-hepatitis) is an emerging problem with the widening use of CPIs in cancer immunotherapy. Here, we developed a mouse model to characterize the mechanism of CPI-hepatitis and to therapeutically target key pathways driving this pathology. METHODS: C57BL/6 wild-type (WT) mice were dosed with toll-like receptor (TLR)9 agonist (TLR9-L) for hepatic priming combined with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) plus anti-programmed cell death 1 (PD-1) ("CPI") or phosphate buffered saline (PBS) control for up to 7 days. Flow cytometry, histology/immunofluorescence and messenger RNA sequencing were used to characterize liver myeloid/lymphoid subsets and inflammation. Hepatocyte damage was assessed by plasma alanine transaminase (ALT) and cytokeratin-18 (CK-18) measurements. In vivo investigations of CPI-hepatitis were carried out in Rag2-/- and Ccr2rfp/rfp transgenic mice, as well as following anti-CD4, anti-CD8 or cenicriviroc (CVC; CCR2/CCR5 antagonist) treatment. RESULTS: Co-administration of combination CPIs with TLR9-L induced liver pathology closely resembling human disease, with increased infiltration and clustering of granzyme B+perforin+CD8+ T cells and CCR2+ monocytes, 7 days post treatment. This was accompanied by apoptotic hepatocytes surrounding these clusters and elevated ALT and CK-18 plasma levels. Liver RNA sequencing identified key signaling pathways (JAK-STAT, NF-ΚB) and cytokine/chemokine networks (Ifnγ, Cxcl9, Ccl2/Ccr2) as drivers of CPI-hepatitis. Using this model, we show that CD8+ T cells mediate hepatocyte damage in experimental CPI-hepatitis. However, their liver recruitment, clustering, and cytotoxic activity is dependent on the presence of CCR2+ monocytes. The absence of hepatic monocyte recruitment in Ccr2rfp/rfp mice and CCR2 inhibition by CVC treatment in WT mice was able to prevent the development and reverse established experimental CPI-hepatitis. CONCLUSION: This newly established mouse model provides a platform for in vivo mechanistic studies of CPI-hepatitis. Using this model, we demonstrate the central role of liver infiltrating CCR2+ monocyte interaction with tissue-destructive CD8+ T cells in the pathogenesis of CPI-hepatitis and highlight CCR2 inhibition as a novel therapeutic target.

Development of the Fit&Fab Exercise Intervention for Women With Obesity: A Community Advisory Board Informed Process.

BACKGROUND: Women with higher body mass index report low rates of and face unique barriers to exercise. Increasing exercise participation can improve mental and physical health independent of weight loss; however, most exercise programs targeting this population focus predominately on losing weight. This paper aims to describe the development of Fit&Fab, a community-based exercise intervention focused on increasing exercise participation and enjoyment for women with obesity. METHODS: In partnership with the YMCA, we recruited women ages 35-64 years (body mass index ≥ 30) to participate in 4 focus groups to understand exercise preferences. Formative work was used to identify theory constructs and associated intervention components. Women from the focus groups were recruited for a community advisory board that finalized the intervention design, recruitment, and evaluation plan. RESULTS: Focus groups participants (N = 29) preferred to exercise without men and wanted a cohort-style class that included women of similar exercise levels and body types, incorporated social support, fun activities, and broke exercise into smaller bouts. They wanted a supportive instructor who was fit but understood weight-related challenges. The community advisory board and research team used focus group findings to inform design of the final intervention including group exercise classes, psychosocial support sessions, personalized training, exercise tracking, outcome monitoring, and rewards. CONCLUSIONS: Our findings emphasize the need to focus on exercise enjoyment and benefits other than losing weight to improve exercise participation among women with higher body mass index. In addition to having outcomes other than weight loss, exercise interventions with this population should also consider group composition, instructor, and class format.

Distinctive cell-free DNA methylation characterizes presymptomatic genetic frontotemporal dementia.

OBJECTIVE: Methylation of plasma cell-free DNA (cfDNA) has potential as a marker of brain damage in neurodegenerative diseases such as frontotemporal dementia (FTD). Here, we study methylation of cfDNA in presymptomatic and symptomatic carriers of genetic FTD pathogenic variants, next to healthy controls. METHODS: cfDNA was isolated from cross-sectional plasma of 10 presymptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), 10 symptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), and 9 healthy controls. Genome-wide methylation of cfDNA was determined using a high-resolution sequencing technique (MeD-seq). Cumulative scores based on the identified differentially methylated regions (DMRs) were estimated for presymptomatic carriers (vs. controls and symptomatic carriers), and reevaluated in a validation cohort (8 presymptomatic: 3 C9orf72, 3 GRN, and 2 MAPT; 26 symptomatic: 7 C9orf72, 6 GRN, 12 MAPT, and 1 TARDBP; 13 noncarriers from genetic FTD families). RESULTS: Presymptomatic carriers showed a distinctive methylation profile compared to healthy controls and symptomatic carriers. Cumulative DMR scores in presymptomatic carriers enabled to significantly differentiate presymptomatic carriers from healthy controls (p < 0.001) and symptomatic carriers (p < 0.001). In the validation cohort, these scores differentiated presymptomatic carriers from symptomatic carriers (p ≤ 0.007) only. Transcription-start-site methylation in presymptomatic carriers, generally associated with gene downregulation, was enriched for genes involved in ubiquitin-dependent processes, while gene body methylation, generally associated with gene upregulation, was enriched for genes involved in neuronal cell processes. INTERPRETATION: A distinctive methylation profile of cfDNA characterizes the presymptomatic stage of genetic FTD, and could reflect neuronal death in this stage.

A longitudinal causal graph analysis investigating modifiable risk factors and obesity in a European cohort of children and adolescents.

Childhood obesity is a complex disorder that appears to be influenced by an interacting system of many factors. Taking this complexity into account, we aim to investigate the causal structure underlying childhood obesity. Our focus is on identifying potential early, direct or indirect, causes of obesity which may be promising targets for prevention strategies. Using a causal discovery algorithm, we estimate a cohort causal graph (CCG) over the life course from childhood to adolescence. We adapt a popular method, the so-called PC-algorithm, to deal with missing values by multiple imputation, with mixed discrete and continuous variables, and that takes background knowledge such as the time-structure of cohort data into account. The algorithm is then applied to learn the causal structure among 51 variables including obesity, early life factors, diet, lifestyle, insulin resistance, puberty stage and cultural background of 5112 children from the European IDEFICS/I.Family cohort across three waves (2007-2014). The robustness of the learned causal structure is addressed in a series of alternative and sensitivity analyses; in particular, we use bootstrap resamples to assess the stability of aspects of the learned CCG. Our results suggest some but only indirect possible causal paths from early modifiable risk factors, such as audio-visual media consumption and physical activity, to obesity (measured by age- and sex-adjusted BMI z-scores) 6 years later.

Incident use of hydroxychloroquine for the treatment of rheumatoid arthritis and systemic lupus erythematosus during the COVID-19 pandemic.

OBJECTIVE: We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (IMASIS) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population, and in RA and SLE patients. Methotrexate (MTX) was use was estimated as a control. RESULTS: Over 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS respectively, to decrease in May 2020. Usage rates of HCQ went back to pre-pandemic trends in Spain, but remained high in the US, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment. CONCLUSIONS: Use of HCQ increased dramatically in the general population in both Spain and the US during March and April 2020. While Spain returned to pre-pandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the US. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the US. This article is protected by copyright. All rights reserved.

Interleukin-4 downregulates transcription factor BCL6 to promote memory B cell selection in germinal centers.

Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we showed that IL-4 cytokine signaling in GC B cells directly downregulated the transcription factor BCL6 via negative autoregulation to release cells from the GC program and to promote MBC formation. This selection event required additional survival cues and could therefore result in either GC exit or death. We demonstrate that both increasing IL-4 bioavailability or limiting IL-4 signaling disrupted MBC selection stringency. In this way, IL-4 control of BCL6 expression serves as a tunable switch within the GC to tightly regulate MBC selection and affinity maturation.

Using implementation mapping to refine strategies to improve implementation of an evidence-based mobile market intervention: a study protocol.

Objectives: The Veggie Van model is a mobile market model that is efficacious in increasing fruit and vegetable consumption for lower-income participants. The model is currently being evaluated for its effectiveness in a multi-state trial. Preliminary implementation data, collected through process measures surveys and implementation interviews, indicate that there are several barriers to implementation among partner organizations and implementation fidelity to the Veggie Van model was low. Consideration and planning for implementation ought to occur early and often throughout the research process order to ensure Veggie Van model effectiveness. This paper describes the step-by-step process for creating strategies to enhance implementation of Veggie Van model components. Methods: Implementation mapping is a systematic process to develop implementation strategies through engagement with key stakeholders. We conducted a series of interviews (n = 31 representatives) with partner organizations (n = 8) to identify facilitators and barriers to Veggie Van model implementation. We then applied interview findings to an Implementation Mapping process to develop theory and practice-driven strategies to be integrated into existing implementation tools and technical assistance. Results: We identified implementation outcomes (e.g., staff implement the Veggie Van model component of nutrition education with fidelity) and performance objectives (e.g., offer nutrition education, in the form of food lessons and/or food demonstrations, at least bi-weekly) to achieve them. We conducted a secondary qualitative analysis of the findings from implementation interviews with partner organizations to identify behavioral determinants (e.g., attitudinal beliefs, social support) which were combined with the performance objectives to generate change objectives (e.g., view the Veggie Van model as advantageous to an organization and communities served). To achieve the change objectives, we developed implementation strategies that would be integrated into existing Veggie Van training resources including an online toolkit, webinars and trainings, an annual mobile market conference, and technical assistance. Conclusion: The development of theory and practice-driven implementation strategies will enable us to improve our implementation tools, thereby improving fidelity to the Veggie Van model among organizations and increasing the likelihood of its effectiveness. Detailing the design of a multifaceted implementation strategy using Implementation Mapping also provides a model to design similar strategies for other community-based interventions.

Optimal Defaults in Online Grocery Shopping: A Secondary Analysis to Explore Impacts in Multiresident Households and Families.

OBJECTIVE: To examine whether household type (eg, families with children) moderated the effects of an optimal defaults grocery intervention and examine intervention effects on grocery purchases to be consumed by the participant vs others in the household. METHODS: Participants (n = 65) diagnosed with or at risk for type 2 diabetes were recruited and randomized into an optimal default online grocery intervention or an online or in-person control group. Grocery receipt data were coded into Dietary Approaches to Stop Hypertension nutritional quality scores, and energy, carbohydrate, and sugar content were calculated. Repeated measures analysis of variance examined household types (eg, single vs multi-resident) as moderators of intervention effects. Parallel models explored foods purchased for the participant and foods purchased for other household members separately. RESULTS: Household type was not a significant moderator of intervention effects on nutritional quality or other nutrients of interest (P > 0.10). The default intervention significantly increased the nutritional quality of groceries purchased across household types and for other household members besides the participant (P < 0.05). CONCLUSIONS AND IMPLICATIONS: Optimal defaults may improve grocery purchases across different household types and extend to others in the household, supporting use across household types.

Shades of white: The Petunia long corolla tube clade evolutionary history.

Delimiting species is challenging in recently diverged species, and adaptive radiation is fundamental to understanding the evolutionary processes because it requires multiple ecological opportunities associated with adaptation to biotic and abiotic environments. The young Petunia genus (Solanaceae) is an excellent opportunity to study speciation because of its association with pollinators and unique microenvironments. This study evaluated the phylogenetic relationships among a Petunia clade species with different floral syndromes that inhabit several environments. We based our work on multiple individuals per lineage and employed nuclear and plastid phylogenetic markers and nuclear microsatellites. The phylogenetic tree revealed two main groups regarding the elevation of the distribution range, whereas microsatellites showed high polymorphism-sharing splitting lineages into three clusters. Isolation by distance, migration followed by new environment colonization, and shifts in floral syndrome were the motors for lineage differentiation, including infraspecific structuring, which suggests the need for taxonomic revision in the genus.

Maternal seafood consumption is associated with improved selenium status: Implications for child health.

Selenium (Se) is required for synthesis of selenocysteine (Sec), an amino acid expressed in the active sites of Se-dependent enzymes (selenoenzymes), including forms with essential functions in fetal development, brain activities, thyroid hormone metabolism, calcium regulation, and to prevent or reverse oxidative damage. Homeostatic mechanisms normally ensure the brain is preferentially supplied with Se to maintain selenoenzymes, but high methylmercury (CH3Hg) exposures irreversibly inhibit their activities and impair Sec synthesis. Due to Hg's high affinity for sulfur, CH3Hg initially binds with the cysteine (Cys) moieties of thiomolecules which are selenoenzyme substrates. These CH3Hg-Cys adducts enter selenoenzyme active sites and transfer CH3Hg to Sec, thus irreversibly inhibiting their activities. High CH3Hg exposures are uniquely able to induce a conditioned Se-deficiency that impairs synthesis of brain selenoenzymes. Since the fetal brain lacks Se reserves, it is far more vulnerable to CH3Hg exposures than adult brains. This prompted concerns that maternal exposures to CH3Hg present in seafood might impair child neurodevelopment. However, typical varieties of ocean fish contain far more Se than CH3Hg. Therefore, eating them should augment Se-status and thus prevent Hg-dependent loss of fetal selenoenzyme activities. To assess this hypothesis, umbilical cord blood and placental tissue samples were collected following delivery of a cohort of 100 babies born on Oahu, Hawaii. Dietary food frequency surveys of the mother's last month of pregnancy identified groups with no (0 g/wk), low (0-12 g/wk), or high (12 + g/wk) levels of ocean fish consumption. Maternal seafood consumption increased Hg contents in fetal tissues and resulted in ∼34% of cord blood samples exceeding the EPA Hg reference level of 5.8 ppb (0.029 µM). However, Se concentrations in these tissues were orders of magnitude higher and ocean fish consumption caused cord blood Se to increase ∼9.4 times faster than Hg. Therefore, this study supports the hypothesis that maternal consumption of typical varieties of ocean fish provides substantial amounts of Se that protect against Hg-dependent losses in Se bioavailability. Recognizing the pivotal nature of the Hg:Se relationship provides a consilient perspective of seafood benefits vs. risks and clarifies the reasons for the contrasting findings of certain early studies.

The role of psychosocial well-being and emotion-driven impulsiveness in food choices of European adolescents.

BACKGROUND: It is unclear whether a hypothetical intervention targeting either psychosocial well-being or emotion-driven impulsiveness is more effective in reducing unhealthy food choices. Therefore, we aimed to compare the (separate) causal effects of psychosocial well-being and emotion-driven impulsiveness on European adolescents' sweet and fat propensity. METHODS: We included 2,065 participants of the IDEFICS/I.Family cohort (mean age: 13.4) providing self-reported data on sweet propensity (score range: 0 to 68.4), fat propensity (range: 0 to 72.6), emotion-driven impulsiveness using the UPPS-P negative urgency subscale, and psychosocial well-being using the KINDLR Questionnaire. We estimated, separately, the average causal effects of psychosocial well-being and emotion-driven impulsiveness on sweet and fat propensity applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). Further, we investigated a potential indirect effect of psychosocial well-being on sweet and fat propensity mediated via emotion-driven impulsiveness using a causal mediation analysis. RESULTS: If all adolescents, hypothetically, had high levels of psychosocial well-being, compared to low levels, we estimated a decrease in average sweet propensity by 1.43 [95%-confidence interval: 0.25 to 2.61]. A smaller effect was estimated for fat propensity. Similarly, if all adolescents had high levels of emotion-driven impulsiveness, compared to low levels, average sweet propensity would be decreased by 2.07 [0.87 to 3.26] and average fat propensity by 1.85 [0.81 to 2.88]. The indirect effect of psychosocial well-being via emotion-driven impulsiveness was 0.61 [0.24 to 1.09] for average sweet propensity and 0.55 [0.13 to 0.86] for average fat propensity. CONCLUSIONS: An intervention targeting emotion-driven impulsiveness, compared to psychosocial well-being, would be marginally more effective in reducing sweet and fat propensity in adolescents.

Characterisation, symptom pattern and symptom clusters from a retrospective cohort of Long COVID patients in primary care in Catalonia.

BACKGROUND: Around 10% of people infected by SARS-COV-2 report symptoms that persist longer than 3 months. Little has been reported about sex differences in symptoms and clustering over time of non-hospitalised patients in primary care settings. METHODS: This is a descriptive study of a cohort of mainly non-hospitalized patients with a persistence of symptoms longer than 3 months from the clinical onset in co-creation with the Long Covid Catalan affected group using an online survey. Recruitment was from March 2020 to June 2021. Exclusion criteria were being admitted to an ICU, < 18 years of age and not living in Catalonia. We focused on 117 symptoms gathered in 18 groups and performed cluster analysis over the first 21 days of infection, at 22-60 days, and ≥ 3 months. RESULTS: We analysed responses of 905 participants (80.3% women). Median time between symptom onset and the questionnaire response date was 8.7 months. General symptoms (as fatigue) were the most prevalent with no differences by sex, age, or wave although its frequency decreased over time (from 91.8 to 78.3%). Dermatological (52.1% in women, 28.5% in men), olfactory (34.9% women, 20.9% men) and neurocognitive symptoms (70.1% women, 55.8% men) showed the greatest differences by sex. Cluster analysis showed five clusters with a predominance of Taste & smell (24.9%) and Multisystemic clusters (26.5%) at baseline and _Multisystemic (34.59%) and Heterogeneous (24.0%) at ≥3 months. The Multisystemic cluster was more prevalent in men. The Menstrual cluster was the most stable over time, while most transitions occurred from the Heterogeneous cluster to the Multisystemic cluster and from Taste & smell to Heterogeneous. CONCLUSIONS: General symptoms were the most prevalent in both sexes at three-time cut-off points. Major sex differences were observed in dermatological, olfactory and neurocognitive symptoms. The increase of the Heterogeneous cluster might suggest an adaptation to symptoms or a non-specific evolution of the condition which can hinder its detection at medical appointments. A carefully symptom collection and patients' participation in research may generate useful knowledge about Long Covid presentation in primary care settings.

Examining the consistency in bilingualism and white matter research: A meta-analysis.

This study aimed to systematically investigate the relationship between bilingualism, age, L2 onset age of acquisition (AoA), and white matter integrity (operationalized as fractional anisotropy, FA), addressing inconsistencies in the literature. We conducted a meta-analysis of 23 studies and used meta-regression models to assess the influence of age and L2AoA on effect sizes in studies comparing monolinguals and bilinguals. Even though the overall between-group effect size across the whole brain was unreliable, bilingualism was associated with increased white matter integrity in specific tracts and in groups with a limited range of age and L2AoA. Age had a small, negative effect on white matter integrity, with differences between monolinguals and bilinguals more pronounced in younger adults, consistent with a view of an initial increase in white matter integrity, followed by remodeling for efficiency over time. In contrast, later L2AoA was associated with greater white matter integrity in bilinguals than monolinguals, again consistent with the remodeling for efficiency model. Our findings highlight the importance of considering age and L2AoA when examining the neural basis of bilingualism on white matter in the brain and how bilingualism contributes to structural changes that stave off cognitive decline in older age.

Addressing food insecurity in HIV care: perspectives from healthcare and social service providers in New York state.

Ending the HIV epidemic in the United States will require addressing social determinants contributing to poor care engagement among people living with HIV (PLH), such as food insecurity. Food insecurity is associated with poor care engagement among PLH. Yet, few studies have examined the perspectives of healthcare and social services providers on addressing food insecurity in HIV care. Guided by the Social Ecological Model, we conducted semi-structured interviews with 18 providers in New York State to understand barriers and facilitators to addressing food insecurity in HIV care. Thematic analysis illustrated eight themes across various levels of the Social Ecological Model. At the patient-level, providers perceived patients' feelings of embarrassment, shame, and judgement, and low health literacy as barriers. At the provider-level, challenges included limited time. Facilitators included fostering strong, patient-provider relationships. Barriers at the clinic-level included limited funding, while clinic resources served as facilitators. At the community-level, challenges included intersecting stigmas arising from community norms towards PLH and people who receive food assistance and limited access to healthy food. Findings suggest the need to incorporate their insights into the development of interventions that address food insecurity in HIV care.

The motivation and process for developing a consortium-wide time and motion study to estimate resource implications of innovations in the use of genome sequencing to inform patient care.

Costs of implementing genomic testing innovations extend beyond the cost of sequencing, affecting personnel and infrastructure for which little data are available. We developed a time and motion (T&M) study within the Clinical Sequencing Evidence-Generating Research (CSER) consortium to address this gap, and herein describe challenges of conducting T&M studies within a research consortium and the approaches we developed to overcome them. CSER investigators created a subgroup to carry out the T&M study (authors). We describe logistical and administrative challenges associated with resource use data collection across heterogeneous projects conducted in real-world clinical settings, and our solutions for completing this study and harmonizing data across projects. We delineate processes for feasible data collection on workflow, personnel, and resources required to deliver genetic testing innovations in each CSER project. A critical early step involved developing detailed project-specific process flow diagrams of innovation implementation in projects' clinical settings. Analyzing diagrams across sites, we identified common process-step themes, used to organize project-specific data collection and cross-project analysis. Given the heterogeneity of innovations, study design, and workflows, which affect resources required to deliver genetic testing innovations, flexibility was necessary to harmonize data collection. Despite its challenges, this heterogeneity provides rich insights about variation in clinical processes and resource implications for implementing genetic testing innovations.

Metabolic Syndrome Components in Patients with Pituitary Adenoma.

Pituitary adenomas are benign tumors of the anterior portion of the pituitary gland (adenohypophysis), representing the 25% of all the tumor alterations. Pituitary adenomas are classified by the type of hormone secreted, cellularity, size, and structural alterations by the hormonal segregation. The diagnosis consists on the histopathological identification of cell types and the image-guided by magnetic resonance or tomography; the treatment can be both pharmacological and surgical. Metabolic Syndrome is the set of clinical conditions that increase the risk of cardiovascular diseases with an estimated prevalence of 25% worldwide. The alterations of metabolic syndrome are obesity, hypertension, dyslipidemia, insulin resistance, and diabetes mellitus type II. Pituitary adenomas and metabolic syndrome have an important relationship, hormone-secreting by pituitary adenomas affects a myriad of signaling pathways, which allows a favorable environment for the appearance of the metabolic syndrome. Moreover, patients with pituitary adenomas are shown to have an improvement in metabolic parameters after the medical/surgical treatment. The objective of this review is to explore the possible mechanisms through which PAs contributes to MetSx.

Online cognitive-behavioral intervention for stress among English as a second language teachers: implications for school health policy.

Introduction: Stress is one of the highest-ranked work-related injuries worldwide and has become almost universal among the Nigerian workforce. English as a Second Language (ESL) teachers face enormous work-related threats that lead to occupational stress. When ESL teachers are stressed, students' language development and entire educational progress are at risk. This is mostly underscored as English, though a second language, serves as the language of instruction in Nigerian schools. As a result, managing occupational stress is particularly important for ESL teachers, as it is among the definitive ways of improving ESL learning and overall educational outcomes. This study examined the effectiveness of online cognitive behavioral intervention (o-CBI) in lowering occupational stress among ESL teachers. Method: ESL teachers with at least 1 year of experience were among the participants (N = 89). Participants were divided into two groups: the intervention group (N = 44) and the control group (N = 45). For 9 weeks, the experimental group engaged in nine sessions of 2 h of the o-CBI program. The Single Item Stress Questionnaire (SISQ), the Satisfaction with Therapy and Therapist Scale-Revised (STTS-R), and the Teachers' Stress Inventory (TSI) were the measures used to collect primary and secondary data. Four sets of data were collected at baseline, post-test, and follow-up 1 and 2 evaluations. The data were analyzed using mean, standard deviation, t-test statistics, repeated measures ANOVA, and bar charts. Results and discussion: Compared to the control group, the o-CBT group had significantly lower TSI scores at the post-test (Time 2) and follow-up evaluations (Times 3 and 4). Between pre-, post-, and follow-up 1 and 2 measurements, there were no significant differences in occupational stress index scores in the control group. It was concluded that o-CBI is effective in job-stress treatment among ESL teachers. In addition, implications for school health policy are discussed. The o-CBI for occupational stress was well received by the participants, showing high acceptability among ESL teachers.

Maternal Consumption of Non-Nutritive Sweeteners during Pregnancy Is Associated with Alterations in the Colostrum Microbiota.

Non-nutritive sweeteners (NNSs) provide a sweet taste to foods and beverages without significantly adding calories. Still, their consumption has been linked to modifications in adult's and children's gut microbiota and the disruption of blood glucose control. Human milk microbiota are paramount in establishing infants' gut microbiota, but very little is known about whether the consumption of sweeteners can alter it. To address this question, we sequenced DNA extracted colostrum samples from a group of mothers, who had different levels of NNS consumption, using the Ion Torrent Platform. Our results show that the "core" of colostrum microbiota, composed of the genera Bifidobacterium, Blautia, Cutibacteium, Staphylococcus, and Streptococcus, remains practically unchanged with the consumption of NNS during pregnancy, but specific genera display significant alterations, such as Staphylococcus and Streptococcus. A significant increase in the unclassified archaea Methanobrevibacter spp. was observed as the consumption frequency of NNS increased. The increase in the abundance of this archaea has been previously linked to obesity in Mexican children. NNS consumption during pregnancy could be related to changes in colostrum microbiota and may affect infants' gut microbiota seeding and their future health.