Key Clinical and Histopathological Features of a Pterygium-Like Induced Lesion in a Rabbit Model.

Purpose: Surgery is the definitive treatment for pterygium; therefore, reliable animal models are required for translational research. The goal of this investigation was to establish a standardized preclinical model of pterygium-like lesion. Methods: A subconjunctival injection of fibroblasts (NIH3T3) and extracellular matrix was administered to 22 New Zealand rabbits. Clinical evaluation was assessed at different points, the severity of the lesion was scored according to four grades and correlated with the area of hyperemia and the histopathological findings on day 23. Results: Thirteen of 22 eyes (60%) developed pterygium-like lesions after 7 days and progressed through different grades. Initially, grade 3, characterized by an elevated and fleshiness conjunctiva with tortuous hyperemia, was evident on day 7. By day 15, lesion decreased to grade 2, with less elevation and hyperemia. Subsequent improvement was noted, with grade 1 on day 18. Finally, day 23 was marked by a white‒yellow lesion, classified as grade 4. The area of hyperemia increased from grade 2 to grade 3 (P < 0.05) and decreased from grade 3 to grade 4 (P ≤ 0.05). Histopathological analysis revealed a tendency toward increasing inflammation at grades 2, 3, and 4. There was a correlation between clinical features and the degree of inflammation. Conclusions: Subconjunctival injection of NIH3T3 and extracellular matrix induces a pterygium-like lesion that progresses across four grades, beginning with an acute inflammatory process that evolve a chronic form. This study provides a replicable model for simulating pterygium. Translational Relevance: The development of a standardized preclinical model of pterygium to evaluate new pharmacological or surgical treatments.

Barriers to adherence to secondary prevention therapy in patients with ischemic heart disease: a cross-sectional study of a Mexican reference center.

Objective: This article aims to assess the adherence level to second-line therapy for cardiovascular prevention in a tertiary hospital in Mexico City and identify key barriers to adequate pharmacological adherence. Methods: A single-center prospective cross-sectional study was conducted between August 2018 and February 2020. Sociodemographic data were collected, and the Morisky medication adherence scale was performed. Directed interviews during medical consultations were also conducted to determine reasons for non-adherence. Results: Showed that out of 991 patients included with a median age of 65 (58.72) years, 70.3% exhibited inadequate adherence, with forgetfulness being the most common reason (55.4%). Patients receiving combined therapy with coronary revascularization showed higher adherence compared to those on optimal medical therapy alone. Low educational level (OR 1.68, IC 95% 1.23-2.23, p = 0.0001) and the use of optimal medical therapy alone (OR 1.2, I 95% 1.11-2.007 p = 0.007) were identified as predictors of poor adherence. Conclusion: Among patients with ischemic heart disease and pharmacological therapy for secondary prevention, inadequate adherence is observed in 70% of cases. Factors associated with poor pharmacological adherence were low educational level and prescription of medical therapy without revascularization.

Objetivo: Determinar el nivel de adherencia a la terapia secundaria de prevención cardiovascular en un hospital terciario de la Ciudad de México e identificar las barreras que contribuyen a la inadecuada adherencia farmacológica. Métodos: Se realizó un estudio transversal entre agosto de 2018 y febrero de 2020. Se obtuvieron los datos sociodemográficos, la escala de adherencia a la medicación de Morisky, y se realizó una entrevista sobre las razones de la no adherencia. Resultados: 991 pacientes fueron incluidos con una mediana de edad de 65 (58,72) años. La adherencia inadecuada fue de 70.3%, siendo el olvido la causa más frecuente (55.4%). Aquellos pacientes en terapia farmacológica combinada con revascularización coronaria fueron más adherentes que aquellos en terapia médica óptima. El bajo nivel educativo (OR 1.68, IC95%1.23-2.3, p = 0.001) y el uso de tratamiento médico óptimo solo (OR 1.52, IC95%1.11-2.07, p = 0.007) fueron predictores de mala adherencia. Conclusión: En pacientes con cardiopatia isquemica y terapia farmacológica para prevención secundaria se observa adherencia inadecuada en 70%. Los factores asociados a mala adherencia farmacológica fueron el bajo nivel educativo y la prescripción de tratamiento médico sin revascularización.

L4-L5 anatomy classification system for lateral lumbar interbody fusion.

Lateral lumbar interbody fusion (LLIF), developed by Dr. Luiz Pimenta in 2006, allows access to the spinal column through the psoas major muscle. The technique has many advantages, such as reduced bone and muscular tissue damage, indirect decompression, larger implants, and lordosis correction capabilities. However, this technique also has drawbacks, with the most notorious being the risk of spinal pathologies due to indirect injury of the lumbar plexus, but with low rates of persistent injuries. Therefore, several groups have proposed classifications to help identify patients at a greater risk of presenting with neurological deficits. The present work proposes a classification system that relies on simple observation of easily identifiable key structures to guide lateral L4-L5 LLIF decision-making. Patients aged > 18 years who underwent preoperative magnetic resonance imaging (MRI) between 2022 and 2023 were included until 50 high-quality images were acquired. And excluded as follow Anatomical changes in the vertebral body or major psoas muscles prevent the identification of key structures or poor-quality MRIs. Each anatomy was classified as type I, type II, or type III according to the consensus among the three observers. Fifty anatomical sites were included in this study. 70% of the L4-L5 anatomy were type I, 18% were type II, and 12% were type III. None of the type 3 L4-L5 anatomies were approached using a lateral technique. The proposed classification is an easy and simple method for evaluating the feasibility of a lateral approach to-L4-L5.

Early Pregnancy Plasma Per- and Polyfluoroalkyl Substances (PFAS) and Maternal Midlife Adiposity.

CONTEXT: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity. OBJECTIVE: Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife. METHODS: We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI: 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI: 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight: 7.7 kg [95% CI: 4.0, 11.5]; TFM: 1.2 kg [95% CI: 0.0, 2.3]; TBFM: 3.0 kg [95% CI: 0.8, 5.2]), but inverse associations with perfluorononanoate (weight: -6.0 kg [95% CI: -8.5, -3.5]; WC: -1.8 cm [95% CI: -3.2, -0.3]; TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.7, -0.3]) and perfluorohexane sulfonate (TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.6, -0.2]). No associations were observed with the overall PFAS mixture. CONCLUSION: Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health.

Characterizing self-reported physical activity before and during a subsequent pregnancy among parents in a familial autism cohort.

LAY ABSTRACT: Parents of autistic children may have limited time and resources to participate in physical activity, a key aspect of health. Previous studies have been small and included mostly mothers, rather than fathers. No studies have examined physical activity in these parents during another pregnancy, when physical activity is especially important for maternal and fetal health. We aimed to fill this gap by examining physical activity levels among mothers and fathers caring for an autistic child before and during a subsequent pregnancy. We used data from a study which followed pregnant individuals who already had a child with autism. We asked mothers and fathers to report their levels of moderate and vigorous physical activity. We found that mothers and fathers of autistic children reported lower physical activity levels than the national average and were unlikely to meet Physical Activity Guidelines for Americans. Pregnant mothers were the least likely to participate in physical activity, particularly if their autistic child scored highly on a measure of autistic traits. Given that parental physical activity has benefits for parents and children, family-based interventions may be needed to help support parents' physical activity levels.

History of infertility and anti-Müllerian hormone levels among participants in the Nurses' Health Study II.

OBJECTIVES: To better understand whether history of infertility is associated with anti-Müllerian hormone (AMH) levels later in life, outside of reproduction. METHODS: Among 1,758 premenopausal women in the Nurses' Health Study II with measured AMH, we used multivariable generalized linear models to compare log-transformed plasma AMH for women with a history of infertility compared with fertile women. We investigated AMH levels by cause of infertility and effect modification by menstrual cycle regularity. Lastly, we investigated AMH levels by history of primary and secondary infertility and age at reported infertility. RESULTS: Mean age at blood collection was 40 years. We observed no association between overall history of infertility and AMH levels (% difference AMH: -8.1% [CI, -19.4 to 4.8]). The association between overall infertility and AMH was strongest among women who first reported infertility at >30 years (-17.7% [CI, -32.1 to -0.3]). CONCLUSIONS: Overall, we observed no association between the history of infertility and AMH levels later in life. However, specific subgroups of women with a history of infertility may have lower AMH levels throughout life compared with fertile women. This association was observed among subgroups, such as those who first experienced infertility at >30 years. These findings have implications for mechanisms through which infertility may be associated with premature menopause and chronic disease risk.

Lifetime history of gestational diabetes and cognitive function in parous women in midlife.

AIMS/HYPOTHESIS: We aimed to determine whether a history of gestational diabetes mellitus (GDM) is associated with cognitive function in midlife. METHODS: We conducted a secondary data analysis of the prospective Nurses' Health Study II. From 1989 to 2001, and then in 2009, participants reported their history of GDM. A subset participated in a cognition sub-study in 2014-2019 (wave 1) or 2018-2022 (wave 2). We included 15,906 parous participants (≥1 birth at ≥18 years) who completed a cognitive assessment and were free of CVD, cancer and diabetes before their first birth. The primary exposure was a history of GDM. Additionally, we studied exposure to GDM and subsequent type 2 diabetes mellitus (neither GDM nor type 2 diabetes, GDM only, type 2 diabetes only or GDM followed by type 2 diabetes) and conducted mediation analysis by type 2 diabetes. The outcomes were composite z scores measuring psychomotor speed/attention, learning/working memory and global cognition obtained with the Cogstate brief battery. Mean differences (ß and 95% CI) in cognitive function by GDM were estimated using linear regression. RESULTS: The 15,906 participants were a mean of 62.0 years (SD 4.9) at cognitive assessment, and 4.7% (n=749) had a history of GDM. In models adjusted for age at cognitive assessment, race and ethnicity, education, wave of enrolment in the cognition sub-study, socioeconomic status and pre-pregnancy characteristics, women with a history of GDM had lower performance in psychomotor speed/attention (ß -0.08; 95% CI -0.14, -0.01) and global cognition (ß -0.06; 95% CI -0.11, -0.01) than those without a history of GDM. The lower cognitive performance in women with GDM was only partially explained by the development of type 2 diabetes. CONCLUSIONS/INTERPRETATION: Women with a history of GDM had poorer cognition than those without GDM. If replicated, our findings support future research on early risk modification strategies for women with a history of GDM as a potential avenue to decrease their risk of cognitive impairment.

Mitochondrial Variation in Anopheles gambiae and Anopheles coluzzii: Phylogeographic Legacy and Mitonuclear Associations With Metabolic Resistance to Pathogens and Insecticides.

Mitochondrial DNA has been a popular marker in phylogeography, phylogeny, and molecular ecology, but its complex evolution is increasingly recognized. Here, we investigated mitochondrial DNA variation in Anopheles gambiae and Anopheles coluzzii, in relation to other species in the Anopheles gambiae complex, by assembling the mitogenomes of 1,219 mosquitoes across Africa. The mitochondrial DNA phylogeny of the Anopheles gambiae complex was consistent with previously reported highly reticulated evolutionary history, revealing important discordances with the species tree. The three most widespread species (An. gambiae, An. coluzzii, and Anopheles arabiensis), known for extensive historical introgression, could not be discriminated based on mitogenomes. Furthermore, a monophyletic clustering of the three saltwater-tolerant species (Anopheles merus, Anopheles melas, and Anopheles bwambae) in the Anopheles gambiae complex also suggested that introgression and possibly selection shaped mitochondrial DNA evolution. Mitochondrial DNA variation in An. gambiae and An. coluzzii across Africa revealed significant partitioning among populations and species. A peculiar mitochondrial DNA lineage found predominantly in An. coluzzii and in the hybrid taxon of the African "far-west" exhibited divergence comparable to the interspecies divergence in the Anopheles gambiae complex, with a geographic distribution matching closely An. coluzzii's geographic range. This phylogeographic relict of the An. coluzzii and An. gambiae split was associated with population and species structure, but not with the rare Wolbachia occurrence. The lineage was significantly associated with single nucleotide polymorphisms in the nuclear genome, particularly in genes associated with pathogen and insecticide resistance. These findings underline potential mitonuclear coevolution history and the role played by mitochondria in shaping metabolic responses to pathogens and insecticides in Anopheles.

Advancing Cholangiocarcinoma Care: Insights and Innovations in T Cell Therapy.

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.

EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial.

Hyperstable arousal regulation during a 15-min resting electroencephalogram (EEG) has been linked to a favorable response to antidepressants. The EMBARC study, a multicenter randomized placebo-controlled clinical trial, provides an opportunity to examine arousal stability as putative antidepressant response predictor in short EEG recordings. We tested the hypothesis that high arousal stability during a 2-min resting EEG at baseline is related to better outcome in the sertraline arm and explored the specificity of this effect. Outpatients with chronic/recurrent MDD were recruited from four university hospitals and randomized to treatment with sertraline (n = 100) or placebo (n = 104). The change in the Hamilton Rating Scale for Depression (HRSD-17) was the main outcome. Patients were stratified into high and low arousal stability groups. In mixed-model repeated measures (MMRM) analysis HRSD-17 change differed significantly between arousal groups, with high arousal stability being associated with a better outcome in the sertraline arm, and worse outcome in the placebo arm at week 4, with moderate effect sizes. When considering both treatment arms, a significant arousal group x time x treatment interaction emerged, highlighting specificity to the sertraline arm. Although findings indicate that arousal stability is likely to be a treatment-specific marker of response, further out-of-sample validation is warranted.

Feasibility of increasing calcium content of drinking tap water following quality regulations to improve calcium intake at population level.

Background: Calcium intake is below recommendations in several parts of the world. Improving calcium intake has benefits not only for bone health but also helps to prevent pregnancy hypertension disorders. Calcium concentration of tap water is usually low The aim of the present study was to determine the maximum amount of calcium that can be added to tap water while complying with drinking water Argentine regulations. Methods: Tap water samples were collected from the Province of Buenos Aires (Argentina). Physicochemical properties and saturation index were measured. Different incremental concentrations of calcium chloride were added to the experimental aliquots. Results: Baseline water had a mean calcium concentration of 22.00 ± 2.54 mg/L, water hardness of 89.9 ± 6.4 mg/L CaCO 3, and a saturation index of -1.50 ± 0.11. After the addition of 0.4554 ± 0.0071 g of salt, water hard-ness reached 355.0 ± 7.1 mg/L CaCO 3, a calcium concentration of 140.50 ± 2.12 mg/L, and a saturation index -0.53 ± 0.02. Conclusions: This study shows that at laboratory level it is feasible to increase calcium concentration of drinking water by adding calcium chloride while complying with national standards. Calcium concentration of drinking tap water could be evaluated and minimum calcium concentration of tap water regulated so as to improve calcium intake in populations with low calcium intake.

Current and Stray Flux Combined Analysis for Sparking Detection in DC Motors/Generators Using Shannon Entropy.

Brushed DC motors and generators (DCMs) are extensively used in various industrial applications, including the automotive industry, where they are critical for electric vehicles (EVs) due to their high torque, power, and efficiency. Despite their advantages, DCMs are prone to premature failure due to sparking between brushes and commutators, which can lead to significant economic losses. This study proposes two approaches for determining the temporal and frequency evolution of Shannon entropy in armature current and stray flux signals. One approach indirectly achieves this through prior analysis using the Short-Time Fourier Transform (STFT), while the other applies the Stockwell Transform (S-Transform) directly. Experimental results show that increased sparking activity generates significant low-frequency harmonics, which are more pronounced compared to mid and high-frequency ranges, leading to a substantial rise in system entropy. This finding enables the introduction of fault-severity indicators or Key Performance Indicators (KPIs) that relate the current condition of commutation quality to a baseline established under healthy conditions. The proposed technique can be used as a predictive maintenance tool to detect and assess sparking phenomena in DCMs, providing early warnings of component failure and performance degradation, thereby enhancing the reliability and availability of these machines.

Variation in the Diet of Hatchling Morelet's Crocodile (Crocodylus moreletii) in the Wild.

The relationship between diet and behavior is essential to understanding an animal's strategies to obtain food, considering ontogenical changes. In reptiles, there is a relationship between the length of the individual and the size of the prey it consumes. Studies have focused on the ontogenetic changes in reptile diets from hatchling to adult, but only a few studies have focused on the transition from hatchling to juvenile. We aimed to describe and analyze the composition, variation, diversity, and overlap in the diet of hatchling Morelet's crocodiles (Crocodylus moreletii) for three size intervals during the hatchling-juvenile transition. We captured 31 hatchling Morelet's crocodiles in an urbanized lagoon in Tabasco. We performed stomach-flushing to determine the diet. Additionally, we estimated the volume, frequency of occurrence, and relative importance of diet items and analyzed the relationship between prey type and the total length of the individuals. The diversity of the hatchling prey suggests a generalist diet. We observed two items not previously described in the diet of hatchling crocodiles. In addition, we found differences in diet between the initial and final size intervals, as increases in the length of prey appeared that they did not consume when they were hatchlings. Our results contribute new information to the dietary changes that occur during the hatchling-juvenile transition.

Bibliometric Review of the Step Test: A Comprehensive Analysis of Research Trends and Development.

BACKGROUND: The step test provides valuable information on cardiorespiratory parameters such as maximal oxygen uptake and heart rate. Cardiorespiratory capacity is critical to health-related fitness, with heart rate recovery after exercise serving as a predictor of mortality risk. MAIN BODY: The primary objective of this review was to identify trends, key contributors, and emerging themes in the step test literature through 2023 using the Web of Science Core Collection. Bibliometric data extraction and analysis were performed using a dedicated bibliometric software (VOSviewer). The analysis showed continued interest through 2021. The research categories highlight the multidisciplinary nature of the step test, covering cardiovascular systems, respiratory systems, sports sciences, and medicine. It has gained global attention, with 31 countries involved, with Brazil and the United States leading the way. The diversity of contributing nations is increasing, reflecting a growing global interest. With 111 journals involved, such as Respiratory Care and Medicine and Science in Sports and Exercise, step test research is spread across the academic landscape. With 761 contributing researchers, there is a collaborative and diverse community. The top 10 institutions, including the University of Alabama System and Monash University, illustrate the variety of settings in which step test studies are conducted. Step test studies span multiple disciplines, underscoring their adaptability. The clusters identified in this bibliometric analysis of the step test literature guide future research, suggesting avenues for refining protocols, exploring health implications, optimizing tests for specific conditions such as chronic obstructive pulmonary disease, and adapting step tests in diverse populations. CONCLUSIONS: Practical implications highlight the role of the step test in cardiovascular risk assessment, fitness monitoring, and rehabilitation. This broad review underscores the relevance of the step test in diverse settings, reflecting its adaptability and ease of application across occupational and clinical settings.

Mixtures of Urinary Phenol and Phthalate Metabolite Concentrations in Relation to Serum Lipid Levels among Pregnant Women: Results from the EARTH Study.

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings.

Exploring the role of therapeutic alliance and biobehavioural synchrony in musculoskeletal care: Insights from a qualitative study.

BACKGROUND: Person-centred care underscores the therapeutic alliance (TA) as fundamental, fostering positive treatment outcomes through collaborative patient-clinician interactions. Biobehavioural synchrony within the TA, essential for effective care, reflects an adaptive process where organisms align responses during interactions. Enactivism and active inference provide profound insights into human perception, reshaping musculoskeletal care understanding. Touch and verbal communication, integral to the TA, foster synchrony and alignment of personal beliefs. AIM: This study aimed to identify the tools used by manual therapists in musculoskeletal care to establish a TA with patients. Furthermore, it endeavours to evaluate the alignment of these strategies with current literature and their correlation with biobehavioural synchrony, enactivism, and the role of touch in active inference. METHODS: The methodology followed rigorous qualitative research principles, particularly Grounded Theory and interpretative-constructivist principles, conducting eleven semi-structured interviews with open-ended questions. RESULTS: The core category identified in the study is elucidated as follows: "Interwoven Connection: The Fabric of Therapeutic Synchrony." The interviews unveiled three main categories, each comprising sub-categories: (1) Creating a meaningful dialogue; (2) Promoting active patient participation; (3) Synchronisation. CONCLUSION: Fostering meaningful dialogue, patient involvement, and therapeutic synchrony is crucial for a robust therapeutic alliance in musculoskeletal care. This underscores the importance of establishing a deep connection between clinicians and patients, central to effective person-centred care. Clinicians must prioritise two-way communication, empathy, and patient collaboration in defining personalised goals. Emphasizing touch and seeking patient feedback are also pivotal. Further research is needed to explore these elements and their impact.

Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae.

AIMS: To investigate the molecular events associated with acquiring macrolide resistance genes [mefE/mel (Mega) or ermB] in Streptococcus pneumoniae (Spn) during nasopharyngeal colonization. METHODS AND RESULTS: Genomic analysis of 128 macrolide-resistant Spn isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn916-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn916-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (>23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose. CONCLUSIONS: Pneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.

Integrative multi-omics characterization of hepatocellular carcinoma in hispanic patients.

BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanic individuals in the United States are much higher than in non-Hispanic white people. We conducted multi-omics analyses to elucidate molecular alterations in HCC among Hispanic patients. METHODS: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCCs in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC. RESULTS: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/ß-catenin pathway. TERT promoter mutations were also significantly more frequent in the Hispanic cohort (Fisher's exact test, p < .05). Cell cycles and liver function were positively and negatively enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in serum samples of HCC patients (paired t-test, p < .0001). Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. Patients with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. They also had higher levels of immune checkpoint and immune exhaustion markers. CONCLUSIONS: Our study revealed specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management. It provides a unique resource for studying Hispanic HCC.

Insights on the Selection of the Coefficient of Variation to Assess Speed Fluctuation in Swimming.

The aim of this study was to compare swimming speed and speed fluctuations in front crawl between swimmers of different performance levels using discrete variables against statistical parametric mapping (SPM). The sample was composed of 34 male swimmers divided into three groups: (i) group #1-recreational swimmers; (ii) group #2-competitive swimmers aged 12 to 14 years; (iii) group #3-competitive swimmers aged 15 to 17 years. Swimming speed and speed fluctuations (calculated based on four different conditions) were used as discrete variables. Using these discrete variables, ANOVA one-way was used to verify differences between groups, and Bonferroni post-hoc correction for pairwise comparison whenever suitable. SPM (with similar statistical tests) was used to analyze the swimming speed and fluctuation as a continuous variable. Overall, both statistical approaches revealed significant differences (p < 0.001) in swimming speed and speed fluctuations. However, as discrete variables (in four different conditions), the speed fluctuation was not able to detect significant differences between groups #2 and #3. Conversely, SPM was more sensitive and did yield significant differences between these two groups. Therefore, researchers and coaches should be aware that the speed fluctuation as a discrete variable may not identify differences in swimming speed fluctuations when the average value between groups is marginal. On the other hand, SPM was more sensitive in analyzing all groups.