Epidemiology of cardiometabolic health in Latin America and strategies to address disparities.

In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to address this growing cardiometabolic burden include both population-wide and individual-based initiatives tailored to the specific challenges faced by different LAC countries, which are heterogeneous. The implementation of public policies to reduce smoking and health system approaches to control hypertension are examples of scalable strategies. The challenges faced by LAC are also opportunities to foster innovative approaches to combat the high burden of cardiometabolic diseases such as implementing digital health interventions and team-based initiatives. This Review provides a summary of trends in the epidemiology of cardiometabolic diseases and their risk factors in LAC as well as context-specific disease determinants and potential solutions to improve cardiometabolic health in the region.

Mapping multimorbidity progression among 190 diseases.

BACKGROUND: Current clustering of multimorbidity based on the frequency of common disease combinations is inadequate. We estimated the causal relationships among prevalent diseases and mapped out the clusters of multimorbidity progression among them. METHODS: In this cohort study, we examined the progression of multimorbidity among 190 diseases among over 500,000 UK Biobank participants over 12.7 years of follow-up. Using a machine learning method for causal inference, we analyzed patterns of how diseases influenced and were influenced by others in females and males. We used clustering analysis and visualization algorithms to identify multimorbidity progress constellations. RESULTS: We show the top influential and influenced diseases largely overlap between sexes in chronic diseases, with sex-specific ones tending to be acute diseases. Patterns of diseases that influence and are influenced by other diseases also emerged (clustering significance Pau > 0.87), with the top influential diseases affecting many clusters and the top influenced diseases concentrating on a few, suggesting that complex mechanisms are at play for the diseases that increase the development of other diseases while share underlying causes exist among the diseases whose development are increased by others. Bi-directional multimorbidity progress presents substantial clustering tendencies both within and across International Classification Disease chapters, compared to uni-directional ones, which can inform future studies for developing cross-specialty strategies for multimorbidity. Finally, we identify 10 multimorbidity progress constellations for females and 9 for males (clustering stability, adjusted Rand index >0.75), showing interesting differences between sexes. CONCLUSION: Our findings could inform the future development of targeted interventions and provide an essential foundation for future studies seeking to improve the prevention and management of multimorbidity.

Mapping out clusters of diseases is crucial to addressing the rising challenge of co-occurrence of multiple diseases, known as multimorbidity. However, the current way of grouping diseases based on their associations isn't enough to understand how they develop over time. We've come up with a new approach to map out how groups of diseases progress together based on the strength of their causal relationships. By looking at how each disease affects the development of others, we can get a better understanding of how they form clusters. Our research goes beyond just showing which diseases occur together, and it's a step toward improving how we prevent and manage multiple health conditions in the future.

Recombinant Antibody-Producing Stable CHOK1 Pool Stability Study.

Mammalian cell line stability is an important consideration when establishing a biologics manufacturing process in the biopharmaceutical and in vitro diagnostics (IVD) industries. Traditional Chinese hamster ovary (CHO) cell line development methods use a random integration approach that requires transfection, selection, optional amplification, screenings, and single-cell cloning to select clones with acceptable productivity, product quality, and genetic stability. Site-specific integration reduces these disadvantages, and new technologies have been developed to mitigate risks associated with genetic instability. In this study, we applied the Leap-In® transposase-mediated expression system from ATUM to generate stable CHOK1 pools for the production of four recombinant antibody reagents for IVD immunoassays. CHO cell line stability is defined by consistent antibody production over time. Three of the CHOK1 pools maintained productivity suitable for manufacturing, with high antibody yields. The productivity of the remaining CHOK1 pool decreased over time; however, derivative clones showed acceptable stability. l-glutamine had variable effects on CHOK1 cell line or stable pool stability and significantly affected antibody product titer. Compared with traditional random integration methods, the ATUM Leap-In system can reduce the time needed to develop new immunoassays by using semi site-specific integration to generate high-yield stable pools that meet manufacturing stability requirements.

Tracking changes in weight status in primary school children in Birmingham: an analysis of the National Child Measurement Programme - a retrospective cohort study.

One-in-four 4-5 years and more than one-in-three 10-11 years have excess weight in England. AIM: To identify characteristics associated with (1) having overweight, obesity and severe obesity at 11 years and (2) rapid weight gain (defined as increasing weight status by one or more body mass index (BMI) categories) between the ages of 4-5 and 10-11 years. METHOD: Using National Child Measurement Programme data, BMI at reception (4-5 years) and year 6 (10-11 years) were linked for 15 390 children. Weight categories were identified at both time points using BMI centile classifications.For each child, the number of BMI categories they crossed between reception and year 6 was identified. Logistic regression models were fitted to explore associations with sociodemographic characteristics of children with excess weight at age 10-11 years and with children experiencing rapid weight gain between reception and year 6. RESULTS: Overall, 61.9% of children remained in their original weight category; 30% whose weight increased by ≥1 weight categories and 11.7% by ≥2 weight categories. Only 7.8% had decreased ≥1 weight categories and 0.9% had decreased ≥2 weight categories.Adjusting for other sociodemographic characteristics, girls were less likely than boys to increase ≥2 weight categories between reception and year 6 (OR 0.64; 95% CI 0.58 to 0.71; p<0.001). Compared to white children, Asian and mixed-ethnicity children had higher odds of rapid weight gain. Children with the highest deprivation were over 6 times more likely to increase ≥2 weight categories between reception and year 6 compared with children with the lowest deprivation (OR 6.1; 95% CI 1.92 to 19.10; p<0.01). CONCLUSION: Male children, children of Asian and mixed ethnicity and children with high deprivation are at higher risk of rapid weight gain and should be targeted for intervention.

Commensal-pathogen dynamics structure disease outcomes during Clostridioides difficile colonization.

Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in clinical presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C. difficile have a range of outcomes. Microbiota-humanization of germ-free mice with fecal samples from toxigenic C. difficile carriers revealed a spectrum of virulence among clade 1 lineages and identified commensal Blautia associated with markers of non-pathogenic colonization. Using gnotobiotic mice engrafted with defined human microbiota, we observed strain-specific CDI severity across clade 1 strains. Yet, mice engrafted with a higher diversity community were protected from severe disease across all strains without suppression of C. difficile colonization. These results indicate that when colonization resistance has been breached without overt infection, commensals can attenuate a diversity of virulent strains without inhibiting pathogen colonization, providing insight into determinants of stable C. difficile carriage.

Involving different stakeholders in prioritising outcomes to assess healthcare systems response for type 1 diabetes management: Using co-creation approaches in Peru.

BACKGROUND: Engaging diverse stakeholders in developing core outcome sets (COSs) can produce more meaningful metrics as well as research responsive to patient needs. The most common COS prioritisation method, Delphi surveys, has limitations related to selection bias and participant understanding, while qualitative methods like group discussions are less frequently used. This study aims to test a co-creation approach to COS development for type 1 diabetes (T1DM) in Peru. METHODS: Using a co-creation approach, we aimed to prioritise outcomes for T1DM management in Peru, incorporating perspectives from people with T1DM, caregivers, healthcare professionals, and decision-makers. A set of outcomes were previously identified through a systematic review and qualitative evidence synthesis. Through qualitative descriptive methods, including in-person workshops, each group of stakeholders contributed to the ranking of outcomes. Decision-makers also discussed the feasibility of measuring these outcomes within the Peruvian healthcare system. RESULTS: While priorities varied among participant groups, all underscored the significance of monitoring healthcare system functionality over mortality. Participants recognized the interconnected nature of healthcare system performance, clinical outcomes, self-management, and quality of life. When combining the rankings from all the groups, metrics related to economic impact on the individual and structural support, policies promoting health, and protecting those living with T1DM were deemed more important in comparison to measuring clinical outcomes. CONCLUSION: We present the first COS for T1DM focused on low-and-middle-income countries and show aspects of care that are relevant in this setting. Diverse prioritisation among participant groups underscores the need of inclusive decision-making processes. By incorporating varied perspectives, healthcare systems can better address patient needs and enhance overall care quality.

Use of subcutaneous maropitant at two dosages for pain management in domestic rabbits (Oryctolagus cuniculus) undergoing elective ovariohysterectomy or orchiectomy.

OBJECTIVE: To describe the effect of two doses of maropitant on pain scores, food intake, and fecal output in domestic rabbits (Oryctolagus cuniculus) undergoing elective ovariohysterectomy or orchiectomy. ANIMALS: 26 (11 female, 15 male) rabbits from three institutions. PROCEDURES: Rabbits were randomly assigned to one of three treatment groups: low-dose maropitant (LDM; 2 mg/kg SC once; n=8), moderate-dose maropitant (MDM; 4 mg/kg SC once; n=10), and control (saline equivalent to 4 mg/kg maropitant SC once; n=8), administered prior to surgery. Following surgery, all rabbits were provided buprenorphine (0.06 mg/kg q 8 hours) and meloxicam (1 mg/kg q 24 hours) intramuscularly. Rabbits were monitored using video surveillance postoperatively until 24 hours after surgery or discharge from the hospital, whichever came first. Pain scores were assessed by three blinded observers, and results were grouped into early (0-4 hours), mid (5-8 hours), and late (12-24 hours) time frames. Food intake and fecal output were compared between groups. Statistical analysis was performed using Chi square, Fisher's exact tests, and a mixed model approach. RESULTS: There were no adverse effects with maropitant administration. Rabbits that received MDM had significantly lower pain scores in the mid-time frame and behavior scores in the late-time frame compared to controls. Male rabbits consumed more food than females and rabbits hospitalized longer than 12 hours consumed more food than those that were discharged prior. No significant differences were detected in facial grimace scale scores, food intake, or fecal production among treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Moderate dose maropitant decreased pain related behaviors in the mid-time frame and behavior scores in the late-time frame after surgery. Further studies are necessary to better characterize the potential use of maropitant in postoperative analgesia.

Mycoplasma spp. pneumonia and subsequent pulmonary hypertension in a domestic ferret (Mustela putorius furo).

Treatment of Mycoplasma spp. pneumonia has rarely been described in domestic ferrets (Mustela putorius furo). A 10-month-old, 0.53 kg, female spayed domestic ferret was presented for oxygen-dependent, chronic dyspnea of one-month's duration. Physical examination findings included dyspnea, tachypnea, increased bronchovesicular sounds bilaterally, and an intermittent non-productive cough. Bloodwork abnormalities included a mild leukocytosis (8.6×103/µL), mild neutrophilia (4.0×103/µL), mild hypoalbuminemia (2.7 g/dL), mild hyperglobulinemia (3.3 g/dL), mild hyponatremia (147 mEq/L), and mild hypochloremia (111.4 mEq/L). Radiographs revealed a marked diffuse bronchial pattern with peribronchial cuffing, a mild main pulmonary artery bulge, distended caudal lobar pulmonary arteries, and decreased serosal detail within the abdomen. An echocardiogram revealed indications of moderate pulmonary hypertension and systolic anterior motion of the mitral valve. Polymerase chain reaction testing for Mycoplasma spp. was positive, and treatment was initiated with doxycycline (10 mg/kg PO q 12 h for 16 weeks), prednisolone (0.4 mg/kg PO q 12 h for 13 weeks, tapered to 0.2 mg/kg PO q 12 h for two weeks, then eventually increased to 0.7 mg/kg PO q 12 h until further notice), sildenafil (0.3 mg/kg PO q 24 h for 13 weeks), and oxygen supplementation via an oxygen cage for six weeks. On repeat echocardiogram eleven weeks after initiation of doxycycline therapy, the pulmonary hypertension had resolved. At follow up six months later, the ferret was stable on previously prescribed medications and did not require oxygen supplementation. Mycoplasma spp. and pulmonary hypertension should be considered in cases of respiratory distress in ferrets.

The neurocognitive and neuropsychiatric manifestations of Susac syndrome: a brief review of the literature and future directions.

Encephalopathy is part of the clinical triad of Susac syndrome, but a detailed understanding of the neurocognitive and neuropsychiatric profile of this condition is lacking. Existing literature indicates that cognitive deficits range in severity from subtle to profound. Executive function and short-term recall are affected frequently. Psychiatric manifestations may be absent or may include anxiety, mood disorders or psychosis. If psychiatric phenomena develop during the disease course, it can be hard to disentangle whether symptoms directly relate to the pathology of Susac syndrome or are secondary to treatment-related side effects. In this article, we review what is known about the cognitive and psychiatric morbidity of Susac syndrome and identify areas where knowledge is deficient. Importantly, we also provide a framework for future research, arguing that better phenotyping, understanding of pathophysiology, evaluation of treatments on cognitive and psychiatric outcomes, and longitudinal data capture are vital to improving patient outcomes.

Controlling Charge Percolation in Solutions of Metal Redox Active Polymers: Implications of Microscopic Polyelectrolyte Dynamics on Macroscopic Energy Storage.

Soluble redox-active polymers (RAPs) enable size-exclusion nonaqueous redox flow batteries (NaRFBs) which promise high energy density. Pendants along the RAPs not only store charge but also engage in electron transfer to varying extents based on their designs. Here, we explore these phenomena in Metal-containing Redox Active Polymers (M-RAPs, M = Ru, Fe, Co). We assess by using cyclic voltammetry and chronoamperometry with ultramicroelectrodes the current response to electrolyte concentration spanning 3 orders of magnitude. Currents scaled as Ru-RAP > Fe-RAP ≫ Co-RAP, consistent with electron self-exchange trends in the small molecule analogues of the MII/III redox pair. Varying the ionic strength of the electrolyte also revealed nonmonotonic behavior, evidencing the impact of polyelectrolytic dynamics on M-RAP redox response. We developed a model to account for the behavior by combining kinetic Monte Carlo and Brownian dynamics near a boundary representing an electrode. While 1D pendant-to-pendant charge transfer along the chain is not a strong function of electrolyte concentration, the microstructure of the RAP at different electrolyte concentrations is decisively impacted, yielding qualitative trends to those observed experimentally. M-RAP size-exclusion NaRFBs using a poly viologen as negolyte varied in average potential with ∼1.54 V for Ru-RAP, ∼1.37 V for Fe-RAP, and ∼0.52 V for Co-RAP. Comparison of batteries at their optimal and suboptimal solution conditions as gauged from analytical experiments showed clear correlations in performance. This work provides a blueprint for understanding the factors underpinning charge transfer in solutions of RAPs for batteries and beyond.

Research Translation to Promote Urban Health in Latin America: The SALURBAL Experience.

In highly urbanized and unequal Latin America, urban health and health equity research are essential to effective policymaking. To ensure the application of relevant and context-specific evidence to efforts to reduce urban health inequities, urban health research in Latin America must incorporate strategic research translation efforts. Beginning in 2017, the Urban Health in Latin America (SALURBAL) project implemented policy-relevant research and engaged policymakers and the public to support the translation of research findings. Over 6 years, more than 200 researchers across eight countries contributed to SALURBAL's interdisciplinary network. This network allowed SALURBAL to adapt research and engagement activities to local contexts and priorities, thereby maximizing the policy relevance of research findings and their application to promote policy action, inform urban interventions, and drive societal change. SALURBAL achieved significant visibility and credibility among academic and nonacademic urban health stakeholders, resulting in the development of evidence and tools to support urban policymakers, planners, and policy development processes across the region. These efforts and their outcomes reveal important lessons regarding maintaining flexibility and accounting for local context in research, ensuring that resources are dedicated to policy engagement and dissemination activities, and recognizing that assessing policy impact requires a nuanced understanding of complex policymaking processes. These reflections are relevant for promoting urban health and health equity research translation across the global south and worldwide. This paper presents SALURBAL's strategy for dissemination and policy translation, highlights innovative initiatives and their outcomes, discusses lessons learned, and shares recommendations for future efforts to promote effective translation of research findings.

Location also matters: The oxidative response of the intertidal purple mussel Perumytilus purpuratus during tidal cycle.

For sessile intertidal organisms, periods of low tide impose both cellular and physiological challenges that can determine bathymetric distribution. To understand how intertidal location influences the cellular response of the bivalve Perumytilus purpuratus during the tidal cycle (immersion-emersion-immersion), specimens from the upper intertidal (UI) and lower intertidal (LI) of bathymetric distribution were sampled every 2 h over a 10-h period during a summer tidal cycle. Parallelly, organisms from the UI and LI were reciprocally transplanted and sampled throughout the same tidal cycle. Levels of oxidative damage (lipid peroxidation and protein carbonyls) as well as total antioxidant capacity and total carotenoids were evaluated as cellular responses to variations in environmental conditions throughout the tidal cycle. The results indicate that both the location in the intertidal zone (UI/LI), the level of aerial exposure, and the interaction of both factors are determinants of oxidative levels and total antioxidant capacity of P. purpuratus. Although oxidative damage levels are triggered during the low tide period (aerial exposure), it is the UI specimens that induce higher levels of lipid peroxidation compared to those from the LI, which is consistent with the elevated levels of total antioxidant capacity. On the other hand, organisms from the LI transplanted to the UI increase the levels of lipid peroxidation but not the levels of protein carbonyls, a situation that is also reflected in higher levels of antioxidant response and total carotenoids than those from the UI transplanted to the LI. The bathymetric distribution of P. purpuratus in the intertidal zone implies differentiated responses between organisms of the lower and upper limits, influenced by their life history. A high phenotypic plasticity allows this mussel to adjust its metabolism to respond to abrupt changes in the surrounding environmental conditions.

Development, synthesis, and application of magnetic layered double hydroxides (Fe3O4@SiO-LDH/DS-) as an efficient adsorbent for the removal of tetracyclines from milk samples.

This work presents the development, synthesis, and application of a layered double hydroxide (LDH) coupled to magnetic particles for the removal of antibiotics as tetracyclines (TC´s): tetracycline (TC), chlortetracycline (CT), oxytetracycline (OT), and doxycycline (DT) from milk samples. The LDH synthesis conditions, reaction time (30-90 min), molar ratios Mg2+/Al3+ (7:1-1:7), interlayer anion (NO3-, Cl-, CO32-, and dodecyl sulphate (DS-)) were evaluated. Under synthesis conditions (reaction time of 30 min, Mg2+/Al3+ molar ratio of 7:1, and DS- as interlayer anion), the LDH was coupled in a magnetic solid phase microextraction (MSPµE) methodology. At the optimal extraction conditions (pH 6, 5 min of contact time, 10 mg of adsorbent), a removal percentage of 99.0 % was obtained for each tetracycline. FTIR, TGA, SEM, and adsorption isotherms were employed to characterize the optimal adsorbent. Each experiment was corroborated by large-volume sample stacking capillary electrophoresis (LVSS-CE). The adsorbent was applied directly to positive milk samples (previously tested) for TC´s removal.

The use of soapy water and freezing as secondary steps for euthanasia in cave (Blaberus giganteus) and Madagascar hissing (Gromphadorhina portentosa) cockroaches.

OBJECTIVE: To evaluate methods for euthanizing cave cockroaches (CCs; Blaberus giganteus) and Madagascar hissing cockroaches (MHCs; Gromphadorhina portentosa). It was hypothesized that both suggested methods would be effective for humane mass euthanasia of both species. SAMPLE: Approximately 800 CC. METHODS: The CCs were separated into replicate groups of 25, 50, 75, 100, and 150 grams and placed into 3.8-L plastic bags. Twenty-seven MHCs were divided into groups of 2 to 3. The study took place from January to March 2023. All CC groups were exposed to 100% carbon dioxide (CO2) at a rate of 4 L/min until the bag was full. Madagascar hissing cockroaches were similarly anesthetized using either CO2 or 2 mL of isoflurane on a cotton ball in a 1-L container or a combination of CO2 and isoflurane. Once cockroaches were immobile, secondary euthanasia steps were performed. One bag of CCs per weight category was exposed to soapy water (5% Dawn dishwashing liquid), and the second was placed into a -80 °C freezer. The containers of MHCs were evenly exposed to the 2 euthanasia methods. Individuals remained in their secondary euthanasia method for 30 minutes. RESULTS: Regardless of the weight of the CCs within each bag, there was no impact on time (1.8 ± 0.4 minutes [mean ± SD]) to immobility. The failure rates for both species were 0.2% CI (-0.1% to 1.5% [1/413]) for soapy water and 0.5% CI (0.005% to 1.9% [2/414]) for the freezer method. These results support the use of both 2-step euthanasia methods in CCs and MHCs. CLINICAL RELEVANCE: These methods will serve as an evidence-based alternative for humane mass euthanasia in cockroaches.

Allostasis, health, and development in Latin America.

The lifespan is influenced by adverse childhood experiences that create predispositions to poor health outcomes. Here we propose an allostatic framework of childhood experiences and their impact on health across the lifespan, focusing on Latin American and Caribbean countries. This region is marked by significant social and health inequalities nested in environmental and social stressors, such as exposure to pollution, violence, and nutritional deficiencies, which critically influence current and later-life health outcomes. We review several manifestations across cognition, behavior, and the body, observed at the psychological (e.g., cognitive, socioemotional, and behavioral dysfunctions), brain (e.g., alteration of the development, structure, and function of the brain), and physiological levels (e.g., dysregulation of the body systems and damage to organs). To address the complexity of the interactions between environmental and health-related factors, we present an allostatic framework regarding the cumulative burden of environmental stressors on physiological systems (e.g., cardiovascular, metabolic, immune, and neuroendocrine) related to health across the life course. Lastly, we explore the relevance of this allostatic integrative approach in informing regional interventions and public policy recommendations. We also propose a research agenda, potentially providing detailed profiling and personalized care by assessing the social and environmental conditions. This framework could facilitate the delivery of evidence-based interventions and informed childhood-centered policy-making.

Crosswalk between the PROMIS physical function CAT and PROMIS upper extremity CAT v1.2 in a hand surgery population.

BACKGROUND: There is no gold standard patient-reported outcome measure (PROM) in hand surgery. As a result, a diverse array of PROM instruments have been utilized across centers over time. Lack of score interchangeability limits the ability to compare or conglomerate scores when new instruments are introduced. Our aim was to develop a linkage for the PROMIS UE CAT v1.2 and PROMIS PF CAT scores and develop crosswalk tables for interconversion between these PROMs. METHODS: Retrospective review was conducted to identify adult (≥ 18y) patients seen by orthopaedic hand surgeons at a single academic tertiary care hospital who had completed PROMIS UE CAT v1.2 and PROMIS PF CAT score at the same visit. For those with multiple visits, only one randomly selected visit was included in the analyses. Pearson's correlation was calculated to determine the linear relationship between the scores. Linkage from PF to UE was performed utilizing several commonly utilized equating models (identity, mean, linear, equipercentile and circle-arc methods). The performance of the models was assessed using intraclass correlation (ICC) between observed PROMIS UE CAT v1.2 and estimated PROMIS UE CAT v1.2 scores generated using the model as well as Root Mean Square Error (RMSE). The model chosen as the 'best' was further assessed for population invariance using root expected mean squared difference (REMSD) where < 0.08 were considered good. RESULTS: Of 10,081 included patients, mean age was 48.3 (SD = 17.0), and 54% were female (5,477/10,081). Mean UE CAT v1.2 and PF CAT scores were 37 (SD = 9.8) and 46 (SD = 10.0), respectively. There was a strong correlation between the scores (Pearson correlation r = 0.70). All methods performed acceptably (ICC ≥ 0.66 and RMSE < = 7.52 for all). The equipercentile method had the highest ICC (ICC = 0.70 (95% CI 0.69-0.71)) while the mean and circle arc methods had the lowest RMSE. The circle arc method is the most reliable with the smallest standard error and has satisfactory population invariance across age group (REMSD 0.065) and sex (REMSD 0.036). CONCLUSIONS: Crosswalk tables to be used for bidirectional conversion between scores were created. LEVEL OF EVIDENCE: III.

Nanoarchitectonics of an acetogenin-enriched nanosystem mediated by an aqueous extract ofAnnona cherimolaMill with anti-inflammatory and proapoptotic activity against HepG2 cell line.

For the first time, this study shows the nanoarchitectonic process to obtain an acetogenin-enriched nanosystem (AuNPs-Ac) using an aqueous extract fromAnnona cherimolaMill (ACM) composed of gold nanoparticles embedded in an organic matrix that acts as stabilizing agent and presents anti-inflammatory activity and cytotoxical effect against HepG2 cell line, promoting apoptosis. The synthesis of AuNPs-Ac was confirmed by x-ray diffraction analysis, showing metallic gold as the only phase, and the scanning transmission microscope showed an organic cap covering the AuNPs-Ac. Fourier-transformed infrared suggests that the organic cap comprises a combination of different annonaceous acetogenins, alkaloids, and phenols by the presence of bands corresponding to aromatic rings and hydroxyl groups. High-Performance Liquid Chromatography has demonstrated the presence of annonacin, a potent acetogenin, in the extract of ACM. Anin vitroanti-inflammatory activity of the extract of ACM and the AuNPs-Ac was performed using the albumin denaturation method, showing a nonlinear response, which is better than sodium diclofenac salt in a wide range of concentrations that goes from 200 to 400µg ml-1with both samples. The viability assay was studied using trypan blue, treating IMR90 and HepG2 at different concentrations of AuNPs-Ac. The results defined a median lethal dose of 800µg ml-1against HepG2 through apoptosis according to the ratio of caspase-cleaved 9/alpha-tubulin evaluated. It was also demonstrated that the nanosystem presents a higher cytotoxic effect on the HepG2 cell line than in IMR90, suggesting a targeted mechanism. In addition, the nanosystem performs better than using only the extract of ACM in the anti-inflammatory or antiproliferative test, attributed to their higher surface area.

Microplastic exposure is associated with epigenomic effects in the model organism Pimephales promelas (fathead minnow).

Microplastics have evolutionary and ecological impacts across species, affecting organisms' development, reproduction, and behavior along with contributing to genotoxicity and stress. As plastic pollution is increasing and ubiquitous, gaining a better understanding of organismal responses to microplastics is necessary. Epigenetic processes such as DNA methylation are heritable forms of molecular regulation influenced by environmental conditions. Therefore, determining such epigenetic responses to microplastics will reveal potential chronic consequences of this environmental pollutant. We performed an experiment across two generations of fathead minnows (Pimephales promelas) to elucidate transgenerational epigenetic effects of microplastic exposure. We exposed the first generation of fish to four different treatments of microplastics: two concentrations of each of pre-consumer polyethylene (PE) and PE collected from Lake Ontario. We then raised the first filial generation with no microplastic exposure. We used enzymatic methylation sequencing on adult liver tissue and homogenized larvae to evaluate DNA methylation differences among treatments, sexes, and generations. Our findings show the origin of the plastic had a larger effect in female minnows whereas the effect of concentration was stronger in the males. We also observed transgenerational effects, highlighting a mechanism in which parents can pass on the effects of microplastic exposure to their offspring. Many of the genes found within differentially methylated regions in our analyses are known to interact with estrogenic chemicals associated with plastic and are related to metabolism. This study highlights the persistent and potentially serious impacts of microplastic pollution on gene regulation in freshwater systems.