Analysis of Microbiome Data.

The microbiome represents a hidden world of tiny organisms populating not only our surroundings but also our own bodies. By enabling comprehensive profiling of these invisible creatures, modern genomic sequencing tools have given us an unprecedented ability to characterize these populations and uncover their outsize impact on our environment and health. Statistical analysis of microbiome data is critical to infer patterns from the observed abundances. The application and development of analytical methods in this area require careful consideration of the unique aspects of microbiome profiles. We begin this review with a brief overview of microbiome data collection and processing and describe the resulting data structure. We then provide an overview of statistical methods for key tasks in microbiome data analysis, including data visualization, comparison of microbial abundance across groups, regression modeling, and network inference. We conclude with a discussion and highlight interesting future directions.

A Marginalized Zero-Inflated Negative Binomial Model for Spatial Data: Modeling COVID-19 Deaths in Georgia.

Spatial count data with an abundance of zeros arise commonly in disease mapping studies. Typically, these data are analyzed using zero-inflated models, which comprise a mixture of a point mass at zero and an ordinary count distribution, such as the Poisson or negative binomial. However, due to their mixture representation, conventional zero-inflated models are challenging to explain in practice because the parameter estimates have conditional latent-class interpretations. As an alternative, several authors have proposed marginalized zero-inflated models that simultaneously model the excess zeros and the marginal mean, leading to a parameterization that more closely aligns with ordinary count models. Motivated by a study examining predictors of COVID-19 death rates, we develop a spatiotemporal marginalized zero-inflated negative binomial model that directly models the marginal mean, thus extending marginalized zero-inflated models to the spatial setting. To capture the spatiotemporal heterogeneity in the data, we introduce region-level covariates, smooth temporal effects, and spatially correlated random effects to model both the excess zeros and the marginal mean. For estimation, we adopt a Bayesian approach that combines full-conditional Gibbs sampling and Metropolis-Hastings steps. We investigate features of the model and use the model to identify key predictors of COVID-19 deaths in the US state of Georgia during the 2021 calendar year.

Model selection of GLMMs in the analysis of count data in single-case studies: A Monte Carlo simulation.

Generalized linear mixed models (GLMMs) have great potential to deal with count data in single-case experimental designs (SCEDs). However, applied researchers have faced challenges in making various statistical decisions when using such advanced statistical techniques in their own research. This study focused on a critical issue by investigating the selection of an appropriate distribution to handle different types of count data in SCEDs due to overdispersion and/or zero-inflation. To achieve this, I proposed two model selection frameworks, one based on calculating information criteria (AIC and BIC) and another based on utilizing a multistage-model selection procedure. Four data scenarios were simulated including Poisson, negative binominal (NB), zero-inflated Poisson (ZIP), and zero-inflated negative binomial (ZINB). The same set of models (i.e., Poisson, NB, ZIP, and ZINB) were fitted for each scenario. In the simulation, I evaluated 10 model selection strategies within the two frameworks by assessing the model selection bias and its consequences on the accuracy of the treatment effect estimates and inferential statistics. Based on the simulation results and previous work, I provide recommendations regarding which model selection methods should be adopted in different scenarios. The implications, limitations, and future research directions are also discussed.

Validation of the food inflation impact on consumer behavior scale: a comparative measurement instrument with focus on food security.

This study aimed to compare the change in consumer behaviour in the face of high inflation with respect to food security in the Turkish population by developing a 3-factor The Impact of Food Inflation on Consumer Behaviour (IFI-ConB) scale. Item generation and expert evaluation, item purification by preliminary application, and final administration were conducted. The moderate to severe food insecure individuals exhibited a higher inflation impact score on food consumption patterns, food shopping behaviours, and food purchasing motives factors compared to secure to mild insecure individuals. A positive correlation was found between the inflation impact score by IFI-ConB and the price motive for food choice. The primary food choice motive was health among the secure to mild insecure individuals, while for the moderate to severe food insecure individuals, it was price. The findings indicate that food insecure individuals are more affected by high food inflation compared to food secure individuals.

Evolving Economics: The Erosion of Medicare Reimbursement in Breast Surgery (2003-2023).

INTRODUCTION: Medicare significantly influences reimbursement rates, setting a standard that impacts private insurance policies. Despite declining rates in various specialties, the magnitude of these trends has not been examined in breast surgery. This study examines Medicare reimbursement trends for breast surgery operations. METHODS: Data for 10 breast operations from 2003 to 2023 were collected from the Medicare Physician Fee Look-Up Tool and yearly reimbursement was computed using the conversion factor. The year-to-year percentage change in reimbursement was calculated, and the overall median change was compared with the consumer price index (CPI) for inflation evaluation. All data were adjusted to 2023 United States dollars. The compound annual growth rate (CAGR) was calculated using inflation-adjusted data. RESULTS: Over the study period, reimbursement for the 10 breast operations had a mean unadjusted percentage increase of + 25.17%, while the CPI increased by 69.15% (p < 0.001). However, after adjustment, overall reimbursement decreased by - 20.70%. Only two operations (lumpectomy and simple mastectomy) saw increased inflation-adjusted Medicare reimbursement (+ 0.37% and + 3.58%, respectively). The CAGR was - 1.54% overall but remained positive for the same two operations (+ 0.02% and + 0.18%, respectively). Based on these findings, breast surgeons were estimated to be reimbursed $107,605,444 less in 2023 than if rates had kept pace with inflation over the past decade. CONCLUSION: Inflation-adjusted Medicare reimbursement rates for breast surgeries have declined from 2003 to 2023. This downward trend may strain resources, potentially leading to compromises in care quality. Surgeons, administrators, and policymakers must take proactive measures to address these issues and ensure the ongoing accessibility and quality of breast surgery.

Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

A GLM-based zero-inflated generalized Poisson factor model for analyzing microbiome data.

Motivation: High-throughput sequencing technology facilitates the quantitative analysis of microbial communities, improving the capacity to investigate the associations between the human microbiome and diseases. Our primary motivating application is to explore the association between gut microbes and obesity. The complex characteristics of microbiome data, including high dimensionality, zero inflation, and over-dispersion, pose new statistical challenges for downstream analysis. Results: We propose a GLM-based zero-inflated generalized Poisson factor analysis (GZIGPFA) model to analyze microbiome data with complex characteristics. The GZIGPFA model is based on a zero-inflated generalized Poisson (ZIGP) distribution for modeling microbiome count data. A link function between the generalized Poisson rate and the probability of excess zeros is established within the generalized linear model (GLM) framework. The latent parameters of the GZIGPFA model constitute a low-rank matrix comprising a low-dimensional score matrix and a loading matrix. An alternating maximum likelihood algorithm is employed to estimate the unknown parameters, and cross-validation is utilized to determine the rank of the model in this study. The proposed GZIGPFA model demonstrates superior performance and advantages through comprehensive simulation studies and real data applications.

Contribution of Treatment with Ear Popper for Hearing in Children with Middle Ear Effusion.

OBJECTIVES: we aim to assess the contribution of the EarPopper device to hearing in children with middle ear effusion (MEE). METHODS: The study has three parts, including 1. tympanometry and audiometry before and six weeks after using the EarPopper to evaluate the treatment's effect over time compared to a control group; 2. tympanometry before and immediately after using the EarPopper to evaluate immediate changes in middle ear pressure (MEP); 3. length of effect 90 min after use to assess pressure fluctuations over time. RESULTS: Part 1 was a follow-up six weeks after using the device, and the patients in the study group that completed the study showed a significant improvement in hearing threshold. The average gain in hearing threshold ranged from 9.1 dB to 14 dB compared to the control group's max improvement of 1.1 dB. In addition, MEP was significantly improved in the study group, as most Type Bs improved to Type A and C. Part 2 was the tympanometry immediately after using EarPopper and showed the majority of Type Cs turned into Type As. The majority of Type Bs remained unchanged. Part 3 was a follow-up 90 min after use; Type Cs that had improved to Type A demonstrated a decrease in pressure and return to negative pressure. CONCLUSIONS: use of the EarPopper device for six weeks is associated with an improved hearing threshold and middle ear status.

The evolution of passive dispersal versus habitat selection have differing emergent consequences in metacommunities.

Dispersal among local communities is fundamental to the metacommunity concept but is only important to the metacommunity structure if dispersal causes distortions of species abundances away from what local ecological conditions favour. We know from much previous work that dispersal can cause such abundance distortions. However, almost all previous theoretical studies have only considered one species alone or two interacting species (e.g. competitors or predator and prey). Moreover, a systematic analysis is needed of whether different dispersal strategies (e.g. passive dispersal versus demographic habitat selection) result in different abundance distortion patterns, how these distortion patterns change with local food web structure, and how the dispersal propensities of the interacting species might evolve in response to one another. In this article, we show using computer simulations and analytical models that abundance distortions occur in simple food webs with both passive dispersal and habitat selection, but habitat selection causes larger distortions. Additionally, patterns in the evolution of dispersal propensity in interacting species are very different for these two dispersal strategies. This study identifies that the dispersal strategies employed by interacting species critically shape how dispersal will influence metacommunity structure. This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.

GEOMETRIC CHARACTERIZATION OF RAT URINARY BLADDER WALL DURING EX-VIVO FILLING USING MICRO-COMPUTED TOMOGRAPHY (MICRO-CT).

Current mechanical models of the bladder largely idealize the bladder as spherical with uniform thickness. This present study aims to investigate this idealization using micro-CT to generate 3D reconstructed models of rat bladders at 10-20 micrometer resolution in both voided and filled states. Applied to three rat bladders, this approach identifies shape, volume, and thickness variations under different pressures. These results demonstrate the filling/voiding process is far from the idealized spherical inflation/contraction. However, the geometry idealizations may be reasonable in cases where the filled bladder geometry is of importance, such as in studies of growth and remodeling.

The generation gap in endocrine disruption: Can the integrated fish endocrine disruptor test (iFEDT) bridge the gap by assessing intergenerational effects of thyroid hormone system disruption?

Thyroid hormones (THs) act early in ontogenesis, even prior to the differentiation of thyrocytes. Maternal transfer of THs is therefore known to play an essential role in early development. Current OECD test guidelines for the assessment of TH system disruption (THSD) do not address inter- or transgenerational effects. The integrated fish endocrine disruptor test (iFEDT), a test combining parental and developmental exposure of filial fish, may fill this gap. We tested the ability of the iFEDT to detect intergenerational effects in zebrafish (Danio rerio): Parental fish were exposed to propylthiouracil (PTU), an inhibitor of TH synthesis, or not exposed. The offspring was submitted to a crossed experimental design to obtain four exposure scenarios: (1) no exposure at all, (2) parental exposure only, (3) embryonic exposure only, and (4) combined parental and embryonic exposure. Swim bladder inflation, visual motor response (VMR) and gene expression of the progeny were analysed. Parental, but not embryonic PTU exposure reduced the size of the swim bladder of 5 d old embryos, indicating the existence of intergenerational effects. The VMR test produced opposite responses in 4.5 d old embryos exposed to PTU vs. embryos derived from exposed parents. Embryonic exposure, but not parental exposure increased gene expression of thyroperoxidase, the target of PTU, most likely due to a compensatory mechanism. The gene expression of pde-6h (phosphodiesterase) was reduced by embryonic, but not parental exposure, suggesting downregulation of phototransduction pathways. Hence, adverse effects on swim bladder inflation appear more sensitive to parental than embryonic exposure and the iFEDT represents an improvement in the testing strategy for THSD.

Biomechanical and histological changes associated with riboflavin ultraviolet-A-induced CXL with different irradiances in young human corneal stroma.

Keratoconus (KC) is a degenerative condition affecting the cornea, characterized by progressive thinning and bulging, which can ultimately result in serious visual impairment. The onset and progression of KC are closely tied to the gradual weakening of the cornea's biomechanical properties. KC progression can be prevented with corneal cross-linking (CXL), but this treatment has shortcomings, and evaluating its tissue stiffening effect is important for determining its efficacy. In this field, the shortage of human corneas has made it necessary for most previous studies to rely on animal corneas, which have different microstructure and may be affected differently from human corneas. In this research, we have used the lenticules obtained through small incision lenticule extraction (SMILE) surgeries as a source of human tissue to assess CXL. And to further improve the results' reliability, we used inflation testing, personalized finite element modeling, numerical optimization and histology microstructure analysis. These methods enabled determining the biomechanical and histological effects of CXL protocols involving different irradiation intensities of 3, 9, 18, and 30 mW/cm2, all delivering the same total energy dose of 5.4 J/cm2. The results showed that the CXL effect did not vary significantly with protocols using 3-18 mW/cm2 irradiance, but there was a significant efficacy drop with 30 mW/cm2 irradiance. This study validated the updated algorithm and provided guidance for corneal lenticule reuse and the effects of different CXL protocols on the biomechanical properties of the human corneal stroma.

Analyzing the impact of remittance, FDI and inflation rate on GDP: A comparative study of Bangladesh, Pakistan and Sri-Lanka using VAR and BEKK-GARCH approach.

This study examines the impact, conditional correlation and volatility spillover effect of remittances, foreign direct investment and inflation rate on GDP in Bangladesh, Pakistan, and Sri-Lanka, three Asian nations that are particularly vulnerable. While numerous studies have examined the relationship between remittances, FDI and IR on GDP but this paper approaches advanced econometric techniques to capture spillover effect and the dynamic interactions between the variables. For estimation purposes the study employs different econometric techniques such as Augmented Dickey-Fuller (ADF) test, VAR model, Granger causality tests, Impulse Response function, Variance Decomposition and BEKK-GARCH model. Bangladesh and Sri Lanka's REM, FDI and IR have no significant effects on GDP according to the VAR model. BEKK-GARCH demonstrates that three countries have both unidirectional and bidirectional transmissions of volatility, with the exception of Pakistan's REM and Bangladesh's FDI. We find that VAR model may not be adequate in capturing the complex dynamics between variables, which can be better captured by BEKK-GARCH model. Our comparison research shows how these variables affect GDP differently and similarly in each of the three nations, giving policymakers information they can use to create customized policies that encourage economic growth.

An examination of acute physiological and perceptual responses following blood flow restriction exercise using a traditional research device or novel, automated system.

Objective. To compare the acute physiological and perceptual responses to blood flow restriction (BFR) exercise using a traditional research device or novel, automated system.Methods. Forty-four resistance trained individuals performed four sets of unilateral elbow flexion exercise (30% one-repetition maximum) to volitional failure using two distinct restrictive devices [SmartCuffs PRO BFR Model (SMARTCUFF), Hokanson E20 Rapid Inflation device (HOKANSON)] and with two levels of BFR [40% limb occlusion pressure (LOP), 80% LOP]. Blood pressure (BP), muscle thickness (MT), and isometric strength (ISO) were assessed prior to and following exercise. Perceptual responses [ratings of perceived exertion (RPE), discomfort] were assessed prior to exercise and following each exercise set.Main results. Data are displayed as means (SD). Immediately following exercise with 40% LOP, there were no statistical differences between devices for BP, MT, and ISO. However, only following Set 1 of exercise, RPE was greater with SMARTCUFF compared to HOKANSON (p< 0.05). In addition, only following Set 2 of exercise, discomfort was greater with HOKANSON compared to SMARTCUFF (p< 0.001). Immediately following exercise with 80% LOP, there were no statistical differences between devices for BP, MT, and ISO. However, only following Set 4 of exercise, RPE was greater with HOKANSON compared to SMARTCUFF (p< 0.05). In addition, following all exercise sets, discomfort was greater with HOKANSON compared to SMARTCUFF (p< 0.001). For repetitions completed with 40% LOP there were no statistical differences between SMARTCUFF and HOKANSON across any exercise sets. For repetitions completed with 80% LOP there were no statistical differences between SMARTCUFF and HOKANSON across Set 1 of exercise (p= 0.34), however, for Sets 2-4 of exercise, significantly greater number of repetitions were completed during SMARTCUFF than HOKANSON.Significance. The present study provides valuable insight into the efficacy of a novel, automated BFR system (SMARTCUFF) eliciting comparable acute physiological responses to BFR exercise and in some cases favorable perceptual responses when compared to a traditional research device (HOKANSON).

The Effect of PEEP on Pulmonary Vascular Resistance Depends on Lung Recruitability in ARDS Patients.

Rationale. A U-shape relationship should exist between lung volume and pulmonary vascular resistance (PVR), with minimal PVR at functional residual capacity. Thus, positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) should increase PVR if it induces significant lung distension compared to recruitment. However, this has never been proven in patients. Objectives. To study the effects of PEEP on PVR according to lung recruitability, evaluated by the recruitment-to-inflation (R/I) ratio. Methods. In patients with ARDS, we measured hemodynamic (pulmonary artery catheter), echocardiographic and ventilatory variables (including esophageal pressure), at both low PEEP and higher PEEP by 10 cmH2O. Preload responsiveness was assessed by the passive leg raising test at high PEEP. Measurements and Main Results. We enrolled 23 patients, including 10 low recruiters (R/I <0.5) and 13 high recruiters (R/I ≥0.5). Raising PEEP from 4 (2-5) to 14 (12-15) cmH2O increased PVR in low recruiters (from 160 (120-297) to 243 (166-380) dyn.s/cm5, p<0.01), while PVR was unchanged in high recruiters (from 224 (185-289) to 235 (168-300) dyn.s/cm5, p=0.55). Right-to-left ventricular end-diastolic areas ratio simultaneously increased in low recruiters (from 0.54 (0.50-0.59) to 0.64 (0.56-0.70), p<0.01), while remaining stable in high recruiters (from 0.70 (0.65-0.79) to 0.68 (0.58-0.80), p=0.48). Raising PEEP decreased cardiac index only in preload responsive patients. Conclusions. PEEP increases PVR only when it induces significant lung distension compared to recruitment according to the recruitment-to-inflation ratio. Tailoring PEEP on this recruitability index should mitigate its hemodynamic effects.

A Lindley-binomial model for analyzing the proportions with sparseness and excessive zeros.

Proportional data arise frequently in a wide variety of fields of study. Such data often exhibit extra variation such as over/under dispersion, sparseness and zero inflation. For example, the hepatitis data present both sparseness and zero inflation with 19 contributing non-zero denominators of 5 or less and with 36 having zero seropositive out of 83 annual age groups. The whitefly data consists of 640 observations with 339 zeros (53%), which demonstrates extra zero inflation. The catheter management data involve excessive zeros with over 60% zeros averagely for outcomes of 193 urinary tract infections, 194 outcomes of catheter blockages and 193 outcomes of catheter displacements. However, the existing models cannot always address such features appropriately. In this paper, a new two-parameter probability distribution called Lindley-binomial (LB) distribution is proposed to analyze the proportional data with such features. The probabilistic properties of the distribution such as moment, moment generating function are derived. The Fisher scoring algorithm and EM algorithm are presented for the computation of estimates of parameters in the proposed LB regression model. The issues on goodness of fit for the LB model are discussed. A limited simulation study is also performed to evaluate the performance of derived EM algorithms for the estimation of parameters in the model with/without covariates. The proposed model is illustrated through three aforementioned proportional datasets.

Taxonomic inflation as a conservation trap for inbred populations.

Conservation is prioritized based on accepted taxa. As a consequence, a conservation incentive exists to emphasize inter-population differences to define taxa, potentially leading to taxonomic inflation. But stressing the uniqueness of threatened populations has the side effect of hindering conservation actions that promote inter-population gene flow, such as genetic rescue. These actions may be of critical importance for severely inbred populations involved in extinction vortices, for which an inflated taxonomy can become a conservation trap. Here, we exemplify this scenario with the western capercaillie (Tetrao urogallus, Phasianidae) population in the Cantabrian Mountains, described and legally listed as a subspecies not supported by recent molecular data. The Cantabrian capercaillie population is Critically Endangered after a long-lasting decline and a recent demographic collapse. It shows clear signs of inbreeding depression, including striking clutch size decreases as well as reduced hatchability and chick survival. This critical situation could be alleviated through a genetic rescue, but this possibility is hindered by inertias rooted in the putative uniqueness of the Cantabrian capercaillie. It had been previously argued that poor taxonomy could hamper conservation, through the oblivion of populations deserving, but not having, a taxonomic status. We show that taxonomic inflation can also become an obstacle for effective conservation.

Predicting the short and long term effects of food price inflation, armed conflicts, and climate variability on global acute malnutrition in Somalia.

BACKGROUND: Malnutrition poses a substantial challenge in Somalia, impacting approximately 1.8 million children. This critical issue is exacerbated by a multifaceted interplay of factors. Consequently, this study seeks to examine the long-term and short-term effects of armed conflicts, food price inflation, and climate variability on global acute malnutrition in Somalia. METHODS: The study utilized secondary data spanning from January 2015 to December 2022, sourced from relevant databases. Two distinct analytical approaches were employed to comprehensively investigate the dynamics of global acute malnutrition in Somalia. Firstly, dynamic autoregressive distributed lag (ARDL) simulations were applied, allowing for a nuanced understanding of the short and long-term effects of armed conflicts, food price inflation, and climate variability on malnutrition. Additionally, the study employed kernel-based regularized least squares, a sophisticated statistical technique, to further enhance the robustness of the findings. The analysis was conducted using STATA version 17. RESULTS: In the short run, armed conflicts and food price inflation exhibit positive associations with global acute malnutrition, particularly in conflict-prone areas and during inflationary periods. Moreover, climatic variables, specifically temperature and rainfall, demonstrate positive associations. It is important to note that temperature lacks a statistically significant relationship with global acute malnutrition in the short run. In the long run, armed conflicts and food price inflation maintain persistent impacts on global acute malnutrition, as confirmed by the dynamic ARDL simulations model. Furthermore, both temperature and rainfall continue to show positive associations with global acute malnutrition, but it is worth noting that temperature still exhibits a non-significant relationship. The results from kernel-based regularized least squares were consistent, further enhancing the robustness of the findings. CONCLUSIONS: Increased armed conflicts, food price inflation, temperature, and rainfall were associated with increased global acute malnutrition. Strategies such as stabilizing conflict-prone regions, diplomatic interventions, and peace-building initiatives are crucial, along with measures to control food price inflation. Implementing climate adaptation strategies is vital to counter temperature changes and fluctuating rainfall patterns, emphasizing the need for resilience-building. Policymakers and humanitarian organizations can leverage these insights to design targeted interventions, focusing on conflict resolution, food security, and climate resilience to enhance Somalia's overall nutritional well-being.

Medicare Should Cover Weight Loss Drugs as Long as the Prices are Affordable.

Glucagon-like peptide-1 receptor agonists are effective for treating obesity, but the high cost of these medications endangers the financial viability of our health care system. To ensure that these drugs are available to Medicare beneficiaries, pharmaceutical manufacturers must lower their prices.

Effect of short-term exposure to the strobilurin fungicide dimoxystrobin: Morphofunctional, behavioural and mitochondrial alterations in Danio rerio embryos and larvae.

Strobilurins, among the most used fungicides worldwide, are considered non-toxic to mammals and birds, but there is growing evidence that these compounds are highly toxic to aquatic species. Dimoxystrobin has been included in the 3rd Watch List of the European Commission, and it has been classified as very toxic to aquatic life. However, previous studies focused on acute toxicity and only two reports are available on its impact on fish, and none on its effects during the early life stages. Here, we evaluated for the first time the effects induced on zebrafish embryos and larvae by two dimoxystrobin sublethal concentrations (6.56 and 13.13 µg/L) falling in the range of predicted environmental concentrations. We demonstrated that short-term exposure to dimoxystrobin may exert adverse effects on multiple targets, inducing severe morphological alterations. Moreover, we showed enhanced mRNA levels of genes related to the mitochondrial respiratory chain and ATP production. Impairment of the swim bladder inflation has also been recorded, which may be related to the observed swimming performance alterations.