Physiological Endpoints Research Articles

Exposure and Recovery of the Gulf Toadfish (Opsanus beta) to Weathered Deepwater Horizon Slick Oil: Impacts on Liver and Blood Endpoints.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants that can be responsible for a variety of deleterious effects on organisms. These adverse outcomes are relatively well studied, but at concentrations rarely found in the environment. Among the documented effects of sublethal acute PAH exposure are reductions in osmoregulatory capacity and immune function, and changes in the function of critical metabolic organs such as the liver. Gulf toadfish (Opsanus beta) were exposed to control seawater (0.006 µg tPAH50 /L) or water accommodated fractions of Deepwater Horizon spill oil diluted to 3 flow-through exposure regimes (0.009, 0.059, and 2.82 µg tPAH50 /L) for 7 d, with a recovery period of equal duration. We hypothesized that these chronic exposures would induce the aryl hydrocarbon receptor (AhR)-mediated pathways and result in significant impacts on markers of osmoregulatory, immune, and metabolic function. We further hypothesized that measurable reversal of these impacts would be observed during the recovery period. Our results indicate that activation of cytochrome P 450 (CYP)1A1 was achieved during exposure and reversed during the recovery phase. The only significant deviations from controls measured were a reduction in plasma glucose in fish exposed to medium and high levels of PAH after 7 d of exposure and a reduction in plasma osmolality fish exposed to high levels of PAHs after 7 d of recovery, when CYP1A1 messenger (m)RNA levels had returned to control levels. Our study illustrates a disconnect between the activation of CYP1A1 in response to environmentally realistic PAHs concentrations and several physiological endpoints and supports the idea that the AhR might not be associated with mediating osmoregulatory, immune, and metabolic changes in Gulf toadfish. Environ Toxicol Chem 2021;40:1075-1086. © 2020 SETAC.

Devices and techniques used to obtain and analyze three-dimensional cell cultures.

Cell cultures are indispensable for both basic and applied research. Advancements in cell culture and analysis increase their utility for basic research and translational applications. A marked development in this direction is advent of three-dimensional (3D) cultures. The extent of advancement in 3D cell culture methods over the past decade has warranted referring to a single cell type being cultured as an aggregate or spheroid using simple scaffolds as "traditional." In recent years, the development of "next-generation" devices has enabled cultured cells to mimic their natural environments much better than the traditional 3D culture systems. Automated platforms like chip-based devices, magnetic- and acoustics-based assembly devices, di-electrophoresis (DEP), micro pocket cultures (MPoC), and 3D bio-printing provide a dynamic environment compared to the rather static conditions of the traditional simple scaffold-based 3D cultures. Chip-based technologies, which are centered on principles of microfluidics, are revolutionizing the ways in which cell culture and analysis can be compacted into table-top instruments. A parallel evolution in analytical devices enabled efficient assessment of various complex physiological and pathological endpoints. This is augmented by concurrent development of software enabling rapid large-scale automated data acquisition and analysis like image cytometry, elastography, optical coherence tomography, surface-enhanced Raman scattering (SERS), and biosensors. The techniques and devices utilized for the purpose of 3D cell culture and subsequent analysis depend primarily on the requirement of the study. We present here an in-depth account of the devices for obtaining and analyzing 3D cell cultures.

From bioavailability to risk assessment of polluted soil using snails: link between excess transfer and inhibition of sexual maturation.

An accurate assessment of the environmental risk of soils contaminated by metal(loid)s (MEs) requires quantifying exposure and knowing the toxicity of contaminants transferred to biota. For this purpose, two indices have been developed with the bioindicator Cantareus aspersus to assess exposure (SET: sum of the excess of transfer) and risk (ERITME: evaluation of the risk of the transferred metal elements) of multi-contaminated soils. If the SET and ERITME indices allow characterization of exposure and risk based on unspecific toxicity points, then the link between these indices and real effects on some toxicological endpoints, such as growth or sexual maturation, remains to be demonstrated. For this purpose, sub-adult snails were exposed for 28days to 38 ME-contaminated soils. Relationships between the SET and/or ERITME indices and health alterations in C. aspersus were determined usingSpearman correlations, linear regressions, univariate regression trees, and kinetic models. Relationships were determined between the values of the SET and ERITME indices, bioaccumulation as an indicator of ME bioavailability, and the alteration in physiological endpoints, such as the shell development used as a non-invasive indicator of sexual maturation. The results enabled the determination of three levels of risk according to the differences in reaching sexual maturity: no risk, uncertain, and proven risk depended on whether the value of ERITME was below, in, or beyond the interval [2574-22720], respectively. This study provides the first benchmarks with the SET and ERITME indices to interpret the risk of contaminated soils to snails and to relate the environmental and toxicological bioavailability of ME mixtures.

Phase II Investigation of the Efficacy of Antimycobacterial Therapy in Chronic Pulmonary Sarcoidosis

BackgroundA Phase I, single-center investigation found that 8 weeks of antimycobacterial therapy improved sarcoidosis FVC. Safety and efficacy assessments have not been performed in a multicenter cohort.Research QuestionThe objective of this study was to determine the safety and efficacy of antimycobacterial therapy on the physiological and immunologic end points of sarcoidosis.Study Design and MethodsIn a double-blind, placebo-controlled, multicenter investigation, patients with pulmonary sarcoidosis were randomly assigned to receive 16 weeks of concomitant levofloxacin, ethambutol, azithromycin, and rifabutin (CLEAR) or matching placebo to investigate the effect on FVC. The primary outcome was a comparison of change in percentage of predicted FVC among patients randomized to receive CLEAR or placebo in addition to their baseline immunosuppressive regimen. Secondary outcomes included 6-min walk distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ) score, adverse events, and decrease in mycobacterial early secreted antigenic target of 6 kDa (ESAT-6) immune responses.ResultsThe intention-to-treat analysis revealed no significant differences in change in FVC among the 49 patients randomized to receive CLEAR (1.1% decrease) compared with the 48 randomized to receive placebo (0.02% increase) (P = .64). Physiological parameters such as the change in 6MWD were likewise similar (P = .91); change in SGRQ favored placebo (–8.0 for placebo vs –1.5 for CLEAR; P = .028). The per-protocol analysis revealed no significant change in FVC at 16 weeks between CLEAR and placebo. There was no significant change in 6MWD (36.4 m vs 6.3 m; P = .24) or SGRQ (–2.3 vs –7.0; P = .14). A decline in ESAT-6 immune responses at 16 weeks was noted among CLEAR-treated patients (P = .0003) but not patients receiving placebo (P = .24).InterpretationDespite a significant decline in ESAT-6 immune responses, a 16-week CLEAR regimen provided no physiological benefit in FVC or 6MWD among patients with sarcoidosis.

American lobster postlarvae alter gene regulation in response to ocean warming and acidification.

Anthropogenic carbon emissions released into the atmosphere is driving rapid, concurrent increases in temperature and acidity across the world's oceans. Disentangling the interactive effects of warming and acidification on vulnerable life stages is important to our understanding of responses of marine species to climate change. This study evaluates the interactive effects of these stressors on the acute response of gene expression of postlarval American lobster (Homarus americanus), a species whose geographic range is warming and acidifying faster than most of the world's oceans. In the context of our experiment, we found two especially noteworthy results: First, although physiological end points have consistently been shown to be more responsive to warming in similar experimental designs, our study found gene regulation to be considerably more responsive to elevated pCO2. Furthermore, the combined effect of both stressors on gene regulation was significantly greater than either stressor alone. Using a full factorial experimental design, lobsters were raised in control and elevated pCO2 concentrations (400 ppm and 1,200 ppm) and temperatures (16°C and 19°C). A transcriptome was assembled from an identified 414,517 unique transcripts. Overall, 1,108 transcripts were differentially expressed across treatments, several of which were related to stress response and shell formation. When temperature alone was elevated (19°C), larvae downregulated genes related to cuticle development; when pCO2 alone was elevated (1,200 ppm), larvae upregulated chitinase as well as genes related to stress response and immune function. The joint effects of end‐century stressors (19°C, 1,200 ppm) resulted in the upregulation of those same genes, as well as cellulase, the downregulation of calcified cuticle proteins, and a greater upregulation of genes related to immune response and function. These results indicate that changes in gene expression in larval lobster provide a mechanism to respond to stressors resulting from a rapidly changing environment.

A comprehensive assessment of multi-system responses to a renal inoculation of uropathogenic E. coli in swine.

The systemic responses to infection and its progression to sepsis remains poorly understood. Progress in the field has been stifled by the shortcomings of experimental models which include poor replication of the human condition. To address these challenges, we developed and piloted a novel large animal model of severe infection that is capable of generating multi-system clinically relevant data. Male swine (n = 5) were anesthetized, mechanically ventilated, and surgically instrumented for continuous hemodynamic monitoring and serial blood sampling. Animals were inoculated with uropathogenic E. coli by direct injection into the renal parenchyma and were maintained until a priori endpoints were met. The natural history of the infection was studied. Animals were not resuscitated. Multi-system data were collected hourly to 6 hours; all animals were euthanized at predetermined physiologic endpoints. Core body temperature progressively increased from mean (SD) 37.9(0.8)°C at baseline to 43.0(1.2)°C at experiment termination (p = 0.006). Mean arterial pressure did not begin to decline until 6h post inoculation, dropping from 86(9) mmHg at baseline to 28(5) mmHg (p = 0.005) at termination. Blood glucose progressively declined but lactate levels did not elevate until the last hours of the experiment. There were also temporal changes in whole blood concentrations of a number of metabolites including increases in the catecholamine precursors, tyrosine (p = 0.005) and phenylalanine (p = 0.005). Lung, liver, and kidney function parameters worsened as infection progressed and at study termination there was histopathological evidence of injury in these end-organs. We demonstrate a versatile, multi-system, longitudinal, swine model of infection that could be used to further our understanding of the mechanisms that underlie infection-induced multi-organ dysfunction and failure, optimize resuscitation protocols and test therapeutic interventions. Such a model could improve translation of findings from the bench to the bedside, circumventing a significant obstacle in sepsis research.

Long-term monitoring of two snake species reveals immune-endocrine interactions and the importance of ecological context.

While there is huge promise in monitoring physiological parameters in free-living organisms, we also find high amounts of variability over time and space. This variation requires us to capitalize on long-term physiological monitoring to adequately address questions of population health, conservation status, or evolutionary trends as long-term sampling can examine ecoimmunological and endocrine interactions in wild populations while accounting for the variation that often makes ecophysiological field studies difficult to compare. In this study, we tested how immune efficacy and endocrinology interact while accounting for ecological context and environmental conditions in two snake species. Specifically, we measured bacterial killing ability, steroid hormones, and morphological characteristics in multiple populations of the Western Terrestrial Gartersnake (Thamnophis elegans) and Common Gartersnake (T. sirtalis) for multiple seasons over 6 years. Leveraging this long-term dataset, we tested how a broad immune measure and endocrine endpoints interact while accounting for individual traits, sampling date, and environmental conditions. Across both species, we found bacterial killing ability to be directly related to corticosterone(CORT) and temperature and greater overall in the spring compared to the fall. We found CORT and testosterone yielded relationships with individual sex, sampling temperature, and time of year. Wild populations can exhibit high amounts of variation in commonly collected physiological endpoints, highlighting the complexity and difficulty inherent in interpreting single endpoints without taking ecological and environmental conditions into account. Our study emphasizes the importance of reporting the environmental conditions under which the sampling occurred to allow for better contextualization and comparison between studies.

Production and characterization of Graphene Nanoplatelet-based ink for smart textile strain sensors via screen printing technique

Wearable systems are becoming highly attractive in different application areas. Recently, particular attention has been focused on the development of personal portable devices for monitoring occupational safety and health. Smart clothes based on strain sensors integrated on fabric seem to be a promising solution for real-time measurement of physiological endpoints. However, the development through a simple and cost-effective process of smart textiles characterized by high sensitivity, wearability and stable response even during physical activity, in case of exposition to environmental conditions and after washing is still challenging. In this work, the authors have developed a novel strain sensor made of graphene nanoplatelets (GNPs) properly dispersed into a water-based transparent ink, then deposited via screen printing technique on a synthetic fabric. Rheological investigations of the GNP-filled inks, morphological characterization of coated fabrics, electrical measurements of films obtained with different GNPs concentrations were performed. Smart textile specimens loaded with 3%wt and 3.8%wt of GNP-based inks were characterized through quasi-static tensile tests to investigate the electromechanical response, even after a washing cycle. Specimens have shown a sensitivity of about 30 for a strain of 5%. This performance is interesting for different applications such as monitoring of respiratory and heart rates.

Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice.

Unimolecular peptides targeting the receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (GLP-1/GIP co-agonist) have been shown to outperform each single peptide in the treatment of obesity and cardiometabolic disease in preclinical and clinical trials. By combining physiological treatment endpoints with plasma proteomic profiling (PPP), we aimed to identify biomarkers to advance non-invasive metabolic monitoring of compound treatment success and exploration of ulterior treatment effects on an individual basis. We performed metabolic phenotyping along with PPP in body weight-matched male and female diet-induced obese (DIO) mice treated for 21 days with phosphate-buffered saline, single GIP and GLP-1 mono-agonists, or a GLP-1/GIP co-agonist. GLP-1R/GIPR co-agonism improved obesity, glucose intolerance, non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia with superior efficacy in both male and female mice compared with mono-agonist treatments. PPP revealed broader changes of plasma proteins after GLP-1/GIP co-agonist compared with mono-agonist treatments in both sexes, including established and potential novel biomarkers for systemic inflammation, NAFLD and atherosclerosis. Subtle sex-specific differences have been observed in metabolic phenotyping and PPP. We herein show that a recently developed unimolecular GLP-1/GIP co-agonist is more efficient in improving metabolic disease than either mono-agonist in both sexes. PPP led to the identification of a sex-independent protein panel with the potential to monitor non-invasively the treatment efficacies on metabolic function of this clinically advancing GLP-1/GIP co-agonist.

ARA or no ARA in infant formulae, that is the question

Recently, the European Commission issued a Delegated Regulation updating the compositional and information requirements for infant and follow-on formulae that are to be applied at the latest in February 2021. This new regulation changes the status of docosahexaenoic acid (DHA) from an optional ingredient to a mandatory nutrient in these formulae at levels between 20 and 50mg/100kcal (0.5–1% of fatty acids). By contrast, arachidonic acid (ARA) becomes an optional nutrient. Following publication of the new regulation, global scientific experts have expressed concerns regarding the potential health risks of new infant formulae containing only DHA, especially at levels higher than those in breast milk and infant formulae marketed to date. Both DHA and ARA play a crucial role in infant development. First, breast milk, the gold standard for infant feeding, contains both DHA and ARA. Second, during development, the conversion of linoleic acid into ARA through desaturation steps is not sufficient to meet nutritional needs, especially in carriers of newly identified genetic variants in fatty acid desaturases, which weaken the biosynthetic production of ARA. Third, circulating levels of DHA and ARA in breastfed infants can only be matched with the addition of both fatty acids to formulae. And fourth, most studies performed to date have demonstrated that important physiological and developmental endpoints are sensitive to the ratio of dietary ARA:DHA. The precautionary principle applies when implementing the new EU regulation for infant and follow-on formulae. As a consequence, given the vulnerability of developing infants as well as the absence of conclusive evidence that formulae with at least 20mg DHA/100kcal, but no ARA, are safe and suitable to support the growth and development of infants similar to their breastfed peers, it remains necessary to still market formulas containing both ARA and DHA until proved otherwise.

Behavioral and physiological responses of Daphnia magna to salicylic acid

Salicylic acid (SA), a metabolite of acetylsalicylic acid is a monohydroxybenzoic acid a common non-steroidal analgesic and anti-inflammatory drug (NSAID) frequently detected in various aquatic ecosystems at concentrations up to 19.50 μg L−1 in surface waters near livestock farms and 59.6 μg L−1 in wastewaters. Little is known on the effects of short-term exposure of freshwater crustaceans to salicylic acid. Therefore, the aim of our study was to determine the effects of SA at concentrations of 5 μg L−1, 500 μg L−1, 5 mg L−1, 50 mg L−1 and 500 mg L−1 on the behavior (swimming speed, swimming height, distance travelled) and physiological endpoints (heart rate, mandible movement) of Daphnia magna exposed for 24 h, 48 h and 72 h. The results showed that SA inhibited the swimming speed, swimming height and distance travelled, heart rate and mandible movement at 5 mg L−1, 50 mg L−1 and 500 mg L−1 when compared to the control. On the other hand, SA at 5 μg L−1 and 500 μg L−1 transiently increased swimming speed and distance travelled after 24 h of the exposure, except for swimming height. Behavioral and physiological disturbances were observed much earlier than lethality. Our study showed SA at environmental levels may be an ecotoxicological agent imparing behavior and physiology of freshwater crustaceans.

Critical window of exposure of CMIT/MIT with respect to developmental effects on zebrafish embryos: Multi-level endpoint and proteomics analysis

Systemic toxicity, particularly, developmental defects of humidifier disinfectant chemicals that have caused lung injuries in Korean children, remains to be elucidated. This study evaluated the mechanisms of the adverse effects of 5-chloro-2-methyl-4-isothiazoline-3-one/2methyl-4-isothiazolin-3-one (CMIT/MIT), one of the main biocides of the Korean tragedy, and identify the most susceptible developmental stage when exposed in early life. To this end, the study was designed to analyze several endpoints (morphology, heart rate, behavior, global DNA methylation, gene expressions of DNA methyl-transferases (dnmts) and protein profiling) in exposed zebrafish (Danio rerio) embryos at various developmental stages. The results showed that CMIT/MIT exposure causes bent tail, pericardial edema, altered heart rates, global DNA hypermethylation and significant alterations in the locomotion behavior. Consistent with the morphological and physiological endpoints, proteomics profiling with bioinformatics analysis suggested that the suppression of cardiac muscle contractions and energy metabolism (oxidative phosphorylation) were possible pivotal underlying mechanisms of the CMIT/MIT mediated adverse effects. Briefly, multi-level endpoint analysis indicated the most susceptible window of exposure to be≤6 hpf followed by≤48 hpf for CMIT/MIT. These results could potentially be translated to a risk assessment of the developmental exposure effects to the humidifier disinfectants.

Physiological and functional responses of water-cooled versus traditional radiofrequency ablation of peripheral nerves in rats

Background and objectivesSeveral clinical studies have focused on assessing the effectiveness of different radiofrequency ablation (RFA) modalities in pain management. While a direct head-to-head clinical study is needed, results from...

Nopal fiber (Opuntia ficus-indica) improves symptoms in irritable bowel syndrome in the short term: a randomized controlled trial.

Clinical guidelines provide limited and conflicting recommendations regarding dietary fiber supplementation in irritable bowel syndrome (IBS). Nopal (Opuntia ficus-indica) is a cactus plant fiber containing both insoluble and soluble fibers that may have therapeutic potential in IBS. Our aim was to evaluate the dose-response effect of extracted nopal fiber powder on symptoms in IBS. We performed a 4-arm, double-blind, parallel, randomized controlled trial in 60 patients fulfilling Rome IV criteria for IBS. Patients were randomized and blindly allocated to receive either nopal fiber (10, 20, or 30g/day) or placebo (30g/day dextrose) for one week and to keep their usual diet. Symptom severity (Global Symptom Question, IBS-SSS, Gastrointestinal Symptom Rating Scale), stool frequency and consistency (Bristol Stool Form Scale), breath hydrogen response, and stool short-chain fatty acids (SCFA) were measured at baseline and follow-up. Significantly more patients reported adequate relief of symptoms after 20g/day (87%, p=0.008) and 30g/day (80%, p=0.025) of nopal fiber compared to placebo (33%). More patients receiving 20g/day nopal fiber (67%) had a>50% reduction in IBS-SSS compared to placebo (20%, p=0.027), whereas the 30g/day dose induced more loose stools (p=0.027). Response rates were similar among IBS subtypes. There were no differences in breath hydrogen or stool SCFA between groups. Nopal fiber supplementation at doses of 20 and 30g/day was associated with short-term improvement in IBS symptoms, warranting a fully powered clinical trial of longer duration with symptomatic, physiological, and microbiological endpoints.

Ecotoxicological Effects of Diethyl Phthalate on Caenorhabditis elegans under Environmentally Relevant Concentrations

Diethyl phthalate(DEP)is a typical plasticizer that has been widely detected in the environment.DEP possesses potential neurological and reproductive toxicities,which can affect the development motion behavior as well as certain biochemical parameters of organisms.The present study was designed to evaluate the eco-toxicity of DEP under different exposure scenarios(24 h,72 h and 10 d)at environmentally relevant concentrations(0,0.0002,0.002,0.02,0.2,2 mg /L)on Caenorhabditis elegans,a typical model animal.To this end,the body length width,head thrashing frequency,and biochemical indicators of C.elegans were applied as test endpoints to evaluate the ecotoxicological effects of DEP.The results revealed that under 24 h exposure scenario,compared to the control group,DEP exhibited no distinct effect on the development of C.elegans at all exposure levels(P>0.05).In the case of 72 h exposure,DEP was found to inhibit the development of C.elegans compared with the control group.Specifically,the body length declined by 3.21%(P<0.05)at a DEP level of 2 mg/ L.Under 0.0002 mg /L DEP exposure,the body width was found to increase.Head thrashing frequency displayed stimulating effect when exposed to low DEP levels(<0.2 mg /L).When it was 0.0002 mg/ L,it increased by 5.52%(P<0.01).In addition,the physiological endpoints,including body length,body width and head thrashing frequency,decreased significantly by comparison with the control group at all exposure levels after 10 d exposure.Moreover,the levels of reactive oxygen species,lipofuscin and apoptosis increased significantly at 2 mg/ L.The results revealed that DEP exposure exhibited different toxicological effects on C.elegans,depending on the concentration and exposure scenarios.

A comparison of behavioral and reproductive parameters between wild-type, transgenic and mutant zebrafish: Could they all be considered the same “zebrafish” for reglementary assays on endocrine disruption?

Transgenic zebrafish models are efficiently used to study the effects of endocrine disrupting chemicals (EDC); thereby informing on their mechanisms of action. However, given the reported differences between zebrafish strains at the genetical, physiological and behavioral levels; care should be taken before using these transgenic models for EDC testing. In the present study, we undertook a set of experiments in different transgenic and/or mutant zebrafish strains of interest for EDC testing: casper, cyp19a1a-eGFP, cyp19a1a-eGFP-casper, cyp11c1-eGFP, cyp11c1-eGFP-casper. Some behavioral traits, and some biochemical and reproductive physiological endpoints commonly used in EDC testing were assessed and compared to those obtained in WT AB zebrafish to ensure that transgene insertion and/or mutations do not negatively modify basal reproductive physiology or behavior of the fish.Behavioral traits considered as anxiety and sociality have been monitored. Sociality was evaluated by monitoring the time spent near congeners in a shuttle box while anxiety was evaluated using the Novel tank diving test. No critical difference was observed between strains for either sociality or anxiety level. Concerning reproduction, no significant difference in the number of eggs laid per female, in the viability of eggs or in the female circulating VTG concentrations was noted between the 5 transgenic/mutants and the WT AB zebrafish studied.In summary, the transgene insertion and the mutations had no influence on the endpoints measured in basal conditions. These results were a prerequisite to the use of these transgenic/mutant models for EDC testing. Next step will be to determine the sensitivity of these biological models to chemical exposure to accurately validate their use in existing fish assays for EDC testing.

Rapid plastic responses to chronic hypoxia in the bearded fireworm, Hermodice carunculata (Annelida: Amphinomidae)

Hypoxia is a widespread and increasing phenomenon in marine environments, including coral reefs. The bearded fireworm (Hermodice carunculata) is a large corallivorous amphinomid polychaete, with a high tolerance of environmental stress, including temperature, salinity, and dissolved oxygen (DO). Currently, little is known about the response of H. carunculata to chronic (≥ 18 h) hypoxia, although this knowledge is crucial to understand its impact on coral reef health under hypoxia scenarios. We tested the hypothesis that the number of branchial filaments (previously used as a diagnostic character for species identification) increases in response to chronic hypoxia. We subjected wild-caught fireworms to two levels of reduced DO (Mid: 4.5 ± 0.25 mg O2 L−1 and Low: 2.5 ± 0.25 mg O2 L−1) to explore their morphological and physiological responses to seven days of chronic hypoxia. Hypoxia exposure resulted in a higher number of branchial filaments (low = 57.2 ± 5.3, mid = 57.4 ± 6.1, and normal = 47.4 ± 11.2) after seven days. Fireworms exposed to hypoxia further reduced their rate of regeneration, but returned to normal regenerative rates after fifteen weeks under normoxic conditions. There was no difference in regeneration rates between low and mid DO groups. Our results demonstrate the importance of considering multiple physiological and morphological endpoints as well as phenotypic plasticity in species delimitations. Indeed, the results suggest that morphological variation can be indicative of environmental conditions.

Growth and reproduction of Donax trunculus from the Gulf of Annaba (Northeast Algeria) in relation to environmental conditions.

This study was aimed to evaluate the physiological reproductive end points (sex ratio, gametogenic cycle) and biological indices (condition index, length-weight relationship) in D. trunculus collected monthly over the year 2016, from two sites of the Gulf of Annaba (Northeast Algeria): El Battah (relatively unpolluted site) and Sidi Salem (polluted site). The results showed that gametogenesis takes place from December to August in both sites, with an autumnal resting phase. Also, the spawning occurred between March and August with two major spawning phases: April and August in El Battah vs May and August in Sidi Salem. The condition index showed a significant decrease in Sidi Salem site and positive correlation with gonad index. Moreover, the sites exert a significant effect on the allometric relationship and no significant effect on sex ratio. The observed reproductive events are discussed with the changes in the biological indices and the levels of pollution in the studied sites.

Visceral fat reduction and increase of intracellular fluid in weight loss participants on antihypertension medication.

Complex physiological interactions between hypertension and obesity contribute to and perpetuate a heightened morbidity and mortality. With the prevalence of both hypertension and obesity reaching epidemic proportions, we asked whether antihypertensive medications affect the ability of participants to achieve the same level of body composition improvements as other participants in a comprehensive weight loss program focused on reduction of visceral adipose tissue. Data was analyzed from 2200 subjects completing a commercially available, expert supervised weight loss program including ~6 weeks of a proprietary, nutritionally complete, very low-calorie diet (VLCD) followed by a ~3-week structured transition back to a normal dietary intake. Overall, 33% of the subjects reported taking at least one prescription antihypertensive medication. Our data show participants in both groups (± antihypertensive drugs) achieved clinically relevant and statistically significant improvements in standard measures of weight loss and endpoints directly related to inflammation and hypertension. A nonpharmacologic, nonsurgical VLCD-based weight loss and metabolic health program is capable of producing clinically meaningful improvements in body composition and physiological endpoints, including those linked to hypertension, cardiovascular disease and inflammation, and is as equally effective for adults taking prescription antihypertensives as it is for those participants who are not.

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

“Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA) was a comprehensive “industry-standard” Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints. The goal of this report is to integrate the findings from the investigator-initiated studies into a comprehensive overview of the observed impacts of BPA across the multiple organs and systems analyzed. For each organ system, we provide the rationale for the study, an overview of methodology, and summarize major findings. We then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. Finally, we discuss potential influences that contributed to differences between studies. Developmental exposure to BPA can lead to adverse effects in multiple organs systems, including the brain, prostate gland, urinary tract, ovary, mammary gland, and heart. As published previously, many effects were at the lowest dose tested, 2.5μg/kg /day, and many of the responses were non-monotonic. Because the low dose of BPA affected endpoints in the same animals across organs evaluated in different labs, we conclude that these are biologically – and toxicologically – relevant.