How Far Are We From Achieving Delabeling of False Penicillin/ß-Lactam Allergy Alerts? A Population Problem.

BACKGROUND: Interest in finding efficient ways to remove penicillin allergy alerts has grown as a result of awareness of the considerable excess of false-negative diagnoses in patients with penicillin allergy labels (90%-95%), the poorer course with non-ß-lactam antibiotics, the increase in bacterial resistance, and the fact that these problems can affect up to 20% of the population in some countries. The strategies proposed have generated many publications in countries where the number of allergists to conduct such studies is low. In many cases where delabeling is performed, the risk of ß-lactam allergy is low, and a single penicillin challenge is sufficient to delabel the alert. However, other less "ultrarapid" strategies can be used to administer a ß-lactam during an admission for infection and thus postpone delabeling until traditional drug allergy consultations. However, the definitive withdrawal of ß-lactam alerts is threatened by nonremoval of alerts in electronic health records and by the reactivation or nonsynchronization of alerts between electronic systems at different levels of care. Allergy departments need to reflect on how to implement practices that enable rapid and efficient delabeling of drug allergy alerts, especially in patients with major comorbidities.

Molecular, immunological, and physiological evidences of a sphingosine-activated plasma membrane Ca2+-channel in Trypanosoma equiperdum.

The hemoparasite Trypanosoma equiperdum belongs to the Trypanozoon subgenus and includes several species that are pathogenic to animals and humans in tropical and subtropical areas across the world. As with all eukaryotic organisms, Ca2+ is essential for these parasites to perform cellular processes thus ensuring their survival across their life cycle. Despite the established paradigm to study proteins related to Ca2+ homeostasis as potential drug targets, so far little is known about Ca2+ entry into trypanosomes. Therefore, in the present study, the presence of a plasma membrane Ca2+-channel in T. equiperdum (TeCC), activated by sphingosine and inhibited by verapamil, is described. The TeCC was cloned and analyzed using bioinformatic resources, which confirmed the presence of several domains, motifs, and a topology similar to the Ca2+ channels found in higher eukaryotes. Biochemical and confocal microscopy assays using antibodies raised against an internal region of human L-type Ca2+ channels indicate the presence of a protein with similar predicted molar mass to the sequence analyzed, located at the plasma membrane of T. equiperdum. Physiological assays based on Fura-2 signals and Mn2+ quenching performed on whole parasites showed a unidirectional Ca2+ entry, which is activated by sphingosine and blocked by verapamil, with the distinctive feature of insensitivity to nifedipine and Bay K 8644. This suggests a second Ca2+ entry for T. equiperdum, different from the store-operated Ca2+ entry (SOCE) previously described. Moreover, the evidence presented here for the TeCC indicates molecular and pharmacological differences with their mammal counterparts, which deserve further studies to evaluate the potential of this channel as a drug target.

A review of the injuries caused by occupational footwear.

BACKGROUND: Occupational footwear is intended to provide protection against the risks associated with work activities. The choice of footwear is complex due to the welfare, health and safety conditions of workers. AIMS: To identify the injuries and problems caused by occupational footwear through a systematic review of the existing literature. METHODS: A literature search was carried out in the Cumulative Index to Nursing and Allied Health Literature, Dialnet Plus, Pubmed, Scientific Electronic Library Online, Medline, Scopus and Web of Science databases over the period 2000-23, following the PRISMA Declaration guidelines. RESULTS: A total of 27 studies were included in the review. The results indicated that there is a wide variety of injuries caused by occupational footwear: from dermal injuries (e.g. calluses) and injuries to the nail apparatus to inflammatory pathologies such as plantar fasciitis or bursitis. In addition, inappropriate footwear can cause pain in the ankle and foot, knees, hips and lower back. Other results include the discomfort derived from the footwear itself. CONCLUSIONS: Inappropriate footwear can cause injuries to the foot and other related bone structures. Further studies are needed on the detection of foot injuries caused by occupational footwear and the levels of action at this level to improve the worker's health, the adaptability of the footwear to the wearer, and the worker's comfort and adherence to the footwear.

Brain Growth Charts for Quantitative Analysis of Pediatric Clinical Brain MRI Scans with Limited Imaging Pathology.

Background Clinically acquired brain MRI scans represent a valuable but underused resource for investigating neurodevelopment due to their technical heterogeneity and lack of appropriate controls. These barriers have curtailed retrospective studies of clinical brain MRI scans compared with more costly prospectively acquired research-quality brain MRI scans. Purpose To provide a benchmark for neuroanatomic variability in clinically acquired brain MRI scans with limited imaging pathology (SLIPs) and to evaluate if growth charts from curated clinical MRI scans differed from research-quality MRI scans or were influenced by clinical indication for the scan. Materials and Methods In this secondary analysis of preexisting data, clinical brain MRI SLIPs from an urban pediatric health care system (individuals aged ≤22 years) were scanned across nine 3.0-T MRI scanners. The curation process included manual review of signed radiology reports and automated and manual quality review of images without gross pathology. Global and regional volumetric imaging phenotypes were measured using two image segmentation pipelines, and clinical brain growth charts were quantitatively compared with charts derived from a large set of research controls in the same age range by means of Pearson correlation and age at peak volume. Results The curated clinical data set included 532 patients (277 male; median age, 10 years [IQR, 5-14 years]; age range, 28 days after birth to 22 years) scanned between 2005 and 2020. Clinical brain growth charts were highly correlated with growth charts derived from research data sets (22 studies, 8346 individuals [4947 male]; age range, 152 days after birth to 22 years) in terms of normative developmental trajectories predicted by the models (median r = 0.979). Conclusion The clinical indication of the scans did not significantly bias the output of clinical brain charts. Brain growth charts derived from clinical controls with limited imaging pathology were highly correlated with brain charts from research controls, suggesting the potential of curated clinical MRI scans to supplement research data sets. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ertl-Wagner and Pai in this issue.

Realistic scenarios of pesticide exposure alters multiple biomarkers in BOANA PULCHELLA (ANURA) Adult Frogs.

Imazethapyr, a post-emergent herbicide used in worldwide soybean and corn crops, induces genetic and biochemical alterations in aquatic vertebrates. This study examined the relationship between biomarkers at different organization levels and imazethapyr real-life route exposure in Boana pulchella adults. Frogs were exposed to imazethapyr-based formulation Pivot® H (10.59%) at concentrations representing possible acute routes: field runoff (S1:10 mg.L-1), exposure after direct foliar application (S2:100 mg.L-1) and during direct foliar application (S3:1000 mg.L-1). Post-exposure, endpoints levels were evaluated: organism alterations, biochemical activities and cytogenetic assays. Forty-eight hours post-exposure, antioxidant enzymes decrease, micronuclei induction and DNA damage were observed in all scenarios, while cholinesterase activity increase and body condition reduction were observed in frog-exposed to S3. Ninety-six hours post-exposure, frogs showed glutathione-S-transferase inhibition in S1, micronuclei induction in S2 and S3, and DNA-damage increase in S3. Herbicides routes of exposures in real-life could indicate that authorized applications have a risk to amphibian populations.

Multiple Level Effects of Imazethapyr on Leptodactylus latinasus (Anura) Adult Frogs.

Imazethapyr is an herbicide that is used in a variety of crops worldwide, including soybean and corn. The aim of the present study was to evaluate the biomarkers responses of adult Leptodactylus latinasus exposed to the formulation Pivot® H (10.59% imazethapyr) in the laboratory at concentrations and under conditions that simulate two potential field exposure scenarios: an immersion in field runoff (Scenario 1: 10 mg/L) and a direct exposure to the droplets emitted by spray noozles (Scenario 2: 1000 mg/L). In both scenarios, the experimental procedure involved completely immersing the frogs over a period of 15 s. Different endpoints were evaluated at several ecotoxicological levels 48 and 96 h after the herbicide exposure. These included individual (biometric indices and behavior alterations), histological (liver pigments and lesions), biochemical (catalase, glutathione system and cholinesterase activities) and genotoxic effects (micronuclei induction and nuclear abnormalities). Forty-eight hours after imazethapyr exposure, frogs submitted to Scenario 1 presented an inhibition of liver glutathione-S-transferase activity, whereas histological alterations and increased hepatic cholinesterase levels were observed in frogs exposed under Scenario 2. Ninety-six hours after exposure to the imazethapyr formulation, frogs from the Scenario 1 treatment presented a decrease in liver melanin and hemosiderin, increased hepatic catalase activity and micronuclei induction. For their part, frogs exposed to Scenario 2 presented a decrease in the hepatosomatic index, an increase in liver alterations, melanin reduction and micronuclei induction. The multivariate analysis enables correlations to be made between biomarkers of different organizational level in exposed anurans. Our result indicates that real exposure to imazethapyr formulations under field conditions may pose a risk to Leptodactylus latinasus populations living in the agroecosystems.

Advances in catalytic routes for the production of carboxylic acids from biomass: a step forward for sustainable polymers.

Polymers are ubiquitously present in our daily life because they can meet a wide range of needs and fields of applications. This success, based on an irresponsible linear consumption of plastics and the access to cheap oil, is creating serious environmental problems. Two lines of actions are needed to cope with them: to adopt a circular consumption of plastics and to produce renewable carbon-neutral monomers. This review analyses the recent advances in the chemocatalytic processes for producing biomass-derived carboxylic acids. These renewable carboxylic acids are involved in the synthesis of relevant general purpose and specialty polyesters and polyamides; some of them are currently derived from oil, while others can become surrogates of petrochemical polymers due to their excellent performance properties. Polyesters and polyamides are very suitable to be depolymerised to other valuable chemicals or to their constituent monomers, what facilitates the circular reutilisation of these monomers. Different types of carboxylic acids have been included in this review: monocarboxylic acids (like glycolic, lactic, hydroxypropanoic, methyl vinyl glycolic, methyl-4-methoxy-2-hydroxybutanoic, 2,5-dihydroxypent-3-enoic, 2,5,6-trihydroxyhex-3-enoic acids, diphenolic, acrylic and δ-amino levulinic acids), dicarboxylic acids (2,5-furandicarboxylic, maleic, succinic, adipic and terephthalic acids) and sugar acids (like gluconic and glucaric acids). The review evaluates the technology status and the advantages and drawbacks of each route in terms of feedstock, reaction pathways, catalysts and economic and environmental evaluation. The prospects and the new research that should be undertaken to overcome the main problems threatening their economic viability or the weaknesses that prevent their commercial implementation have also been underlined.

Indications and practice of diverting ileostomy after colorectal resection and anastomosis in ovarian cancer cytoreduction.

OBJECTIVE: To determine the factors related with diverting ileostomy performance after colorectal resection and anastomosis, in advanced ovarian cancer cytoreductive surgery. METHODS: We have previously demonstrated the risk factors associated with anastomotic leak after colorectal anastomosis: Advanced age at surgery, low serum albumin level, additional bowel resections, manual anastomosis and distance of the anastomosis from the anal verge. However, use of diverting ileostomy is strongly variable and depends on individual surgeon preferences and training. Eight hospitals participated in this retrospective study. Data of 695 patients operated for ovarian cancer with primary colorectal anastomosis were included (January 2010-June 2018). Fourteen pre-/intraoperatively defined variables were identified and analysed as justification factors for use of diverting ileostomy. RESULTS: The rate of diverting ileostomy in the entire cohort was 19.13% (133/695; range within individual centers 4.6-24.32%). Previous treatment with bevacizumab [OR 2.8 (1.3-6.1); p=0.01]; additional bowel resections [OR 3.0 (1.8-5.1); p<0.001]; extended operating time [OR 1.005 (1.003-1.006); p<0.001] and intra-operative red blood transfusion [OR 2.7 (1.4-5.3); p<0.001] were found to be independently associated with diverting ileostomy performance. Assuming a 7% AL rate cut-off, up to 51.8% of DI presented an AL risk below 7% and might have been spared. CONCLUSIONS: The risk factors that drive the gynecologic oncology surgeons to perform a diverting ileostomy, seem to differ from the actual risk factors that we have identified to be associated with postoperative anastomotic leak. Broader awareness of the risk factors that contribute to a higher perioperative risk profile, will facilitate a better risk stratification process and possibly avoid unnecessary stoma formation in ovarian cancer patients.

Evaluation of the intraoperative human papillomavirus test as a marker of early cure at 12 months after electrosurgical excision procedure in women with cervical high-grade squamous intraepithelial lesion: a prospective cohort study.

OBJECTIVE: To evaluate if the intraoperative human papillomavirus (IOP-HPV) test has the same prognostic value as the HPV test performed at 6 months after treatment of high-grade squamous intraepithelial lesion (HSIL) to predict treatment failure. DESIGN: Prospective cohort study. SETTING: Barcelona, Spain. POPULATION: A cohort of 216 women diagnosed with HSIL and treated with loop electrosurgical excision procedure (LEEP). METHODS: After LEEP, an HPV test was performed using the Hybrid Capture 2 system. If this was positive, genotyping was performed with the CLART HPV2 technique. The IOP-HPV test was compared with HPV test at 6 months and with surgical margins. MAIN OUTCOME MEASURE: Treatment failure. RESULTS: Recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, positive HPV 16 genotype, positive surgical margins and HSIL recurrence. Sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were 85.7, 80.8,24.0 and 98.8% and of the HPV test at 6 months were 76.9, 75.8, 17.2 and 98.0%. CONCLUSION: Intraoperative HPV test accurately predicts treatment failure in women with cervical intraepithelial neoplasia grade 2/3. This new approach may allow early identification of patients with recurrent disease, which will not delay the treatment. Genotyping could be useful in detecting high-risk patients. TWEETABLE ABSTRACT: IOP-HPV test accurately predicts treatment failure in women with CIN 2/3.

Price and income elasticities of demand for cigarette consumption: what is the association of price and economic activity with cigarette consumption in Spain from 1957 to 2016?

OBJECTIVES: Extensive empirical and theoretical studies have been devoted to analyzing the relationship between tobacco and income. The price and income elasticities of demand for cigarette consumption are the main focus of studies in this body of literature. However, few empirical studies exist that analyze how economic growth affects the cigarette market, and no one has studied the effects of economic expansions and recessions. Spain, as in the other countries of the European Union, has suffered a strong recession since 2008. Therefore, this article aims to detect if income elasticity takes different values in economic growth and recession and, in addition, to check whether price elasticity in Spain is consistent with previous studies. STUDY DESIGN: This is an observational epidemiological study. METHODS: In this article, the price and income elasticities of demand for cigarette consumption are measured for the Spanish cigarette market using time series data from 1957 to 2016 and by applying a non-linear autoregressive dynamics lag model. The novel specification proposed in this study is the determination of the possible effects of asymmetries in the economic shocks on cigarette consumption. RESULTS: Our results reveal that cigarette consumption maintains a notable asymmetric relationship. In particular, our results show that in expansion shocks, cigarette consumption increases (a 10% economic growth is associated with a 4.05% increase in cigarette consumption), whereas in recession shocks, cigarette consumption decreases dramatically, with a more pronounced pattern in recession phases than in expansion phases (a 10% economic decline is associated with a 58.16% decrease in cigarette consumption). On the other hand, price elasticity maintains the same behavior shown in the previous literature (a 10% price increase is associated with a 2% decrease in cigarette consumption). CONCLUSIONS: Higher cigarette prices are associated with decreased smoking. In addition, the economic recession helps in decreasing cigarette consumption. Therefore, it is strongly recommended that tax authorities have our results in mind before establishing health policies. If the authorities do not, it is possible that they will not obtain the expected results in terms of decreased tobacco consumption.

Risk factors for anastomotic leakage after colorectal resection in ovarian cancer surgery: A multi-centre study.

OBJECTIVE: To determine pre-/intraoperative risk factors for anastomotic leak after modified posterior pelvic exenteration (MPE) or colorectal resection in ovarian cancer and to create a practical instrument for predicting anastomotic leak risk. BACKGROUND: In advanced ovarian cancer surgery, there is rather limited published evidence, drawn from a small sample, providing information about risk factors for anastomotic leak. METHODS: Eight hospitals participated in this retrospective study. Data on 695 patients operated for ovarian cancer with primary anastomosis were included (January 2010-June 2018). Twelve pre-/intraoperative variables were analysed as potential independent risk factors for anastomotic leak. A predictive model was created to stablish the risk of anastomotic leak for a given patient. RESULTS: The anastomotic leak rate was 6.6% (46/695; range 1.7%-12.5%). A total of 457 patients were included in the final multivariate analysis. The following variables were found to be independently associated with anastomotic leakage: age at surgery (OR 1.046, 95% CI 1.013-1.080, p = 0.005), serum albumin level (OR 0.621, 95% CI 0.407-0.948, p = 0.027), one or more additional small bowel resections (OR 3.544, 95% CI 1.228-10.23, p = 0.019), manual anastomosis (OR 8.356, 95% CI 1.777-39.301, p = 0.007) and distance of the anastomosis from the anal verge (OR 0.839, 95% CI 0.726-0.971, p = 0.018). CONCLUSIONS: Due to the low incidence of AL in ovarian cancer patients, a restrictive stoma policy based on the presence of risk factors should be the actual recommendation. Hand-sewn anastomosis should be avoided.

Progression from selective to general involvement of hippocampal subfields in schizophrenia.

Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Data set 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Data set 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label seven hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Data set 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Data set 2. Consistent with this pattern, the longitudinal analysis of Data set 1 revealed progressive illness-related volume loss (~2-6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time.

High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas.

The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100-150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders.

Selection of reliable reference genes for RT-qPCR studies in Octopus vulgaris paralarvae during development and immune-stimulation.

The common octopus, Octopus vulgaris is a new candidate species for aquaculture. However, rearing of octopus paralarvae is hampered by high mortality and poor growth rates that impede its entire culture. The study of genes involved in the octopus development and immune response capability could help to understand the key of paralarvae survival and thus, to complete the octopus life cycle. Quantitative real-time PCR (RT-qPCR) is the most frequently tool used to quantify the gene expression because of specificity and sensitivity. However, reliability of RT-qPCR requires the selection of appropriate normalization genes whose expression must be stable across the different experimental conditions of the study. Hence, the aim of the present work is to evaluate the stability of six candidate genes: ß-actin (ACT), elongation factor 1-α (EF), ubiquitin (UBI), ß-tubulin (TUB), glyceraldehyde 3-phosphate dehydrogenase (GADPH) and ribosomal RNA 18 (18S) in order to select the best reference gene. The stability of gene expression was analyzed using geNorm, NormFinder and Bestkeeper, in octopus paralarvae of seven developmental stages (embryo, paralarvae of 0, 10, 15, 20, 30 and 34days) and paralarvae of 20days after challenge with Vibrio lentus and Vibrio splendidus. The results were validated by measuring the expression of PGRP, a stimuli-specific gene. Our results showed UBI, EF and 18S as the most suitable reference genes during development of octopus paralarvae, and UBI, ACT and 18S for bacterial infection. These results provide a basis for further studies exploring molecular mechanism of their development and innate immune defense.

Biological removal of pharmaceutical compounds using white-rot fungi with concomitant FAME production of the residual biomass.

The efficiency of two white-rot fungi (WRF), Trametes versicolor and Ganoderma lucidum, to eliminate thirteen pharmaceutical pollutants with concomitant biodiesel production from the accumulating lipid content after treatment, was examined. The removal efficiency was studied using both individual and combined strains. The results of individual and combined strains showed a total removal (100%) of diclofenac (DCF), gemfibrozil (GFZ), ibuprofen (IBP), progesterone (PGT) and ranitidine (RNT). Lower removals were achieved for 4-acetamidoantipyrin (AAA), clofibric acid (ACF), atenolol (ATN), caffeine (CFN), carbamazepine (CZP), hydrochlorothiazide (HCT), sulfamethoxazole (SMX) and sulpiride (SPD), although the combination of both strains enhanced the system's efficiency, with removals ranging from 15 to 41%. This increase of the removal efficiency when combining both strains was attributed to the interactions developed between them (i.e., competition). Results from enzymatic and cytochrome P450 examination suggested that both extracellular (laccase, MnP, LiP) and intracellular oxidation mechanisms participate in the biological removal of pharmaceuticals. On the other hand, the "green" potential of the fungal sludge generated during the biological removal process was assessed for biodiesel production by means of one-step direct (in-situ) transformation. This process consists of the simultaneous extraction and conversion of lipids contained in the sludge by catalytic esterification/transesterification using a robust acid heterogeneous Zr-SBA-15 catalyst. This catalytic system provided conversions close to 80% of the saponifiable fraction (including free fatty acids and glycerides) in the presence of high amount of impurities. The overall weight FAME yield, based on the initial dried mass, was close to 30% for both strains.

Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: towards a harmonized segmentation protocol.

OBJECTIVE: An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. METHOD: MRI scans of a single healthy adult human subject were acquired both at 3 T and 7 T. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement. RESULTS: The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail. CONCLUSIONS: The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies.

Toxic and genotoxic effects of the imazethapyr-based herbicide formulation Pivot H® on montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).

Acute lethal and sublethal toxicity of the imidazolinone imazethapyr (IMZT)-based commercial formulation herbicide Pivot H® (10.59% IMZT) was evaluated on Hypsiboas pulchellus tadpoles. Whereas mortality was used as the end point for lethality, frequency of micronuclei (MNs) and other nuclear abnormalities as well as DNA single-strand breaks evaluated by the single cell gel electrophoresis assay were employed to test genotoxicity. Behavioral, growth, developmental, and morphological abnormalities were also employed as sublethal end points. Mortality studies revealed equivalent LC50 (96h) values of 1.49mg/L (confidence limit, 1.09-1.63) and 1.55mg/L (confidence limit, 1.51-1.60) IMZT for Gosner stage (GS) 25 and GS36, respectively. Behavioral changes, i.e., irregular swimming and immobility, as well as a decreased frequency of keratodonts were observed. The herbicide increased the frequency of MNs in circulating erythrocytes of tadpoles exposed for 48h to the highest concentration assayed (1.17mg/L). However, regardless of the concentration of the herbicide assayed, an enhanced frequency of MNs was observed in tadpoles exposed for 96h. The herbicide was able to induce other nuclear abnormalities, i.e., blebbed and notched nuclei, only when tadpoles were exposed for 96h. In addition, we observed that exposure to IMZT within the 0.39-1.17mg/L range increased the genetic damage index in treatments lasting for both 48 and 96h. This study represents the first evidence of acute lethal and sublethal effects exerted by IMZT on amphibians. Finally, our findings highlight the properties of this herbicide that jeopardize nontarget living species exposed to IMZT.