An invasive mussel is in trouble: How do glyphosate, 2,4-D and its mixture affect Limnoperna fortunei's survival?

Contamination and biological invasions are important factors that alter the functioning of freshwater systems. We carried out two experiments involving daily measurements of dissolved oxygen (DO) and Limnoperna fortunei mortality: 1) the impact of DO on mussel survival mediated by glyphosate, 2,4-D and their mixture was analysed in a 22-day indoor experiment (IE) under controlled conditions using microcosms with L. fortunei, with and without air supply; and 2) the effect of each herbicide and their mixture on mussel accumulated mortality was compared in a 18-day outdoor experiment (OE) using mesocosms without air supply, with and without L. fortunei. Results showed that glyphosate, alone or mixed affected L. fortunei survival both directly and indirectly. In IE we observed direct toxicity of glyphosate in treatments with air supply, with accumulated mortality of 20.0% for glyphosate and 10.0% for the mixture. In OE, L. fortunei deepened the changes in the patterns of DO fluctuations driven by the herbicides, which led to hypoxia in the system. The accumulated mortality was 46.7, 8.6 and 48.2% for glyphosate, 2,4-D and the mixture, respectively. This study contributes to the understanding of the mechanisms that control the invasion of L. fortunei in freshwater systems influenced by agrochemicals.

New findings on the effect of glyphosate on autotrophic and heterotrophic picoplankton structure: A microcosm approach.

Massive use of glyphosate-based herbicides in agricultural activities has led to the appearance of this herbicide in freshwater systems, which represents a potential threat to these systems and their communities. These herbicides can affect autotrophic and heterotrophic picoplankton abundance. However, little is known about glyphosate impact on the whole structure of these assemblages. Herein, we used an 8-day long microcosm approach under indoor controlled conditions to analyze changes in the structure of picoplankton exposed to a single pulse of glyphosate. The analyzed picoplankton correspond to two outdoor ponds with contrasting states: "clear" (chlorophyll-a = 3.48 µg L-1± 1.15; nephelometric turbidity, NTU = 1) and "turbid" (chlorophyll-a = 105.96 µg L-1 ± 15.3; NTU = 48). We evaluated herbicide impact on different picoplankton cytometric populations and further explored changes in bacterial dominant operational taxonomic units (OTUs) fingerprinting. We observed that glyphosate induced a drastic decrease in the abundance of phycocyanin-rich picocyanobacteria. Particularly, in the turbid system this effect resulted in an 85 % decrease in the abundance of the whole autotrophic picoplankton. Glyphosate also changed the structure of the heterotrophic fraction by means of changing bacterial dominant OTUs fingerprinting patterns in both systems and by shifting the relative abundances of cytometric groups in the clear scenario. These results demonstrate that upon glyphosate exposure picoplanktonic fractions face not only the already reported changes in abundance, but also alterations in the composition of cytometric groups and of bacterial dominant operational taxonomic units. This research provides suitable and still little explored tools to analyze agrochemical effects on picoplanktonic communities.

Differences in responsiveness and sensitivity to exogenous disruptors of the thyroid gland in three anuran species.

Anuran larval development comprises tissues/organs/systems that are: exclusively of larvae, able to be remodelled, and those of postmetamorphic stages. Also, the anuran larval development is characterized by inter-related parameters: time, size and shape forming part of growth and differentiation. The anuran metamorphosis starts when growth and differentiation achieve a threshold that differs among species since it is regulated by a number of external (environmental) and internal (hormonal) processes. Here we explore the consequences of exogenous disruptors on the thyroid gland (e.g., methimazole and thyroxine as T4) of three species by immersing premetamorphic tadpoles in predetermined concentrations of the disruptors for short periods (10 or 16 days). The species were Pleurodema borellii, Leptodactylus chaquensis, and Dermatonotus muelleri, which all breed in small temporary ponds during the summer, but differ in their ecomorphology. The experiments were conducted to evaluate the effects of these substances on larval development (based in Gosner larval stages), morphometric variation in body parameters (snout-vent and total length by larval stages), and thyroid gland histopathology at the end of the assays. In P. borelli and L. chaquensis, methimazole produces significant increment of size measurements (nonparametric Kruskal-Wallis, p < .05) during stages of digit differentiation and induced thyroid gland hypertrophy. In the three species, T4 exposure accelerated limb development and caused atrophy of thyroid gland. Prolonged T4 exposure in L. chaquensis and D. muelleri triggered metamorphic transformation in the gut and skull cartilages. Discussion about interspecific differences in responsiveness and sensitivity elucidates the importance of hormonal signals to morphological evolution.

Sex-dependent impact of Roundup on the rat gut microbiome.

A growing body of research suggests that dysbiosis of the gut microbiota induced by environmental pollutants, such as pesticides, could have a role in the development of metabolic disorders. We have examined the long-term effects of 3 doses of the Roundup(R) herbicide (made of glyphosate and formulants) on the gut microbiota in male and female Sprague-Dawley rats. A total of 141 bacteria families were identified by a 16S sequencing analysis approach. An OPLS-DA analysis revealed an increased Bacteroidetes family S24-7 and a decreased Lactobacillaceae in 8 out of the 9 females treated with 3 different doses of R (n = 3, for each dose). These effects were confirmed by repetitive sequence-based PCR fingerprinting showing a clustering of treated females. A culture-based method showed that R had a direct effect on rat gut microbiota. Cultivable species showed different sensitivities to R, including the presence of a high tolerant or resistant strain identified as Escherichia coli by 16S rRNA sequencing. The high tolerance of this E. Coli strain was explained by the absence of the EPSPS gene (coding glyphosate target enzyme) as shown by DNA amplification. Overall, these gut microbiome disturbances showed a substantial overlap with those associated with liver dysfunction in other studies. In conclusion, we revealed that an environmental concentration of R (0.1 ppb) and other two concentrations (400 ppm and 5,000 ppm) have a sex-dependent impact on rat gut microbiome composition and thus warrants further investigation.

Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels.

Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

Eficacia del apósito de plástico en aerosol Nobecutan. En la disminución del dolor asociado al trauma perineal tras el parto vaginal / Effectiveness of Nobecutan plastic dressing spray in reducing pain associated with perineal trauma after vaginal delivery

Objetivo. Comparar la diferencia en el dolor perineal entre las mujeres con apósito y sin apósito aplicado en el trauma perineal después de su reparación. Diseño. Estudio experimental controlado y aleatorizado. Lugar. Hospital Universitario Fundación Alcorcón, hospital público perteneciente a la Comunidad de Madrid. Muestra. En el estudio participaron ochenta y dos mujeres nulíparas, con episiotomía o desgarro perineal de segundo grado durante el parto. Método. Fueron asignadas al azar a cada uno de los grupos. Al grupo experimental se aplicó el apósito plástico directamente sobre la herida, mientras que al grupo control se le aplicó el apósito en la piel circundante a la herida. Mediciones de lo s resultados principales. Se preguntó a las participantes en relación con la sensación de dolor (escala 0-100) en reposo y durante diferentes actividades (como sentarse, caminar, micción o defecación) y con el uso de analgésicos a las 24 y 48 horas posparto. Resultados. Las mujeres tratadas con el apósito adhesivo en aerosol en la herida presentan menos dolor en reposo, al sentarse, deambulación, micción y defecación, a las 24 horas y a las 48 horas del parto, frente a las mujeres sin apósito adhesivo en la herida. Solo alcanza significación estadística (p = 0.024) la diferencia de medias del dolor en la micción a las 48 h, siendo la diferencia de 9.5 mm (IC 95 %; 1.2 a 17.4) y el tamaño de efecto (d de Cohen): d = 0.51. La necesidad de analgesia fue mayor en el grupo control que en el experimental, aunque no alcanzó significación estadística. Conclusión. Este estudio sugiere que la aplicación de apósito plástico en aerosol en el trauma perineal inmediatamente después de su reparación puede contribuir a disminuir las molestias en mujeres primíparas en las primeras 48 horas posparto (AU)

Objective. The aim of this study was to compare the difference in perineal pain between women with dressing spray versus no dressing spray applied after perineal repair. Design. Randomized controlled trial. Setting. The Hospital Universitario Fundación Alcorcón, a state hospital belonging to the Community of Madrid. Sample. The study involved eighty-two nulliparous women, who had undergone vaginal delivery with episiotomy or second-degree perineal laceration. Method. They were randomized. One group was applied the dressing spray directly on the wound (experimental group). The other group was applied the dressing spray on the skin around the wound (control group). Main outcome measures. The participants were questioned regarding the sensation of pain (0-100 scale) in repose and during different activities (such as sitting, walking, urinating and during defecation), and the use of painkillers at 24 and 48 hours postpartum. Results. Women treated with plastic dressing spray on the wound had less pain at repose, sitting, walking, urinating and during defecation at 24 hours and 48 hours postpartum. Only reached statistical significance the pain in urination at 48 hours. The difference was 9.5 mm (95 %; 1.2 to 17.4) and the effect size (Cohen’s d): d = 0.51). The need for analgesia was higher in the control group than in the experimental, but not significant differences being observed. Conclusions. Findings suggest that Nobecutan® plastic dressing spray can decrease perineal pain in nulliparous women in the first 48 hours after birth (AU)

[EFFECTIVENESS OF NOBECUTAN® PLASTIC DRESSING SPRAY IN REDUCING PAIN ASSOCIATED WITH PERINEAL TRAUMA AFTER VAGINAL DELIVERY]. / Eficacia del apósito plástico en aerosol Nobecutan®: EN LA DISMINUCIÓN DEL DOLOR ASOCIADO AL TRAUMA PERINEAL TRAS EL PARTO VAGINAL.

OBJECTIVE: The aim of this study was to compare the difference in perineal pain between women with dressing spray versus no dressing spray applied after perineal repair. DESIGN: Randomized controlled trial. SETTING: The Hospital Universitario Fundación Alcorcón, a state hospital belonging to the Community of Madrid. SAMPLE: The study involved eighty-two nulliparous women, who had undergone vaginal delivery with episiotomy or second-degree perineal laceration. METHOD: They were randomized. One group was applied the dressing spray directly on the wound (experimental group). The other group was applied the dressing spray on the skin around the wound (control group). MAIN OUTCOME MEASURES: The participants were questioned regarding the sensation of pain (0-100 scale) in repose and during different activities (such as sitting, walking, urinating and during defecation), and the use of painkillers at 24 and 48 hours postpartum. RESULTS: Women treated with plastic dressing spray on the wound had less pain at repose, sitting, walking, urinating and during defecation at 24 hours and 48 hours postpartum. Only reached statistical significance the pain in urination at 48 hours. The difference was 9.5 mm (95 %; 1.2 to 17.4) and the effect size (Cohen's d): d = 0.51). The need for analgesia was higher in the control group than in the experimental, but not significant differences being observed. CONCLUSIONS. Findings suggest that Nobecutan® plastic dressing spray can decrease perineal pain in nulliparous women in the first 48 hours after birth.

Assessing sub-optimal performance with the Test of Memory Malingering in Spanish speaking patients with TBI.

PRIMARY OBJECTIVES: To examine the clinical utility of the Test of Memory Malingering (TOMM) with US Spanish speaking patients diagnosed with traumatic brain injury (TBI). RESEARCH DESIGN: The demographic characteristics and neuropsychological functioning of Spanish speaking patients with TBI with valid vs suboptimal performance were compared. METHODS AND PROCEDURES: Demographic and neuropsychological data were retrospectively collected from charts of patients who underwent neurocognitive evaluations for clinical, med-legal and workmen's compensation purposes. Slick et al. criteria for malingered neurocognitive dysfunction were employed for clinical determination of the validity of participants' neuropsychological profiles, resulting in 16 valid and four suboptimal performers. MAIN OUTCOMES AND RESULTS: Valid performers obtained significantly greater scores than suboptimal performers on all trials of the TOMM and generally demonstrated less impairment across neuropsychological domains. The traditional cut-off score for the TOMM misclassified 18.8% of participants not suspected of malingering and lower levels of education appeared to reduce performance on this measure within the valid group. CONCLUSIONS: The current findings generally support the use of the TOMM with US primarily Spanish speaking patients diagnosed with TBI. However, caution is recommended when utilizing this measure with individuals having minimal levels of education. Future research with a larger sample and a non-neurological age- and education-matched sample should investigate lower cut-off scores for use with such patients.

Transepithelial transport of biperiden hydrochloride in Caco-2 cell monolayers.

The aim of this research has been to determine the biperiden hydrochloride permeability in Caco-2 model, in order to classify it based on the Biopharmaceutics Classification System (BCS). The World Health Organization (WHO) as well as many other authors have provisionally assigned the drug as BCS class I (high solubility-high permeability) or III (high solubility-low permeability), based on different methods. We determined biperiden BCS class by comparing its permeability to 5 pre-defined compounds: atenolol and ranitidine hydrochloride (low permeability group) and metoprolol tartrate, sodium naproxen and theophylline (high permeability group). Since biperiden permeability was higher than those obtained for high permeability drugs, we classified it as a BCS class I compound. On the other hand, as no differences were obtained for permeability values when apical to basolateral and basolateral to apical fluxes were studied, this drug cannot act as a substrate of efflux transporters. As a consequence of our results, we suggest that the widely used antiparkinsonian drug, biperiden, should be candidate for a waiver of in vivo bioequivalence studies.