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Paleoclimatic data are essential for fingerprinting the climate of the earth before the advent of modern recording instruments. They enable us to recognize past climatic events and predict future trends. Within this framework, a conceptual and logical model was drawn to physically implement a paleoclimatic database named WDB-Paleo that includes the paleoclimatic proxies data of marine sediment cores of the Mediterranean Basin. Twenty entities were defined to record four main categories of data: a) the features of oceanographic cruises and cores (metadata); b) the presence/absence of paleoclimatic proxies pulled from about 200 scientific papers; c) the quantitative analysis of planktonic and benthonic foraminifera, pollen, calcareous nannoplankton, magnetic susceptibility, stable isotopes, radionuclides values of about 14 cores recovered by Institute for Coastal Marine Environment (IAMC) of Italian National Research Council (CNR) in the framework of several past research projects; d) specific entities recording quantitative data on δ18O, AMS 14C (Accelerator Mass Spectrometry) and tephra layers available in scientific papers. Published data concerning paleoclimatic proxies in the Mediterranean Basin are recorded only for 400 out of 6000 cores retrieved in the area and they show a very irregular geographical distribution. Moreover, the data availability decreases when a constrained time interval is investigated or more than one proxy is required. We present three applications of WDB-Paleo for the Younger Dryas (YD) paleoclimatic event at Mediterranean scale and point out the potentiality of this tool for integrated stratigraphy studies.

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Reproductive and population-level responses are ecologically relevant diagnostic tools for revealing the cost of long-term tolerance to contaminants. Spatial density distribution, seasonal density, biomass, size frequency histograms and oocytes stages inPerinereis gualpensis(Polychaeta: Nereididae) from a highly anthropogenically impacted estuary (Lenga, south-central Chile) were compared with low-polluted estuaries (Tubul and Raqui). Spatial distribution showed that the highestP. gualpensisabundances occur in the central (middle) estuarine area, establishing them as suitable zones for comparisons of estuaries. Middle areas also showed differences among estuaries in terms of population and reproductive responses. Mature stage oocytes and juvenile recruitment limited to certain seasons and low adult survival led to significant low densities and biomasses in Lenga individuals (p < .05). Conversely, high densities and biomass, continuous recruitment and mature oocyte occurrence were observed in Tubul–Raqui estuaries. These results reflected population and reproductive differences among high- and low-polluted estuaries, suggesting that chronic pollution status in Lenga estuary is a factor to be considered when evaluating these responses. [ABSTRACT FROM PUBLISHER]

Sickle cell anemia (SCA) is the most common genetic disease worldwide. There are countries with massive public health programs for early detection of this condition. In the literature, several specific haplotypes or single-base polymorphic variants (SNPs) have been associated with the SCA prognosis., Objective: To demonstrate the significant correlation of SNPs relevant to the diagnosis and prognosis of SCA among different ethnic groups., Methodology: we analyzed population frequencies and correlations of several SNPs related to the prognosis of SCA (i.e., baseline fetal hemoglobin levels), response to hydroxyurea treatment, and response to other drugs used in the SCA treatment, collected from validated genomic databases among different ethnic groups., Results: The calculation of the Hardy-Weinberg equilibrium and the logistic regression was successful in classifying the ethnic groups as African (0 = 0.78, 1 = 0.89), and with a lower efficiency as American (AMR) (0 = 0.88, 1 = 0.00), East Asian (EAS) (0 = 0.80, 1 = 0.00), European (EUR) (0 = 0.79, 1 = 0.00), and South Asian (SAS) (0 = 0.80, 1 = 0.00)., Conclusions: The results extend those from previous reports and show that the profile of most of the SNPs studied presented statistically significant distributions among general ethnic groups, pointing to the need to carry out massive early screening of relevant SNPs for SCA in patients diagnosed with this disease. It is concluded that the application of a broad mutation detection program will lead to a more personalized and efficient response in the treatment of SCA.

Background: Sympathetic stress stimulates norepinephrine (NE) release from sympathetic nerves. During pregnancy, it modifies the fetal environment, increases NE to the fetus through the placental NE transporter, and affects adult physiological functions. Gestating rats were exposed to stress, and then the heart function and sensitivity to in vivo adrenergic stimulation were studied in male progeny., Methods: Pregnant Sprague-Dawley rats were exposed to cold stress (4 °C/3 h/day); rats' male progeny were euthanized at 20 and 60 days old, and their hearts were used to determine the β-adrenergic receptor (βAR) (radioligand binding) and NE concentration. The in vivo arterial pressure response to isoproterenol (ISO, 1 mg/kg weight/day/10 days) was monitored in real time (microchip in the descending aorta)., Results: Stressed male progeny presented no differences in ventricular weight, the cardiac NE was lower, and high corticosterone plasma levels were recorded at 20 and 60 days old. The relative abundance of β1 adrenergic receptors decreased by 36% and 45%, respectively ( p < 0.01), determined by Western blot analysis without changes in β2 adrenergic receptors. A decrease in the ratio between β1/β2 receptors was found. Displacement of 3 H-dihydroalprenolol (DHA) from a membrane fraction with propranolol (β antagonist), atenolol (β1 antagonist), or zinterol (β2 agonist) shows decreased affinity but no changes in the β-adrenergic receptor number. In vivo exposure to ISO to induce a β-adrenergic overload provoked death in 50% of stressed males by day 3 of ISO treatment., Conclusion: These data suggest permanent changes to the heart's adrenergic response after rat progeny were stressed in the uterus.

It has recently been demonstrated that aromatic bromination at C(2) abolishes all typical psychomotor, and some key prosocial effects of the entactogen MDMA in rats. Nevertheless, the influence of aromatic bromination on MDMA-like effects on higher cognitive functions remains unexplored. In the present work, the effects of MDMA and its brominated analog 2Br-4,5-MDMA (1 mg/kg and 10 mg/kg i.p. each) on visuospatial learning, using a radial, octagonal Olton maze (4 × 4) which may discriminate between short-term and long-term memory, were compared with their influence on in vivo long-term potentiation (LTP) in the prefrontal cortex in rats. The results obtained indicate that MDMA diminishes both short- and long-term visuospatial memory but increases LTP. In contrast, 2Br-4,5-MDMA preserves long-term visuospatial memory and slightly accelerates the occurrence of short-term memory compared to controls, but increases LTP, like MDMA. Taken together, these data are consistent with the notion that the modulatory effects induced by the aromatic bromination of the MDMA template, which abolishes typical entactogenic-like responses, might be extended to those effects affecting higher cognitive functions, such as visuospatial learning. This effect seems not to be associated with the increase of LTP in the prefrontal cortex.

The vesicular nucleotide transporter (VNUT) is critical for sympathetic co-transmission and purinergic transmission maintenance. To examine this proposal, we assessed whether the bisphosphonate clodronate, claimed as a potent in vitro VNUT blocker, modified spontaneous and/or the electrically evoked overflow of ATP/metabolites and NA from mesentery sympathetic perivascular nerve terminals. Additionally, in primary endothelial cell cultures derived from this tissue, we also evaluated whether clodronate interfered with ATP/metabolite cell outflow and metabolism of N 6 -etheno adenosine 5'-triphosphate (eATP), N 6 -etheno adenosine (eADO), and adenosine deaminase enzyme activity. Rat mesenteries were perfused in the absence or presence of .01-1,000 nM clodronate, 1-1,000 nM Evans blue (EB), and 1-10 µM DIDS; tissue perfusates were collected to determine ATP/metabolites and NA before, during, and after perivascular electrical nerve terminal depolarization. An amount of 1-1,000 nM clodronate did not modify the time course of ATP or NA overflow elicited by nerve terminal depolarization, and only 10 nM clodronate significantly augmented perfusate adenosine. Electrical nerve terminal stimulation increased tissue perfusion pressure that was significantly reduced only by 10 nM clodronate [90.0 ± 18.6 ( n = 8) to 35.0 ± 10.4 ( n = 7), p = .0277]. As controls, EB, DIDS, or reserpine treatment reduced the overflow of ATP/metabolites and NA in a concentration-dependent manner elicited by nerve terminal depolarization. Moreover, mechanical stimulation of primary endothelial cell cultures from the rat mesentery added with 10 or 100 nM clodronate increased adenosine in the cell media. eATP was metabolized by endothelial cells to the same extent with and without 1-1,000 nM clodronate, suggesting the bisphosphonate did not interfere with nucleotide ectoenzyme metabolism. In contrast, extracellular eADO remained intact, indicating that this nucleoside is neither metabolized nor transported intracellularly. Furthermore, only 10 nM clodronate inhibited (15.5%) adenosine metabolism to inosine in endothelial cells as well as in a commercial crude adenosine deaminase enzyme preparation (12.7%), and both effects proved the significance ( p < .05). Altogether, present data allow inferring that clodronate inhibits adenosine deaminase activity in isolated endothelial cells as in a crude extract preparation, a finding that may account for adenosine accumulation following clodronate mesentery perfusion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Donoso, Hernández, Barra and Huidobro-Toro.)

A crucial etiological component in fetal programming is early nutrition. Indeed, early undernutrition may cause a chronic increase in blood pressure and cardiovascular diseases, including stroke and heart failure. In this regard, current evidence has sustained several pathological mechanisms involving changes in central and peripheral targets. In the present review, we summarize the neuroendocrine and neuroplastic modifications that underlie maladaptive mechanisms related to chronic hypertension programming after early undernutrition. First, we analyzed the role of glucocorticoids on the mechanism of long-term programming of hypertension. Secondly, we discussed the pathological plastic changes at the paraventricular nucleus of the hypothalamus that contribute to the development of chronic hypertension in animal models of prenatal undernutrition, dissecting the neural network that reciprocally communicates this nucleus with the locus coeruleus. Finally, we propose an integrated and updated view of the main neuroendocrine and central circuital alterations that support the occurrence of chronic increases of blood pressure in prenatally undernourished animals.

A loss of neuroplastic control on nucleus accumbens (NAc) neuronal activity exerted by the medial prefrontal cortex (mPFC) through long-term depression (LTD) is involved in triggering drug-seeking behavior and relapse on several substances of abuse due to impaired glutamate homeostasis in tripartite synapses of the nucleus accumbens (NAc) core. To test whether this maladaptive neuroplastic mechanism underlies the addiction-like behavior induced in young mice by a high-fat diet (HFD), we utilized 28-days-old male mice fed HFD ad-libitum over 2 weeks, followed by 5 days of HFD abstinence. Control groups were fed a regular diet. HFD fed mice showed increased ΔFosB levels in the NAc core region, whereas LTD triggered from the mPFC became suppressed. Interestingly, LTD suppression was prevented by an i.p. injection of 100 mg/kg N-acetylcysteine 2.5 h before inducing LTD from the mPFC. In addition, excessive weight gain due to HFD feeding was diminished by adding 2mg/mL N-acetylcysteine in drinking water. Those results show a loss of neuroplastic mPFC control over NAc core activity induced by HFD consumption in young subjects. In conclusion, ad libitum consumption of HFD can lead to neuroplastic changes an addiction-like behavior that can be prevented by N-acetylcysteine, helping to decrease the rate of excessive weight gain.

Neuropathic pain reduces GABA and glycine receptor (GlyR)-mediated activity in spinal and supraspinal regions associated with pain processing. Interleukin-1β (IL-1β) alters Central Amygdala (CeA) excitability by reducing glycinergic inhibition in a mechanism that involves the auxiliary β-subunit of GlyR (βGlyR), which is highly expressed in this region. However, GlyR activity and its modulation by IL-1β in supraspinal brain regions under neuropathic pain have not been studied. We performed chronic constriction injury (CCI) of the sciatic nerve in male Sprague Dawley rats, a procedure that induces hind paw plantar hyperalgesia and neuropathic pain. Ten days later, the rats were euthanized, and their brains were sliced. Glycinergic spontaneous inhibitory currents (sIPSCs) were recorded in the CeA slices. The sIPSCs from CeA neurons of CCI animals show a bimodal amplitude distribution, different from the normal distribution in Sham animals, with small and large amplitudes of similar decay constants. The perfusion of IL-1β (10 ng/mL) in these slices reduced the amplitudes within the first five minutes, with a pronounced effect on the largest amplitudes. Our data support a possible role for CeA GlyRs in pain processing and in the neuroimmune modulation of pain perception.

Pannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and P2X7R-dependent nociceptive signaling in neuropathic rats require the activation of Panx1 channels to generate spinal central sensitization, as assessed by behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up potentiation) indexes. Administration of either a selective NMDAR agonist i.t. (NMDA, 2 mM) or a P2X7R agonist (BzATP, 150 μM) significantly increased both the mechanical hyperalgesia and the C-reflex wind-up potentiation, effects that were rapidly reversed (minutes) by i.t. administration of a selective pannexin 1 antagonist (10panx peptide, 300 μM), with the scores even reaching values of rats without neuropathy. Accordingly, 300 μM 10panx completely prevented the effects of NMDA and BzATP administered 1 h later, on mechanical hyperalgesia and C-reflex wind-up potentiation. Confocal immunofluorescence imaging revealed coexpression of Panx1 with NeuN protein in intrinsic dorsal horn neurons of neuropathic rats. The results indicate that both NMDAR- and P2X7R-mediated increases in mechanical hyperalgesia and C-reflex wind-up potentiation require neuronal Panx1 channel activation to initiate and maintain nociceptive signaling in neuropathic rats.

Background: Omega-3 fatty acids enhance immune response and modulate inflammation. This study aimed to determine the relationship between omega-3 fatty acid status and the severity of SARS-CoV-2 infection. Methods: Using a case−control design, we compared hospitalized patients with severe SARS-CoV-2 infection (cases, n = 73) with a group of ambulatory patients with mild SARS-CoV-2 infection (controls, n = 71). No patients were vaccinated against SARS-CoV-2. Results: The cases were older (p = 0.003), less educated (p = 0.001), had larger neck and smaller waist circumferences (p = 0.035 and p = 0.003, respectively), more frequently had diabetes (p < 0.001), consumed less fish (p < 0.001), consumed higher proportions of fried fish (p = 0.001), and had lower Omega-3 Index (O3I) values (p = 0.001) than controls. Cases had significantly lower rates of upper airway symptoms than controls. Lower O3I was associated with an increased likelihood of developing severe COVID-19 after adjusting for potential confounders (OR: 0.52; CI 0.32−0.86). Diabetes (OR: 4.41; CI 1.60−12.12), neck circumference (OR: 1.12; CI 1.03−1.21), and older age (OR: 1.03; CI 1.002−1.062) were also linked to COVID-19 severity. Fried fish consumption and low educational level were independent risk factors for severe COVID-19. Conclusions: This study suggests incorporating nutritional interventions to improve omega-3 status within nonpharmacological measures may help to reduce the severity of COVID-19.

The exposure to sympathetic stress during the entire period of gestation (4 °C/3 h/day) strongly affects the postnatal reproductive performance of the first generation of female offspring and their fertility capacity. The aim of this work was to determine whether this exposure to sympathetic stress affects the reproductive capacity of the next three generations of female offspring as adults. Adult female Sprague-Dawley rats were mated with males of proven fertility. We studied the reproductive capacity of the second, third, and fourth generations of female offspring (the percentage of pregnancy and the number and weight of female offspring). The estrus cycle activity of the progenies was studied, and a morphological analysis of the ovaries was carried out to study the follicular population. The second generation had a lower number of pups per litter and a 20% decrease in fertile capacity. The estrus cycle activity of the third generation decreased even more, and they had a 50% decrease in their fertile capacity, and their ovaries presented polycystic morphology. The fourth generation however, recovered their reproductive capacity but not the amount of newborns pups. Most probably, the chronic intrauterine exposure to the sympathetic stress programs the female gonads to be stressed in a stressful environment; since the fourth generation was the first born with no direct exposure to stress during development, it opens studies on intrauterine factors affecting early follicular development.

In this study, the occurrence and diffusive air-water exchange of POPs in Panguipulli Lake (39°42'S-72°13'W), an oligotrophic lake located in northern Patagonia (Chile), were determined. Air and water samples were collected between March and August 2017 (autumn-winter) and analyzed for concentrations of OCPs (α-HCH, β-HCH, γ-HCH and HCB) and PCBs (PCB-28,-52,-101,-118,-153,-158,-180) using gas chromatography coupled with an electron capture detector. The direction of air-water exchange direction was evaluated using a fugacity approach (ƒ w ƒ a -1 ), and net diffusive exchange fluxes (F AW , ng m -2 d -1 ) were also estimated. Total ∑ 4 OCP levels in air ranged from 0.31 to 37 pg m -3 , with a maximum for β-HCH, while Σ 7 PCB levels ranged from 3.05 to 43 pg m -3 . The most abundant congener was PCB-153, accounting for 60% of the total PCBs in air. Surface water ∑ 4 OCPs measured in this study ranged from 1.01 to 3.9 pg L -1 , with γ-HCH predominating, while surface water Σ 7 PCB levels ranged from 0.32 to 24 pg L -1 , with PCB-101, PCB-118, and PCB-153 presenting the highest levels. Diffusive air-water exchanges of HCB, α-HCH, γ-HCH and PCBs in the form of volatilization from the lake to air predominated; in contrast, for β-HCH net deposition dominated during the sampling period. Estimates suggested faster microbial degradation in the dissolved phase compared to atmospheric degradation for all analyzed POPs. Overall, these results could indicate that the oligotrophic lakes of northern Patagonia act as a secondary source of atmospheric POPs, mainly PCBs and some OCPs. This study is a first attempt to understand the occurrence of POPs in air and water, as well as their dynamics in oligotrophic lakes in the southern hemisphere., (Copyright © 2021. Published by Elsevier Inc.)

The aim of the present study was to evaluate the effects of exposure to Chilean pulp mill effluent extracts on developing postfertilized medaka embryos before and after sex definition relative to sex steroids (testosterone and 17beta-estradiol) and a wood phytoestrogen (beta-sitosterol). Our study included 2 waterborne semichronic exposure experiments, using a 24-h post fertilization (hpf) unknown-sex FLFII (female leucophore free) group and a second 72-hpf FLFII phenotypic sex-identified group (male autofluorescence leucophore) strain of medaka embryos. Chronic exposure of both FLFII strain embryo groups showed similar delay in time to hatch and decreased hatchability. Teratogenic responses such as vertebral malformation (fusion, incomplete formation, and lack of vertebral formation process) and pericardial edema were observed in both experiments, with a high percentage related to FLFII fluorescent leucophore-identified males. In addition, high mortality associated with severe malformations was observed in male and female embryos exposed to testosterone. Our research has demonstrated that exposure to Chilean mill effluent extracts caused severe male medaka embryotoxicity (in postfertilized embryos) before and after sex definition and, irrespective of the experimental group and effluent treatment, suggests partial removal following secondary treatment. Furthermore, differences in the severity and type of teratogenic effects with previous experiments (d-rR medaka strain), are associated with the unique phenotypes of this medaka mutant strain. Environ Toxicol Chem 2021;40:2297-2305. © 2021 SETAC., (© 2021 SETAC.)

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α 1 -adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α 1 -adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α 1 -adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α 1 -adrenoceptor density in whole hypothalamus and the expression levels of α 1A -adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α 1 -adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α 1A -adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular-coerulear excitatory interactions in prenatally undernourished young-adult rats.

To evaluate the physiological state of the wild fish inhabiting the Biobío River in South-Central Chile, susceptible to the chemical contamination from different sources, biochemical and physiological biomarkers were applied to wild fish Percilia irwini and Trichomycterus areolatus in situ. Fish caught in the Biobío river in low, medium, and high anthropic impacts areas, with different pollution degrees along the river. Ethoxyresorufin O-O deethylase (EROD) activity was evaluated in fish liver. Length, weight, Gonad weight and Liver weight, Physiological Index, and gill and liver histopathology were conducted. Physicochemical parameters (pH, Temperature, Conductivity, and TDS) were measured at each sampling site. The results indicated a deteriorating condition in the biological parameters of both species in a high anthropic zone. Fishes show an increase in physiological indices and EROD liver activity, agreeing with previous studies supporting evidence of reproductive change development as we move downstream the river. Also, an increase in histopathological lesions towards the lower third stretch of the Biobío River. The Integrated Index of Physiological Biomarkers (IPBR) indicated that sites located in the high impact area (P. irwini: BC: 4.09; RC: 3.38; PC: 3.50; SJ: 2.34 and T. areolatus BC: 6.06, PC: 5.37; SJ: 5.42) have the most detrimental environmental quality, compared to reference area. The integrated biomarker analysis demonstrates that the alterations observed are related to the high anthropic activity levels downstream from the sites with the least intervention, demonstrating that the IPBR used is a complementary tool for studies of the Environmental Effects Monitoring approach.

Interleukin-1β (IL-1β) is an important cytokine that modulates peripheral and central pain sensitization at the spinal level. Among its effects, it increases spinal cord excitability by reducing inhibitory Glycinergic and GABAergic neurotransmission. In the brain, IL-1β is released by glial cells in regions associated with pain processing during neuropathic pain. It also has important roles in neuroinflammation and in regulating NMDA receptor activity required for learning and memory. The modulation of glycine-mediated inhibitory activity via IL-1β may play a critical role in the perception of different levels of pain. The central nucleus of the amygdala (CeA) participates in receiving and processing pain information. Interestingly, this nucleus is enriched in the regulatory auxiliary glycine receptor (GlyR) β subunit (βGlyR); however, no studies have evaluated the effect of IL-1β on glycinergic neurotransmission in the brain. Hence, we hypothesized that IL-1β may modulate GlyR-mediated inhibitory activity via interactions with the βGlyR subunit. Our results show that the application of IL-1β (10 ng/ml) to CeA brain slices has a biphasic effect; transiently increases and then reduces sIPSC amplitude of CeA glycinergic currents. Additionally, we performed molecular docking, site-directed mutagenesis, and whole-cell voltage-clamp electrophysiological experiments in HEK cells transfected with GlyRs containing different GlyR subunits. These data indicate that IL-1β modulates GlyR activity by establishing hydrogen bonds with at least one key amino acid residue located in the back of the loop C at the ECD domain of the βGlyR subunit. The present results suggest that IL-1β in the CeA controls glycinergic neurotransmission, possibly via interactions with the βGlyR subunit. This effect could be relevant for understanding how IL-1β released by glia modulates central processing of pain, learning and memory, and is involved in neuroinflammation., Competing Interests: The authors hui declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Solorza, Oliva, Castillo, Amestica, Maldifassi, López-Cortés, Barra, Stehberg, Piesche, Sáez-Briones, González, Arenas-Salinas and Mariqueo.)

Polycyclic aromatic hydrocarbons (PAHs) are semivolatile organic compounds of environmental concern. This study aims to investigate the influence of local sources of anthropogenic PAHs and their air-water exchange fluxes in an oligotrophic North-Patagonian lake in Chile. The monitoring was carried out in Panguipulli Lake during a six-month period during the autumn and winter seasons (March to August 2017) using a high-volume air sampler and a pump system for water samples. We detected and quantified fifteen PAHs in the gas phase (mean ∑ 15 PAHs = 11.6 ng m -3 ) and dissolved water phase (mean ∑ 15 PAHs = 961.8 pg L -1 ). Methylphenanthrenes and pyrene dominated the concentrations of PAHs in the studied phases. To determine sources of PAHs we used the PAH ratios of Light Molecular Weight/Heavy Molecular Weight (∑LMW/∑HMW) and Phenanthrene/Anthracene (Phe/Ant). The PAH ratio results revealed a pyrogenic source. We estimated the air-water diffusive exchange fluxes and fugacity ratios for the studied compounds. In general, air-water diffusive exchanges of PAHs showed a net volatilization for the less hydrophobic (log K OW  < 4) and lighter PAHs (MW ≤ 170 g mol -1 ), and a net deposition trend for the more hydrophobic (log K OW 4-7) and higher molecular weight PAHs (MW ≥ 178 g mol -1 ). We found a significant correlation between log water/air fugacity ratios and log K OW of PAHs. Therefore, it is suggested that this oligotrophic lake acts as a sink by accumulating hydrophobic and mid-high molecular weight PAHs derived mainly from pyrogenic sources. This study is the first attempt to understand the sources and behavior of PAHs in oligotrophic lakes in the Southern Chile where information is scarce regarding the occurrence of PAHs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Dengue is a global health problem requiring an effective, safe dengue vaccine., Methods: We report the results of a phase II, randomized, open-label, single-center trial in adults aged 18 to 45 years in the United States designed to explore the effects of the Chimeric Yellow Fever Derived Tetravalent Dengue Vaccine (CYD-TDV, Dengvaxia) when administered on its designated schedule (months 0, 6, and 12) or on an accelerated dosing schedule (months 0, 2, and 6) and/or given before, or concomitantly with, a vaccine against Japanese encephalitis (JE)., Results: Based on dengue virus serotype-specific neutralizing antibody (NAb), the accelerated dosing schedule was comparable to the 0, 6, and 12-month schedule. Giving JE vaccine concurrently with CYD-TDV did not result in an increase in overall NAb titers. Immunophenotyping of peripheral blood mononuclear cells revealed an increase in activated CD8+ T cells after CYD-TDV vaccination, a phenomenon that was greatest for the JE vaccine primed., Conclusions: We conclude that an accelerated dosing schedule of CYD-TDV results in essentially equivalent dengue serotype-specific NAb titers as the currently used schedule, and there may be an early benefit in antibody titers and activated CD8+ T cells by the administration of the JE vaccine before CYD-TDV vaccination., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Moderate reduction of dietary protein (from 25% to 8% casein) in pregnant rats, calorically compensated by carbohydrates, gives rise to 'hidden prenatal malnutrition' (HPM) in the offspring since it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to decreased β-adrenoceptor signaling and brain derived neurotrophic factor (BDNF) levels in the pup' brain, altogether with defective cortical long-term potentiation (LTP) and lowered visuospatial memory performance. Since early postnatal environmental enrichment (EE) has been shown to exert plastic effects on the developing brain and neuroprotection both on cognition and on structural properties of the neocortex, in the present study we addressed the question of whether early postnatal EE during the lactation period could exert compensatory changes in the expression of ®-adrenergic receptors and BDNF in the neocortex of HPM rats, and if these effects are associated with an improvement or even a restore of both neocortical LTP in vivo and cognitive performance induced by HPM. The results obtained show that EE restored β-adrenoceptor density, BDNF expression and the ability to support LTP at prefrontal and occipital cortices of HPM rats. Besides, EE improved learning performance in visuospatial and operant conditioning tasks. The latter support the notion that adequate maternal protein nutrition during pregnancy is required for proper brain development and function. Further, the results highlight the role of environmental enrichment during early postnatal life in increasing later brain plasticity and exerting neuroprotection against brain deficits induced by prenatal malnutrition., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bioactive substances in the Biobio River Basin in Chile were examined by deploying Semi Permeable Membrane Devices (SPMDs) upstream and downstream of 4 pulp mill effluent discharges. Androgenic and estrogenic activity of SPMD extracts were then evaluated using in vitro fish sex steroid receptor binding assays. The results indicated the occurrence of estrogenic type compounds associated with one of the mill discharges. A significant correlation among the presence of these compounds, an increase in gonadosomatic index GSI and induction of hepatic EROD activity of two native fish species was observed. However, no significant presence of mature oocytes in female gonads was detected. Although EROD induction was observed in sites impacted by mill effluents, an increase of its activity occurred towards the downstream areas, suggesting other non-mill sources. More research is needed to understand the environmental changes in context of the new technological improvements in treatment systems to MBBR (Moving Bed Biofilm Reactor) recently implemented by the pulp mill industries., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Environmental concentrations of Pb have been increased due to anthropogenic activities, which have provoked the released of this element to the environment in large amounts. To understand how Pb behaves in remote southern marine ecosystems, we measured Pb concentrations and isotope ratios in biota from coastal marine ecosystems of the Chilean Patagonia and the Antarctic Peninsula area. Lead concentrations in the aquatic organisms ranged from 0.02 to 1.19 mg kg -1 d.w. In Patagonia, higher Pb levels were found in fish than in invertebrates (crab, shrimp, porifera, limpet and shellfish). In comparison with the baseline reference values from other parts of the world, fishes exhibited lower Pb levels. The results of Pb isotopic compositions indicated that the bioaccumulation of Pb in marine organisms come from different anthropogenic sources. These Pb levels might be useful for further studies that allow a deeper evaluation of sources for Pb contamination in these remote ecosystems., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The entactogen MDMA (3,4-methylenedioxy-methamphetamine, "Ecstasy") exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulation of typical entactogenic effects, using analogs derived from the MDMA template, are still not fully understood. Among many possibilities, aromatic halogenation of the phenylalkylamine moiety may favor distribution to the brain due to increased lipophilicity, and sometimes renders psychotropic substances of high affinity for their molecular targets and high potency in humans. In the present work, a new MDMA analog brominated at C(2) of the aromatic ring (2-Br-4,5-MDMA) has been synthesized and pharmacologically characterized in vitro and in vivo . First, binding competition experiments against the SERT-blocker citalopram were carried out in human platelets and compared with MDMA. Besides, its effects on platelet aggregation were performed in platelet enriched human plasma using collagen as aggregation inductor. Second, as platelets are considered an appropriate peripheral model for estimating central serotonin availability, the functional effects of 2-Br-4,5-MDMA and MDMA on ATP release during human platelet aggregation were evaluated. The results obtained showed that 2-Br-4,5-MDMA exhibits higher affinity for SERT than MDMA and fully abolishes both platelet aggregation and ATP release, resembling the pharmacological profile of citalopram. Subsequent in vivo evaluation in rats at three dose levels showed that 2-Br-4,5-MDMA lacks all key MDMA-like behavioral responses in rats, including hyperlocomotion, enhanced active avoidance conditioning responses and increased social interaction. Taken together, the results obtained are consistent with the notion that 2-Br-4,5-MDMA should not be expected to be an MDMA-like substrate of SERT, indicating that aromatic bromination at C(2) modulates the pharmacodynamic properties of the substrate MDMA, yielding a citalopram-like compound.