Modulation of marble-burying behavior in adult versus adolescent C57BL/6J mice of both sexes by ethologically relevant chemosensory stimuli.

The marble-burying test is a pharmacologically validated paradigm used to study anxiety-like behaviors in laboratory rodents. Our laboratory has employed this assay as part of a behavioral screen to examine drug-induced negative affective states. Historically, the majority of our prior binge alcohol-drinking studies employed male subjects exclusively and reliably detected adolescent-adult differences in both basal and alcohol withdrawal-induced negative affect. However, age-related differences in marble-burying behavior were either absent or opposite those observed in our prior work when female subjects were included in the experimental design. As chemosensory cues from females are reported to be anxiolytic in males, the present study examined how odors from adult members of the opposite and same sex (obtained from soiled bedding) influence marble-burying behavior in adult, as well as adolescent, mice. Control studies examined the responsiveness of mice in the presence of novel neutral (vanilla) and aversive (tea tree) odors. Adult males exhibited reduced signs of anxiety-like behavior in the presence of female-soiled bedding, while adult females and adolescent mice of both sexes increased marble-burying behavior in the presence of both male- and female-soiled bedding. All mice exhibited increased burying in the presence of an aversive odor, while only adolescents increased marble-burying in response to the novel neutral odor. These data indicate sex by age interactions in the effects of volatile and nonvolatile odors from sexually-naive adult conspecifics on indices of anxiety-like behavior in the marble-burying test of relevance to the experimental design and procedural timing of experiments including sex as a biological variable.

CH bond activation in aromatic ketones mediated by iridium-tris(pyrazolyl)borate complexes.

Reaction of complex [TpMe2Ir(η4-CH2C(Me)C(Me)C2)] (1) with a series of aromatic ketones at 130 °C renders, by means of a selective ortho-CH activation, Ir(III)-metallacycles 2-5, which display an Ir-H bond. When [TpMe2Ir(C6H5)2N2] (6) is treated with 2-(trifluoromethyl)acetophenone and 2-fluoroacetophenone at 80 °C, the formation of dimeric (7) and trimeric architectures (8) is achieved through the meta- and para-CH activation of the aromatic ketone, respectively. The generation of complexes 2-5 is proposed to occur by the initial formation of Ir(III) η1-ketone adducts as key intermediates, followed by aromatic CH activations and the release of a butadiene ligand. The formation of complexes 7 and 8 involves an assisted process in which a metal center activation of the less sterically hindered C-H bond of the aromatic ketone takes place (releasing a benzene molecule), followed by the coordination of the carbonyl group, which generates the respective dimeric and trimeric structures. Complexes 7 and 8 are efficient catalysts for the transfer hydrogenation of ketones and aldehydes using isopropanol as the hydrogen source. All complexes have been fully characterized by NMR spectroscopy, FT-IR, elemental analysis and, in the cases of 7 and 8, X-ray crystallography. Details of the reaction conditions, isolation of the products, and proposals for the pathways of formation of complexes 2-5 and 7-8 are discussed.

A subchronic history of binge-drinking elicits mild, age- and sex-selective, affective, and cognitive anomalies in C57BL/6J mice.

Introduction: Alcohol abuse is a risk factor for affective and cognitive disorders, with evidence indicating that adolescent-onset excessive drinking can result in long-term deficiencies in emotional regulation and cognition, with females more susceptible to the negative emotional and cognitive consequences of excessive alcohol consumption. However, our prior examination of the interactions between sex and the age of drinking-onset indicated minimal signs of anxiety-like behavior during alcohol withdrawal, which may have related to the concurrent anxiety testing of male and female subjects. Methods: The present study addressed this potential confound by assaying for alcohol withdrawal-induced negative affect separately in males and females and expanded our investigation to include measures of spatial and working memory. Results: Following 14 days of drinking under modified Drinking-in-the-Dark procedures (10, 20, and 40% alcohol v/v; 2 h/day), adolescent and adult binge-drinking mice of both sexes exhibited, respectively, fewer and more signs of negative affect in the light-dark shuttle-box and forced swim tests than their water-drinking counterparts. Adolescent-onset binge-drinking mice also exhibited signs of impaired working memory early during radial arm maze training during early alcohol withdrawal. When tested in late (30 days) withdrawal, only adult female binge-drinking mice buried more marbles than their water-drinking counterparts. However, adolescent-onset binge-drinking mice exhibited poorer spatial memory recall in a Morris water maze. Discussion: These findings indicate that a subchronic (14-day) binge-drinking history induces mild, age- and sex-selective, changes in negative affect and cognition of potential relevance to understanding individual variability in the etiology and treatment of alcohol abuse and alcohol use disorder.

Measurement of 2D density profiles using a second-harmonic, dispersion interferometer.

A second-harmonic, dispersion interferometer is used to image large-area (≃5 cm2) plasma-jet and gas-jet density profiles. Achromatic telescopes magnify the diameters of the primary-laser beam (1064 nm) and its second-harmonic (532 nm) before probing the sample and de-magnify the beam diameters after the sample, where the primary beam transfers its phase change to a second, second-harmonic beam, allowing the sample's dispersive-phase change to be measured between two, orthogonally polarized second harmonic beams. The telescopes produce an azimuthally symmetric, dispersive-phase shift in the sample + background phase-change image and in the background phase-change image, which is removed by digital subtraction. The interferometer's performance was verified using standard-optical components as dispersive elements (BK7 lenses and wedge plates), resolving a minimum, phase-change sensitivity of Δϕmin ≳ 15 mrad and spatial resolution of Δxres ≃ 100 µm. The phase change produced by unknown-density objects (a pulsed-plasma-jet and a pulsed-gas-jet) was measured, and their data were used to recover the original, 2D density profiles using an inverse Abel transform: peak-number density, Ngas ≃ 6 × 1020 cm-3 and Ne ≃ 5 × 1016 cm-3; line-integrated density, ∫Ngasdl ∼ 2 × 1019cm-2 and ∫Nedl ∼ 1 × 1016cm-2. The techniques and methods developed here are scalable to even larger probe-beam diameters and frame-capture rates, leading to a diagnostic capability that is well-suited for applications involving the real-time measurement of density.

Evidence for Phosphorylation-Dependent, Dynamic, Regulation of mGlu5 and Homer2 in Expression of Cocaine Aversion in Mice.

Cocaine-induced changes in the expression of the glutamate-related scaffolding protein Homer2 influence this drug's psychostimulant and rewarding properties. In response to neuronal activity, Homer2 is phosphorylated on S117/S216 by calcium-calmodulin kinase IIα (CaMKIIα), which induces a rapid dissociation of mGlu5-Homer2 scaffolds. Herein, we examined the requirement for Homer2 phosphorylation in cocaine-induced changes in mGlu5-Homer2 coupling, to include behavioral sensitivity to cocaine. For this, mice with alanine point mutations at (S117/216)-Homer2 (Homer2AA/AA ) were generated, and we determined their affective, cognitive and sensorimotor phenotypes, as well as cocaine-induced changes in conditioned reward and motor hyperactivity. The Homer2AA/AA mutation prevented activity-dependent phosphorylation of S216 Homer2 in cortical neurons, but Homer2AA/AA mice did not differ from wild-type (WT) controls with respect to Morris maze performance, acoustic startle, spontaneous or cocaine-induced locomotion. Homer2AA/AA mice exhibited signs of hypoanxiety similar to the phenotype of transgenic mice with a deficit in signal-regulated mGluR5 phosphorylation (Grm5AA/AA ). However, opposite of Grm5AA/AA mice, Homer2AA/AA mice were less sensitive to the aversive properties of high-dose cocaine under both place-conditioning and taste-conditioning procedures. Acute injection with cocaine caused dissociation of mGluR5 and Homer2 in striatal lysates from WT, but not Homer2AA/AA mice, suggesting a molecular basis for the deficit in cocaine aversion. These findings indicate that CaMKIIα-dependent phosphorylation of Homer2 gates the negative motivational valence of high-dose cocaine via regulation of mGlu5 binding, furthering an important role for dynamic changes in mGlu5-Homer interactions in addiction vulnerability.

Shining light on the transcriptome: Molecular regulatory networks leading to a fast-growth phenotype by continuous light in an environmentally sensitive teleost (Atherinopsidae).

Photoperiod can profoundly affect the physiology of teleost fish, including accelerated growth here defined as "fast growth phenotypes". However, molecular regulatory networks (MRNs) and biological processes being affected by continuous illumination and which allow some teleost species evident plasticity to thrive under this condition are not yet clear. Therefore, to provide a broad perspective of such mechanisms, Chirostoma estor fish were raised and sampled for growth under a simulated control (LD) 12 h Light: 12 h Dark or a continuous illumination (LL) 24 h Light: 0 h Dark since fertilization. The experiment lasted 12 weeks after hatching (wah), the time at which fish were sampled for growth, length, and whole-body cortisol levels. Additionally, 3 heads of fish from each treatment were used to perform a de novo transcriptome analysis using Next-Generation Sequencing. Fish in LL developed the fast growth phenotype with significant differences visible at 4 wah and gained 66% more mass by 12 wah than LD fish. Cortisol levels under LL were below basal levels at all times compared to fish in LD, suggesting circadian dysregulation effects. A strong effect of LL was observed in samples with a generalized down-regulation of genes except for Reactive Oxygen Species responses, genome stability, and growth biological processes. To our knowledge, this work is the first study using a transcriptomic approach to understand environmentally sensitive MRNs that mediate phenotypic plasticity in fish submitted to continuous illumination. This study gives new insights into the plasticity mechanisms of teleost fish under constant illumination.

Alcohol-Drinking Under Limited-Access Procedures During Mature Adulthood Accelerates the Onset of Cognitive Impairment in Mice.

A history of heavy drinking increases vulnerability to, and the severity of, Alzheimer's disease (AD) and related dementias, with alcohol use disorder identified as the strongest modifiable risk factor for early-onset dementia. Heavy drinking has increased markedly in women over the past 10 years, particularly in mature adult women during the coronavirus (COVID-19) pandemic. This is concerning as women are more sensitive to many alcohol-related disease states, including AD and related dementias. Herein, we conducted two studies to determine if a 1-month period of binge drinking during mature adulthood (i.e., 5-9 months of age) impairs spatial and working memory to a greater extent in female vs. male C57BL/6J (B6J) mice. The anxiogenic and cognitive-impairing effects of binge drinking were also compared between mature adult and old B6J mice (18 months of age) in a third study. Throughout, females consumed more alcohol than males, indicating that a sex difference in binge drinking persists into old age. Despite the sex difference in intake, we detected no consistent sex difference in our measures of alcohol withdrawal-induced anxiety during a behavioral test battery. Although mature adult females exhibited more cognitive deficits than males, the precise outcome exhibiting a female-selective effect varied across studies. Old mice drank lower amounts of alcohol than mature adult mice, yet their blood ethanol concentrations (BECs) were within error of the 80 mg/dl criterion for binge drinking, indicative of an age-related slowing of alcohol metabolism. As expected, 18-month-old controls exhibited more signs of cognitive impairment than their 6-month-old counterparts, and binge drinking history impaired the Morris water maze performance of mice of both ages. In contrast, binge drinking history impaired the radial arm maze performance of 6-month-old mice only, and the extent of the impairment was comparable to the behavior exhibited by the older mice. We conclude from our studies that: (1) both biological sex and the age of drinking onset are subject factors that impact voluntary alcohol consumption by mice into old age; (2) binge drinking during later life elicits a negative affective state that is relatively sex-independent; (3) binge drinking during both mature adulthood and old age impairs spatial learning and memory; (4) binge drinking during mature adulthood accelerates deficits in working memory; and (5) mature adult females tend to exhibit more alcohol-induced cognitive impairments than males. If relevant to humans, these findings suggest that binge-like drinking by older adult men and women induces a negative affective state and cognitive decline, but that mature adult women, in particular, may be more sensitive to both the immediate and persistent cognitive-impairing effects of heavy drinking.

Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains.

Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0-1.0 mg/kg) on alcohol drinking in both female and male mice from two genetically distinct C57BL/6 substrains. Under two different binge-drinking procedures, A33 pretreatment reduced alcohol intake in male and female mice of both substrains. In both drinking studies, there was no evidence for carry-over effects the next day; however, we did observe some sign of tolerance to A33's effect on alcohol intake upon repeated, intermittent, treatment (5 injections of 1.0 mg/kg, every other day). Pretreatment with 1.0 mg/kg of A33 augmented sucrose intake by C57BL/6NJ, but not C57BL/6J, mice. In mice with a prior history of A33 pretreatment during alcohol-drinking, A33 (1.0 mg/kg) did not alter spontaneous locomotor activity or basal motor coordination, nor did it alter alcohol's effects on motor activity, coordination or sedation. In a distinct cohort of alcohol-naïve mice, acute pretreatment with 1.0 mg/kg of A33 did not alter motor performance on a rotarod and reduced sensitivity to the acute intoxicating effects of alcohol. These data provide the first evidence that selective PDE4B inhibition is an effective strategy for reducing excessive alcohol intake in murine models of binge drinking, with minimal off-target effects. Despite reducing sensitivity to acute alcohol intoxication, PDE4B inhibition reduces binge alcohol drinking, without influencing behavioral sensitivity to alcohol in alcohol-experienced mice. Furthermore, A33 is equally effective in males and females and exerts a quantitatively similar reduction in alcohol intake in mice with a genetic predisposition for high versus moderate alcohol preference. Such findings further support the safety and potential clinical utility of targeting PDE4 for treating AUD.

Preclinical evidence to support repurposing everolimus for craving reduction during protracted drug withdrawal.

Cue-elicited drug-craving is a cardinal feature of addiction that intensifies (incubates) during protracted withdrawal. In a rat model, these addiction-related behavioral pathologies are mediated, respectively, by time-dependent increases in PI3K/Akt1 signaling and reduced Group 1 metabotropic glutamate receptor (mGlu) expression, within the ventromedial prefrontal cortex (vmPFC). Herein, we examined the capacity of single oral dosing with everolimus, an FDA-approved inhibitor of the PI3K/Akt effector mTOR, to reduce incubated cocaine-craving and reverse incubation-associated changes in vmPFC kinase activity and mGlu expression. Rats were trained to lever-press for intravenous infusions of cocaine or delivery of sucrose pellets and then subjected to tests for cue-reinforced responding during early (3 days) or late (30-46 days) withdrawal. Rats were gavage-infused with everolimus (0-1.0 mg/kg), either prior to testing to examine for effects upon reinforcer-seeking behavior, or immediately following testing to probe effects upon the consolidation of extinction learning. Single oral dosing with everolimus dose-dependently blocked cocaine-seeking during late withdrawal and the effect lasted at least 24 h. No everolimus effects were observed for cue-elicited sucrose-seeking or cocaine-seeking in early withdrawal. In addition, everolimus treatment, following initial cue-testing, reduced subsequent cue hyper-responsivity exhibited observed during late withdrawal, arguing a facilitation of extinction memory consolidation. everolimus' "anti-incubation" effect was associated with a reversal of withdrawal-induced changes in indices of PI3K/Akt1/mTOR activity, as well as Homer protein and mGlu1/5 expression, within the prelimbic (PL) subregion of the prefrontal cortex. Our results indicate mTOR inhibition as a viable strategy for interrupting heightened cocaine-craving and facilitating addiction recovery during protracted withdrawal.

Efecto del catéter de hemodiálisis en la permeabilidad de fístulas arteriovenosas / The impact of hemodialysis catheter on arteriovenous fistula permeability

Resumen Objetivo: Evaluar el impacto que tiene el uso de catéteres de hemodiálisis en la permeabilidad de fístulas arteriovenosas. Materiales y Método: Estudio observacional, analítico, tipo cohorte retrospectiva. Se calculó un tamaño muestral de 195 pacientes, seleccionados aleatoriamente a partir del total de pacientes diagnosticados con enfermedad renal crónica (ERC) terminal, a quienes se les realizó su primera fístula arteriovenosa (FAV) entre enero de 2014 y diciembre de 2018. Como variables resultado se consideraron la trombosis de FAV y el tiempo de permeabilidad. Para el análisis inferencial se utilizaron las pruebas de Chi cuadrado; RR (IC 95%); curvas Kaplan-Meier; regresión de Cox; considerando un valor de p significativo < 0,05. Resultados: El 52,3% utilizó catéter de hemodiálisis, de los cuales el 49,5% presentó trombosis de su FAV versus el 17,7% del grupo sin este antecedente (p < 0,001); estimándose en el análisis univariado un riesgo de trombosis 2,7 veces mayor en pacientes con catéter previo a la confección de su FAV (IC 95% 1,7 a 4,4). En el análisis multivariado, se identificó como único factor significativo el antecedente de catéter de hemodiálisis, estimándose que los pacientes usuarios de catéter previo a la confección de su FAV tienen 2,8 veces más riesgo de trombosis en el tiempo que quienes no utilizaron catéter (IC 95% 1,6 a 4,9), quienes además presentaron un tiempo de permeabilidad significativamente menor (p < 0,001) en comparación con pacientes sin antecedente de catéter (28,1 vs 43,9 meses). Conclusión: Identificamos el uso del catéter de hemodiálisis como un factor de riesgo de trombosis de fístulas arteriovenosas, afectando significativamente su permeabilidad en el tiempo.

Objective: To evaluate the effects of hemodialysis catheter on arteriovenous fistula (AVF) permeability. Materials and Method: We conducted a retrospective cohort study, including 195 patients randomly selected from all patients diagnosed with chronic renal failure, who had their first arteriovenous fistula between January 2014 and December 2018. The outcomes were arteriovenous fistula thrombosis and permeability. For data analysis we used Chi-square test; Relative-Risk (CI 95%); Kaplan-Meier analysis and Cox regression; p value less than 0.05 were considered as significant. Results: The 52.3% of the patients used hemodialysis catheter, from this group, the 49.5% had AVF thrombosis versus the 17.7% of the group without history of hemodialysis catheter (p < 0.001), estimating in the univariate analysis a risk of thrombosis 2.7 times higher in patients with catheter before the creation of their AVF (CI 95% 1.7 a 4.4), as well as, in the multivariate analysis the risk of AVF thrombosis was 2.8 times higher in this group of patients, being identified the history of hemodialysis catheter as the only significative risk factor for thrombosis. Additionally, the AVF permeability time in this group was significantly less (p < 0.001) than patients without history of hemodialysis catheter (28.1 vs 43.9 months). Conclusion: We identified the hemodialysis catheter as a risk factor of arteriovenous fistula thrombosis, decreasing significantly its permeability time.

Hnrnph1 is a novel regulator of alcohol reward.

BACKGROUND: Hnrnph1 is a validated quantitative trait gene for methamphetamine behavioral sensitivity that encodes for heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1). This RNA-binding protein is involved in all stages of RNA metabolism that impacts mesocorticolimbic dopamine neurotransmission to influence addiction-related behavior. METHODS: We characterized the alcohol behavioral phenotypes of mice heterozygous for a deletion in the first coding exon of Hnrnph1 (Hnrnph1+/-). We examined alcohol intake under both continuous- and limited-access procedures, as well as alcohol-induced place-conditioning. Follow-up studies examined genotypic differences in the psychomotor-activating and sedative-hypnotic effects of acute and repeated alcohol, and a behavioral test battery was employed to determine the effects of Hnrnph1 deletion on the manifestation of negative affect during alcohol withdrawal. RESULTS: Relative to wild-type (WT) controls, Hnrnph1+/- males exhibited blunted intake of high alcohol concentrations under both drinking procedures. Hnrnph1 deletion did not impact the conditioned rewarding properties of low-dose alcohol, but reversed the conditioned place-aversion elicited by higher alcohol doses (2 and 4 g/kg), with more robust effects in male versus female mice. No genotypic differences were observed for alcohol-induced locomotor activity. Hnrnph1+/- mice exhibited a modest increase in sensitivity to alcohol's sedative-hypnotic effects, but did not differ from WT mice with regard to tolerance to alcohol's sedative-hypnotic effects or alcohol metabolism, Inconsistent effects of Hnrnph1 deletion were observed in models for withdrawal-induced negative affect. CONCLUSIONS: These data identify Hnrnph1 as a novel, male-selective, driver of alcohol consumption and high-dose alcohol aversion that is potentially relevant to the neurobiology of alcohol abuse and alcoholism.

How long do people stick to a diet resolution? A digital epidemiological estimation of weight loss diet persistence.

OBJECTIVE: To use Internet search data to compare duration of compliance for various diets. DESIGN: Using a passive surveillance digital epidemiological approach, we estimated the average duration of diet compliance by examining monthly Internet searches for recipes related to popular diets. We fit a mathematical model to these data to estimate the time spent on a diet by new January dieters (NJD) and to estimate the percentage of dieters dropping out during the American winter holiday season between Thanksgiving and the end of December. SETTING: Internet searches in the USA for recipes related to popular diets over a 15-year period from 2004 to 2019. PARTICIPANTS: Individuals in the USA performing Internet searches for recipes related to popular diets. RESULTS: All diets exhibited significant seasonality in recipe-related Internet searches, with sharp spikes every January followed by a decline in the number of searches and a further decline in the winter holiday season. The Paleo diet had the longest average compliance times among NJD (5.32 ± 0.68 weeks) and the lowest dropout during the winter holiday season (only 14 ± 3 % dropping out in December). The South Beach diet had the shortest compliance time among NJD (3.12 ± 0.64 weeks) and the highest dropout during the holiday season (33 ± 7 % dropping out in December). CONCLUSIONS: The current study is the first of its kind to use passive surveillance data to compare the duration of adherence with different diets and underscores the potential usefulness of digital epidemiological approaches to understanding health behaviours.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística

Resumen La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

Incubation of Negative Affect during Protracted Alcohol Withdrawal Is Age-, but Not Sex-Selective.

A prior history of excessive drinking induces a negative affective state in both humans and laboratory rodents, the manifestation of which varies with the age of drinking-onset. In adolescent male mice, negative affect incubates over the course of a 30-day alcohol withdrawal period. In contrast, the negative affect exhibited by adult male mice is robust at 1 day withdrawal, but dissipates with the passage of time. As females tend to consume more alcohol than males, we aimed to explore the affective disturbances exhibited by adolescent and adult C57BL/6J mice of both sexes during more protracted alcohol withdrawal and to relate any behavioral changes observed to plasma corticosterone levels as a biochemical index of stress. Male and female, adolescent and adult, mice were subjected to 14 consecutive days of binge alcohol-drinking using a multi-bottle-choice Drinking-in-the-Dark (DID) procedure (5, 10, 20 and 40% v/v). Age- and sex-matched control mice consumed water only. On either withdrawal day 1 or 70, subgroups of animals were subjected a to 1-day behavioral test battery that included the light-dark box shuttle test, marble-burying test, and Porsolt forced swim test. As expected, adolescent mice consumed more alcohol than adults and females consumed more alcohol than males. However, despite binge-like levels of alcohol consumption, we detected relatively few signs of alcohol withdrawal-induced negative affect and there was no correlation between affective behavior and circulating corticosterone levels. We discuss these findings within the context of our published work, highlighting procedural differences that might account for the relatively weak effect of binge-drinking history upon anxiety and depressive-like behavior observed herein.

Discontinuous spirals of stability in an optically injected semiconductor laser.

We report a new kind of discontinuous spiral with stable periodic orbits in the parameter space of an optically injected semiconductor laser model, which is a combination of the intercalation of fish-like and cuspidal-like structures (the two normal forms of complex cubic dynamics). The spiral has a tridimensional structure that rolls up in at least three directions. A turn of approximately 2π radians along the spiral and toward the center increases the number of peaks in the laser intensity by one, which does not occur when traversing the discontinuities. We show that as we vary the linewidth enhancement factor (α), discontinuities are created (destroyed) through disaggregation (collapses) from (into) the so-called shrimp-like structures. Future experimental verification and applications, as well as theoretical studies to explain its origin and relation with homoclinic spirals that exist in its neighborhood, are needed.

Tricorn-like structures in an optically injected semiconductor laser.

This study reports the existence of tricorn-like structures of stable periodic orbits in the parameter plane of an optically injected semiconductor laser model (a continuous-time dynamical system). These tricorns appear inside tongue-like structures that are created through simple Shi'lnikov bifurcations. As the linewidth enhancement factor-α of the laser increases, these tongues invade the laser locking zone and extends over the zone of stable period-1 orbits. This invasion provokes a rich overlap dynamics of the parameter planes that produces an abundant multistability. As α increases, the tricorn exhibits a phenomenon of codimension-3 rotating in the clockwise and counterclockwise directions in the plane of the injected field rate K vs its detuning ω. We hope that the numerical evidence of the tricorns presented herein motivates the study of mathematical conditions for their genesis. We also encourage the experimental verification of these tricorn-like structures because our results also open new possibilities for optical switching between several different laser outputs in the neighborhood of these structures.

Silver nanoparticles are lethal to the ciliate model Tetrahymena and safe to the pike silverside Chirostoma estor.

Ciliate ectoparasites are one of the most important groups of pathogens in fish culture, and the traditional treatments are sometimes harmful to the fish and the environment. Thus, the search for novel compounds that are effective at low concentrations and safe for fish are necessary to optimise treatments in aquaculture. The antiprotozoal capacity of silver nanoparticles (AgNPs) against the ciliate Tetrahymena has been documented; however, their toxicity may vary with the synthesis methodology and nanoparticle size. The objectives of this study were a) to evaluate the acute toxicity in vitro of two AgNPs (Argovit™ and UTSA) on Tetrahymena sp., a biological model for ciliated ectoparasites of fish and b) to test the safety of lethal and higher doses of UTSA AgNPs for ciliates on the fish C. estor. Light microscopy and scanning electron microscopy (SEM) were used to determine whether AgNPs affected the structure of the cell surface of Tetrahymena. The mortality, histopathological alterations and metagenomics of the fish were used to determine the major effects of UTSA AgNPs. In Tetrahymena, the median lethal concentration (LC50) for Argovit™ was 2501 ± 1717 ng/L at 15 min and 796 ± 510 ng/L at 60 min, while the LC50 for UTSA AgNPs was 4 ± 2 and 1 ± 0.6 ng/L at 15 min and 60 min, respectively. A concentration of 3300 ng/L Argovit™ and 10.6 ng/L UTSA AgNPs for 15 and 60 min, respectively, was 100% effective against Tetrahymena. After 60 min of exposure to 0.25 and 0.50 ng/L UTSA AgNPs, the number of cilia significantly reduced, there were small holes on the cell surface, and the cellular membrane was ruptured. In fish exposed to lethal (10.6 ng/L) and higher (31.8 and 95.4 ng/L) doses of UTSA, the AgNPs did not affect fish survival after 96 h, and there were no signs of histopathological damage or gut microbial changes. This study is the first report on microscopic and ultrastructural changes in Tetrahymena after exposure to significantly low concentrations of UTSA AgNPs with antiprotozoal efficacy without evidence of harmful effects on fish. These results provide the basis for further studies of both pet aquarium and commercial fish that may validate these findings at a larger experimental scale, taking into account AgNPs bioaccumulation, safety for human consumption and environmental impact.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística / Chilean consensus for the integral care of children and adults with cystic fibrosis

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Initial results from the New Horizons exploration of 2014 MU69, a small Kuiper Belt object.

The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU69, a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU69's origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes.