Early-life adversity increases anxiety-like behavior and modifies synaptic protein expression in a region-specific manner.

Early-life adversity (ELA) can induce persistent neurological changes and increase the risk for developing affective or substance use disorders. Disruptions to the reward circuitry of the brain and pathways serving motivation and emotion have been implicated in the link between ELA and altered adult behavior. The molecular mechanisms that mediate the long-term effects of ELA, however, are not fully understood. We examined whether ELA in the form of neonatal maternal separation (MatSep) modifies behavior and synaptic protein expression in adults. We hypothesized that MatSep would affect dopaminergic and glutamatergic signaling and enhance sensitivity to methamphetamine (Meth) reward or increase anxiety. Male Wistar rats were subjected to MatSep for 180 min/d on postnatal days (PND) 2-14 and allowed to grow to adulthood (PND 60) with no further manipulation. The hippocampus (Hipp), medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and caudate putamen (CPu) were isolated from one subgroup of animals and subjected to Western blot and protein quantitation for tyrosine hydroxylase (TH), α-synuclein (ALPHA), NMDA receptor (NMDAR), dopamine receptor-1 (D1) and -2 (D2), dopamine transporter (DAT), and postsynaptic density 95 (PSD95). Separate group of animals were tested for anxiety-like behavior and conditioned place preference (CPP) to Meth at 0.0, 0.1, and 1.0 mg/kg doses. MatSep rats displayed an increase in basal levels of anxiety-like behavior compared to control animals. MatSep rats also demonstrated CPP to Meth, but their responses did not differ significantly from controls at any drug dose. Increased NMDAR, D2, and ALPHA expression was observed in the NAc and CPu following MatSep; D2 and ALPHA levels were also elevated in the mPFC, along with DAT. MatSep rats had reduced D1 expression in the mPFC and Hipp, with the Hipp also showing a reduction in D2. Only the CPu showed elevated TH and decreased DAT expression levels. No significant changes were found in PSD95 expression in MatSep rats. In conclusion, ELA is associated with long-lasting and region-specific changes in synaptic protein expression that diminish dopamine neurotransmission and increase anxiety-like behavior in adults. These findings illustrate potential mechanisms through which ELA may increase vulnerability to stress-related illness.

Response to osmotic stress and temperature of the fungus Ustilago maydis.

Ustilago maydis is a fungal pathogen which is exposed during its life cycle to both abiotic and biotic stresses before and after the infection of maize. To cope with extreme environmental changes, microorganisms usually accumulate the disaccharide trehalose. We have investigated both the accumulation of trehalose and the activity of trehalase during the adaptation of U. maydis haploid cells to thermal, sorbitol, and NaCl stresses. Sorbitol and sodium chloride induced sustained accumulation of trehalose, while a transient increase was observed under heat stress. Sorbitol stressed cells showed higher trehalase activity compared with control cells and to those stressed by NaCl and high temperature. Addition of cycloheximide, a protein synthesis inhibitor, did not affect the trehalose accumulation during the first 15 min, but basal levels of trehalose were reached after the second period of 15 min. The proteomic analysis of the response of U. maydis to temperature, sorbitol, and salt stresses indicated a complex pattern which highlights the change of 18 proteins involved in carbohydrate and amino acid metabolism, protein folding, redox regulation, ion homeostasis, and stress response. We hypothesize that trehalose accumulation during sorbitol stress in U. maydis might be related to the adaptation of this organism during plant infection.

Psychological and neurobiological aspects of suicide in adolescents: Current outlooks.

Suicidality is one of the leading causes of death among young adults in the United States and represents a significant health problem worldwide. The suicide rate among adolescents in the United States has increased dramatically in the latest years and has been accompanied by considerable changes in youth suicide, especially among young girls. Henceforth, we need a good understanding of the risk factors contributing to suicidal behavior in youth. An explanatory model for suicidal behavior that links clinical and psychological risk factors to the underlying neurobiological, neuropsychological abnormalities related to suicidal behavior might predict to help identify treatment options and have empirical value. Our explanatory model proposes that developmental, biological factors (genetics, proteomics, epigenetics, immunological) and psychological or clinical (childhood adversities) may have causal relevance to the changes associated with suicidal behavior. In this way, our model integrates findings from several perspectives in suicidality and attempts to explain the relationship between various neurobiological, genetic, and clinical observations in suicide research, offering a comprehensive hypothesis to facilitate understanding of this complex outcome. Unraveling the knowledge of the complex interplay of psychological, biological, sociobiological, and clinical risk factors is highly essential, concerning the development of effective prevention strategy plans for suicidal ideation and suicide.

Discovery of GlyT2 Inhibitors Using Structure-Based Pharmacophore Screening and Selectivity Studies by FEP+ Calculations.

In recent years, mammalian Glycine transporter 2 (GlyT2) has emerged as a promising target for the development of compounds against chronic pain states. In our current work, we discovered a new set of promising hits that inhibit the glycine transporter at nano- and micromolar activity and have excellent selectivity over GlyT1 (as shown by in vitro studies) using a newly designed virtual screening (VS) protocol that combines a structure-based pharmacophore and docking screens with a success rate of 75%. Furthermore, the free energy perturbation calculations and molecular dynamics (MD) studies revealed the GlyT2 amino acid residues critical for the binding and selectivity of both Glycine and our Hit1 compound. The FEP+ results well-matched with the available literature mutational data proving the quality of the generated GlyT2 structure. On the basis of these results, we propose that our hit compounds may lead to new chronic pain agents to address unmet and challenging clinical needs.

Extended access to methamphetamine self-administration up-regulates dopamine transporter levels 72 hours after withdrawal in rats.

Previous studies have demonstrated that there are persistent changes in dopamine systems following withdrawal from methamphetamine (METH). This study examined changes in striatal dopamine transporter (DAT), tyrosine hydroxylase (TH) and dopamine receptor 2 (D2) 72 h after withdrawal from METH intravenous self- administration (IVSA). Rats were given limited (1h) or extended (6h) access to METH IVSA (0.05 mg/kg/0.1 ml infusion) for 22 days. Controls did not receive METH IVSA. The rats given extended access to IVSA displayed higher METH intake during the first hour of drug access compared to rats given limited access. Extended access to METH also produced a concomitant increase in striatal DAT levels relative to drug-naïve controls. There were no changes in TH or D2 levels across groups. Previous studies have reported a decrease in striatal DAT levels during protracted periods (>7 days) of withdrawal from METH IVSA. This study extends previous work by showing an increase in striatal DAT protein expression during an earlier time point of withdrawal from this drug. These results are an important step toward understanding the dynamic changes in dopamine systems that occur during different time points of withdrawal from METH IVSA.

¿Afecta el apoyo temprano la estabilidad de la rodilla en cirugía reconstructiva de esquinas? Estudio clinico comparativo aleatorizado / Does the early support affect knee stability in corner reconstructive surgery?

Introducción: El objetivo de este estudio fue comparar en un grupo de pacientes sometidos a cirugía reconstructiva de las esquinas postero medial (EPM), y posterolateral de la rodilla (EPL), el efecto en la estabilidad medio-lateral con dos métodos de rehabilitación diferentes, en el que a un grupo de pacientes se les asigno aleatoriamente el apoyo temprano (grupo A) y a otros el apoyo tardío a partir de la 6 semana (Grupo B) de la extremidad intervenida. Métodos: Estudio prospectivo donde se incluyeron a todos los pacientes tratados con cirugía reparativa/reconstructiva de la EPM y EPL de la rodilla, en el periodo comprendido entre enero del 2016 a Septiembre del 2017. El procedimiento quirúrgico utilizado en la EPM fue la plicatura del ligamento colateral medial/profundo y Ligamento Oblicuo Posterior (LOP), y en la EPL, la reconstrucción ligamentaria utilizando las técnicas de Arciero (no anatómica) y LaPrade (anatómica) según el caso. Todos los pacientes tuvieron asociado una reconstrucción del ligamento cruzado anterior y/o posterior. Resultados: De un total de 104 pacientes intervenidos por cirugía ligamentaria de rodilla, 31 pacientes cumplían con los criterios de inclusión, solo 20 pacientes completaron la evaluación y seguimiento en un periodo no menor a 6 meses del post operatorio. Diez pacientes conformaron el Grupo A o de apoyo temprano inmediato y 10 del Grupo B o de apoyo tardío. De los cuales 10 fueron del género masculino y 10 del género femenino con una edad que oscilo entre los 20 y 50 años con promedio de 35 años. Se evaluó a los 6 meses la estabilidad medio/lateral medida con las pruebas del bostezo lateral/medial en extensión y flexión de 30 grados, el dial test a 30 grados para la esquina posterolateral, el cajón Postero lateral y el dial test reverso para la esquina posteromedial. El estudio mostró que los pacientes que recibieron apoyo temprano tienen un riesgo mayor de afectarse la estabilidad lateral de la rodilla comparado con los que apoyaron después de la 6 semana. El estudio mostro que los pacientes a los que se les practico reconstrucción medial el apoyo no afecto su estabilidad a los 6 meses. Conclusiones: Este estudio soporta la hipótesis que el apoyo temprano de la extremidad intervenida en cirugía de esquinas posterolateral de la rodilla tiene un efecto negativo en la estabilidad articular lateral. Tipo de estudio: Serie de casos. Nivel de Evidencia: III

Introduction: The purpose of this study was to compare in a group of patients undergoing reconstructive postero- lateral and postero-medial knee corners, the effect of the medio-lateral stability with two different methods of rehabilitation in which a group of patients were assigned randomly early weight bearing and ( group A) and late weight bearing after 6 weeks (group B). Methods: The study included all patients treated with postero-lateral and postero-medial knee corner reconstruction between January 2016 and September 2017. Surgical technique in the postero-medial side consisted in a plication of the deep and superficial Medial Collateral Ligament (MCL) and Posterior oblique ligament (POL), and on the postero-lateral side using the Arciero or LaPrade technique according to the case. All patients had an anterior cruciate ligament (ACL) and/or Posterior Cruciate Ligament reconstruction. Results: 103 patients were operated for reconstructive knee ligament surgery in that period, 31 patients met the inclusion criteria and 20 patients completed the evaluation and follow up of 6 months post operatory. 10 patients formed the group A or early weight bearing and 10 patients group B or late weight bearing, 10 Men and 10 Women, in ages between 20-50, average 35. All patients were evaluated 6 months after the surgery with the standard test for postero-lateral and postero-medial instability; For the lateral side we used the opening test in flexion of 30 grades and in full extension, postero-lateral drawer test and dial test in 30 and 90 degrees and for the medial side we used the medial opening test in 30 degrees of flexion and full extension and the reverse Dial test. The study showed that patients undergoing postero-lateral corner reconstruction and early weight bearing have a higher risk of presenting residual lateral instability measure 6 months post op compared with the patients who their weight bearing was late. Conclusions: This study support the hypothesis of early weight bearing will produce a negative effect of the Lateral Stability in patients undergoing postero-lateral but no in patients undergoing to postero-medial plication. Type of study: Case series. Level of evidence: III

Healthy food procurement policy: an important intervention to aid the reduction in chronic noncommunicable diseases.

In 2010, unhealthy diets were estimated to be the leading risk for death and disability in Canada and globally. Although important, policies aimed at improving individual's skills in selecting and eating healthy foods has had a limited effect. Policies that create healthy eating environments are strongly recommended but have not yet been effectively and/or broadly implemented in Canada. Widespread adoption of healthy food procurement policies are strongly recommended in this policy statement from the Hypertension Advisory Committee with support from 15 major national health organizations. The policy statement calls on governments to take a leadership role, but also outlines key roles for the commercial and noncommercial sectors including health and scientific organizations and the Canadian public. The policy statement is based on a systematic review of healthy food procurement interventions that found them to be almost uniformly effective at improving sales and purchases of healthy foods. Successful food procurement policies are nearly always accompanied by supporting education programs and some by pricing policies. Ensuring access and availability to affordable healthy foods and beverages in public and private sector settings could play a substantive role in the prevention of noncommunicable diseases and health risks such as obesity, hypertension, and ultimately improve cardiovascular health.

Guía de instrucción en artroscopia de rodilla nivel intermedio / Instruction guide in knee arthroscopy: Intermediate level

La evolución de las técnicas quirúrgicas tradicionales y los modelos de formación de los cirujanos exigen cambios, por esta razón el centro de investigación y entrenamiento en cirugía de mínima invasión (CLEMI) ha desarrollado y aplicado modelos de enseñanza que permiten entrenar técnicas quirúrgicas mínimamente invasivas como la artroscopia de rodilla. CLEMI propone un modelo basado en simulación impartido en un ambiente controlado, estructurado y progresivo que vaya al ritmo individual de cada uno de los estudiantes. Inicialmente el estudiante encontrará conceptos teóricos de instrumental, equipos y ergonomía, posteriormente en la fase práctica usando un modelo sintético anatómico de la rodilla y finalmente usando un modelo biológico con el que se realizan ejercicios para desarrollar destrezas exigidas por las técnicas quirúrgicas. El entrenamiento en modelos bajo ambiente controlado disminuye el período de aprendizaje y eleva la competencia del estudiante.

Changes are needed due to the evolution of traditional surgical techniques and surgeon training models. For this reason the minimally invasive surgery research and training centre (CLEMI) has developed and applied teaching models to help in the training of minimally invasive surgical techniques, such as knee arthroscopy. CLEMI proposes a model based on simulation taught in a controlled, structured, and progressive environment that is tailored to the individual rhythm of each of the students. Initially, the student will encounter theoretical concepts of instruments, equipment and, ergonomics. Later, in the practical phase, an anatomical synthetic model of the knee will be used in the practical phase, followed by a biological model in order to perform exercises to develop the skills required for the surgical techniques. Training in models under a controlled environment decreases the learning period and increases student skills.

Comparison of stroke warning sign campaigns in Australia, England, and Canada.

BACKGROUND: Public awareness of the signs of stroke is essential to ensure that those affected by stroke arrive at the hospital in time for lifesaving therapies. It is unclear how well stroke awareness campaigns improve awareness of stroke signs and whether people translate this into action. METHODS: We evaluated stroke awareness campaigns conducted in England, Australia, and Canada using pre- and post-campaign surveys. We assessed the proportion of people who could name the main signs of stroke, and compared the proportion naming these correctly between locations. We also assessed whether people would call emergency services in the event of a stroke. Proportion responding correctly was compared using chi-square analysis. RESULTS: The amount spent on the campaigns was different in each country. The post-campaign survey was conducted among 400 people in Australia, 1921 in England, and 2703 in Canada. Sixty-eight per cent of people in Australia and 57% in Canada could name two or more signs of stroke (P < 0.001). After the campaign, knowledge of each of the elements of the campaign (face, arm, speech, time) was significantly greater in England than in Australia (P < 0.001 for each item). A high proportion of participants reported that they would call emergency services in the event of a stroke (97% in England, 90% in Australia, and 67% in Canada). CONCLUSION: Knowledge of stroke signs and the action to be taken can be improved with awareness campaigns. The effectiveness of these campaigns may be enhanced by spend on media, media mix, and key messages. It is critical to ensure that campaigns provide the clear and bold message that prompt action is an essential ingredient to reduce death and disability following stroke.

Building a strategy for obesity prevention one piece at a time: the case of sugar-sweetened beverage taxation.

Obesity is a major public health issue in Canada that is reaching historically high levels in spite of efforts, targeted primarily at individual behaviour, to promote changes in diet and physical activity. Urgency for change at the population level compels moving "upstream" toward multilevel, societal approaches for obesity prevention. Public health researchers, advocates and policy makers are increasingly recognizing the current food environment, including availability, pricing, and marketing of foods and beverages, promotes overconsumption of unhealthy food and beverage choices and have identified the food environment as a point for intervention for obesity prevention. In April 2011, a consensus conference with invited experts from research, policy and practice fields was held. The conference aimed to build consensus around policy levers to address environmental determinants of obesity, including next logical steps toward further policy action. Using economic policies, such as taxation of sugar-sweetened beverages (SSB), was discussed as one opportunity to promote healthy eating. This article reports on the consensus discussion that led to recommendations to tax sugar-sweetened beverages as one step in a multipronged comprehensive approach to obesity prevention. This recommendation is based on a synthesis of available evidence, including evidence regarding political feasibility, and potential impacts of a tax. In addition, we present additional primary research using current SSB consumption data to model the economic and behavioural impact of such a tax in Canada.