Brain connectivity changes to fast versus slow dopamine increases.

The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced dopamine increases impacts brain network communication remains unresolved. We manipulated route of MP administration to generate fast versus slow dopamine increases. We hypothesized that fast versus slow dopamine increases would result in a differential pattern of global brain connectivity (GBC) in association with regional levels of dopamine D1 receptors, which are critical for drug reward. Twenty healthy adults received MP intravenously (0.5 mg/kg; fast dopamine increases) and orally (60 mg; slow dopamine increases) during simultaneous [11C]raclopride PET-fMRI scans (double-blind, placebo-controlled). We tested how GBC was temporally associated with slow and fast dopamine increases on a minute-to-minute basis. Connectivity patterns were strikingly different for slow versus fast dopamine increases, and whole-brain spatial patterns were negatively correlated with one another (rho = -0.54, pspin < 0.001). GBC showed "fast>slow" associations in dorsal prefrontal cortex, insula, posterior thalamus and brainstem, caudate and precuneus; and "slow>fast" associations in ventral striatum, orbitofrontal cortex, and frontopolar cortex (pFDR < 0.05). "Fast>slow" GBC patterns showed significant spatial correspondence with D1 receptor availability (estimated via normative maps of [11C]SCH23390 binding; rho = 0.22, pspin < 0.05). Further, hippocampal GBC to fast dopamine increases was significantly negatively correlated with self-reported 'high' ratings to intravenous MP across individuals (r(19) = -0.68, pbonferroni = 0.015). Different routes of MP administration produce divergent patterns of brain connectivity. Fast dopamine increases are uniquely associated with connectivity patterns that have relevance for the subjective experience of drug reward.

Disrupted brain state dynamics in opioid and alcohol use disorder: attenuation by nicotine use.

Substance use disorder (SUD) is a chronic relapsing disorder with long-lasting changes in brain intrinsic networks. While most research to date has focused on static functional connectivity, less is known about the effect of chronic drug use on dynamics of brain networks. Here we investigated brain state dynamics in individuals with opioid use (OUD) and alcohol use disorder (AUD) and assessed how concomitant nicotine use, which is frequent among individuals with OUD and AUD, affects brain dynamics. Resting-state functional magnetic resonance imaging data of 27 OUD, 107 AUD, and 137 healthy participants were included in the analyses. To identify recurrent brain states and their dynamics, we applied a data-driven clustering approach that determines brain states at a single time frame. We found that OUD and AUD non-smokers displayed similar changes in brain state dynamics including decreased fractional occupancy or dwell time in default mode network (DMN)-dominated brain states and increased appearance rate in visual network (VIS)-dominated brain states, which were also reflected in transition probabilities of related brain states. Interestingly, co-use of nicotine affected brain states in an opposite manner by lowering VIS-dominated and enhancing DMN-dominated brain states in both OUD and AUD participants. Our finding revealed a similar pattern of brain state dynamics in OUD and AUD participants that differed from controls, with an opposite effect for nicotine use suggesting distinct effects of various drugs on brain state dynamics. Different strategies for treating SUD may need to be implemented based on patterns of co-morbid drug use.

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review.

Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); however, PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH. Chronic use of these substances disrupts brain function, structure, and cognition. PLWH with SUD have poor health outcomes driven by complex interactions between biological, neurocognitive, and social factors. Here we review the effects of comorbid HIV and psychostimulant use disorders by discussing the distinct and common effects of HIV and chronic cocaine and methamphetamine use on behavioral and neurological impairments using evidence from rodent models of HIV-associated neurocognitive impairments (Tat or gp120 protein expression) and clinical studies. We also provide a biopsychosocial perspective by discussing behavioral impairment in differentially impacted social groups and proposing interventions at both patient and population levels.

Ketamine use disorder: preclinical, clinical, and neuroimaging evidence to support proposed mechanisms of actions.

Ketamine, a noncompetitive NMDA receptor antagonist, has been exclusively used as an anesthetic in medicine and has led to new insights into the pathophysiology of neuropsychiatric disorders. Clinical studies have shown that low subanesthetic doses of ketamine produce antidepressant effects for individuals with depression. However, its use as a treatment for psychiatric disorders has been limited due to its reinforcing effects and high potential for diversion and misuse. Preclinical studies have focused on understanding the molecular mechanisms underlying ketamine's antidepressant effects, but a precise mechanism had yet to be elucidated. Here we review different hypotheses for ketamine's mechanism of action including the direct inhibition and disinhibition of NMDA receptors, AMPAR activation, and heightened activation of monoaminergic systems. The proposed mechanisms are not mutually exclusive, and their combined influence may exert the observed structural and functional neural impairments. Long term use of ketamine induces brain structural, functional impairments, and neurodevelopmental effects in both rodents and humans. Its misuse has increased rapidly in the past 20 years and is one of the most common addictive drugs used in Asia. The proposed mechanisms of action and supporting neuroimaging data allow for the development of tools to identify 'biotypes' of ketamine use disorder (KUD) using machine learning approaches, which could inform intervention and treatment.

Novel Magnetic Polymeric Filters with Laccase-Based Nanoparticles for Improving Congo Red Decolorization in Bioreactors.

In this work, five different magnetic biofilters, containing magnetic nanoparticles (142 nm), immobilized laccase on nanoparticles (190 nm) and permanent magnetic elements, such as neodymium magnets and metallic meshes, were designed, manufactured and tested. The five types of filters were compared by measuring the decolorization of Congo Red dye inside bioreactors, the half-life of the filters and the amount of magnetic nanoparticle and enzyme lost during multiple cycles of operation. Filters containing laccase immobilized on magnetite (Laccase-magnetite), permanent magnets and metallic mesh presented the highest Congo Red decolorization (27%) and the largest half-life among all types of filters (seven cycles). The overall dye decolorization efficiencies were 5%, 13%, 17%, 23%, and 27% for the paper filter, paper filter with magnetite, paper filter with Laccase-magnetite, paper filter with Laccase-magnetite with magnets and paper filter with Laccase-magnetite with magnets and metallic mesh, respectively. Although the highest losses of magnetite occurred when using the filters containing magnets (57 mg), the use of permanent magnetic elements in the filters increased the half-life of the filter three-fold compared to the filters without enzymatic properties and two-fold compared to the filters with Laccase-magnetite. Results indicate that the novel use of permanent magnetic elements improved the nanoparticle retention in the filters and promoted the mass transfer between the dye and the biocatalyst to enhance wastewater treatment.

Continuous Nanoprecipitation of Polycaprolactone in Additively Manufactured Micromixers.

The polymeric ouzo effect is an energy-efficient and robust method to create nanoparticles with biologically degradable polymers. Usually, a discontinuous or semi-continuous process is employed due to its low technical effort and the fact that the amount of dispersions needed in a laboratory is relatively small. However, the number of particles produced in this method is not enough to make this process economically feasible. Therefore, it is necessary to improve the productivity of the process and create a controllable and robust continuous process with the potential to control parameters, such as the particle size or surface properties. In this study, nanoparticles were formulated from polycaprolactone (PCL) in a continuous process using additively manufactured micromixers. The main goal was to be able to exert control on the particle parameters in terms of size and zeta potential. The results showed that particle size could be adjusted in the range of 130 to 465 nm by using different flow rates of the organic and aqueous phase and varying concentrations of PCL dissolved in the organic phase. Particle surface charge was successfully shifted from a slightly negative potential of -14.1 mV to a negative, positive, or neutral value applying the appropriate surfactant. In summary, a continuous process of nanoprecipitation not only improves the cost of the method, but furthermore increases the control over the particle's parameters.

Comparison of Acetaminophen Degradation by Laccases Immobilized by Two Different Methods via a Continuous Flow Microreactor Process Scheme.

The presence of micropollutants in wastewater is one of the most significant environmental challenges. Particularly, pollutants such as pharmaceutical residues present high stability and resistance to conventional physicochemical and biological degradation processes. Thus, we aimed at immobilizing a laccase enzyme by two different methods: the first one was based on producing alginate-laccase microcapsules through a droplet-based microfluidic system; the second one was based on covalent binding of the laccase molecules on aluminum oxide (Al2O3) pellets. Immobilization efficiencies approached 92.18% and 98.22%, respectively. Laccase immobilized by the two different methods were packed into continuous flow microreactors to evaluate the degradation efficiency of acetaminophen present in artificial wastewater. After cyclic operation, enzyme losses were found to be up to 75 µg/mL and 66 µg/mL per operation cycle, with a maximum acetaminophen removal of 72% and 15% and a retention time of 30 min, for the laccase-alginate microcapsules and laccase-Al2O3 pellets, respectively. The superior catalytic performance of laccase-alginate microcapsules was attributed to their higher porosity, which enhances retention and, consequently, increased the chances for more substrate-enzyme interactions. Finally, phytotoxicity of the treated water was lower than that of the untreated wastewater, especially when using laccase immobilized in alginate microcapsules. Future work will be dedicated to elucidating the routes for scaling-up and optimizing the process to assure profitability.

Development of an extrusion-based 3D-printing strategy for clustering of human neural progenitor cells.

3D bioprinting offers a simplified solution for the engineering of complex tissue parts for in-vitro drug discovery or, in-vivo implantation. However, significant amount of challenges exist in 3D bioprinting of neural tissues, as these are sensitive cell types to handle via extrusion bioprinting techniques. We assessed the feasibility of bioprinting human neural progenitor cells (NPCs) in 3D hydrogel lattices using a fibrinogen-alginate-chitosan bioink, previously optimized for neural-cell growth, and subsequently modified for structural support during extrusion printing, in this study. The original bioink used in this study was made by adding optimized amounts of high- and medium-viscosity alginate to the fibrinogen-chitosan-based bioink and making it extrudable under shear pressure. The mechanically robust 3D constructs promoted NPC cluster formation and maintained their morphology and viability during the entire culture period. This strategy may be useful for co-culturing of NPCs along with other cell types such as cardiac, vascular, and other cells during 3D bioprinting.

Fabrication and Characterization of a Low-Cost Microfluidic System for the Manufacture of Alginate-Lacasse Microcapsules.

The development of microfluidics-based systems in the recent years has provided a rapid and controlled method for the generation of monodisperse microencapsulates for multiple applications. Here, we explore the design, manufacture and characterization of a low-cost microsystem for the encapsulation of the fungal laccase from Pycnoporus sanguineus CS43 in alginate microcapsules. Multiphysics simulations were used to overview the fluid behavior within the device and estimate the resulting capsule size. Polymethylmethacrylate (PMMA) sheets were used for final microsystem manufacture. Different flow rates of the continuous (Qc) and discrete (Qd) phases in the ranges of 83-293 mL/h and 1-5 mL/h, respectively, were evaluated for microcapsule fabrication. Universal Serial Bus (USB) microscope and image analysis was used to measure the final particle size. Laccase encapsulation was evaluated using spectrophotometry and with the aid of fluorescent dyes and confocal microscopy. Results showed microcapsule size was in the range of 203.13-716.00 µm and Qc was found as the dominant parameter to control capsule size. There was an effective enzyme encapsulation of 65.94% with respect to the initial laccase solution.

Proposal and Evaluation of a Telerehabilitation Platform Designed for Patients With Partial Rotator Cuff Tears: A Preliminary Study.

OBJECTIVE: To propose and evaluate the effectiveness of a telerehabilitation platform designed for patients with rotator cuff (RC) tears. METHODS: During the first study phase, a virtual service platform that included information on RC tear pathology, joint care, and a series of instructions regarding therapeutic exercise was designed and created. Subsequently, in the clinical phase, a quasi-experimental study was performed. The platform was tested on patients and evaluated at baseline and at 1, 2, 3, and 6 months with respect to their pain levels and functionality on the Constant-Murley (CM) scale. RESULTS: Eleven patients were included, 5 women and 6 men, with a median age of 55 years (range, 42-68 years). Pain diminished from a baseline value of 64 mm (range, 40-80 mm) to 16 mm (range, 0-30 mm) at 6 months (p<0.001). Points on the CM scale rose from a baseline value of 54 points (range, 51-66 points) to 85 points (range, 70-100 points) at 6 months (p=0.001). Functionality in daily living and work activities, movement, and strength exhibited significant changes at 6 months (p<0.05). CONCLUSION: Significant changes were observed in pain and functionality in this group of participants who used a telerehabilitation platform. To the best of our knowledge, this is the first study that included a specific program for RC tears.

Nivel de sedentarismo en los estudiantes de fisioterapia de la fundación universitaria María Cano, Popayán / Sedentary nature level of physiotherapy program students at the Maria Cano University Foundation, Popayán / Nivel de sedentarismo nos estudantes de fisioterapía da fundação universitaria María Cano, Popayán

Objetivo: Determinar el nivel de sedentarismo en los estudiantes del programa de fisioterapia durante el II periodo de 2014 de la Fundación Universitaria María Cano, extensión Popayán. Materiales y Métodos: Investigación descriptiva de corte transversal, con enfoque cuantitativo; la muestra estuvo constituida por 230 estudiantes universitarios de pregrado del programa de fisioterapia de la Fundación Universitaria María Cano, extensión Popayán; para la recolección de la información se utilizaron dos instrumentos, el primero diseñado para recolectar información acerca de variables sociodemográficas, antropométricas y de estilos de vida; el segundo es el Test de sedentarismo modificado de Pérez-RojasGarcía que permite identificar el nivel de sedentarismo. Resultados: El 97% del total de la población evaluada se clasificó como sedentarias y solo el 3% como activas; con respecto al IMC se evidenció que las personas con un IMC normal o por debajo de este se encontraron dentro de la clasificación de sedentarias. Conclusiones: Según el Test de sedentarismo modificado de Pérez-Rojas-García los estudiantes de dicha institución presentan alto nivel de sedentarismo, conllevando a tener una gran probabilidad a que esta población tienda a sufrir a largo plazo enfermedades o condiciones patológicas, las cuales generan altos índices de morbimortalidad; por tal motivo, es una prioridad y necesidad crear conciencia sobre las implicaciones que conlleva en un futuro el sedentarismo y aún más acompañado de estilos de vida no saludables.

Objective: To determine the level of sedentary nature of the physiotherapy program students during the second period 2014 at the María Cano University Foundation, Popayán. Methodology: Cross-sectional descriptive study with quantitative approach; the sample consisted of 230 undergraduate students of the physical therapy program at the María Cano University Foundation, Popayán; two instruments were used for collecting information: the first designed to collect information about sociodemographic, anthropometric and lifestyle variables; the second is the Rojas García Pérez modified sedentary Test which identifies the level of sedentary nature. Results: 97% of the total population evaluated was classified as sedentary and only 3% as active; with respect to BMI it was evident that people with a normal BMI or below this were within the classification of sedentary. Conclusions: According to the Rojas García Pérez modified Sedentary Test students of that institution have high level of inactivity leading to having a high probability to suffer long-term diseases or pathological conditions which generate high rates of morbidity and mortality; for that reason it is a priority and a need to raise awareness of the implications the sedentary nature has in the future even more when it is accompanied by unhealthy life styles.

Objetivo: Determinar o nível de sedentarismo nos estudantes do programa de fisioterapia durante o II período de 2014 da Fundação Universitária Maria Cano, extensão Popayán. Materiais e Métodos: Pesquisa descritiva de corte transversal, com enfoque quantitativo; a amostra esteve constituída por 230 estudantes universitários de pré-graduação programa de fisioterapia da Fundação Universitária Maria Cano, extensão Popayán; para a coleta da informação se utilizaram dois instrumentos, o primeiro desenhado para coletar informação acerca de variáveis sociodemográficas, antropométricas e de estilos de vida; o segundo é o Teste de sedentarismo modificado de Pérez-Rojas-García que permite identificar o nível de sedentarismo. Resultados: O 97% do total da povoação avaliada se classificou como sedentárias é só o 3% como ativas; com respeito ao IMC se evidenciou que as pessoas com um IMC normal o por debaixo deste se encontraram dentro da classificação de sedentárias. Conclusões: Segundo o Teste de sedentarismo modificado de Pérez-Rojas-García os estudantes de dita instituição apresentam alto nível de sedentarismo, levando a ter una grande probabilidade a que esta povoação tende a sofrer em longo prazo doenças ou condições patológicas, as quais geram altos índices de morbidade e mortalidade; por tal motivo, é uma prioridade e necessidade criar consciência sobre as implicações que leva em um futuro o sedentarismo e ainda mais acompanhada de estilos de vida não saudáveis.

Detección de antibióticos en leches: un problema de salud pública / Detecting antibiotics in milk: a public health problem

Objetivo Determinar la presencia de antibióticos en leches crudas y procesadas en el municipio de Montería. Materiales y métodos Se realizaron tres muestreos con intervalo de dos meses, en una empresa acopiadora de leche en la ciudad de Montería, además, se analizaron muestras de leche pasteurizadas de seis marcas comerciales. A todas las muestras de leche se les realizó la prueba de la acidez por alcoholimetría, también se determinó la presencia del antiséptico H2O2 a través de KI al 35 por ciento y V2O5 al 1 por ciento en H2SO4 diluido. Posteriormente se detecto la presencia de antibióticos (Total antibiotic Bio K 331 (BioX Diagnostic® Jemelle, Belgique). Se determinó el límite de sensibilidad de la prueba con controles positivos de penicilina 0.004UI/ml, oxitetraciclina 0.100 μg/ml y cloramfenicol 5.000 μg/ml, realizando diluciones seriadas dobles. Para cada muestreo se emplearon leches como controles negativos y positivos. El primer muestreo evaluó 212 muestras de leche, el segundo 167 y el tercero 66, para un total de 445 muestras. Resultados todas las muestras fueron negativas a la acidez por alcoholimetría, se evidenció la presencia de antibióticos en 111(25 por ciento) muestras de leches crudas; en ninguna leche pasteurizada se detectaron antibióticos. La sensibilidad de la prueba demostró que penicillina fue detectable a 0.002UI/ml; oxitetraciclina a 0.005μg/ml y cloramfenicol a 1,25 μg/ ml. Conclusiones El 25 por ciento de trazas de antibióticos en leches demuestra la inexistencia de un control sanitario, así como evidencia el uso indiscriminado de antibióticos en la industria pecuaria y un riesgo para la salud pública.

Objective Determining the presence of antibiotics in raw and processed milk in the city of Monteria. Materials and methods Three samplings were three samples were taken in a dairy company in the city of Monteria at two-month intervals. Pasteurised milk samples were taken from six trademarks. All milk samples were tested for acidity by alcoholometry; the presence of antiseptic H2O2 was determined by using 35 percent KI and 1 percent V2O5 diluted in H2SO4. The incidence of antibiotics (Total antibiotic Bio K 331 (Diagnostic Jemelle dioxide, Belgique) was then determined. The test’s sensitivity limit was determined by using 0.004 UI/ml penicillin, 0.100 mg/ml oxytetracycline and 5,000 mg/ml chloramphenicol as positive controls in two-fold serial dilutions. Aliquots of milk were used as positive and negative controls for each sample. The first sampling evaluated 212 samples of milk, the second 167 and the third 66, for a total of 445 samples. Results All samples were negative for alcoholometry acidity. Antibiotics were detected in 111 (25 percent) samples of raw milk; however, no antibiotics were detected in the pasteurised milk. The test’s sensitivity revealed that penicillin was detectable in a maximum 0.002UI/ml dilution, oxytetracycline in 0.005ìg/ml and chloramphenicol in 1.25 mg / ml. Conclusions Traces of antibiotics being found in 25 percent of milk samples revealed a lack of public health controls, as well as evidence of the indiscriminate use of antibiotics in the livestock industry and a risk to public health.

[Detecting antibiotics in milk: a public health problem]. / Detección de Antibióticos en Leches: Un Problema de Salud Pública.

OBJECTIVE: Determining the presence of antibiotics in raw and processed milk in the city of Monteria. MATERIALS AND METHODS: Three samplings were three samples were taken in a dairy company in the city of Monteria at two-month intervals. Pasteurised milk samples were taken from six trademarks. All milk samples were tested for acidity by alcoholometry; the presence of antiseptic H2O2 was determined by using 35 % KI and 1 % V2O5 diluted in H2SO4. The incidence of antibiotics (Total antibiotic Bio K 331 (Diagnostic Jemelle dioxide, Belgique) was then determined. The test's sensitivity limit was determined by using 0.004 UI/ml penicillin, 0.100 mg/ml oxytetracycline and 5,000 mg/ml chloramphenicol as positive controls in two-fold serial dilutions. Aliquots of milk were used as positive and negative controls for each sample. The first sampling evaluated 212 samples of milk, the second 167 and the third 66, for a total of 445 samples. RESULTS: All samples were negative for alcoholometry acidity. Antibiotics were detected in 111 (25 %) samples of raw milk; however, no antibiotics were detected in the pasteurised milk. The test's sensitivity revealed that penicillin was detectable in a maximum 0.002UI/ml dilution, oxytetracycline in 0.005ìg/ml and chloramphenicol in 1.25 mg/ml. CONCLUSIONS: Traces of antibiotics being found in 25 % of milk samples revealed a lack of public health controls, as well as evidence of the indiscriminate use of antibiotics in the livestock industry and a risk to public health.