Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms.

BACKGROUND AND PURPOSE: Demand for new antidepressants has resulted in a re-evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin-containing "magic" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects. EXPERIMENTAL APPROACH: We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood-brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound. KEY RESULTS: In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood-brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5-HT2A-mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. CONCLUSIONS AND IMPLICATIONS: Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations.

Cholinergic mu-opioid receptor deletion alters reward preference and aversion-resistance.

The endogenous opioid system has been implicated in alcohol consumption and preference in both humans and animals. The mu opioid receptor (MOR) is expressed on multiple cells in the striatum, however little is known about the contributions of specific MOR populations to alcohol drinking behaviors. The current study used mice with a genetic deletion of MOR in cholinergic cells (ChAT-Cre/Oprm1fl/fl) to examine the role of MORs expressed in cholinergic interneurons (CINs) in home cage self-administration paradigms. Male and female ChAT-Cre/Oprm1fl/fl mice were generated and heterozygous Cre+ (knockout) and Cre- (control) mice were tested for alcohol consumption in two drinking paradigms: limited access "Drinking in the Dark" and intermittent access. Quinine was added to the drinking bottles in the DID experiment to test aversion-resistant, "compulsive" drinking. Nicotine and sucrose drinking were also assessed so comparisons could be made with other rewarding substances. Cholinergic MOR deletion did not influence consumption or preference for ethanol (EtOH) in either drinking task. Differences were observed in aversion-resistance in males with Cre + mice tolerating lower concentrations of quinine than Cre-. In contrast to EtOH, preference for nicotine was reduced following cholinergic MOR deletion while sucrose consumption and preference was increased in Cre+ (vs. Cre-) females. Locomotor activity was also greater in females following the deletion. These results suggest that cholinergic MORs participate in preference for rewarding substances. Further, while they are not required for consumption of alcohol alone, cholinergic MORs may influence the tendency to drink despite negative consequences.

High-resolution scanning tunneling microscope and its adaptation for local thermopower measurements in 2D materials.

We present the design, fabrication and discuss the performance of a new combined high-resolution Scanning Tunneling and Thermopower Microscope (STM/SThEM). We also describe the development of the electronic control, the user interface, the vacuum system, and arrangements to reduce acoustical noise and vibrations. We demonstrate the microscope's performance with atomic-resolution topographic images of highly oriented pyrolytic graphite (HOPG) and local thermopower measurements in the semimetal Bi2Te3. Our system offers a tool to investigate the relationship between electronic structure and thermoelectric properties at the nanoscale.

Mu-opioid receptor knockout on Foxp2-expressing neurons leads to reduced aversion-resistant reward seeking.

Mu-opioid receptors (MORs) in the amygdala and striatum are important in addictive and rewarding behaviors. Foxp2 is a marker of intercalated (ITC) cells in the amygdala and a subset of striatal medium spiny neurons (MSNs), both of which express MORs in wild-type mice. For the current series of studies, we characterized the behavior of mice with genetic deletion of the MOR gene Oprm1 in Foxp2-expressing neurons (Foxp2-Cre/Oprm1 fl/fl ). Male and female Foxp2-Cre/Oprm1 fl/fl mice were generated and heterozygous Cre+ (knockout) and homozygous Cre-(control) animals were tested for aversion-resistant alcohol consumption using an intermittent access (IA) task, operant responding for a sucrose reward, conditioned place aversion (CPA) to morphine withdrawal, and locomotor sensitization to morphine. In IA, mice with the MOR-knockout were more sensitive to quinine-adulterated ethanol (EtOH) and less aversion-resistant, as they decreased EtOH consumption from baseline at all quinine concentrations, while control animals did not. In operant conditioning, Cre+ mice similarly exhibited less aversion-resistant reward seeking than Cre-mice when sucrose was adulterated with quinine. For CPA, both control and MOR-knockout mice demonstrated withdrawal-induced aversion. For locomotor sensitization, Cre+ mice demonstrated decreased locomotion following morphine injection compared to Cre-mice. The results of these studies suggest that MOR expression on Foxp2-expressing neurons is not necessary for rewarded behaviors or expression of opioid withdrawal but may be involved in aversion-resistance.

Botulinum toxin A (IncobotulinumtoxinA) and pneumoperitoneum image-guided for hernia repair with loss of dominance.

Post-incisional ventral hernia is estimated at 5-30%, when the content of the abdominal cavity migrates to the hernial sac (HSV), with a HSV/abdominal cavity volume ratio > 25%, conditioning systemic changes defined as "loss of domain". A 27-year-old male presented with ventral hernia with loss of domain that required pre-operative preparation techniques, using application of botulinum toxin A (IncobotulinumtoxinA) and pneumoperitoneum, both guided by image. A ventral plasty was performed with adequate return of the viscera to the abdominal cavity. The combination of both techniques seems to be a safe procedure to carry out a tension-free repair.

La hernia ventral postincisional se estima en 5 al 30%, cuando el contenido de la cavidad abdominal migra al saco herniario, con una relación VSH/VCA > 25% condicionando cambios sistémicos se define como "pérdida de dominio". Masculino de 27 años con hernia ventral con pérdida de dominio que ameritó técnicas de preparación preoperatoria, utilizando toxina botulínica A (IncobotulinumtoxinA) y neumoperitoneo, ambos guíados por imagen. Se realizó una plastia ventral con adecuado regreso de las vísceras a la cavidad abdominal. La combinación de ambas técnicas es un procedimiento seguro para realizar una reparación libre de tensión.

Conceptos actuales en osteotomías en doble nivel alrededor de la rodilla / Current concepts in double-level osteotomies around the knee

Con la osteotomía en un solo nivel, se puede lograr la corrección del eje de la extremidad en pacientes con deformidades combinadas femoral y tibial, pero de forma simultánea generará una alteración patológica de oblicuidad de la interlínea articular, lo que conducirá a elongación ligamentaria, inestabilidad, degeneración condral y, en última instancia, comprometerá su sobrevida y los resultados funcionales. En virtud del análisis de la literatura más reciente, podemos concluir que existe un número significativo de pacientes que requieren de un procedimiento combinado para lograr un objetivo biomecánico óptimo. La finalidad de una osteotomía en doble nivel alrededor de la rodilla consiste en restablecer la anatomía normal, descargar el compartimiento afectado, normalizar los ángulos mecánicos y la orientación de la interlínea articular. Los ejes fisiológicos pueden restablecerse a través de un análisis preoperatorio exhaustivo, respetando principios biomecánicos y fijación estable con placas bloqueadas. Es un procedimiento demandante y con indicaciones en evolución, que progresivamente se ha instaurado como una alternativa de tratamiento justificada en estudios clínicos y biomecánicos para el manejo de deformidades severas alrededor de la rodilla.

With single-level osteotomy, correction of the limb axis in patients with combined femoral and tibial deformities can be achieved. This correction, however, will generate a pathological alteration in the joint line oblicuity, leading to ligament elongation, instability, joint degeneration and, ultimately, it will compromise the longevity and functional results of the correction. By analyzing the most recent literature, we can conclude that there is a significant number of patients who require a combined procedure to achieve an optimal biomechanical goal. The purpose of a double-level osteotomy around the knee is to restore normal anatomy, unload the affected compartment, normalize the mechanical angles and the orientation of the joint line. Physiological axes can be reestablished by means of a thorough preoperative analysis, observing the biomechanical principles and stable fixation with locked plates. It is a demanding procedure with increasing indications, which has progressively been established in clinical and biomechanical studies as a justified treatment alternative for the management of severe deformities around the knee.

Detection and Quantification of HspX Antigen in Sputum Samples Using Plasmonic Biosensing: Toward a Real Point-of-Care (POC) for Tuberculosis Diagnosis.

Advancements that occurred during the last years in the diagnosis of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis infection, have prompted increased survival rates of patients. However, limitations related to the inefficiency of an early detection still remain; some techniques and laboratory methods do not have enough specificity and most instruments are expensive and require handling by trained staff. In order to contribute to a prompt and effective diagnosis of tuberculosis, we report the development of a portable, user-friendly, and low-cost biosensor device for its early detection. By using a label-free surface plasmon resonance (SPR) biosensor, we have established a direct immunoassay for the direct detection and quantification of the heat shock protein X (HspX) of Mtb, a well-established biomarker of this pathogen, directly in pretreated sputum samples. The method relies on highly specific monoclonal antibodies that are previously immobilized on the plasmonic sensor surface. This technology allows for the direct detection of the biomarker without amplification steps, showing a limit of detection (LOD) of 0.63 ng mL-1 and a limit of quantification (LOQ) of 2.12 ng mL-1. The direct analysis in pretreated sputum shows significant differences in the HspX concentration in patients with tuberculosis (with concentration levels in the order of 116-175 ng mL-1) compared with non-tuberculosis infected patients (values below the LOQ of the assay).

Polarization diversity phase modulator for measuring frequency-bin entanglement of a biphoton frequency comb in a depolarized channel.

Phase modulation has emerged as a technique to create and manipulate high-dimensional frequency-bin entanglement. A necessary step to extending this technique to depolarized channels, such as those in a quantum networking environment, is the ability to perform phase modulation independent of photon polarization. This is also necessary to harness hyperentanglement in the polarization and frequency degrees of freedom for operations such as Bell state discrimination. However, practical phase modulators are generally sensitive to the polarization of light, and this makes them unsuited to such applications. We overcome this limitation by implementing a polarization diversity scheme to measure frequency-bin entanglement for arbitrary orientations of co- and cross-polarized time-energy entangled photon pairs.

Characterizing pump line phase offset of a single-soliton Kerr comb by dual comb interferometry.

We report phase retrieval of a single-soliton Kerr comb using electric field cross-correlation implemented via dual-comb interferometry. The phase profile of the Kerr comb is acquired through the heterodyne beat between the Kerr comb and an electro-optic comb with a pre-characterized phase profile. The soliton Kerr comb has a nearly flat phase profile, and the pump line is observed to show a phase offset which depends on the pumping parameters. The experimental results are in agreement with numerical simulations.

Principios quirúrgicos y biomecánicos de los métodos de fijación actual en el tratamiento de fracturas de Hoffa / Surgical and biomechanical principles of current fixation methods, in treatment of Hoffa fractures

Las fracturas de los cóndilos femorales en el plano coronal (Hoffa), son lesiones que afectan directamente la biomecánica de la rodilla. Están expuestas a un factor intrínseco de inestabilidad causado por el compromiso de los ligamentos y tendones insertados al fragmento condilar fracturado y a un factor extrínseco de inestabilidad dependiente del estrés mecánico en varo/valgo durante la fase de apoyo de la marcha y movimientos de flexo-extensión. El tratamiento quirúrgico con tornillos canulados sólo permite la compresión interfragmentaria y cierto grado de estabilidad rotacional, sin embargo, ese tipo de fijación podría no ser suficiente para soportar o neutralizar las cargas. Distintos autores han publicado otros métodos de osteosíntesis con el uso de placas en el plano lateral o posterior más la colocación de tornillos en sentido postero-anterior, pero siguen siendo opciones controversiales debido al tipo de morbilidad inherente a cada constructo. El objetivo de este artículo es realizar una revisión de la literatura para analizar la validez de los principios quirúrgicos y biomecánicos en el tratamiento de fracturas tipo hoffa.

Coronal plane fractures of the femoral condyles are commonly known as Hoffa fractures. These are intraarticular fractures that directly affect the biomechanics of the knee and have intrinsic and extrinsic instability patterns. The tendons and ligaments that remain attached to the condylar fragment produce the intrinsic instability. The extrinsic instability is due to the varus/valgus stress applied during the stance phase in the gait cycle as well as the flexion-extension movements. Surgical treatment with cannulated screws only achieves interfragmentary compression and certain amount of rotational stability that is not enough to support or neutralize the loads. Some authors have published different methods of osteosynthesis with lateral or posterior plates in conjunction with screws implanted in the posterior-anterior direction, still these techniques remain controversial due to the morbidity inherent to each construct. The purpose of this article is to review the current concepts of Hoffa fractures including biomechanics and surgical principles with the intention of analyzing their treatment efficacy.

Principios quirúrgicos en fracturas de platillos tibiales con compromiso de columna posterior / Surgical principles in posterior column tibial plateau fractures

Las fracturas de platillos tibiales son lesiones complejas que incluyen una variedad de patrones morfológicos cada vez mejor caracterizados en la literatura. Históricamente, los esquemas de clasificación se han basado en evaluar los rasgos de fractura en el plano frontal y las técnicas quirúrgicas en lograr la fijación de esos fragmentos, sin tomar en consideración el compromiso óseo que ocurre en la región posterior de los platillos tibiales. Con el advenimiento de la clasificación columnar basada en tomografía computada, se han logrado desarrollar estrategias de fijación optimizada, dando cada vez más relevancia a la columna posterior. Este artículo realiza una revisión extensa de la literatura, otorgando los fundamentos quirúrgicos que explican la importancia del tratamiento específico de la columna posterolateral y posteromedial, con el fin de restablecer la biomecánica normal de la rodilla y el razonamiento quirúrgico de las diversas vías de abordaje específicas para una reducción y osteosíntesis satisfactoria de esos fragmentos.

Tibial plateau fractures are complex injuries which include a variety of morphological patterns that have been increasingly better characterized in the literature. Historically, classifications have focused on description of fracture patterns in the frontal plane, while surgical techniques have focused on reduction of these fragments not considering the osseous defects that occur on the posterior region of the tibial plateau. With new CT scan column based classifications, strategies to optimize fixation have been developed, giving relevance to the posterior column. This article is an exhaustive review of the literature, providing the surgical foundations that explain the importance of specific treatment of the posterolateral and posteromedial column, aiming to restore normal knee biomechanics. Furthermore, this article provides the diverse specific surgical approaches rationale for a satisfactory open reduction and internal fixation of these fragments.

Diseño y Evaluación de un micro viscosímetro de bajo costo utilizando un resonador de cristal de cuarzo y Arduino / Designing and evaluating a low-cost micro-viscometer using a quartz crystal resonator (QCR) and an Arduino DUE microcontroller board / Desenho e Avaliação de um micro viscosímetro de baixo custo usando um ressonador de cristal de quartzo e Arduino

Resumen El objetivo principal de este artículo es proponer el diseño de un micro viscosímetro de bajo coste utilizando un resonador de cristal de cuarzo (QCR) y una tarjeta Arduino DUE. En el artículo se explican los pasos del diseño del sensor y también su evaluación con dos líquidos de diferentes características: diluciones de glicerol en agua (comportamiento Newtoniano) y diluciones de albúmina de huevo extraída de huevos frescos en agua (comportamiento No-Newtoniano). Este estudio está relacionado con el interés de desarrollar nuevas herramientas para el diagnóstico de enfermedades cardiovasculares y artríticas.

Abstract This article outlines a design for a low-cost micro-viscometer, using a quartz crystal resonator (QCR) and an Arduino DUE programmable microcontroller board. The article explains the steps involved in designing the sensor and also how it was evaluated regarding two liquids having different characteristics: dilute aqueous glycerol (Newtonian behaviour) and dilutions of egg-white extracted from fresh eggs in water (non-Newtonian behaviour). This study was related to interest in developing new tools for diagnosing cardiovascular and arthritic diseases.

Resumo O principal objetivo deste trabalho é propor o projeto de um micro viscosímetro de baixo custo usando um ressonador de cristal de quartzo (QCR) e um cartão Arduino DUE. O artigo explica as etapas do desenho do sensor e também sua avaliação com dois líquidos de diferentes características: diluições de glicerol em água (comportamento newtoniano) e diluições de albumina de ovo extraídas de ovos frescos em água (comportamento não newtoniano). Este estudo está relacionado ao interesse de desenvolver novas ferramentas para o diagnóstico de doenças cardiovasculares e artríticas.

High-speed stimulated hyperspectral Raman imaging using rapid acousto-optic delay lines.

Stimulated Raman scattering (SRS) is a powerful, label-free imaging technique that holds significant potential for medical imaging. To allow chemical specificity and minimize spectral distortion in the imaging of live species, a high-speed multiplex SRS imaging platform is needed. By combining a spectral focusing excitation technique with a rapid acousto-optic delay line, we demonstrate a hyperspectral SRS imaging platform capable of measuring a 3-dB spectral window of ∼200 cm-1 within 12.8 µs with a scan rate of 30 KHz. We present hyperspectral images of a mixture of two different microsphere polymers as well as live fungal cells mixed with human blood.

Evaluation of Hyaluronic Acid Dilutions at Different Concentrations Using a Quartz Crystal Resonator (QCR) for the Potential Diagnosis of Arthritic Diseases.

The main objective of this article is to demonstrate through experimental means the capacity of the quartz crystal resonator (QCR) to characterize biological samples of aqueous dilutions of hyaluronic acid according to their viscosity and how this capacity may be useful in the potential diagnosis of arthritic diseases. The synovial fluid is viscous due to the presence of hyaluronic acid, synthesized by synovial lining cells (type B), and secreted into the synovial fluid thus making the fluid viscous. In consequence, aqueous dilutions of hyaluronic acid may be used as samples to emulate the synovial fluid. Due to the viscoelastic and pseudo-plastic behavior of hyaluronic acid, it is necessary to use the Rouse model in order to obtain viscosity values comparable with viscometer measures. A Fungilab viscometer (rheometer) was used to obtain reference measures of the viscosity in each sample in order to compare them with the QCR prototype measures.

Relación de la edad cronológica y la maduración sexual con la maduración ósea por resonancia magnética nuclear de la epífisis del radio distal en futbolistas adolescentes / Relationship of chronological age and sexual maturity with skeletal maturity by magnetic resonance imaging of the distal radial epiphysis in adolescent football players

Introducción: Aunque el grado de fusión de la epífisis del radio distal izquierdo (ERDI) por resonancia magnética nuclear (RMN) se ha relacionado con la edad cronológica (EC), se desconoce su relación con el Tanner genital en población latinoamericana. Objetivo: Evaluar la relación de la EC y la maduración sexual con la maduración ósea (MO) por RMN de la ERDI en futbolistas adolescentes de la ciudad de Medellín, Colombia. Materiales y métodos: Estudio transversal que incluyó 60 futbolistas hombres con edad legal certificada entre 12 y 18 años. Se realizó una evaluación médica y una RMN de la ERDI con un resonador de 1.5 T según un protocolo descrito. La lectura de la imagen fue realizada por 3 evaluadores cegados. Se determinó la MO en tres estadios (A: inmaduros; B: en desarrollo; C: maduros) y se evaluó la variabilidad inter e intra-observador. Resultados: Entre los futbolistas incluidos, se encontró un promedio de índice de masa corporal y porcentaje de grasa corporal de 19,6 ± 2,0 Kg/m2 y 1,1 ± 1,2%, respectivamente. Se encontró correlación de la EC y el estadio de maduración por Tanner genital con la MO (Tau_b de Kendall 0,686 y 0,693, respectivamente; p < 0,001). Todos los jugadores clasificados en el grado C tenían 17 o más años y Tanner estadio V. La concordancia inter-observador e intra-observador, mostró un índice kappa de 0,36 (p < 0,001) y 0,60 (p < 0,001), respectivamente. Conclusión: Se encontró relación de la EC y la maduración sexual con la MO por RMN de la ERDI en futbolistas adolescentes. La clasificación por grados de MO en 3 categorías, podría ser más práctica y tener implicaciones para la competencia

Introduction: Although the grade of fusion of the left distal radial epiphysis (LDRE) observed by magnetic resonance imaging (MRI) has been linked to chronological age (CA), its relationship to Tanner stage of the genitals in the Latin American population is unknown. Objective: To evaluate the relationship of CA and sexual maturity with skeletal maturity (SM) determined by MRI of the LDRE in adolescent football players from Medellin, Colombia. Materials and methods: Cross-sectional study that included 60 male football players with certified legal age between 12 and 18 years. Medical evaluation and MRI of the LDRE using a 1.5 T scanner was performed according to a described protocol. The image reading was performed by 3 blinded evaluators. SM was classified as: A: immature; B: developing; C: mature, and interand intra-observer variability was assessed. Results: Among the football players included in the study, the average body mass index and body fat were 19.6 ± 2.0 kg/m2 and 11.1 ± 1.2%, respectively. A correlation of CA and the Tanner stage of genital maturity with SM (Kendall’s Tau b 0.686 and 0.693, respectively; P < .001) was found. All players classified as stage C were 17 or older and Tanner stage V. The inter-observer and intraobserver agreement showed a kappa index of 0.36 (P < .001) and 0.60 (P < .001), respectively

Polyelectrolyte based molecular carriers: the role of self-assembled proteins in permeability properties.

Polyelectrolyte capsules are seen as promising nanotechnology based drug delivery systems. In previous works, we have demonstrated the possibility to fabricate bio-activated surface layer containing capsules with improved features in terms of biocompatibility. In this study, we have characterized the permeability properties of such capsules towards low and high molecular weight molecules, including proteins. The results indicated that the presence of the surface layer strongly affects the permeability properties of the capsules in terms of loading capacity which was found to be higher compared to that of plain capsules. These properties make such systems interesting candidates as drug delivery platforms.

Molecular and structural transactions at human DNA replication origins.

The DNA replication origins of metazoan genomes are the sites of complex sequence-specific protein-DNA interactions determining their precise cycle of activation and deactivation, once only along each cell cycle. Some of the involved proteins have been identified (and particularly the essential six-protein Origin Recognition Complex, ORC) thanks to their homology with the proteins identified in yeast. Whereas in the latter organism ORC has a specific affinity for an origin consensus, metazoan (and human) ORC shows no sequence specificity and no origin consensus is identifiable in their genomes. The modulation of topology around the origin sequence plays an essential role in the function of the human lamin B2 origin and the two topoisomerases interact specifically with it in a cell-cycle modulated way. The two enzymes are never present on the origin at the same time and compete, in different moments of the cell cycle, with the ORC2 subunit for the same sites in the origin area. The topoisomerases could give essential contributions to origin definition, as demonstrated by their capacity to bind specifically, in vitro the lamin B2 origin, either alone (topoisomerase I) or in a multi-protein complex (topoisomerase II). They also play critical roles in the origin activation-deactivation cycle, topoisomerase II probably contributing to attain and/or maintain a topological status fit for prereplicative complex assembly and topoisomerase I allowing the topological adaptations necessary for initiation of bi-directional synthesis.

Functional interactions of DNA topoisomerases with a human replication origin.

The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. The topoisomerases interact in vivo and in vitro with precise bonds ahead of the start sites of bidirectional replication, within the pre-replicative complex region; topoisomerase I is bound in M, early G1 and G1/S border and topoisomerase II in M and the middle of G1. The Orc2 protein competes for the same sites of the origin bound by either topoisomerase in different moments of the cell cycle; furthermore, it interacts on the DNA with topoisomerase II during the assembly of the pre-replicative complex and with DNA-bound topoisomerase I at the G1/S border. Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation.