Human Substantia Nigra Neurons Encode Reward Expectations.

Dopamine (DA) signals originating from substantia nigra (SN) neurons are centrally involved in the regulation of motor and reward processing. DA signals behaviorally relevant events where reward outcomes differ from expectations (reward prediction errors, RPEs). RPEs play a crucial role in learning optimal courses of action and in determining response vigor when an agent expects rewards. Nevertheless, how reward expectations, crucial for RPE calculations, are conveyed to and represented in the dopaminergic system is not fully understood, especially in the human brain where the activity of DA neurons is difficult to study. One possibility, suggested by evidence from animal models, is that DA neurons explicitly encode reward expectations. Alternatively, they may receive RPE information directly from upstream brain regions. To address whether SN neuron activity directly reflects reward expectation information, we directly examined the encoding of reward expectation signals in human putative DA neurons by performing single-unit recordings from the SN of patients undergoing neurosurgery. Patients played a two-armed bandit decision-making task in which they attempted to maximize reward. We show that neuronal firing rates (FR) of putative DA neurons during the reward expectation period explicitly encode reward expectations. First, activity in these neurons was modulated by previous trial outcomes, such that FR were greater after positive outcomes than after neutral or negative outcome trials. Second, this increase in FR was associated with shorter reaction times, consistent with an invigorating effect of DA neuron activity during expectation. These results suggest that human DA neurons explicitly encode reward expectations, providing a neurophysiological substrate for a signal critical for reward learning.

Effect of age, sex, and body size on the blood biochemistry and physiological constants of dogs from 4 wk. to > 52 wk. of age.

BACKGROUND: Blood biochemistry and reference intervals help to differentiate between healthy and ill dogs as well as to provide information for the prognosis, evaluation, and monitoring; however, these intervals are often obtained from adult animals. It is essential to understand that puppies and adults are physiologically different, which justifies the need to obtain age-specific biochemical reference intervals. The aim of this research was to assess the potential effect of age, sex, body size, and their interaction on routine biochemical analytes and physiological constants (body temperature, heart rate, and respiratory rate). To carry out the research, we selected 197 healthy dogs of both sexes and different body sizes (small, medium and large) classified by age: group I (4-8 wk), group II (9-24 wk), group III (25-52 wk), and group IV (> 52 wk). The biochemical analysis included the measurement of the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and the concentrations of cholesterol, triglycerides, total proteins, albumin, globulins, glucose, urea, and creatinine. Statistical analyses used analysis of variance (ANOVA) and a general linear model (GLM), which allows the comparison of multiple factors at two or more levels (p < 0.05). RESULTS: The results of this study showed that ALT, total protein, albumin, globulin, urea, creatinine, and body temperature levels were lower in puppies than in adult dogs of group IV (p < 0.05), while the enzymatic activity of ALP, LDH, glucose concentration, and heart rate were higher. Whereas sex, body size and the interaction did not show a significant effect (p > 0.05). CONCLUSIONS: Some biochemical components are influenced by age. For this reason, this manuscript contributes with additional data for the clinical interpretation of blood biochemical results in puppies.

Toxic Effect of Aflatoxins in Dogs Fed Contaminated Commercial Dry Feed: A Review.

Since its first patent (1897), commercial dry feed (CDF) for dogs has diversified its formulation to meet the nutritional needs of different breeds, age, or special conditions and establish a foundation for integration of these pets into urban lifestyles. The risk of aflatoxicosis in dogs has increased because the ingredients used to formulate CDF have also proliferated, making it difficult to ensure the quality required of each to achieve the safety of the entire CDF. This review contains a description of the fungi and aflatoxins detected in CDF and the ingredients commonly used for their formulation. The mechanisms of action and pathogenic effects of aflatoxins are outlined; as well as the clinical findings, and macroscopic and microscopic lesions found in aflatoxicosis in dogs. In addition, alternatives for diagnosis, treatment, and control of aflatoxins (AF) in CDF are analyzed, such as biomarkers of effect, improvement of blood coagulation, rate of elimination of AF, control of secondary infection, protection of gastric mucosa, reduction of oxidative stress, use of chemo-protectors, sequestrants, grain-free CDF, biocontrol, and maximum permitted limits, are also included.

Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice.

Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism.

Tendencias de la investigación en fonoaudiología: el caso de la universidad de sucre / Trends research in language and hearing sciences: the case of the university of sucre

El presente estudio tiene como objetivo realizar un análisis bibliométrico de la producción inves-tigativa en los últimos nueve años (2005-2013) del programa de Fonoaudiología de la Universidad de Sucre, con la finalidad de conocer la situación actual de la investigación. Para ello, fueron ana-lizados un total de 47 tesis y 28 monografías del repositorio de tesis de la biblioteca de la institu-ción, sistematizados en una base de datos delimitada en las áreas de lenguaje, habla y audición. Para el análisis de esta información se tuvieron en cuenta una serie de indicadores bibliométricos como: área disciplinar, autores, metodología, objetivos y resultados, que permitieron la orga-nización y categorización de la información. Los resultados mostraron predominio del área de lenguaje en la modalidad de grado investigación formativa y de audición en la modalidad de monografía, así como baja productividad en el área de habla. Por otra parte, se evidenció escaso interés por indagar tópicos relacionados con asuntos profesionales, intervención de patologías comunicativas, factores epidemiológicos de los trastornos comunicativos, así como en la proyec-ción de la investigación en escenarios comunitarios. Para finalizar, se propone explorar ejes temá-ticos novedosos en las distintas áreas del conocimiento, que contribuyan al desarrollo disciplinar.

The research output represents a comer stone in the development of any discipline, because of that it became necessary to make a document review of the degree thesis of the Speech, Language and Hearing Sciences program at the Universidad de Sucre, Colombia, during 2005 - 2013. For that purpose it was made a bibliometric analysis of accumulated documents in the repository of thesis at library of the institution, those documents have been systematized in a defined database in language, speech and hearing areas. The results showed a predominance of both language area in the formative research modality and hearing in monographs moda-lity, as well as low ­ productivity in the area of speech. On the other hand, it showed little interest to explore about professional matters, intervention and epidemiological factors. At the same time, the need to generate research allowing the deepening and the exploration of new fields of knowledge is obvious.

In-line quantification of two active ingredients in a batch blending process by near-infrared spectroscopy: influence of physical presentation of the sample.

The aim of this study was to apply near-infrared (NIR) spectroscopy to the simultaneous in-line monitoring of two active pharmaceutical ingredients (APIs) in a pharmaceutical batch blending process. The formulation under study consisted of a high load API (A1), one polymer, a second API (A2) and one lubricant. Additionally, the effects of the presentation of A1 on the spectral data were evaluated. For this purpose, the high load active was blended either as a cohesive powder or as a free flowing material. For improving the flow behavior of the high load active a melt-granulation (MG) step was performed. The NIR spectra of the high load API (A1) before and after MG showed that the polymer wavelength absorption band was the most affected, this wavelength range was also associated with the water band region. Thus, these frequencies carried information from the melt-granulation process and could be influenced by the water content. For the APIs quantification, independent partial least squares (PLS-1) models for each API were generated. Furthermore, a PLS-2 model was also developed for the simultaneous quantification of each API. The PLS models were used for the in-line blend uniformity monitoring of both APIs.

Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: influence of mass flow and rotation speed variations.

The aim of this study was to develop a quantitative Near-Infrared (NIR) method which monitors the homogeneity of a pharmaceutical formulation coming out of a continuous blender. For this purpose, a NIR diode array spectrometer with fast data acquisition was selected. Additionally, the dynamic aspects of a continuous blending process were studied; the results showed a well-defined cluster for the steady state, and the paths for the start-up and emptying stages were clearly identified. The end point of the start-up phase was detected by moving block of standard deviation, relative standard deviation, and principal component analysis. A partial least square (PLS) model was generated for the quantification of the drug, with a standard error of prediction of 0.2% m/m. The PLS model was successfully applied for monitoring the drug level at the outlet of the continuous blender. Furthermore, the PLS model was tested under different flow and stirring rates. Flow and stirring rate variations caused different powder flow dynamics, which were reflected on the NIR measurements. Therefore, the PLS model was sensitive to changes in mass flow and rotation speeds.

Correlation between compactibility values and excipient cluster size using an in silico approach.

BACKGROUND: In silico simulation and percolation theory are important tools in the study of physical and mechanical behavior of pharmaceutical compacts. The aim was to generate a new in silico simulation program that describes the mechanical structure of binary compacts formed from an excipient with excellent compactibility and a drug with null compactibility. MATERIALS AND METHODS: Paracetamol and microcrystalline cellulose powders were compressed under different pressures. Values for the indentation hardness and tensile strength were measured and fitted to the Leuenberger's model. On the other hand, compacts with different composition were in silico simulated. In each system, the biggest excipient cluster was identified and quantified using the Hoshen-Kopelman algorithm. Then, the size of the biggest in silico cluster was correlated with experimental compactibility values. RESULTS AND DISCUSSION: The Leuenberger's model resulted in good fit to the experimental data for all formulations over 40% of excipient load. Formulations with high drug load (≥0.8) had reduced range for forming compacts and gave low compactibility values. The excipient percolation threshold for the simulated system was 0.3395, indicating that over this excipient fraction, a compact with defined mechanical properties will be formed. The compactibility values presented a change in the range of 0.3-0.4 of excipient fraction load, just where the in silico excipient percolation threshold was found. CONCLUSION: Physical measurements of the binary compacts showed good agreement with computational measurements. Subsequently, this in silico approach may be used for the optimization of pharmaceutical powder formulations used in tablet compression.

Caracterización del lenguaje oral de la población indígena zenú / Characterization of oral language of the indigenous population Zenú

Los Zenúes son un pueblo amerindio que hablaba la lengua Guajiba o Guamacó, pero en la ac-tualidad hacen uso exclusivo del español, aunque conservan producciones que evidencian rasgos fonéticos y semánticos específicos poco conocidos. El desconocimiento de su filiación lingüís-tica y el de sus particularidades motivó el presente trabajo, el cual muestra la caracterización del lenguaje oral de la población del resguardo indígena Zenú de San Andrés de Sotavento de Sucre, buscando reconocer las diferencias en contenido, forma y uso que permitirían rescatar su riqueza lingüística y el acervo cultural de ello para la costa Caribe. El estudio fue descriptivo y de corte transversal, incluyó técnicas de recolección mixtas aplicadas a 381 indígenas del resguardo mencionado. Los resultados evidenciaron procesos de simplificación en fonemas y sílabas, omi-sión de elementos sintácticos, preferencia de verbos en presente y pasado, cambios en referentes semánticos, léxico receptivo limitado y básico pero coherente, presencia de sobreextensiones en la significación y argumentación, características conversacionales pasivas para mantener, esperar y ceder turnos y empleo de gestos naturales como mediadores de la interacción. Se concluyó que existen particularidades fonológicas atribuidas al contexto socio cultural de la población; a nivel morfosintáctico predomina el empleo de estructuras gramaticales simples y complejas de tipos yuxtapuestas y coordinadas. En los niveles semántico y pragmático se evidenció reconocimiento de conceptos, empleo de vocablos contextualizados; introversión y escasas destrezas conversacio-nales que dan cuenta de pasividad en la interacción.

The Zenúes are an Amerindian people who spoke the Guamacó language, but today they use the Spanish, although they retain productions that demonstrate specific and little known semantic and phonetic features. The neglect of their linguistic affiliation and their particularities motiva-ted the research team to develop this work, which presents the characterization of oral language of the population of the Zenú indigenous reservation of San Andrés de Sotavento in the depart-ment of Sucre, seeking recognition of the differences in content, form and use, that would allow rescue its rich linguistic and cultural heritage of this for the Caribbean Coast. The study was descriptive and cross-sectional; it included mixed collection techniques which were applied to 381 indigenous people belonging to the reservation mentioned above. The results showed simpli-fication processes in phonemes and syllables, omission of grammatical elements and preference of present and past verbs, changes in semantic referents, limited and basic receptive vocabulary, nevertheless, it is consistent; they also showed presence of overextension in the significance and argumentation, passive conversational features to keep, to wait and to give up the turn and using of natural gestures as mediator of the interaction. In conclusion, this study reveals that there are phonological particularities attributed to socio-cultural population context; it shows predomi-nant use of simple and complex grammatical structures of juxtaposed and coordinated type in the morphosyntactic level; as well as recognition of concepts and use of contextualized words; and at pragmatic level, most people are characterized as introverted, they have poor conversatio-nal skills, so that, they are passive actors in the conversation

[Familial homozygous hypercholesterolemia due to the c2271delT mutation in the LDL receptor gene, detected exclusively in Mexicans]. / Hipercolesterolemia familiar homocigota por la mutación c2271delT del gen del receptor LDL, detectada únicamente en mexicanos.

We present the case of an 18-years old women with homozygous familial hypercholesterolemia in which a LDL receptor mutation (c2271delT) was found. This mutation has been informed only in Mexicans. The patient was born in Oaxaca, Mexico. She has atypical location of tendinous and tuberous xanthomata, coronary atherosclerosis and multiple valve involvement. The response to ezetimibe/high dose statin therapy was poor. This case is an example of the occurrence of homozygous forms of familial hypercholesterolemia in genetically isolated populations of Mexico.

Monte Carlo simulations for the study of drug release from cylindrical matrix systems with an inert nucleus.

In this work, drug release from matrices with an inert nucleus using Monte Carlo simulation was studied. Drug-excipient systems were simulated, where the drug is a soluble material while the excipient is a non-soluble material. In the center of these devices, an inert nucleus was placed. The release of the drug was unidirectional and the results were fitted to the square root of time law (Higuchi law), the power law and the Weibull equation. The percolation threshold of the drug was found to be near 0.35 close to the expected value for the cubic lattice, the difference is due to the finite and rather small size of the systems in study as well as to the fact that the lattice in use is not exactly cubic. Near the percolation threshold, the parameters of the different release models presented a drastic change; this was due to a phase transition of the system. On the other hand, it was found that the size of the matrix system modifies the transport properties of the release platform. In general, the release kinetics was adequately described by the Weibull equation.

[Primary hyperparathyroidism: a report of 67 cases. The experience of 5 years at the IMSS Centro Médico Nacional Siglo XXI Specialties Hospital]. / Hiperparatiroidismo primario, reporte de 67 casos. Experiencia de los últimos cinco años en el Hospital de Especialidades Centro Médico Nacional Siglo XXI.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a frequent disease. It is characterized by hypercalcemia and elevation of parathyroid hormone (PTH) levels. The incidence is variable, being more frequent in women (3:1) in the perimenopauseal period. In the last decades, diagnosis of asymptomatic PHPT has increased due to automatized calcium determinations. Duration of the disease and serum concentrations of calcium and PTH determine symptomatology. Surgery is the definitive treatment. It is important to assess surgical criteria in asymptomatic patients. Successful treatment of this disease depends on a highly specialized team of parathyroid surgeons. MATERIAL AND METHODS: We reviewed the clinical and biochemical background of patients subjected to parathyroidectomy from January 1998 to August 2003 in our medical center. We then analyzed clinical and laboratory data, final histopathologic diagnosis, and surgery outcome. RESULTS: Sixty seven patients were included, with an average age of 50 years (+/- 11.9), 15 men and 52 women. Greatest frequency of PHPT was observed in patients between 40 and 60 years of age. Average calcium value was 11.7 mg/dl (+/- 1.23) and that of PTH was 194.5 pg/ml (+/- 93). Histopathologic diagnosis was adenoma in 56 (83.58%), hyperplasia in 9 (13.43%), and carcinoma in 2 (2.9%) patients. Cure of the disease was achieved in 65 patients (97%). PHPT is a surgically curable disease; it is necessary to confirm diagnosis and decide on surgical treatment in accordance with established criteria even if the disease is asymptomatic.