Modulation of neuronal activity in human centromedian nucleus during an auditory attention and working memory task.

Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been suggested to play a key role in the control of attention, by regulating the flow of information to different brain regions such as the ascending reticular system, basal ganglia, and cortex. While the neurophysiology of attention in visual and auditory systems has been studied in animal models, combined single unit and LFP recordings in human have not, to our knowledge, been reported. Here, we recorded neuronal activity in the CM nucleus in 11 patients prior to insertion of deep brain stimulation electrodes for the treatment of epilepsy while subjects performed an auditory attention task. Patients were requested to attend and count the infrequent (p = 0.2) odd or "deviant" tones, ignore the frequent standard tones and report the total number of deviant tones at trial completion. Spikes were discriminated, and LFPs were band pass filtered (5-45 Hz). Average peri­stimulus time histograms and spectra were constructed by aligning on tone onsets and statistically compared. The firing rate of CM neurons showed selective, multi-phasic responses to deviant tones in 81% of the tested neurons. Local field potential analysis showed selective beta and low gamma (13-45 Hz) modulations in response to deviant tones, also in a multi-phasic pattern. The current study demonstrates that CM neurons are under top-down control and participate in the selective processing during auditory attention and working memory. These results, taken together, implicate the CM in selective auditory attention and working memory and support a role of beta and low gamma oscillatory activity in cognitive processes. It also has potential implications for DBS therapy for epilepsy and non-motor symptoms of PD, such as apathy and other disorders of attention.

Automated extraction of information from free text of Spanish oncology pathology reports.

Background: Pathology reports are stored as unstructured, ungrammatical, fragmented, and abbreviated free text with linguistic variability among pathologists. For this reason, tumor information extraction requires a significant human effort. Recording data in an efficient and high-quality format is essential in implementing and establishing a hospital-based-cancer registry. Objective: This study aimed to describe implementing a natural language processing algorithm for oncology pathology reports. Methods: An algorithm was developed to process oncology pathology reports in Spanish to extract 20 medical descriptors. The approach is based on the successive coincidence of regular expressions. Results: The validation was performed with 140 pathological reports. The topography identification was performed manually by humans and the algorithm in all reports. The human identified morphology in 138 reports and by the algorithm in 137. The average fuzzy matching score was 68.3 for Topography and 89.5 for Morphology. Conclusions: A preliminary algorithm validation against human extraction was performed over a small set of reports with satisfactory results. This shows that a regular-expression approach can accurately and precisely extract multiple specimen attributes from free-text Spanish pathology reports. Additionally, we developed a website to facilitate collaborative validation at a larger scale which may be helpful for future research on the subject.

Introducción: Los reportes de patología están almacenados como texto libre sin estructura, gramática, fragmentados o abreviados, con variabilidad lingüística entre patólogos. Por esta razón, la extracción de información de tumores requiere un esfuerzo humano significativo. Almacenar información en un formato eficiente y de alta calidad es esencial para implementar y establecer un registro hospitalario de cáncer. Objetivo: Este estudio busca describir la implementación de un algoritmo de Procesamiento de Lenguaje Natural para reportes de patología oncológica. Métodos: Desarrollamos un algoritmo para procesar reportes de patología oncológica en Español, con el objetivo de extraer 20 descriptores médicos. El abordaje se basa en la coincidencia sucesiva de expresiones regulares. Resultados: La validación se hizo con 140 reportes de patología. La identificación topográfica se realizó por humanos y por el algoritmo en todos los reportes. La morfología fue identificada por humanos en 138 reportes y por el algoritmo en 137. El valor de coincidencias parciales (fuzzy matches) promedio fue de 68.3 para Topografía y 89.5 para Morfología. Conclusiones: Se hizo una validación preliminar del algoritmo contra extracción humana sobre un pequeño grupo de reportes, con resultados satisfactorios. Esto muestra que múltiples atributos del espécimen pueden ser extraídos de manera precisa de texto libre de reportes de patología en Español, usando un abordaje de expresiones regulares. Adicionalmente, desarrollamos una página web para facilitar la validación colaborativa a gran escala, lo que puede ser beneficioso para futuras investigaciones en el tema.

Carnauba Wax and Beeswax as Structuring Agents for Water-in-Oleogel Emulsions without Added Emulsifiers.

This research aims to explore the potential of waxes as ingredients in the formulation of food-grade water-in-oleogel emulsions without added emulsifiers. The effects of the wax type, wax concentration and water concentration were tested on systems containing exclusively water, sunflower oil, and wax. Beeswax and carnauba wax were used in the formulation of water-in-oleogel emulsions with 20%, 30% and 40% w/w of water. For the continuous phase, three different levels of wax were used, namely 50%, 100%, and 150% of the critical gelling concentration. More specifically, carnauba wax emulsions were prepared at 2.5%, 5.0% and 7.5% of wax, while concentrations of 0.75%, 1.5% and 2.25% of wax were utilized for the beeswax experiments. Samples were assessed over time regarding stability, rheology and microstructure (polarized light microscopy, cryo-scanning electron microscopy and confocal scanning laser microscopy). Our findings suggest that, if present in sufficient concentration, carnauba wax and beeswax can stabilize emulsions in the absence of additional added emulsifiers. The resulting systems were inherently different based on the wax used, as crystal morphology and droplet configurations are determined by wax type. The yield strain was dictated by the nature of the wax, while the complex modulus was mostly influenced by the wax concentration. To test the scaling-up potential, systems were crystallized in a pilot-scale scraped surface heat exchanger, resulting in notably smaller crystal sizes, reduced rigidity and a storage stability of over one year. These findings represent a starting point for the formulation of scalable water-in-oleogel emulsions without added emulsifiers.

Automated extraction of information from free text of Spanish oncology pathology reports

Background: Pathology reports are stored as unstructured, ungrammatical, fragmented, and abbreviated free text with linguistic variability among pathologists. For this reason, tumor information extraction requires a significant human effort. Recording data in an efficient and high-quality format is essential in implementing and establishing a hospital-based-cancer registry Objective: This study aimed to describe implementing a natural language processing algorithm for oncology pathology reports. Methods: An algorithm was developed to process oncology pathology reports in Spanish to extract 20 medical descriptors. The approach is based on the successive coincidence of regular expressions. Results: The validation was performed with 140 pathological reports. The topography identification was performed manually by humans and the algorithm in all reports. The human identified morphology in 138 reports and by the algorithm in 137. The average fuzzy matching score was 68.3 for Topography and 89.5 for Morphology. Conclusions: A preliminary algorithm validation against human extraction was performed over a small set of reports with satisfactory results. This shows that a regular-expression approach can accurately and precisely extract multiple specimen attributes from free-text Spanish pathology reports. Additionally, we developed a website to facilitate collaborative validation at a larger scale which may be helpful for future research on the subject.

Introducción: Los reportes de patología están almacenados como texto libre sin estructura, gramática, fragmentados o abreviados, con variabilidad lingüística entre patólogos. Por esta razón, la extracción de información de tumores requiere un esfuerzo humano significativo. Almacenar información en un formato eficiente y de alta calidad es esencial para implementar y establecer un registro hospitalario de cáncer. Objetivo: Este estudio busca describir la implementación de un algoritmo de Procesamiento de Lenguaje Natural para reportes de patología oncológica. Métodos: Desarrollamos un algoritmo para procesar reportes de patología oncológica en Español, con el objetivo de extraer 20 descriptores médicos. El abordaje se basa en la coincidencia sucesiva de expresiones regulares. Resultados: La validación se hizo con 140 reportes de patología. La identificación topográfica se realizó por humanos y por el algoritmo en todos los reportes. La morfología fue identificada por humanos en 138 reportes y por el algoritmo en 137. El valor de coincidencias parciales (fuzzy matches) promedio fue de 68.3 para Topografía y 89.5 para Morfología. Conclusiones: Se hizo una validación preliminar del algoritmo contra extracción humana sobre un pequeño grupo de reportes, con resultados satisfactorios. Esto muestra que múltiples atributos del espécimen pueden ser extraídos de manera precisa de texto libre de reportes de patología en Español, usando un abordaje de expresiones regulares. Adicionalmente, desarrollamos una página web para facilitar la validación colaborativa a gran escala, lo que puede ser beneficioso para futuras investigaciones en el tema.

Oil Phase Solubility Rather Than Diffusivity Determines the Release of Entrapped Amino Acids and Di-Peptides from Water-in-Oil-in-Water Emulsions.

The permeation of amino acids and di-peptides with different hydrophobicities across the oil phase in W/O/W double emulsions was investigated at different concentrations, considering the pH of the aqueous phase. Moreover, the particle size, yield of entrapped water and release kinetics of the double emulsions was evaluated as a function of time. Regarding the release of the entrapped amino acids and di-peptides, their hydrophobicity and the pH had a significant effect, whereas the concentration of the dissolved compound did not lead to different release kinetics. The release of the amino acids and di-peptides was faster at neutral pH as compared to acidic pH values due to the increased solute solubility in the oil phase for more hydrophobic molecules at neutral pH. Regarding the effect of the type of oil, much faster amino acid transport was observed through MCT oil as compared to LCT oil, which might be due to its higher solubility and/or higher diffusivity. As di-peptides released faster than amino acids, it follows that the increased solubility overruled the effect from the decreased diffusion coefficient of the dissolved compound in the oil phase.

Hidradenitis suppurativa: Basic considerations for its approach: A narrative review.

Hidradenitis suppurativa is a chronic and debilitating skin disease, whose lesions can range from inflammatory nodules to abscesses and fistulas in the armpits, groin, perineum, inframammary region. Diagnosis can be confused with a large number of clinical pictures, and although studies on hidradenitis suppurativa are not so scarce in the literature, doctors are often unaware of this disease and therefore its diagnosis is often late. Pharmacological treatment ranges from retinoids to immunosuppression and radiation therapy, and surgical treatment ranges from incision and drainage to more complete excisions and laser therapies. Hidradenitis suppurativa is a disease seen and treated mainly by dermatologists and general surgeons, however, it is necessary for general practitioners to have basic knowledge about this entity, as they are the first line of care in the health system.

Platelets Restrict the Oxidative Burst in Phagocytes and Facilitate Primary Progressive Tuberculosis.

Rationale: Platelets are generated in the capillaries of the lung, control hemostasis, and display immunological functions. Tuberculosis primarily affects the lung, and patients show platelet changes and hemoptysis. A role of platelets in immunopathology of pulmonary tuberculosis requires careful assessment.Objectives: To identify the dynamics and interaction partners of platelets in the respiratory tissue and establish their impact on the outcome of pulmonary tuberculosis.Methods: Investigations were primarily performed in murine models of primary progressive pulmonary tuberculosis, by analysis of mouse strains with variable susceptibility to Mycobacterium tuberculosis infection using platelet depletion and delivery of antiplatelet drugs.Measurements and Main Results: Platelets were present at the site of infection and formed aggregates with different myeloid subsets during experimental tuberculosis. Such aggregates were also detected in patients with tuberculosis. Platelets were detrimental during the early phase of infection, and this effect was uncoupled from their canonical activation. Platelets left lung cell dynamics and patterns of antimycobacterial T-cell responses unchanged but hampered antimicrobial defense by restricting production of reactive oxygen species in lung-residing myeloid cells.Conclusions: Platelets are detrimental in primary progressive pulmonary tuberculosis, orchestrate lung immunity by modulating innate immune responsiveness, and may be amenable to new interventions for this deadly disease.

Introducción, epidemiología y diagnóstico de la enfermedad de Parkinson / Introduction, epidemiology and diagnosis of Parkinson's disease

RESUMEN La enfermedad de Parkinson es un trastorno neurodegenerativo que tiene múltiples manifestaciones motoras y no motoras. El proceso patológico inicia años o décadas antes del debut de los síntomas no motores, tiempo en el que se desarrollan otros síntomas que muy frecuentemente preceden el inicio clínico. Si bien se ha avanzado mucho en el conocimiento sobre la patogénesis y en el reconocimiento de las numerosas manifestaciones no motoras, el diagnóstico se sigue centrando en el síndrome motor o parkinsonismo. En este capítulo se muestra una actualización sobre datos recientes relacionados con el incremento en la prevalencia mundial de la enfermedad, así como el diagnóstico basado en los nuevos criterios definidos por la Sociedad Internacional de Trastornos del Movimiento en 2015, que se basan en los criterios centrales pero tienen en cuenta banderas rojas para la posible existencia de otros parkinsonismos, criterios de exclusión absoluta y criterios de soporte, éstos últimos reconociendo la utilidad de los síntomas no motores y de algunas ayudas paraclínicas para soportar el diagnóstico in vivo.

SUMMARY Parkinson's disease is a neurodegenerative disorder that has multiple motor and non-motor manifestations. The pathological process begins years or decades before the onset of non-motor symptoms, at which time other symptoms develop that frequently precede clinical debut. Although much progress has been made in the knowledge of pathogenesis and in the recognition of the numerous non-motor manifestations, the diagnosis is still focused on motor syndrome or parkinsonism. This chapter shows an update on recent data related to the increase in the global prevalence of the disease, as well as the diagnosis based on the new criteria defined by the Movement Disorders Society in 2015, which focus on the central criteria but defined red flags for the possible existence of other parkinsonisms, absolute exclusion criteria and support criteria, the latter recognizing the utility of non-motor symptoms and some paraclinical aids to support in vivo diagnosis.

Biogeographic regions and events of isolation and diversification of the endemic biota of the tropical Andes.

Understanding the spatial and temporal evolution of biota in the tropical Andes is a major challenge, given the region's topographic complexity and high beta diversity. We used a network approach to find biogeographic regions (bioregions) based on high-resolution species distribution models for 151 endemic bird taxa. Then, we used dated molecular phylogenies of 14 genera to reconstruct the area history through a sequence of allopatric speciation processes. We identified 15 biogeographical regions and found 26 events of isolation and diversification within their boundaries that are independently confirmed with disjunct distributions of sister taxa. Furthermore, these events are spatially congruent with six geographical barriers related to warm and/or dry river valleys, discontinuities in elevation, and high peaks separating fauna from different range slopes. The most important barrier is the Marañon River Valley, which limits the boundaries of four bioregions and is congruent with eight phylogenetic distribution breaks, separating the Central and Northern Andes, where the most bioregions are found. We also show that many bioregions have diffuse and overlapping structures, with contact and transition zones that challenge previous conceptions of biogeographical regions as spatially simple in structure. This study found evidence that the drivers of our identified bioregions were processes of Andean uplift and mountain dispersal facilitated by temperature oscillations of the Pleistocene. Therefore, Andean bioregions were not formed from one simple biogeographical event in a certain time frame, but from a combination of vicariance and dispersal events, which occurred in different time periods.

Downregulation of Membrane Trafficking Proteins and Lactate Conditioning Determine Loss of Dendritic Cell Function in Lung Cancer.

Restoring antigen presentation for efficient and durable activation of tumor-specific CD8+ T-cell responses is pivotal to immunotherapy, yet the mechanisms that cause subversion of dendritic cell (DC) functions are not entirely understood, limiting the development of targeted approaches. In this study, we show that bona fide DCs resident in lung tumor tissues or DCs exposed to factors derived from whole lung tumors become refractory to endosomal and cytosolic sensor stimulation and fail to secrete IL12 and IFNI. Tumor-conditioned DC exhibited downregulation of the SNARE VAMP3, a regulator of endosomes trafficking critical for cross-presentation of tumor antigens and DC-mediated tumor rejection. Dissection of cell-extrinsic suppressive pathways identified lactic acid in the tumor microenvironment as sufficient to inhibit type-I IFN downstream of TLR3 and STING. DC conditioning by lactate also impacted adaptive function, accelerating antigen degradation and impairing cross-presentation. Importantly, DCs conditioned by lactate failed to prime antitumor responses in vivo These findings provide a new mechanistic viewpoint to the concept of DC suppression and hold potential for future therapeutic approaches.Significance: These findings provide insight into the cell-intrinsic and cell-extrinsic mechanisms that cause loss of presentation of tumor-specific antigens in lung cancer tissues. Cancer Res; 78(7); 1685-99. ©2018 AACR.

The cGAS/STING Pathway Detects Streptococcus pneumoniae but Appears Dispensable for Antipneumococcal Defense in Mice and Humans.

Streptococcus pneumoniae is a frequent colonizer of the upper respiratory tract and a leading cause of bacterial pneumonia. The innate immune system senses pneumococcal cell wall components, toxin, and nucleic acids, which leads to production of inflammatory mediators to initiate and control antibacterial defense. Here, we show that the cGAS (cyclic GMP-AMP [cGAMP] synthase)-STING pathway mediates detection of pneumococcal DNA in mouse macrophages to primarily stimulate type I interferon (IFN) responses. Cells of human individuals carrying HAQ TMEM173, which encodes a common hypomorphic variant of STING, were largely or partly defective in inducing type I IFNs and proinflammatory cytokines upon infection. Subsequent analyses, however, revealed that STING was dispensable for restricting S. pneumoniae during acute pneumonia in mice. Moreover, explorative analyses did not find differences in the allele frequency of HAQ TMEM173 in nonvaccinated pneumococcal pneumonia patients and healthy controls or an association of HAQ TMEM173 carriage with disease severity. Together, our results indicate that the cGAS/STING pathway senses S. pneumoniae but plays no major role in antipneumococcal immunity in mice and humans.

The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele.

TMEM173 encodes MPYS/STING and is an innate immune sensor for cyclic dinucleotides (CDNs) playing a critical role in infection, inflammation, and cancer. The R71H-G230A-R293Q (HAQ) of TMEM173 is the second most common human TMEM173 allele. In this study, using data from the 1000 Genomes Project we found that homozygous HAQ individuals account for ∼16.1% of East Asians and ∼2.8% of Europeans whereas Africans have no homozygous HAQ individuals. Using B cells from homozygous HAQ carriers, we found, surprisingly, that HAQ/HAQ carriers express extremely low MPYS protein and have a decreased TMEM173 transcript. Consequently, the HAQ/HAQ B cells do not respond to CDNs. We subsequently generated an HAQ knock-in mouse expressing a mouse equivalent of the HAQ allele (mHAQ). The mHAQ mouse has decreased MPYS protein in B cells, T cells, Ly6Chi monocytes, bone marrow-derived dendritic cells, and lung tissue. The mHAQ mouse also does not respond to CDNs in vitro and in vivo. Lastly, Pneumovax 23, with an efficacy that depends on TMEM173, is less effective in mHAQ mice than in wild type mice. We conclude that HAQ is a null TMEM173 allele. Our findings have a significant impact on research related to MPYS-mediated human diseases and medicine.

Niveles de impulsividad y riesgo de alcoholismo en personas pertenecientes a barras bravas en la ciudad de Ibagué - Colombia / Levels of impulsivity and risk of alcoholism in adults Belonging to "barras bravas" in the city of ibagué - Colombia

El objetivo de este trabajo es determinar la relación entre niveles de impulsividad y riesgo de alcoholismo en adultos pertenecientes a "barras bravas" en la ciudad de Ibagué (Tolima) a partir de la aplicación del test de CAGE, la Escala de Impulsividad de Plutchik (EI) y una ficha de caracterización sociodemográfica. Se utilizó un modelo correlacional de corte transversal. Los hallazgos evidencian niveles bajos (78%) y promedios de impulsividad (20%). El 28% no presenta problemas relacionados con el alcohol, mientras que el 36% tiene indicios de consumo y el restante 36% dependencia alcohólica. Se hallaron correlaciones bajas entre las puntuaciones, la correlación significativa fue de tipo directamente proporcional entre edad y riesgo de alcoholismo (r= 0,287; p= 0.43), lo que indica que a mayor edad mayor es el riesgo de alcoholismo. © Revista Colombiana de Ciencias Sociales.

The objective of this study was to determine the relationship between levels of impulsivity and risk of alcoholism in adults belonging to "barras bravas" in the city of Ibagué (Tolima) from the application of the CAGE test, the scale of impulsiveness of Plutchik (EI) and a socio-demographic characterization data sheet. A correlational cross-sectional model was used. The findings show low levels (78%) and averages of impulsivity (20%). The 28% do not show problems related with alcohol, while 36% have signs of consumption and 36% alcoholic dependence. There were found low correlations between such scores, the significant correlation was directly proportional between age and risk of alcoholism (r = 0,287, p = 0.43) indicating that a greater age, greater is the risk of alcoholism.