A deep-learning strategy to identify cell types across species from high-density extracellular recordings.

High-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but don't reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals, revealing the computational roles of neurons with distinct functional, molecular, and anatomical properties. We combine optogenetic activation and pharmacology using the cerebellum as a testbed to generate a curated ground-truth library of electrophysiological properties for Purkinje cells, molecular layer interneurons, Golgi cells, and mossy fibers. We train a semi-supervised deep-learning classifier that predicts cell types with greater than 95% accuracy based on waveform, discharge statistics, and layer of the recorded neuron. The classifier's predictions agree with expert classification on recordings using different probes, in different laboratories, from functionally distinct cerebellar regions, and across animal species. Our classifier extends the power of modern dynamical systems analyses by revealing the unique contributions of simultaneously-recorded cell types during behavior.

Mycosis Fungoides in Children and Adolescents: A Series of 23 Cases. / Micosis fungoide en niños y adolescentes: descripción de una serie de 23 casos.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma in adults and children. The prevalence has increased in some countries, but no descriptive studies of MF in the pediatric population have been done in Colombia to date. METHODS: A combined prospective-retrospective study of 128 patients with a diagnosis of MF confirmed by the dermatology department and dermatopathology laboratory of Universidad de Antioquia between 2008 and 2017. We describe the clinical and histopathologic variants, response to treatment, and progression of the disease in 23 patients under 18 years of age. RESULTS: The pediatric cases of MF accounted for 18% of all the cases on record. The median age of onset of lesions was 9 years, the median age at diagnosis was 11 years, and the median time between onset of lesions and diagnosis was 2 years. All patients were in early stages of the disease. Hypopigmented MF was the most common clinical presentation (in 52.2%), followed by classical MF (in 30.4%). Folliculotropic MF was identified in 17.4%. All patients were treated with topical corticosteroids and phototherapy. One patient received chemotherapy while still in the early stage of disease. Complete remission was achieved in 59.1% and a partial response in 40.9%. Only 2 patients remained asymptomatic for 5 years. CONCLUSION: We found hypopigmented MF to be the most common clinical presentation in patients under 18 years of age. The disease did not progress to advanced stages in any of the patients, although recurrence after treatment interruption was common.

Differences in chronic spontaneous urticaria between Europe and Central/South America: results of the multi-center real world AWARE study.

BACKGROUND: Global chronic urticaria (CU) disease experience and management is not well documented. This study descriptively compares these aspects among CU patients residing in Europe (EU) and Central and South America (C/SA). METHODS: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global prospective, non-interventional study of CU in the real-world setting. Patients were ≥ 18 years with a diagnosis of H1-antihistamine-refractory CU for > 2 months. Differences between the EU and C/SA regions in demographic and clinical characteristics, quality of life (QoL), work and activity impairment, pharmacological treatment, and healthcare resource use were examined. RESULTS: In total, 4224 patients were included in the analysis (C/SA 492; EU 3732). Rates of untreated patients were greater in the C/SA region (45.1% vs. 31.9%; P < 0.005) and escalation to third-line therapy was rare in both regions. Differences in disease experience emerged, with C/SA patients more commonly experiencing angioedema (C/SA 50.8% vs. EU 46.1%; P = 0.03) or comorbid chronic inducible urticaria (C/SA 30% vs. EU 22%; P < 0.001). Correspondingly, rates of uncontrolled urticaria were higher among C/SA patients (82.8% vs. 77.5%; P = 0.017) and patients in the C/SA region showed significantly greater work and activity impairment (absenteeism: 10.4 ± 19.7 vs. 6.7 ± 19.0, P = 0.004; presenteeism: 30.3 ± 31.9 vs. 24.4 ± 25.8, P = 0.001; work productivity loss: 33.9 ± 33.9 vs. 26.5 ± 27.5, P < 0.001; activity impairment: 37.7 ± 34.7 vs. 32.7 ± 30.1, P = 0.001). However, QoL impairment was greater in the EU region (Dermatology Life Quality Index: C/SA 6.5 ± 5.9 vs. EU 8.3 ± 7.0; P < 0.001). There was a significant difference in use of healthcare resources, including emergency services (39.6% vs. 29.3%; P < 0.001), hospitalization (7.7% vs 21.9%; P < 0.001) general practitioners (31.7% vs 57.3%; P < 0.001), and additional allergists or dermatologists (50.6% vs. 47.3%, P < 0.001), among patients in the C/SA and EU region, respectively. In both regions, patients with a primary diagnosis of CU with angioedema had significantly greater impairment in work and non-work activities and healthcare resource utilization compared to those without angioedema. CONCLUSIONS: This study revealed that CU is a heterogeneous condition with differences in healthcare utilization and outcomes between EU and C/SA. However, overall there is a high unmet need of H1-antihistamine-refractory CU patients, which is associated with high use of healthcare resources, and has a large negative effect on QoL and work productivity.

Estrés y factores relacionados en padres con hijos en la unidad / Stress and related factors in parents with children in neonatal intensive care unit

Objetivo: identificar el nivel de estrés y los factores relacionados, en padres con hijos en la Unidad de Cuidado Intensivo neonatal de la Clínica Universitaria Bolivariana. Metodología: estudio cuantitativo, de tipo descriptivo, transversal. Se aplicó la escala de Estrés Parental en la Unidad de Cuidado Intensivo, PSS: NICU, desarrollada y validada por Carter y Miles. En total se estudiaron a 50 padres, escogidos a conveniencia. Resultados: la edad promedio de los padres fue de 30.6 años, el 36.7 por ciento tenían escolaridad universitaria, el 42 por ciento con estrato socioeconómico nivel 3. El 62 por ciento eran empleados, el 76 por ciento de género femenino y para el 42 por ciento era su primer hijo. El principal diagnóstico del neonato fue de enfermedad respiratoria (24 por ciento). El 44 por ciento de los padres señaló que el nivel de estrés frente a lo que vio y escuchó en la unidad fue un poco estresante. El comportamiento, el aspecto y los tratamientos del bebé, fueron un poco estresantes para el 34 por ciento. El 32 por ciento de los padres señaló que era muy estresante su relación y rol de padres, valor que fue significativo estadísticamente. La comunicación con el personal de salud, para el 34 por ciento de los padres, fue poco estresante. Para el nivel de estrés general, el 28 por ciento expresó que la experiencia en general de tener a su hijo en la unidad, fue poco estresante, mientras que el 24 por ciento indicó que fue muy estresante. Conclusión: Los padres presentaron mayor estrés, cuando se desempeñan en su rol de padres, valor con significancia estadística.

Objective: To identify the level of stress and related factors in parents of children in the Neonatal Intensive Care Unit of the Clinica Universitaria Bolivariana. Methodology: study quantitative, descriptive, transversal. We applied the Parental Stress Scale in Intensive Care Unit, PSS: NICU, developed and validated by Carter and Miles. A total of 50 parents was studied, chosen for convenience. Results: The mean age of the fathers was 30.6 years; the 36.7 percent had college education, 42 percent with socioeconomic level 3. 62 percent were employed, 76 percent female and in the 42 percent was their first child. The primary diagnosis was neonatal respiratory disease (24 percent). The 44 percent of parents said that the stress level compared to what they had seen and heard in the unit was a bit stressful. The baby behavior, appearance and treatments were a bit stressful for 34 percent. The 32 percent of parents pointed that their relationship and parenting role was very stressful, value which was statistically significant. Communication with health personnel was rushed for the 34 percent of parents. For the general stress level, 28 percent expressed that the overall experience of having your child in the unit, was little stressful, while 24 percent said that it was very stressful. Conclusion: Parents showed more stress when working in their role as parents, statistically significant value.

Human spleen contains different subsets of dendritic cells and regulatory T lymphocytes.

Most knowledge about dendritic cells (DCs) and regulatory T cells in humans has been gathered from circulating cells but little is known about their frequency and distribution in lymphoid organs. This report shows the frequency, phenotype and location of DCs and regulatory T cells in deceased organ donors' spleens. As determined by flow cytometry, conventional/myeloid DCs (cDCs) CD11c(high)HLA-DR(+)CD123(-/low) were 2.3 +/- 0.9% and LIN(-) HLA-DR(+)CD11c(high) 2.1 +/- 0.3% of total spleen cells. Mature CD11c(high)HLA-DR(+)CD83(+) were 1.5 +/- 0.8% and 1.0 +/- 1.6% immature CD11c(high)HLA-DR(+)CD83(-) cDC. There were 0.3 +/- 0.3% plasmacytoid DCs (pDC) CD11c(-/low)HLA-DR(+)CD123(high) and 0.3 +/- 0.1% LIN(-)HLA-DR(+)CD123(high). Cells expressing cDCs markers, BDCA-1 and BDCA-3, and pDCs markers BDCA-2 and BDCA-4 were observed in higher frequencies than DCs with other phenotypes evaluated. CD11c(+), CD123(+) and CD83(+) cells were located in subcapsular zone, T cells areas and B-cell follicles. CD4(+)CD25(high) Tregs were 0.2 +/- 0.2% and CD8(+)CD28(-) comprised 11.5 +/- 8.1% of spleen lymphocytes. FOXP3(+) cells were found in T- and B-cell areas. The improvement in cell separation, manipulation and expansion techniques, will facilitate the manipulation of donor spleen cells as a part of protocols for induction and maintenance of allograft tolerance or treatment of autoimmune diseases.

Enhanced allograft survival and modulation of T-cell alloreactivity induced by inhibition of MMP/ADAM enzymatic activity.

Recent studies have shown significantly increased expression of matrix metalloproteinases (MMP) and disintegrin-type metalloproteinases (ADAM) during allograft rejection. In this regard, our previous studies have demonstrated contrasting roles for MMP-2 and MMP-9 during allograft rejection: MMP-2-deficiency enhanced allograft survival while MMP-9-deficiency decreased allograft survival. The aim of this study was to determine the effect of broad-spectrum MMP/ADAM inhibition on the pathogenesis of allograft rejection. Toward this, heterotopic BALB/c cardiac allografts were transplanted into C57BL/6 recipients treated with MMP/ADAM inhibitors, GM6001 or doxycycline. Systemic MMP/ADAM inhibition significantly enhanced allograft survival. Functioning allografts recovered from MMP/ADAM inhibitor-treated recipients showed lower cellular infiltration and tissue remodeling than rejected allografts recovered from control recipients. In addition, decreased chemotaxis of CD4+ and CD8+ T cells, B cells and macrophages was observed in vitro in the presence of MMP/ADAM inhibitors. Enhanced T-cell alloreactivity was also observed ex vivo in MMP/ADAM inhibitor-treated recipients and in vitro in the presence of MMP/ADAM inhibitors. These observations were associated with enhanced cytokine, chemokine and growth factor production. These results indicate that MMPs and ADAMs play a critical role in the pathogenesis of allograft rejection and may represent novel therapeutic targets for the treatment and/or prevention of this disease.

Optical coherence tomography characteristics of full-thickness traumatic macular holes.

PURPOSE: The objective of this paper is to describe the optical coherence tomography (OCT) characteristics of patients with full-thickness traumatic macular hole (TMH) and to correlate them with biomicroscopy findings. METHODS: Twelve eyes of ten consecutive patients with full-thickness TMH participated in this observational retrospective multicentre study. Patients underwent biomicroscopic fundus examination, colour fundus photography, and OCT. RESULTS: Traumatic macular hole was documented with OCT in five women and five men. Mean (range) time between trauma and macular hole (MH) diagnosis was 8.1 (1-24) months. The shape of TMHs was round in 11 (91.7%) eyes. The posterior vitreous was completely detached in six (50%) eyes, and with an operculum in one (8.3%) eye. The common findings seen on OCT were: (1) full-thickness loss of retinal tissue through the hole with sharp edges, perpendicular to the retinal pigment epithelium in five (41.7%) eyes; (2) TMH with an operculum totally detached from the hole's edge in two (16.7%) eyes; (3) presence of epiretinal membrane around of the hole in three (25%) eyes; and (4) presence of abnormalities of the surrounding retina in all (100%) eyes. The OCT characteristics correlated well with biomicroscopic findings, and these characteristics may be predictive for final visual acuity (VA) in TMHs. Only one of the TMHs closed spontaneously in our series. CONCLUSION: Optical coherence tomography complements biomicroscopy in the evaluation of full-thickness TMHs.

Obtención de oleorresina de pimentón (Capsicum annuum L) / Extraction of oleoresin from sweet pepper (Capsicum annuum L)

La oleorresina de pimentón (Capsicum annuum L.) contiene fundamentalmente carotenoides, capsaicinoides y algunas vitaminas. Tradicionalmente se usa en la industria alimentaria. Se obtiene mediante un proceso en las siguientes etapas: a) escaldado, b) troceado, c) secado, d) molienda, y e) extracción con solventes volátiles (hexano, acetona, acetato de etilo). Los pigmentos que se extraen se analizan mediante HPLC en fase reversa y se comparan con la oleorresina de paprika comercial importada por la empresa TECNAS©.El rendimiento que se obtiene en el laboratorio está entre 3 (por ciento) y 6 (por ciento). Los resultados muestran la importancia del escaldado y del secado: el escaldado permite alcanzar una humedad del 13,56 (por ciento) en 320 min (sin escaldar en el mismo tiempo se llega al 21,01 (por ciento) y el secado posibilita la extracción con solventes.

El Plan de Atención Básica en los municipios descentralizados de Colombia, 2001-2003 / The Basic Health Care Plan (PAB) in decentralized municipalities in Colombia, 2001-2003

El Plan de Atención Básica (PAB) del Sistema General de Seguridad Social de Salud (SGSSS) de Colombia es un paquete de actividades que está orientado a la colectividad para garantizar las condiciones necesarias de la población para que no corra el riesgo de enfermar o morir por causas biológicas, ambientales ni sociales prevenibles. El Ministerio de Salud expidió la Resolución 4288 en 1996 y los lineamientos del PAB en el 2000 que sirvieron de referentes para la evaluación del plan. Objetivo: conocer los aspectos más importantes de la gestión de los planes de atención básica desarrollados en los distintos municipios descentralizados del país, incluyendo elementos de formulación, ejecución y evaluación para determinar la coherencia entre la normatividad y lo que acontece en los espacios locales concretos. Métodos: se realizó un estudio descriptivo, cuantitativo, que tomó una muestra representativa aleatoria de 212 municipios descentralizados y clasificados por categorías, de los cuales respondieron la encuesta 174. Resultados: este estudio permitió identificar aciertos y falencias, concluir sobre los principales problemas de la gestión del PAB y formular recomendaciones que sirvan de guía para la toma de decisiones a escala local, contribuyendo al mejoramiento de la salud pública de la población. El proceso desigual de construcción de autonomía territorial para asumir la salud y la incipiente organización y gestión administrativa del municipio y de la dirección local de salud influyeron en el desarrollo del PAB; además, las necesidades en salud pública de los colombianos superan grandemente las acciones del plan, y es preciso reorientar su enfoque con estrategias basadas en el trabajo intersectorial e interinstitucional, la creación de ambientes favorables y el fortalecimiento de la acción comunitaria para propiciar instancias colectivas que constituyan el soporte para el bienestar de la vida.

Hematologic reconstitution following high-dose and supralethal chemoradiotherapy using stored, noncryopreserved autologous hematopoietic stem cells.

Although cryopreservation is the standard for autotransplantation, it has logistic and financial disadvantages in undeveloped countries such as Colombia. In 47 patients, peripheral blood was refrigerated at 4 degrees C up to 144 h before autotransplantation. For mobilization, 27 men and 20 women of median age 37 years affected with hematologic malignancies received G-CSF. The 17 patients in Group 1 showed pre-refrigeration CFU-GM of 2.62 x 10(5)/kg (range 0.36 to 16.6 x 10(5)/kg) and at re-infusion, 1.36 x 10(5)/kg (range 0 to 6.32 x 10(5)/kg) of 83% viability (range, 78% to 96%). These patients showed >0.5 x 10(9)/L granulocytes on day +11 (range, 9 to 15) and >20 x 10(9)/L platelets on day +16 (range, 11 to 44). The 25 patients in Group 2 showed CD34 of 3.9 x 10(6)/kg (range, 0.16 to 9 x 10(6)/kg) and mononuclear cell count (MNC) of 8.7 x 10(8)/kg, reaching >0.5 x 10(9)/L granulocytes at day +13 (range, 10 to 17) and >20 x 10(9)/L on day +15 (range, 14 to 20). Among the 5 patients in Group 3, the average of MNC of 12.7 x 10(8)/kg was reached and >0.5 x 10(9)/L granulocytes on day 11 (range, 10 to 16) and >20 x 10(9)/L on day 14 (range, 10 to 18). No differences were observed between the groups. Refrigeration of stem cells appears to be a simple, effective, and inexpensive method that should be considered for autotransplants within a few days of harvesting when resources are limited for long-term storage.

Jejunal and cecal 3-oxy-methyl-D-glucose absorption in chicken using a perfusion system in vivo.

3-oxy-methyl-D-glucose (3-OMG) absorption by jejunum and caecum has been studied in the domestic fowl in vivo, with luminal perfusion, during 5 min periods. The diffusion component was evaluated in the presence of phloridzin (10(-3) M) that inhibits the active transport mechanism. Kd of jejunal and cecal diffusion of the monosaccharide have been calculated, showing a similar value. The Kt and Vmax of 3-OMG absorption were calculated using a graphical method for the two intestinal segments. The caecum showed a lower Kt and Vmax than the jejunum did.

Absorption of 3-oxy-methyl-D-glucose by chicken cecum and jejunum in vivo.

Jejunal and cecal 3-oxy-methyl-D-glucose (3-OMG) absorption was studied in 4- to 8-week-old chickens by an in vivo perfusion technique (perfusion rate 1.5 ml/min). Total and phloridzin-insensitive 3-OMG absorption was tested for lumenal substrate concentrations ranging from 1.25 to 20 mmol/l. The estimated apparent Michaelis constants in jejunum and cecum were 5.1 and 4.0 mmol/l (Lineweaver-Burk method) and 3.2 and 3.1 mmol/l (visual inspection method), respectively. Vmax were similar in both segments with either method, about 0.3 mumol/cm2 X 5 min. Passive permeability coefficients were the same in both regions (about 45 l/cm2 X 5 min X 10(3)). The transport properties of the cecal epithelium in vivo suggest a role of these intestinal segments in the absorption of nutrients originated from digestive processes.