Preventable risk factors for type 2 diabetes can be detected using noninvasive spontaneous electroretinogram signals.

Given the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, and some studies suggested its use for preventable risk factors of type 2 diabetes and thereby diabetic retinopathy (DR). Here, we show that in a non-evoked mode, ERG signals contain spontaneous oscillations that predict disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome but not yet diabetes, using one single random forest-based model. Classification performance was both internally and externally validated, and correlation analysis showed that the spontaneous oscillations of the non-evoked ERG are altered before oscillatory potentials, which are the current gold-standard for early DR. Principal component and discriminant analysis suggested that the slow frequency (0.4-0.7 Hz) components are the main discriminators for our predictive model. In addition, we established that the optimal conditions to record these informative signals, are 5-minute duration recordings under daylight conditions, using any ERG sensors, including ones working with portative, non-mydriatic devices. Our study provides an early warning system with promising applications for prevention, monitoring and even the development of new therapies against type 2 diabetes.

Single-Cell mRNA-Seq of In Vitro-Derived Human Neurons Using Smart-Seq2.

Single-cell mRNA sequencing can dissect heterogeneous cell populations as it can identify cell types and cellular states based on their unique transcriptional signatures. We use fluorescence-activated cell sorting (FACS) to isolate individual cultured neurons derived from human-induced pluripotent stem cells (hiPSCs) followed by polyA-based Smart-Seq2 RNA sequencing to analyze the single-cell transcriptional profiles. We provide protocols and guidelines on dissociation, cell selection, and library preparation that can be readily adapted to other cell types or tissue samples.

A risk evaluation framework for the best maintenance strategy: The case of a marine salt manufacture firm.

This paper intends to contribute with a multi-criteria decision-making (MCDM) framework to support risk evaluation for maintenance activities carried out on critical systems in industry. We propose to first select the best maintenance strategy tailored to companies' requirements and systems' features, and second to perform a risk prioritisation aimed at highlighting priorities of intervention. The Analytic Network Process (ANP) is suggested to select the maintenance policy representing the best trade-off considering the complex and varied interdependencies amongst a diversity of clustered elements characterising the system. Then, the main risks related to the interventions associated to the selected maintenance policy are ranked using the ELimination Et Choix Traduisant la REalité III (ELECTRE III) method, using the same criteria weighted by the previous ANP application. This hybrid MCDM framework is applied to a core subsystem of a real-world marine salt manufacture firm.

Modeling Motor Neuron Resilience in ALS Using Stem Cells.

Oculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Toward this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of PHOX2A in neuronal progenitors. We demonstrate, using electrophysiology, immunocytochemistry, and RNA sequencing, that in vitro-generated neurons are bona fide oculomotor neurons based on their cellular properties and similarity to their in vivo counterpart in rodent and man. We also show that in vitro-generated oculomotor neurons display a robust activation of survival-promoting Akt signaling and are more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. Thus, we can generate bona fide oculomotor neurons in vitro that display a resilience similar to that seen in vivo.

Engineering Human Epidermal Growth Receptor 2-Targeting Hepatitis B Virus Core Nanoparticles for siRNA Delivery in Vitro and in Vivo.

Hepatitis B virus core (HBc) particles acquire the capacity to disassemble and reassemble in a controlled manner, allowing entrapment and delivery of drugs and macromolecules to cells. HBc particles are made of 180-240 copies of 21 kDa protein monomers, assembled into 30-34 nm diameter icosahedral particles. In this study, we aimed at formulating HBc particles for the delivery of siRNA for gene silencing in vitro and in vivo. We have previously reported recombinant HBc particles expressing ZHER2 affibodies, specifically targeting human epidermal growth receptor 2 (HER2)-expressing cancer cells (ZHER2-ΔHBc). siRNA was encapsulated within the ZHER2-ΔHBc particles following disassembly and reassembly. The ZHER2-ΔHBc-siRNA hybrids were able to secure the encapsulated siRNA from serum and nucleases in vitro. Enhanced siRNA uptake in HER2-expressing cancer cells treated with ZHER2-ΔHBc-siRNA hybrids was observed compared to the nontargeted HBc-siRNA hybrids in a time- and dose-dependent manner. A successful in vitro polo-like kinase 1 (PLK1) gene knockdown was demonstrated in cancer cells treated with ZHER2-ΔHBc-siPLK1 hybrids, to levels comparable to commercial transfecting reagents. Interestingly, ZHER2-ΔHBc particles exhibit intrinsic capability of reducing the solid tumor mass, independent of siPLK1 therapy, in an intraperitoneal tumor model following intraperitoneal injection.

LCM-Seq: A Method for Spatial Transcriptomic Profiling Using Laser Capture Microdissection Coupled with PolyA-Based RNA Sequencing.

LCM-seq couples laser capture microdissection of cells from frozen tissues with polyA-based RNA sequencing and is applicable to single neurons. The method utilizes off-the-shelf reagents and direct lysis of the cells without RNA purification, making it a simple and relatively cheap method with high reproducibility and sensitivity compared to previous methods. The advantage with LCM-seq is also that tissue sections are kept intact and thus the positional information of each cell is preserved.

CRISPR-Trap: a clean approach for the generation of gene knockouts and gene replacements in human cells.

CRISPR/Cas9-based genome editing offers the possibility to knock out almost any gene of interest in an affordable and simple manner. The most common strategy is the introduction of a frameshift into the open reading frame (ORF) of the target gene which truncates the coding sequence (CDS) and targets the corresponding transcript for degradation by nonsense-mediated mRNA decay (NMD). However, we show that transcripts containing premature termination codons (PTCs) are not always degraded efficiently and can generate C-terminally truncated proteins which might have residual or dominant negative functions. Therefore, we recommend an alternative approach for knocking out genes, which combines CRISPR/Cas9 with gene traps (CRISPR-Trap) and is applicable to ∼50% of all spliced human protein-coding genes and a large subset of lncRNAs. CRISPR-Trap completely prevents the expression of the ORF and avoids expression of C-terminal truncated proteins. We demonstrate the feasibility of CRISPR-Trap by utilizing it to knock out several genes in different human cell lines. Finally, we also show that this approach can be used to efficiently generate gene replacements allowing for modulation of protein levels for otherwise lethal knockouts (KOs). Thus, CRISPR-Trap offers several advantages over conventional KO approaches and allows for generation of clean CRISPR/Cas9-based KOs.

Uso de tecnologías de la información y comunicación para investigación en estudiantes de medicina paraguayos / The use of information and communication technologies in research by Paraguayan medical students

Introducción: las tecnologías de la información y la comunicación agrupan todo el conjunto de técnicas y dispositivos empleados para el tratamiento y la transmisión de datos por lo que constituyen una herramienta fundamental para la investigación. Objetivos: conocer el uso de las tecnologías de la información y comunicación por parte de los estudiantes de medicina de nuestro país, cuáles son las tecnologías de la información y la comunicación a las que tienen acceso y el uso y conocimientos sobre los mismos aplicados a la investigación. Métodos: estudio descriptivo, corte transversal. Incluyó a 100 estudiantes de medicina de diversas facultades. Se incluyó a todos aquellos que aceptaron participar y se excluyó a quienes no completaron adecuadamente el cuestionario. Resultados: la computadora portátil constituye la tecnología que más poseen (87 porciento). El 20 po rciento posee un alto dominio en el manejo de computadoras. El 82 por ciento de los encuestados ha señalado a "Google" como la fuente de búsqueda más utilizada. En cuanto a los gestores de referencias 67 por ciento no sabe utilizar o no los conoce. El 62 por ciento manifiesta saber utilizar los formularios de Google Drive. Conclusión: los resultados de esta investigación pueden ser usados como un recurso para introducir conceptos de informática médica, así como cursos extracurriculares enfocados en el uso de las tecnologías de la información y la comunicación para investigación con especial énfasis en búsqueda bibliográfica, manejo de gestores de referencias e idealmente manejo de herramientas de procesamiento de datos(AU)

Introduction: Information and communication technologies comprise all the techniques and devices used to process and transmit data, which is the reason why they constitute a fundamental tool in research. Objectives: To know the use of information and communication technologies by medical students in our country, what information and communication technologies they have access to, and the use and knowledge about them as applied to research. Methods: Descriptive, cross-sectional study that included 100 medical students from various schools. All those who agreed to participate were included and those who did not complete the questionnaire were excluded. Results: The laptop is the technology equipment they possess the most (87 percent). 20 percent of them have a high command of computers. 82 percent of respondents have referred Google as the most used search source. Regarding bibliography software, 67 percent do not know how to use them or do not know them. 62 percent say they know how to use Google Drive forms. Conclusion: The results of this research can be used as a resource to introduce medical informatics concepts, as well as extracurricular courses focused on the use of information and communication technologies for research, with special emphasis on bibliography search, management of references, and ideal management of data processing tools(AU)

Uso de tecnologías de la información y comunicación para investigación en estudiantes de medicina paraguayos / The use of information and communication technologies in research by Paraguayan medical students

Introducción: las tecnologías de la información y la comunicación agrupan todo el conjunto de técnicas y dispositivos empleados para el tratamiento y la transmisión de datos por lo que constituyen una herramienta fundamental para la investigación. Objetivos: conocer el uso de las tecnologías de la información y comunicación por parte de los estudiantes de medicina de nuestro país, cuáles son las tecnologías de la información y la comunicación a las que tienen acceso y el uso y conocimientos sobre los mismos aplicados a la investigación. Métodos: estudio descriptivo, corte transversal. Incluyó a 100 estudiantes de medicina de diversas facultades. Se incluyó a todos aquellos que aceptaron participar y se excluyó a quienes no completaron adecuadamente el cuestionario. Resultados: la computadora portátil constituye la tecnología que más poseen (87 porciento). El 20 po rciento posee un alto dominio en el manejo de computadoras. El 82 por ciento de los encuestados ha señalado a "Google" como la fuente de búsqueda más utilizada. En cuanto a los gestores de referencias 67 por ciento no sabe utilizar o no los conoce. El 62 por ciento manifiesta saber utilizar los formularios de Google Drive. Conclusión: los resultados de esta investigación pueden ser usados como un recurso para introducir conceptos de informática médica, así como cursos extracurriculares enfocados en el uso de las tecnologías de la información y la comunicación para investigación con especial énfasis en búsqueda bibliográfica, manejo de gestores de referencias e idealmente manejo de herramientas de procesamiento de datos(AU)

Introduction: Information and communication technologies comprise all the techniques and devices used to process and transmit data, which is the reason why they constitute a fundamental tool in research. Objectives: To know the use of information and communication technologies by medical students in our country, what information and communication technologies they have access to, and the use and knowledge about them as applied to research. Methods: Descriptive, cross-sectional study that included 100 medical students from various schools. All those who agreed to participate were included and those who did not complete the questionnaire were excluded. Results: The laptop is the technology equipment they possess the most (87 percent). 20 percent of them have a high command of computers. 82 percent of respondents have referred Google as the most used search source. Regarding bibliography software, 67 percent do not know how to use them or do not know them. 62 percent say they know how to use Google Drive forms. Conclusion: The results of this research can be used as a resource to introduce medical informatics concepts, as well as extracurricular courses focused on the use of information and communication technologies for research, with special emphasis on bibliography search, management of references, and ideal management of data processing tools(AU)

Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons.

Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward the possibility of treating brain injuries or diseases. To date, it has been possible to obtain GABAergic and glutamatergic neurons via in vivo conversion, but the precise phenotype of these cells has not yet been analyzed in detail. Here, we show that neurons reprogrammed using Ascl1, Lmx1a, and Nurr1 functionally mature and integrate into existing brain circuitry and that the majority of the reprogrammed neurons have properties of fast-spiking, parvalbumin-containing interneurons. When testing different combinations of genes for neural conversion with a focus on pro-neural genes and dopamine fate determinants, we found that functional neurons can be generated using different gene combinations and in different brain regions and that most of the reprogrammed neurons become interneurons, independently of the combination of reprogramming factors used.

Revealing allele-specific gene expression by single-cell transcriptomics.

Single-cell sequencing has emerged as a revolutionary method that reveals biological processes with unprecedented resolution and scale, and has already greatly impacted biology and medicine. To investigate processes such as alternative splicing, novel exon detection and allele-specific expression (ASE), full-length based single-cell RNA-seq methods are required for broad sequence coverage and single nucleotide polymorphism (SNP) identification. In this review, we revisit recent achievements from studies that used single-cell RNA-seq to advance our understanding of ASE in the context of both autosomal and X-chromosome genes. We also recapitulate useful bioinformatic tools developed to identify haplotype phase.

Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural effects of heteroleptic oxidovanadium(IV) complexes of salicylaldimines and polypyridyl ligands.

Searching for prospective vanadium-based drugs for cancer treatment, a new series of structurally related [VIVO(L-2H)(NN)] compounds (1-8) was developed. They include a double deprotonated salicylaldimine Schiff base ligand (L-2H) and different NN-polypyridyl co-ligands having DNA intercalating capacity. Compounds were characterized in solid state and in solution. EPR spectroscopy suggests that the NN ligands act as bidentate and bind through both nitrogen donor atoms in an axial-equatorial mode. The cytotoxicity was evaluated in human tumoral cells (ovarian A2780, breast MCF7, prostate PC3). The cytotoxic activity was dependent on type of cell and incubation time. At 24h PC3 cells presented low sensitivity, but at 72h all complexes showed high cytotoxic activity in all cells. Human kidney HEK293 and ovarian cisplatin resistant A2780cisR cells were also included to evaluate selectivity towards cancer cells and potency to overcome cisplatin resistance, respectively. Most complexes showed no detectable interaction with plasmid DNA, except 2 and 7 which depicted low ability to induce single strand breaks in supercoiled DNA. Based on the overall cytotoxic profile, complexes with 2,2´-bipyridine and 1,10-phenanthroline ligands (1 and 2) were selected for further studies, which consisted on cellular distribution and ultrastructural analyses. In the A2780 cells both depicted different distribution profiles; the former accumulates mostly at the membrane and the latter in the cytoskeleton. Morphology of treated cells showed nuclear atypia and membrane alterations, more severe for 1. Complexes induce different cell death pathways, predominantly necrosis for 1 and apoptosis for 2. Complexes alternative mode of cell death motivates the possibility for further developments.

Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation.

Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we "digitalized" XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.

Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling.

Laser capture microscopy (LCM) coupled with global transcriptome profiling could enable precise analyses of cell populations without the need for tissue dissociation, but has so far required relatively large numbers of cells. Here we report a robust and highly efficient strategy for LCM coupled with full-length mRNA-sequencing (LCM-seq) developed for single-cell transcriptomics. Fixed cells are subjected to direct lysis without RNA extraction, which both simplifies the experimental procedures as well as lowers technical noise. We apply LCM-seq on neurons isolated from mouse tissues, human post-mortem tissues, and illustrate its utility down to single captured cells. Importantly, we demonstrate that LCM-seq can provide biological insight on highly similar neuronal populations, including motor neurons isolated from different levels of the mouse spinal cord, as well as human midbrain dopamine neurons of the substantia nigra compacta and the ventral tegmental area.

Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS.

The fatal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons leading to muscle wasting and paralysis. However, motor neurons in the oculomotor nucleus, controlling eye movement, are for unknown reasons spared. We found that insulin-like growth factor 2 (IGF-2) was maintained in oculomotor neurons in ALS and thus could play a role in oculomotor resistance in this disease. We also showed that IGF-1 receptor (IGF-1R), which mediates survival pathways upon IGF binding, was highly expressed in oculomotor neurons and on extraocular muscle endplate. The addition of IGF-2 induced Akt phosphorylation, glycogen synthase kinase-3ß phosphorylation and ß-catenin levels while protecting ALS patient motor neurons. IGF-2 also rescued motor neurons derived from spinal muscular atrophy (SMA) patients from degeneration. Finally, AAV9::IGF-2 delivery to muscles of SOD1(G93A) ALS mice extended life-span by 10%, while preserving motor neurons and inducing motor axon regeneration. Thus, our studies demonstrate that oculomotor-specific expression can be utilized to identify candidates that protect vulnerable motor neurons from degeneration.

Exploring Oxidovanadium(IV) Complexes as YopH Inhibitors: Mechanism of Action and Modeling Studies.

YopH tyrosine phosphatase, a virulence factor produced by pathogenic species of Yersinia, is an attractive drug target. In this work, three oxidovanadium(IV) complexes were assayed against recombinant YopH and showed strong inhibition of the enzyme in the nanomolar range. Molecular modeling indicated that their binding is reinforced by H-bond, cation-π, and π-π interactions conferring specificity toward YopH. These complexes are thus interesting lead molecules for phosphatase inhibitor drug discovery.

Expanding the family of heteroleptic oxidovanadium(IV) compounds with salicylaldehyde semicarbazones and polypyridyl ligands showing anti-Trypanosoma cruzi activity.

Searching for prospective vanadium-based drugs for the treatment of Chagas disease, a new series of heteroleptic [V(IV)O(L-2H)(NN)] compounds was developed by including the lipophilic 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp) NN ligand and seven tridentate salicylaldehyde semicarbazone derivatives (L1-L7). The compounds were characterized in the solid state and in solution. EPR spectroscopy suggests that the NN ligand is bidentate bound through both nitrogen donor atoms in an axial-equatorial mode. The EPR and (51)V-NMR spectra of aerated solutions at room temperature indicate that the compounds are stable to hydrolysis and that no significant oxidation of V(IV) to V(V) takes place at least in 24h. The complexes are more active in vitro against Trypanosoma cruzi, the parasite responsible for Chagas disease, than the reference drug Nifurtimox and most of them are more active than previously reported [V(IV)O(L-2H)(NN)] complexes of other NN co-ligands. Selectivity towards the parasite was analyzed using J-774 murine macrophages as mammalian cell model. Due to both, high activity and high selectivity, L2, L4, L5 and L7 complexes could be considered new hits for further drug development. Lipophilicity probably plays a relevant role in the bioactivity of the new compounds. The [V(IV)O(L-2H)(NN)] compounds were designed aiming DNA as potential molecular target. Therefore, the novel L1-L7 tmp complexes were screened by computational modeling, comparing their DNA-binding features with those of previously reported [V(IV)O(L-2H)(NN)] compounds with different NN co-ligands. Whereas all the complexes interact well with DNA, with binding modes and strength tuned in different extents by the NN and semicarbazone co-ligands, molecular docking suggests that the observed anti-T. cruzi activity cannot be explained upon DNA intercalation as the sole mechanism of action.

Enuresis infantil tratada con imipramina / Imipramine-treated infant enuresis

Introducción: la enuresis, que se define como la emisión involuntaria de orina después de la edad en que el control vesical debía haberse alcanzado, alrededor de los 5 años, es un trastorno conocido desde épocas remotas, que ha merecido la atención de numerosos investigadores, y sobre el cual se plantean aún en la actualidad criterios muy disímiles en relación con su etiología.Objetivo: identificar la efectividad de la imipramina en la enuresis nocturna.Métodos: se investigan 150 niños de ambos sexos procedentes del área de salud del Policlínico Docente Plaza de la Revolución que presentaban enuresis nocturna, previamente estudiados, sin encontrar lesión orgánica. Se les impuso tratamiento con imipramina durante un año. Se analizan en estos pacientes variables como la edad y el sexo, se estudió la escolaridad, la clasificación de la enuresis, la frecuencia de las micciones y el umbral de sueño recogido de forma muy subjetiva.Resultados: se obtuvo que el grupo mayor de niños osciló entre los 6 a 8 años de edad, con predominio del sexo femenino en todos los grupos de edades. La escolaridad fue normal en 145 niños, que representa la inmensa mayoría de la muestra. Predominó ampliamente la enuresis primaria, que se manifestó en 148 pacientes, y fueron más frecuentes las micciones diarias y más de una vez por semana en el grupo de 6 a 8 años de edad. Casi todos los pacientes (132) permanecían dormidos después de orinarse. El tratamiento con imipramina se realizó con dosis crecientes de acuerdo con la edad, hasta una dosis máxima de 75 mg, y resultó eficaz en el 48,6 por ciento de los pacientes, en los cuales desapareció totalmente la sintomatología, y en un 28 por ciento se produjo mejoría en la presentación del síntoma.Conclusiones: la imipramina fue eficaz en la mayoría de los pacientes, pues desapareció totalmente la sintomatología(AU)

Introduction: enuresis, which is said to be the involuntary discharge of urine after the age at which the urinary control should has been achieved, that is, around 5 years-old, is a well-known disorder since ancient times. It has deserved the attention of numerous researchers but there are still very different criteria about its etiology at the present time.Objective: to identify the effectiveness of imipramine to treat night enuresis.Methods: one hundred and fifty children of both sexes with no previous lesions and night enuresis, who were attended at Plaza de la Revolucion teaching polyclinics, were studied. They were treated with imipramine for a year. Several variables such as age, sex, schooling, classification of enuresis, frequency of urination and sleep threshold, the latter being determined in a very subjective way, were all analyzed.Results: the elder group of children aged 6 to 8 years, with females predominating in all the age groups. Schooling was normal in 145 children who accounted for the vast majority of the sample. Primary enuresis extensively prevailed and the most frequent forms were daily involuntary urination and once a week in the 6-8 years-old group. Almost all the patients (132) remained asleep after urination. The imipramine-based treatment was given at growing doses, according to the age, up to maximum dose of 75 mg, and proved to be effective in 48.6 percent of patients, whose symptoms completely disappeared and in 28 percent of them who experienced some improvement in the presentation of symptoms.Conclusions: imipramine was effective in most of patients since the symptoms disappeared completely(AU)

Enuresis infantil tratada con imipramina / Imipramine-treated infant enuresis

Introducción: la enuresis, que se define como la emisión involuntaria de orina después de la edad en que el control vesical debía haberse alcanzado, alrededor de los 5 años, es un trastorno conocido desde épocas remotas, que ha merecido la atención de numerosos investigadores, y sobre el cual se plantean aún en la actualidad criterios muy disímiles en relación con su etiología. Objetivo: identificar la efectividad de la imipramina en la enuresis nocturna. Métodos: se investigan 150 niños de ambos sexos procedentes del área de salud del Policlínico Docente Plaza de la Revolución que presentaban enuresis nocturna, previamente estudiados, sin encontrar lesión orgánica. Se les impuso tratamiento con imipramina durante un año. Se analizan en estos pacientes variables como la edad y el sexo, se estudió la escolaridad, la clasificación de la enuresis, la frecuencia de las micciones y el umbral de sueño recogido de forma muy subjetiva. Resultados: se obtuvo que el grupo mayor de niños osciló entre los 6 a 8 años de edad, con predominio del sexo femenino en todos los grupos de edades. La escolaridad fue normal en 145 niños, que representa la inmensa mayoría de la muestra. Predominó ampliamente la enuresis primaria, que se manifestó en 148 pacientes, y fueron más frecuentes las micciones diarias y más de una vez por semana en el grupo de 6 a 8 años de edad. Casi todos los pacientes (132) permanecían dormidos después de orinarse. El tratamiento con imipramina se realizó con dosis crecientes de acuerdo con la edad, hasta una dosis máxima de 75 mg, y resultó eficaz en el 48,6 por ciento de los pacientes, en los cuales desapareció totalmente la sintomatología, y en un 28 por ciento se produjo mejoría en la presentación del síntoma. Conclusiones: la imipramina fue eficaz en la mayoría de los pacientes, pues desapareció totalmente la sintomatología(AU)

Introduction: enuresis, which is said to be the involuntary discharge of urine after the age at which the urinary control should has been achieved, that is, around 5 years-old, is a well-known disorder since ancient times. It has deserved the attention of numerous researchers but there are still very different criteria about its etiology at the present time. Objective: to identify the effectiveness of imipramine to treat night enuresis. Methods: one hundred and fifty children of both sexes with no previous lesions and night enuresis, who were attended at Plaza de la Revolucion teaching polyclinics, were studied. They were treated with imipramine for a year. Several variables such as age, sex, schooling, classification of enuresis, frequency of urination and sleep threshold, the latter being determined in a very subjective way, were all analyzed. Results: the elder group of children aged 6 to 8 years, with females predominating in all the age groups. Schooling was normal in 145 children who accounted for the vast majority of the sample. Primary enuresis extensively prevailed and the most frequent forms were daily involuntary urination and once a week in the 6-8 years-old group. Almost all the patients (132) remained asleep after urination. The imipramine-based treatment was given at growing doses, according to the age, up to maximum dose of 75 mg, and proved to be effective in 48.6 percent of patients, whose symptoms completely disappeared and in 28 percent of them who experienced some improvement in the presentation of symptoms. Conclusions: imipramine was effective in most of patients since the symptoms disappeared completely(AU)

Enuresis infantil tratada con imipramina / Imipramine-treated infant enuresis

Introducción: la enuresis, que se define como la emisión involuntaria de orina después de la edad en que el control vesical debía haberse alcanzado, alrededor de los 5 años, es un trastorno conocido desde épocas remotas, que ha merecido la atención de numerosos investigadores, y sobre el cual se plantean aún en la actualidad criterios muy disímiles en relación con su etiología. Objetivo: identificar la efectividad de la imipramina en la enuresis nocturna. Métodos: se investigan 150 niños de ambos sexos procedentes del área de salud del Policlínico Docente Plaza de la Revolución que presentaban enuresis nocturna, previamente estudiados, sin encontrar lesión orgánica. Se les impuso tratamiento con imipramina durante un año. Se analizan en estos pacientes variables como la edad y el sexo, se estudió la escolaridad, la clasificación de la enuresis, la frecuencia de las micciones y el umbral de sueño recogido de forma muy subjetiva. Resultados: se obtuvo que el grupo mayor de niños osciló entre los 6 a 8 años de edad, con predominio del sexo femenino en todos los grupos de edades. La escolaridad fue normal en 145 niños, que representa la inmensa mayoría de la muestra. Predominó ampliamente la enuresis primaria, que se manifestó en 148 pacientes, y fueron más frecuentes las micciones diarias y más de una vez por semana en el grupo de 6 a 8 años de edad. Casi todos los pacientes (132) permanecían dormidos después de orinarse. El tratamiento con imipramina se realizó con dosis crecientes de acuerdo con la edad, hasta una dosis máxima de 75 mg, y resultó eficaz en el 48,6 por ciento de los pacientes, en los cuales desapareció totalmente la sintomatología, y en un 28 por ciento se produjo mejoría en la presentación del síntoma. Conclusiones: la imipramina fue eficaz en la mayoría de los pacientes, pues desapareció totalmente la sintomatología

Introduction: enuresis, which is said to be the involuntary discharge of urine after the age at which the urinary control should has been achieved, that is, around 5 years-old, is a well-known disorder since ancient times. It has deserved the attention of numerous researchers but there are still very different criteria about its etiology at the present time. Objective: to identify the effectiveness of imipramine to treat night enuresis. Methods: one hundred and fifty children of both sexes with no previous lesions and night enuresis, who were attended at Plaza de la Revolucion teaching polyclinics, were studied. They were treated with imipramine for a year. Several variables such as age, sex, schooling, classification of enuresis, frequency of urination and sleep threshold, the latter being determined in a very subjective way, were all analyzed. Results: the elder group of children aged 6 to 8 years, with females predominating in all the age groups. Schooling was normal in 145 children who accounted for the vast majority of the sample. Primary enuresis extensively prevailed and the most frequent forms were daily involuntary urination and once a week in the 6-8 years-old group. Almost all the patients (132) remained asleep after urination. The imipramine-based treatment was given at growing doses, according to the age, up to maximum dose of 75 mg, and proved to be effective in 48.6 percent of patients, whose symptoms completely disappeared and in 28 percent of them who experienced some improvement in the presentation of symptoms. Conclusions: imipramine was effective in most of patients since the symptoms disappeared completely