Un caso de Síndrome de Wünderlich y revisión de la bibliografía / A case of Wünderlich syndrome and literature review

El diagnóstico y terapéutica de las malformaciones congénitas todavía hoy constituye una problemática universal. El presente trabajo corresponde al estudio de un caso de una adolescente de 14 años de edad, paciente del Hospital Oncológico Dr. Julio Villacreses Colmont de Manabí (SOLCA), Ecuador, que a partir del mes de septiembre de 2014 inicia con cuadro clínico de dolor pélvico mantenido, leucorrea persistente y fétida, sin menarquia y sin respuesta a tratamiento específico. Realizadas la Ecografía y Resonancia Magnética, se definen múltiples malformaciones congénitas, obteniéndose el diagnóstico del Síndrome de Wünderlich; una patología rara, con frecuencia de un 40%. El objetivo de este trabajo consiste en demostrar la elevada frecuencia de esta morbilidad para disminuir tratamientos quirúrgicos innecesarios (Histerectomía), un factor agravante para su eventual compromiso reproductivo. En Ecuador no reportan estadísticas del síndrome, o existe un subregistro de esta entidad. Abstract The diagnosis and treatment of congenital malformations is still a universal problem nowadays. The present work is a study of a case of a 14-year-old patient at the Cancer Hospital Dr. Julio Villacreces Colmont (SOLCA) in Manabí, Ecuador, that from September 2014 begins with clinical symptoms of steady pelvic pain, a persistent and fetid leukorrhea without menarche and response to a specific treatment. Once carried ultrasound and MRI, multiple congenital malformations are defined to give the diagnosis Wünderlich Syndrome; a rare disease, which is frequent at a 40%. The objective of this work is to demonstrate the high frequency of this disease to reduce unnecessary surgical treatment (hysterectomy), which is an aggravating factor for possible reproductive status. In Ecuador there is no statistical report of this syndrome, or there is underreporting of this disease

Estudio de medios de cultivo para la conservación in vitro de la yuca

Plant tissue culture constitutes an alternative for germplasm conservation in case of vegetatively propagated species. This approach permits to maintain collections in small places free from attach of diseases and catastrophes. Eleven variants from MS culture media were tested. Variants consist of different sucrose (20, 30 and 40 g.l-1) and manitol (0, 10, 20 y 30 g.l-1) concentrations in order to decrease the subculture number in the in vitro storage of ‘Señorita’ and ‘CEMSA 74-725’ clones. Evaluations were carried out nine months after in vitro implantation based on: height (cm), internode number by plant, number of active leave, number of active roots and surviving percentage. After storage, explants were incubated for recovery in the described culture medium for in vitro cassava growing. A culture medium with the addition of 40 g.l-1 sucrose, 0.02 mg.l-1 BAP, 0.1 mg.l-1 de GA3 and 0.01 mg.l-1 ANA is recommended.Key Words: Manihot esculenta, micropropagation, genetics resoursesEl cultivo de tejidos vegetales constituye una alternativa para la conservación del germoplasma de especies que son propagadas vegetativamente. Su utilización permite mantener las colecciones en pequeños espacios, libres del ataque de enfermedades y catástrofes, además de facilitar el intercambio de germoplasma. Se estudiaron 11 variantes del medio de cultivo MS que consistieron en diferentes concentraciones de sacarosa (20, 30 y 40 g.l-1) y de manitol (0, 10, 20 y 30 g.l-1), con el objetivo de disminuir el número de subcultivos en la conservación in vitro de los clones Señorita y CEMSA 74-725. Las evaluaciones se realizaron a los nueve meses de la implantación in vitro, teniendo en cuenta: altura (cm), número de entrenudos por planta, número de hojas activas, número de raíces activas y porcentaje de supervivencia. Los explantes que sobrevivieron, después de la conservación fueron incubados para su recuperación en el medio de cultivo descrito para el crecimiento in vitro de la yuca. El medio de cultivo suplementado con 40 g.l-1 de sacarosa, 0.02 mg.l-1 de BAP, 0.1 mg.l-1 de GA3 y 0.01 mg.l-1 de ANA, resultó la mejor variante para la conservación in vitro de ambos clones.Palabras clave: Manihot esculenta, micropropagación, recursos genético

Incidencia de contaminantes microbianos en la propagación in vitro de Xathosoma spp. clon ‘INIVIT MX-2007’ y Colocasia esculenta (L.) Schott. clon ‘INIVIT MC-2012’

The work was conducted to determine the incidence of microbial contaminants in two clones of taro (‘INIVIT MX-2007’ and ‘INIVIT MC-2012’) on the establishment and multiplication stages. The contaminated culture vials were counted and the percentage of microbial contamination was determined by clone in each subculture. Different contaminants were isolated and characterized morphologically and culturally. A high incidence of microbial contaminants in the two taro clones were found. Bacteria caused the greatest damage in the establishment and multiplication stages.Key words: bacteria, in vitro plants, taroEl trabajo se realizó con el objetivo de determinar la incidencia de contaminantes microbianos en dos clones de malanga (‘INIVIT MX-2007’ e ‘INIVIT MC-2012’) en las fases de establecimiento y multiplicación. Para esto se contabilizaron los frascos de cultivo contaminados y se determinó el porcentaje de contaminación microbiana por clon en cada subcultivo. Se aislaron los contaminantes diferentes y se caracterizaron morfológica y culturalmente. Se comprobó una alta incidencia de contaminantes microbianos en los dos clones de malanga. Las bacterias fueron las que causaron mayores afectaciones en las fases de establecimiento y multiplicación.Palabras clave: bacterias, malanga, plantas in vitr

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease

Background: Given the implication of histone acetylation in memory processes, histone deacetylase inhibitors (HDACIs) have been postulated as potential modulators of cognitive impairment in Alzheimer's disease (AD). However, dose-dependent side effects have been described in patients with the currently available broad-spectrum HDACIs, explaining why their therapeutic potential has not been realized for chronic diseases. Here, by simultaneously targeting two independent enzyme activities, histone deacetylase (HDAC) and phosphodiesterase-5 (PDE5), we propose a novel mode of inhibitory action that might increase the therapeutic specificity of HDACIs. Results: The combination of vorinostat, a pan-HDACI, and tadalafil, a PDE5 inhibitor, rescued the long-term potentiation impaired in slices from APP/PS1 mice. When administered in vivo, the combination of these drugs alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons. Significantly, the combination of vorinostat and tadalafil was more effective than each drug alone, both against the symptoms and in terms of disease modification, and importantly, these effects persisted after a 4-week washout period. Conclusions: The results highlight the pharmacological potential of a combination of molecules that inhibit HDAC and PDE5 as a therapeutic approach for AD treatment

Single nucleotide variations in ZBTB46 are associated with post-thrombolytic parenchymal haematoma

Haemorrhagic transformation is a complication of recombinant tissue-plasminogen activator treatment. The most severe form, parenchymal haematoma, can result in neurological deterioration, disability, and death. Our objective was to identify single nucleotide variations associated with a risk of parenchymal haematoma following thrombolytic therapy in patients with acute ischaemic stroke. A fixed-effect genome-wide meta-analysis was performed combining two-stage genome-wide association studies (n = 1904). The discovery stage (three cohorts) comprised 1324 ischaemic stroke individuals, 5.4% of whom had a parenchymal haematoma. Genetic variants yielding a P-value < 0.05 1 x 10(-5) were analysed in the validation stage (six cohorts), formed by 580 ischaemic stroke patients with 12.1% haemorrhagic events. All participants received recombinant tissue-plasminogen activator; cases were parenchymal haematoma type 1 or 2 as defined by the European Cooperative Acute Stroke Study (ECASS) criteria. Genome-wide significant findings (P < 5 x 10(-8)) were characterized by in silica functional annotation, gene expression, and DNA regulatory elements. We analysed 7 989 272 single nucleotide polymorphisms and identified a genome-wide association locus on chromosome 20 in the discovery cohort; functional annotation indicated that the ZBTB46 gene was driving the association for chromosome 20. The top single nucleotide polymorphism was rs76484331 in the ZBTB46 gene [P = 2.49 x 10(-8); odds ratio (OR): 11.21; 95% confidence interval (CI): 4.82-26.55]. In the replication cohort (n = 580), the rs76484331 polymorphism was associated with parenchymal haematoma (P = 0.01), and the overall association after meta-analysis increased (P = 1.61 x 10(-8), OR: 5.84; 95% CI: 3.16-10.76). ZBTB46 codes the zinc finger and BTB domain-containing protein 46 that acts as a transcription factor. In silica studies indicated that ZBTB46 is expressed in brain tissue by neurons and endothelial cells. Moreover, rs76484331 interacts with the promoter sites located at 20q13. In conclusion, we identified single nucleotide variants in the ZBTB46 gene associated with a higher risk of parenchymal haematoma following recombinant tissue-plasminogen activator treatment.Peer reviewe

Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke

During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Ibanez et al. perform a multi-ancestry meta-analysis to investigate the genetic architecture of early stroke outcomes. Two of the eight genome-wide significant loci identified-ADAM23 and GRIA1-are involved in synaptic excitability, suggesting that excitotoxicity contributes to neurological instability after ischaemic stroke.Peer reviewe

Modelización de las condiciones de transporte y conservación prolongada en frutas y hortalizas

Este documento se generó a partir de la VI Reunión de la Red Temática FRUTURA de CYTED realizada en la ciudad de Buenos Aires, Argentina del 26 al 30 de Setiembre de 2011. Organizado por el Laboratorio de Calidad y Postcosecha de Frutas y Hortalizas de la E.E.A. Balcarce del INTA, el programa de esta reunión se enmarcó dentro del principal objetivo de la Red, que es el desarrollo de un sistema integral de mejora de la calidad y seguridad de las frutas durante la manipulación, el transporte y la comercialización, mediante nuevas tecnologías de inspección y monitorización

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Informe de un paciente diagnosticado de várices colónicas idiopáticas

Colonic varices are an extremely rare disease of the colon, usually detected by colonoscopy and typically suggestive of portal hypertension by liver disease; there are rare cases that are not associated with a disease or they are of idiopathic origin. It is presented a patient of 51 years old with history of anemia of long evolution and occasional mild abdominal pain that was diagnosed colonic varices by colonoscopy. It meant an effort the search of the etiology; the liver disease, the vascular, the congestive heart and adhesions were discarded before the classification as idiopathic colonic varices.Las várices colónicas son una enfermedad extremadamente rara del colon, detectadas usualmente por colonoscopia y típicamente sugerentes de hipertensión portal por hepatopatía; son raros los casos que no se asocian a una enfermedad o que son de origen idiopático. Se presenta un paciente de 51 años con historia de anemia de larga evolución y dolor abdominal ocasional leve al que se le diagnosticó várices colónicas por colonoscopia. Significó un esfuerzo la búsqueda de la etiología; se descartaron la enfermedad hepática, la vascular, la cardíaca congestiva y las adherencias antes de clasificarlo como várices colónicas idiopáticas