Seed ecology of the geophyte Conopodium majus (Apiaceae), indicator species of ancient woodland understories and oligotrophic meadows.

Conopodium majus is a geophyte with pseudomonocotyly, distributed in Atlantic Europe. It is an indicator of two declining European habitats: ancient woodland understories and oligotrophic hay meadows. Attempts to reintroduce it by seed have been hindered by scarce seedling emergence and limited knowledge of its seed biology. Micro-CT scanning was used to assess pseudomonocotyly. Embryo growth and germination were studied in the laboratory and the field, using dissection and image analysis. The effects of temperature, light, nitrate and GA3 on germination were tested. Seed desiccation tolerance was investigated by storage at different RHs and by drying seeds at different stages of embryo growth. Seeds possess morphological but not physiological dormancy. Embryo growth and germination were promoted by temperatures between 0 and 5 °C, arrested above 10 °C, and indifferent to alternating temperatures, light, nitrate and GA3 . Pseudomonocotyly appears to result from cotyledon fusion. While seeds tolerated drying to 15% RH and storage for 1 year at 20 °C, viability was lost when storage was at 60% RH. Seeds imbibed at 5 °C for 84 days had significant internal embryo growth but were still able to tolerate drying to 15% RH. Reproduction by seed in C. majus follows a strategy shared by geophytes adapted to deciduous temperate forests. The evolution of fused cotyledons may enable the radicle and the hypocotyl to reach deeper into the soil where a tuber can develop. The embryo is capable of growth within the seed at low temperatures so that germination is timed for early spring.

Root cone angle is enlarged in docs1 LRR-RLK mutants in rice.

BACKGROUND: The DEFECTIVE IN OUTER CELL LAYER SPECIFICATION 1 (DOCS1) gene belongs to the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) subfamily. It has been discovered few years ago in Oryza sativa (rice) in a screen to isolate mutants with defects in sensitivity to aluminum. The c68 (docs1-1) mutant possessed a nonsense mutation in the C-terminal part of the DOCS1 kinase domain. FINDINGS: We have generated a new loss-of-function mutation in the DOCS1 gene (docs1-2) using the CRISPR-Cas9 technology. This new loss-of-function mutant and docs1-1 present similar phenotypes suggesting the original docs1-1 was a null allele. Besides the aluminum sensitivity phenotype, both docs1 mutants shared also several root phenotypes described previously: less root hairs and mixed identities of the outer cell layers. Moreover, our new results suggest that DOCS1 could also play a role in root cap development. We hypothesized these docs1 root phenotypes may affect gravity responses. As expected, in seedlings, the early gravitropic response was delayed. Furthermore, at adult stage, the root gravitropic set angle of docs1 mutants was also affected since docs1 mutant plants displayed larger root cone angles. CONCLUSIONS: All these observations add new insights into the DOCS1 gene function in gravitropic responses at several stages of plant development.

Long-term improvement of slow-channel congenital myasthenic syndrome with fluoxetine.

We report on a 15-year-old patient who was diagnosed with congenital myasthenic syndrome (CMS) at the age of 7 months. At initial diagnosis, the CMS was not further characterized. The patient was treated for several years with the anticholinesterase drug (Mestinon), without clinical benefit. The patient deteriorated progressively and became dependent on home nocturnal ventilatory support, being unable to take part in daily life activities at age of 12 years. At age 14, the slow-channel syndrome mutation CHRNE L269F (805C>T) was detected and acetylcholinesterase inhibitor therapy was immediately stopped. Fluoxetine therapy was started and gradually increased over 2 months. The boy improved dramatically in strength and endurance and was taken off ventilatory support 1 month after the fluoxetine therapy was initiated. The clinical improvement was confirmed by functional respiratory and electrophysiological tests.

ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome.

Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities. Consistent with this, Trp53bp2-deficient mice show dilation of lateral ventricles resembling the phenotype of 1q41q42 microdeletion patients. Trp53bp2 deficiency causes 100% neonatal lethality in the C57BL/6 background associated with a high incidence of neural tube defects and a range of developmental abnormalities such as congenital heart defects, coloboma, microphthalmia, urogenital and craniofacial abnormalities. Interestingly, abnormalities show a high degree of overlap with 1q41q42 microdeletion-associated abnormalities. These findings identify TP53BP2 as a strong candidate causative gene for central nervous system (CNS) defects in 1q41q42 microdeletion syndrome, and open new avenues for investigation of the mechanisms underlying CNS abnormalities.

Accuracy and reproducibility of patient-specific hemodynamic models of stented intracranial aneurysms: report on the Virtual Intracranial Stenting Challenge 2011.

Validation studies are prerequisites for computational fluid dynamics (CFD) simulations to be accepted as part of clinical decision-making. This paper reports on the 2011 edition of the Virtual Intracranial Stenting Challenge. The challenge aimed to assess the reproducibility with which research groups can simulate the velocity field in an intracranial aneurysm, both untreated and treated with five different configurations of high-porosity stents. Particle imaging velocimetry (PIV) measurements were obtained to validate the untreated velocity field. Six participants, totaling three CFD solvers, were provided with surface meshes of the vascular geometry and the deployed stent geometries, and flow rate boundary conditions for all inlets and outlets. As output, they were invited to submit an abstract to the 8th International Interdisciplinary Cerebrovascular Symposium 2011 (ICS'11), outlining their methods and giving their interpretation of the performance of each stent configuration. After the challenge, all CFD solutions were collected and analyzed. To quantitatively analyze the data, we calculated the root-mean-square error (RMSE) over uniformly distributed nodes on a plane slicing the main flow jet along its axis and normalized it with the maximum velocity on the slice of the untreated case (NRMSE). Good agreement was found between CFD and PIV with a NRMSE of 7.28%. Excellent agreement was found between CFD solutions, both untreated and treated. The maximum difference between any two groups (along a line perpendicular to the main flow jet) was 4.0 mm/s, i.e. 4.1% of the maximum velocity of the untreated case, and the average NRMSE was 0.47% (range 0.28-1.03%). In conclusion, given geometry and flow rates, research groups can accurately simulate the velocity field inside an intracranial aneurysm-as assessed by comparison with in vitro measurements-and find excellent agreement on the hemodynamic effect of different stent configurations.

Tocopherol in inborn errors of intermediary metabolism.

Red blood cell tocopherol was measured in a group of 92 children with inborn errors of intermediary metabolism to evaluate the peroxidative damage in different mitochondrial and cytosolic defects, and to consider the need for treatment or vitamin supplementation. Tocopherol was determined by HPLC with UV detection. Results were expressed in nanomoles red blood cell tocopherol per gram protein. Significant differences (Mann-Whitney; P < 0.001) were found between tocopherol levels in untreated patients: 19 with mitochondrial defects versus 23 with cytosolic enzyme or transport defects, and versus 58 age-matched reference values. In conclusion, mitochondrial enzyme deficiencies, either amino and organic acidurias or defects of energy metabolism, seem to produce an excess of free radicals with the consequent utilization of tocopherol as antioxidant. This is not apparent in the cytosolic enzyme defects studied, whose tocopherol levels are in the normal range. Treatment with tocopherol completely corrects the deficient antioxidant status.

Comparison of the effects of various flavonoids on ethoxycoumarin deethylase activity of rat intestinal and hepatic microsomes.

Fifteen flavonoids were examined for their effects on the activity of 7-ethoxycoumarin O-deethylase in rat hepatic and intestinal microsomes. The effect depended on both the chemical structure of the flavonoid and the origin of the microsomes. Polyhydroxylated flavonoids with a C2-C3 double bond (flavones and flavonols) were more effective inhibitors of the enzyme in both hepatic and intestinal microsomes than were the reduced homologues (flavanonols, flavanones and flavan-3-ols). In contrast, flavones lacking hydroxyl substituents (e.g. 5,6-benzoflavone, 7,8-benzoflavone and flavone) increased ethoxycoumarin deethylase activity in liver microsomes although they had an inhibitory effect in intestinal microsomes.

[Cervical uterus septus. Atypical malformation as a cause of sterility]. / Utérus cloisonné cervical. Malformation atypique comme une cause de stérilité.

A review of the congenital anomalies of the feminine genital apparatus has been carried out with regard to the infrequent finding of a selective septum in cervix with a single uterine cavity and normal morphology in a patient with primary sterility. Colposcopy, hysterosalpingography and laparoscopy have been made for diagnosis confirmation.

[Primary leptomeningeal melanomatosis in a 6-year-old child]. / Melanomatosis leptomeníngea primaria en un niño de 6 años.

A case of primary leptomeningeal melanomatosis without cutaneous lesions is reported. The clinical findings for a six months period were: intracranial hypertension syndrome, progressive cranial polineuropathy and a spinal involvement in a six years old child. CT brain scan showed enlarged subarachnoid spaces without contrast enhancement. MRI brain scan evidenced furthermore a focal lesion in right talamus. MRI spinal scan was normal. Examination of CSF showed elevated protein and reduced glucose concentrations as well as mild pleocytosis. Serologies and cultures investigating viral, bacterial, mycobacterial, fungal or parasitic infections resulted negative. CSF cytologic examination failed to show malignant cells. Postmortem diagnosis after neuropathological examination was made. This is an uncommon case of primary leptomeningeal melanomatosis, presenting the difficulty of diagnosis when cutaneous lesions are not present.

[Ataxia telangiectasia: review of 13 new cases]. / Ataxia telangiectasia: revisión de 13 observaciones.

We report the review of 13 patients who were diagnosed of ataxia telangiectasia before 6 years of age. All of them manifested cerebelous ataxia, oculocutaneus telangiectasias (11), sinopulmonary infections (9), dystonia (9), oculomotor apraxia (9) and Burkitt linfoma (1). We analyse the most common presentation of the disease in early stages and the complementary studies performed. The prompt diagnosis allow us a better control of infections, malignant process and finally the possibility of genetic counseling.

[A ketogenic diet: is this a valid alternative in refractory epilepsy]. / Dieta cetógena: ¿una alternativa válida en epilepsias refractarias?

INTRODUCTION: The ketogenic diet was first used in refractory epilepsy of childhood in the early 1920s. It was forgotten when new antiepileptic drugs were introduced, but recently has been used again. Although its efficacy in the treatment of epilepsy, in some patients, is beyond doubt, its mechanism of action is still not clear. There are three types of diet: the classical diet with a proportion of 4:1 of long chain fatty acids, with MCT oil and with modified MCT oil. OBJECTIVE: To present a protocol recently designed in our hospital. We include the type of diet, form of onset, subsequent follow up of complications, clinical and electroencephalographic response and side effects seen in the patients. PATIENTS AND METHODS: Introduction of the ketogenic diet with MCT oil in six patients aged between 2 and 11 years, with various types of epilepsy, all resistant to treatment, who had been unsuccessfully treated for 28 months in one case and between 4 and 6 months in the others. We evaluated the response on the criteria of Huttenlocher and Panic electroencephalograms. RESULTS: Two of the patients improved with good control of their disorder and the EEG became normal. No serious side effects were seen apart from gastrointestinal symptoms which improved when the quantity of MCT oil was reduced. CONCLUSIONS: In patients with drug resistant epilepsy it is convenient to have a guideline for treatment using a ketogenic diet. It is also useful to have a multi disciplinary team for management, follow up to detect late side effects and obtain the cooperation of the patient s family in following the protocol.

[Respiratory chain and pyruvate metabolism deficiencies in pediatric patients: evaluation of biochemical tests for selective screening]. / Deficiencias de la cadena respiratoria y del metabolismo del piruvato en pacientes pediátricos: evaluación de las pruebas bioquímicas de selección.

INTRODUCTION: The correct selection of pediatric patients with clinical suspicion of mitochondrial diseases is the first step to achieve a definitive diagnosis. MATERIAL AND METHODS: The results of the initial biochemical tests obtained in 35 children diagnosed of respiratory chain or pyruvate metabolism defects were reviewed. The efficiency of basal determinations (lactate, pyruvate, ketone bodies, amino and organic acids and carnitine), cerebrospinal fluid (CSF) analysis, and dynamic tests (exercise, glucose loading and glucose oxidation by lymphocytes) was discussed. RESULTS: Plasma lactate and alanine, and CSF metabolites were the most informative measurements in basal status. Urine organic acids were very useful to confirm the initial suspicion. Glucose loading was the most informative and reliable challenge test for pediatric population, while exercise test was especially useful for older children with fatigability or peripheral nervous system involvement. CONCLUSIONS: Glucose oxidation by lymphocytes might be applied when the other dynamic tests can not be performed or are not informative.

[Thymectomy in juvenile myasthenia gravis]. / Timectomía en la miastenia grave juvenil.

INTRODUCTION: Juvenile myasthenia gravis (JMG) is an infrequent autoimmune disease, the symptoms and therapeutic handling of which do not differ from those of the adult forms. Chronic treatment with corticoids very often causes side effects in childhood, which is why patients are being submitted to thymectomies at younger ages with better results. AIMS. To analyse the clinical and evolutionary profile of JMG treated by thymectomy in our centre. PATIENTS AND METHODS: We report the case of four girls aged between 5 and 13 who were diagnosed as suffering from generalised myasthenia gravis (MG) with bulbar affectation. One of them started with a myasthenic crisis. The four of them were submitted to Tensilon s test, an electrophysiological study, determination of AChR, thoracic CT, and study of autoimmunity and thyroid functioning. After surgery the thymus was analysed histologically. RESULTS: They all gave positive in Tensilon s test and were seropositive for AChR. They were treated with anticholinesterases, up to the maximum tolerated dose, and corticoids, without complete remission being accomplished and so they were submitted to a thymectomy in the first year of evolution. In three cases surgical approach was transsternal and in the other by means of a videothoracoscope. All the thymuses showed lymphoid hyperplasia. After a variable follow up the girls are at present asymptomatic, although none of them has been able to completely give up the pharmacological treatment. CONCLUSIONS: Thymectomy is one of the mainstays of treatment for JMG. The ever more frequent use of videothoracoscopic techniques achieves results that are similar to those obtained by conventional surgery but with fewer post operative and aesthetic problems

[Angelman syndrome: physical characteristics and behavioural phenotype in 37 patients with confirmed genetic diagnosis]. / Síndrome de Angelman: características físicas y fenotipo conductual en 37 pacientes con diagnóstico genético confirmado.

INTRODUCTION: Angelman syndrome (AS) is characterised by mental retardation, ataxic gait, epilepsy, absence of language and a special series of physical traits behavioural phenotype. Its incidence is estimated as one in every 20,000 individuals. On the basis of discoveries made in molecular biology, patients can be classified as belonging to five types: deletion, paternal uniparental disomy (UPD), imprinting defects, mutation of the UBE3A ubiquitin protein ligase gene and unidentified mechanism (15% 20% of patients). Some studies report significant correlations between the phenotype and the genetic cause. PATIENTS AND METHODS: We reviewed, retrospectively, 37 patients suffering from AS with a positive genetic study and who had been controlled for at least two years in the Neurological Service at the Hospital Sant Joan de D u. Data was collected on physical characteristics, behavioural phenotype, type of communication, sleep disorders and the medication they needed, as well as epilepsy, start age, types of seizures, medication, schooling and social integration. RESULTS: 87% of cases were due to de novo deletion, 8% were caused by UPD, and 5% had their origins in imprinting defects. The average age of diagnosis was 6.5 years. The sleep disorders present in 48% of the patients required medication in 67% of cases, and 95% presented epilepsy. The most frequent seizures were myoclonic, tonic clonic and atonic. The electroencephalogram (EEG) was the characteristic found in the AS in 68%. The most effective treatment was afforded by valproate and clonazepam. CONCLUSIONS: As regards the phenotype, no differences were found according to the genetic alteration. The most effective treatment for the sleep disorders was melatonin. Epilepsy was an almost constant finding in our series, as was cognitive affectation. Lastly, it must be pointed out that educational and socio occupational integration is difficult for patients suffering from AS.

[Familiar chronic progressive external ophthalmoplegia of mitochondrial origin]. / Oftalmoplejía crónica progresiva externa familiar de origen mitocondrial.

INTRODUCTION: The syndrome of chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease characterized by ptosis and ophthalmoplegia has that has been associated to the presence of large deletion, single or multiple, in the mitochondrial DNA of skeletal muscle. CASE REPORT: We report a familiar case of chronic progressive external ophthalmoplegia of maternal inheritance that began at birth, and developed with slow progression but with no multisystemic involvement. Non of the affected individuals had ragged-red fibers in skeletal muscle. Genetic analysis of mitochondrial DNA revealed the presence of a single deletion of 4,977 bp that encompasses the nucleotide positions 8,482 to 13,460, flanked by a direct repeat sequence. CONCLUSIONS: The amount of deleted mitochondrial DNA (15%) in this patient's muscle suggests, even if the percentage of the mutation is low, that this deletion is the molecular cause of the phenotypic presentation of this patient. This is one of the few cases described in the literature of CPEO maternally inherited.

[Rett's syndrome in the Spanish population]. / Estudio del síndrome de Rett en la población española.

INTRODUCTION AND OBJECTIVE: Rett syndrome was described in 1966 and became known through the English medical literature in 1983. There are typical and atypical forms. The objective of this study was to record the cases diagnosed in Spain and discover their clinical characteristics in order to describe its phenotype and geographical distribution. PATIENTS AND METHODS: We know of 207 cases and have obtained the records of 168 of these patients. A protocol and data collection programme has been developed giving the criteria for inclusion, and data which support or exclude this. Data collection was by post and the data for identification were the date of birth and the initials of the name and two surnames. With these variables, double-registering of patients was almost impossible. A statistical study with descriptive analysis and a study of continuous and alternating variables was immediately done. RESULTS AND CONCLUSION: The results gave the main characteristics, the differences between typical and atypical cases and a comparative study of variables. It has given clinical data which may be useful for prognosis of the condition in the future.

[BCG in superficial carcinoma of the bladder. Authors' experience]. / BCG en el carcinoma vesical superficial. Nuestra experiencia.

Contribution of 95 patients with surface vesical tumour managed with UTR and endovesical BCG. The response was absence of recurrence in 68.4% cases in Ta stage, 63% in T1 and 66.7% in 'in situ' carcinoma. Therapy tolerability was good, with few side-effects. We conclude that BCG endovesical instillation as co-adjunctive therapy to UTR in surface vesical tumours has been shown to be effective for the period under study.

[Current controversies on the treatment of urinary lithiasis]. / Controversias actuales en el tratamiento de la litiasis urinaria.

With the discovery during the 1960s of an access to the renal sinus and intra-operative radiological monitoring, the lithiasis surgery reached its summit of technical perfection. A comparative study on the various therapeutical options is presented: NLP, URN, ESWL and open surgery, as the single or combined treatment in complex renal lithiasis. Also, intrasinusal and transparenquimatous accesses to the intrarenal tract are compared, evaluating the morbidity, surgical time and economical interpretation of both techniques. Establishment of each treatments' indications and contraindications as well as likely short- and long-term adverse effects of the new technologies.

[Cyst of the prostatic utricle]. / Quiste de utrículo prostático.

Presentation of a case of prostatic utriculus cyst which due to its size and the patient's history suggested a differential diagnosis with a urethral or vesical diverticulum. Awareness of frequent association to urethral malformations and azoospermia would be very useful when choosing a treatment strategy in such cases.