Peripheral inflammation exacerbates α-synuclein toxicity and neuropathology in Parkinson's models.

AIMS: Parkinson's disease and related disorders are devastating neurodegenerative pathologies. Since α-synuclein was identified as a main component of Lewy bodies and neurites, efforts have been made to clarify the pathogenic mechanisms of α-synuclein's detrimental effects. α-synuclein oligomers are the most harmful species and may recruit and activate glial cells. Inflammation is emerging as a bridge between genetic susceptibility and environmental factors co-fostering Parkinson's disease. However, direct evidence linking inflammation to the harmful activities of α-synuclein oligomers or to the Parkinson's disease behavioural phenotype is lacking. METHODS: To clarify whether neuroinflammation influences Parkinson's disease pathogenesis, we developed: (i) a 'double-hit' approach in C57BL/6 naive mice where peripherally administered lipopolysaccharides were followed by intracerebroventricular injection of an inactive oligomer dose; (ii) a transgenic 'double-hit' model where lipopolysaccharides were given to A53T α-synuclein transgenic Parkinson's disease mice. RESULTS: Lipopolysaccharides induced a long-lasting neuroinflammatory response which facilitated the detrimental cognitive activities of oligomers. LPS-activated microglia and astrocytes responded differently to the oligomers with microglia activating further and acquiring a pro-inflammatory M1 phenotype, while astrocytes atrophied. In the transgenic 'double-hit' A53T mouse model, lipopolysaccharides aggravated cognitive deficits and increased microgliosis. Again, astrocytes responded differently to the double challenge. These findings indicate that peripherally induced neuroinflammation potentiates the α-synuclein oligomer's actions and aggravates cognitive deficits in A53T mice. CONCLUSIONS: The fine management of both peripheral and central inflammation may offer a promising therapeutic approach to prevent or slow down some behavioural aspects in α-synucleinopathies.

Autologous dental pulp mesenchymal stem cells for inferior third molar post-extraction socket healing: A split-mouth randomised clinical trial.

BACKGROUND: Since the discovery of adult mesenchymal stem cells extensive research has been conducted to determine their mechanisms of differentiation and effectiveness in cell therapy and regenerative medicine. MATERIAL AND METHODS: To assess the efficacy of autologous dental pulp mesenchymal stem cells delivered in a collagen matrix for post-extraction socket healing, a single-centre, double-blind, randomised, split-mouth, controlled clinical trial was performed. Both impacted mandibular third molars were extracted from 32 patients. Dental pulp was collected and dissociated; the resulting cell suspension, obtained by centrifugation, was incorporated into a resorbable collagen matrix and implanted in 32 experimental post-extraction sockets. Collagen matrices alone were implanted in 32 contralateral, control post-extraction sockets. Two neuroradiologists independently assessed the extent of bone repair at 6 months after the extractions. Computed tomography (CT, Philips Brilliance) and an advanced display platform (IntelliSpace Portal) was used to record extraction socket density, expressed as Hounsfield units (HU) and height (mm) of the distal interdental bone septum of the second molar. Measurements at 6 months post-extraction were compared with measurements obtained immediately after extraction. Data were analysed with the statistical program STATA 14. RESULTS: Two patients dropped out of the study. The final sample consisted of 22 women and 8 men (mean age, 23 years; range: 18-30 years). Clinical, radiological, and surgical characteristics of impacted third molars of the control and experimental groups were homogeneous. Measurements obtained by the two neuroradiologists showed agreement. No significant differences were found in the extent of bone repair during analyses of density (p=0.4203 neuroradiologist 1; p=0.2525 neuroradiologist 2) or interdental septum height (p=0.2280 neuroradiologist 1; p=0.4784 neuroradiologist 2). CONCLUSIONS: In our clinical trial, we were unable to demonstrate that autologous dental pulp mesenchymal stem cells reduce socket bone resorption after inferior third molar extraction.

Efficacy of amoxicillin and amoxicillin/clavulanic acid in the prevention of infection and dry socket after third molar extraction. A systematic review and meta-analysis.

BACKGROUND: Prophylactic use of amoxicillin and amoxicillin/clavulanic acid, although controversial, is common in routine clinical practice in third molar surgery. MATERIAL AND METHODS: Our objective was to assess the efficacy of prophylactic amoxicillin with or without clavulanic acid in reducing the incidence of dry socket and/or infection after third molar extraction. We conducted a systematic review and meta-analysis consulting electronic databases and references in retrieved articles. We included double-blind placebo-controlled randomized clinical trials published up to June 2015 investigating the efficacy of amoxicillin with or without clavulanic acid on the incidence of the aforementioned conditions after third molar extraction. Relative risks (RRs) were estimated with a generic inverse-variance approach and a random effect model using Stata/IC 13 and Review Manager Version 5.2. Stratified analysis was performed by antibiotic type. RESULTS: We included 10 papers in the qualitative review and in the quantitative synthesis (1997 extractions: 1072 in experimental groups and 925 in controls, with 27 and 74 events of dry socket and/or infection, respectively). The overall RR was 0.350 (p<0.001; 95% CI 0.214 to 0.574). We found no evidence of heterogeneity (I2=0%, p=0.470). The number needed to treat was 18 (95% CI 13 to 29). Five studies reported adverse reactions (RR=1.188, 95% CI 0.658 to 2.146, p =0.567). The RRs were 0.563 for amoxicillin (95% CI 0.295 to 1.08, p=0.082) and 0.215 for amoxicillin/clavulanic acid (95% CI 0.117 to 0.395, p<0.001). CONCLUSIONS: Prophylactic use of amoxicillin does not significantly reduce the risk of infection and/or dry socket after third molar extraction. With amoxicillin/clavulanic acid, the risk decreases significantly. Nevertheless, considering the number needed to treat, low prevalence of infection, potential adverse reactions to antibiotics and lack of serious complications in placebo groups, the routine prescription of amoxicillin with or without clavulanic acid is not justified.

Whole genome sequencing in ROHHAD trios proved inconclusive: what's beyond?

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a rare, life-threatening, pediatric disorder of unknown etiology, whose diagnosis is made difficult by poor knowledge of clinical manifestation, and lack of any confirmatory tests. Children with ROHHAD usually present with rapid onset weight gain which may be followed, over months or years, by hypothalamic dysfunction, hypoventilation, autonomic dysfunction, including impaired bowel motility, and tumors of neural crest origin. Despite the lack of evidence of inheritance in ROHHAD, several studies have been conducted in recent years that have explored possible genetic origins, with unsuccessful results. In order to broaden the search for possible genetic risk factors, an attempt was made to analyse the non-coding variants in two trios (proband with parents), recruited in the Gaslini Children's Hospital in Genoa (Italy). Both patients were females, with a typical history of ROHHAD. Gene variants (single nucleotide variants, short insertions/deletions, splice variants or in tandem expansion of homopolymeric tracts) or altered genomic regions (copy number variations or structural variants) shared between the two probands were searched. Currently, we have not found any potentially pathogenic changes, consistent with the ROHHAD clinical phenotype, and involving genes, regions or pathways shared between the two trios. To definitively rule out the genetic etiology, third-generation sequencing technologies (e.g., long-reads sequencing, optical mapping) should be applied, as well as other pathways, including those associated with immunological and autoimmune disorders, should be explored, making use not only of genomics but also of different -omic datasets.

Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation.

OBJECTIVE: NLRP12 mutations have been described in patients affected with peculiar autoinflammatory symptoms. This study was undertaken to characterize NLRP12 mutations in patients with autoinflammatory syndromes, particularly a novel missense mutation, p.D294E, affecting a protein sequence crucial for ATP binding, which was identified in a Caucasian family with familial cold-induced autoinflammatory syndrome in some family members. METHODS: Fifty patients were tested for NLRP12 mutations. A Caucasian family with the p.D294E missense mutation of NLRP12 in some family members was clinically characterized. In vitro analysis of the effects of the mutation on NF-κB activity was performed in HEK 293 cells after cotransfection of the cells with a luciferase NF-κB-responsive element and mutant or wild-type (WT) NLRP12 expression plasmids. NF-κB activity was also evaluated 24 hours after stimulation with tumor necrosis factor α in monocytes from individual family members carrying the mutation. Furthermore, secretion of interleukin-1ß (IL-1ß), production of reactive oxygen species (ROS), and activation of antioxidant systems in patient and healthy donor monocytes, under resting conditions and after stimulation with pathogen-associated molecular patterns (PAMPs), were also assessed. RESULTS: In the family assessed, the p.D294E mutation segregated in association with a particular sensitivity to cold exposure (especially arthralgias and myalgia), but not always with an inflammatory phenotype (e.g., urticarial rash or fever). In vitro, the mutant protein maintained the same inhibitory activity as that shown by WT NLRP12. Consistently, NLRP12-mutated monocytes showed neither increased levels of p65-induced NF-κB activity nor higher secretion of IL-1ß. However, the kinetics of PAMP-induced IL-1ß secretion were significantly accelerated, and high production of ROS and up-regulation of antioxidant systems were demonstrated. CONCLUSION: Even with a variable range of associated manifestations, the extreme sensitivity to cold represents the main clinical hallmark in an individual carrying the p.D294E mutation of the NLRP12 gene. Although regulation of NF-κB activity is not affected in patients, redox alterations and accelerated secretion of IL-1ß are associated with this mild autoinflammatory phenotype.

Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy.

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.

Multiparametric MR imaging to assess response following neoadjuvant systemic treatment in various breast cancer subtypes: Comparison between different definitions of pathologic complete response.

OBJECTIVES: To validate the performance of multiparametric magnetic resonance (MR) imaging to assess pathologic response to neoadjuvant systemic therapy (NST) in various breast cancer subtypes considering two definitions of pCR: absence of any residual invasive cancer or DCIS (ypT0) and absence of invasive tumour cells (ypT0/is). METHODS: Institutional review board-approved retrospective study, with waiver of the need to obtain informed consent. From January 2015 to June 2017, 81 women with 82 breast cancers undergoing NST were included. Eighteen lesions (22%) were immunohistochemically HER2-positive, 12 (15%) triple negative (TN), 42 (51%) luminal B-like and 10 (12%) luminal B-like/HER2-positive. Breast MR imaging was performed before and after NST. A comparative analysis considering pCR as ypT0 and ypT0/is was carried out. Performance of univariate and multivariate models to potentially predict pathologic response were evaluated. RESULTS: ypT0 was attained in 23% (19/82) of cases and ypT0/is in 33% (27/82) of cases. In both scenarios, HER2-positive subtype achieved the best response, 53% and 48%, respectively. A significant relationship was found between late enhancement and pathologic response (p < 0.001) regardless of pCR definition. In the ypT0 scenario, mean ADC ratio in the pCR subgroup was significantly higher than that in the non-pCR subgroup (p = 0.021) but no significant relationship was noted in ypT0/is. A multivariate model including MR late enhancement, ADC ratio and tumor subtype identified pathologic response with 86% and 84% accuracy when ypT0 and ypT0/is were considered, respectively. CONCLUSION: MR imaging late enhancement and ADC ratio along with breast cancer IHC subtype identify pathologic response following NST with high accuracy, achieving the highest NPV in TN and HER2-positive tumors and the highest PPV in luminal B-like subtypes, regardless of the definition of pCR as ypT0 or ypT0/is. In light of these findings and given that residual DCIS does not have an impact on survival rates, ypT0/is seems to be the preferable definition of pCR.

[Application of the ROLL technique in a case of bilateral multifocal breast cancer]. / Aplicación de la técnica ROLL en un caso de cáncer de mama multifocal bilateral.

The increasing number of non-palpable breast lesions and the trend to perform less aggressive surgical procedures have prompted the development of radioguided surgery in breast lesions, alone (ROLL) or with sentinel node detection. We present a 55-year-old woman with four mammary lesions diagnosed by magnetic resonance. The ROLL technique allowed not only their characterisation but also the study of the lymphatic drainage of malignant lesions. Moreover, it was useful as a guide for surgical biopsy of the benign lesions. The combination of different colloid size allowed an accurate study of each lesion and avoided radical surgery. The applications of radioguided surgery are ever increasing. Individualisation of each indication will benefit a greater number of patients.

Ectopic teeth in the maxillary sinus: A case report and literature review.

Ectopic eruption of teeth is a rare phenomenon although there have been reports of teeth in the nasal septum, mandibular condyle, and maxillary sinus. This impaction can present itself in a variety of ways such as chronic or recurrent sinusitis, sepsis, and facial numbness and can also be asymptomatic. The aim of this study was to describe, by means of research literature and by a case report, the characteristics and occurrence of ectopic eruption in the maxillary sinus. We have analyzed and compared clinical cases of ectopic teeth in the maxillary sinus with a search on PubMed utilizing keywords such as "ectopic," "teeth," "sinus," "maxillary," and Boolean operators "or" and "and" up until 2016. Fifty-one cases were found, of which 53% were female. The age ranged between 3 and 72 years, with an average age of 28.36 years. The higher prevalence of ectopic teeth is the 3rd molars. Ten of these teeth are associated with a dentigerous cyst, 1 by an osteoma, and 2 by soft tissue. Standard treatment for an ectopic tooth is extraction, but for other patients, treatment of choice in asymptomatic ectopic tooth cases is continued observation. Ectopic teeth tend to form a cyst or tumor if not managed.

shRNA targeting of ferritin heavy chain activates H19/miR-675 axis in K562 cells.

PURPOSE: The heavy subunit of the iron storage protein ferritin (FHC) is essential for the intracellular iron metabolism and, at the same time, it represents a central hub of iron-independent pathways, such as cell proliferation, angiogenesis, p53 regulation, chemokine signalling, stem cell expansion, miRNAs expression. In this work we have explored the ability of FHC to modulate gene expression in K562 cells, through the up-regulation of the lncRNA H19 and its cognate miR-675. MATERIALS AND METHODS: Targeted silencing of FHC was performed by lentiviral-driven shRNA strategy. FHC reconstitution was obtained by full length FHC cDNA transfection with Lipofectamine 2000. ROS amounts were determined with the redox-sensitive probe H2DCFDA. H19, miR-675, miR-107, Twist1, ID3, EPHB6, GNS, ANK1 and SMAD6 mRNA amounts were quantified by Taqman assay and qPCR analysis. RESULTS: FHC silencing in K562 cells modulates gene expression through the up-regulation of the lncRNA H19 and its cognate miR-675. Experimental findings demonstrate that the molecular mechanism underlying this phenomenon is represented by an FHC knock-down-triggered increase in reactive oxygen species (ROS) production. CONCLUSIONS: In this paper we uncover a so far not described function of the ferritin heavy subunit in the control of lncRNA pathways.

Análisis factorial confirmatorio del cuestionario sobre hábitos saludables en adolescentes ENHASA / Confirmatory factor analysis of the habits questionnaire healthy adolescents ENHASA

Introducción. Las cifras de sobrepeso y obesidad durante la infancia y la adolescencia están creciendo a un ritmoalarmante. Además, se han descrito diferencias en los estilos de vida entre chicos y chicas. Detectar a los individuoscon riesgo de desarrollar exceso de peso es imprescindiblepara un diagnóstico precoz y una intervención tempranaque evite la aparición de comorbilidades. Para ello es devital importancia disponer de instrumentos de cribado decalidad, debidamente analizados.Material y métodos. Se aplicó el cuestionario de HábitosSaludables en Adolescentes (ENHASA) a una muestra deestudiantes de primer curso de educación secundaria obligatoria (ESO) de la Región de Murcia. Se obtuvo además lasomatometría y se clasificaron según IMC. Se realizó análisisfactorial confirmatorio (AFC) según género para valorar laspropiedades psicométricas de la encuesta.Resultados. La muestra final fue de 416 alumnos, de losque el 40,6% presentó exceso de peso; no habiendo diferencias entre sexos. El 28,2% del total reflejó hábitos mejorables; obteniendo las peores puntuaciones en las dimensionesactividad física y uso de nuevas tecnologías. El KMO fuede 0,729 en chicos y de 0,725 en chicas; y la varianza totalexplicada fue del 61,57% y 62,92%, respectivamente. El AFCmostró concordancia estructural con respecto al análisis factorial exploratorio previo en ambos sexos. Conclusiones. Dos de cada 5 adolescentes de la muestra presentó exceso de peso. Se confirma que ENHASA esun cuestionario válido y fiable que puede utilizarse comométodo de cribado en la práctica clínica. (AU)

Introduction. The numbers of overweight and obesity during childhood and adolescence are growing atan alarming rate. In addition, differences in the lifestylesbetween boys and girls have been described. Detectingindividuals at risk of developing excess weight is essentialto carry out an early diagnosis and early intervention, andthus avoid the appearance of comorbidity. For this, it isvitally important to have quality screening instruments,duly analyzed.Methods. We applied the Healthy Habits in Adolescents(ENHASA) questionnaire to a sample of students in thefirst year of secondary education in the Region of Murcia.Somatometry was also obtained and classified accordingto BMI. Confirmatory factor analysis (CFA) was performedaccording to gender to assess the psychometric propertiesof the survey. Results. The final sample was 416 students, of which40.6% were overweight or obesity; there being no differences between the sexes. 28.2% of the total reflected habitsthat could be improved; obtaining the worst scores in thedimensions of physical activity and use of new technologies.The KMO was 0.729 in boys and 0.725 in girls; and the totalexplained variance was 61.57% and 62.92% respectively. TheCFA showed structural agreement with respect to the previous exploratory factor analysis in both sexes.Conclusion. 2 out of 5 adolescents in the sample wereexcess of weight. ENHASA is confirmed to be a valid andreliable questionnaire that can be used as a screening methodin clinical practice. (AU)

Somatic in frame deletions not involving juxtamembranous cysteine residues strongly activate the RET proto-oncogene.

Somatic RET mutations have been identified in a variable proportion (about 30-70%) of sporadic Medullary Thyroid Carcinoma (MTC) cases. They are represented by the Met918Thr substitution (exon 16) typical of Multiple Endocrine Neoplasia type 2B (MEN2B) and, to a lesser extent, by nucleotide changes occurring at one of five critical cysteine residues (exons 10 and 11) typical of MEN type 2A (MEN2A). An in vitro transforming activity has already been demonstrated for these mutations. A few different MTC somatic mutations have been reported so far whose biological activity has still to be tested. In this paper we report the identification, in two MTC tumor samples, of two interstitial deletions of 48 bp and 6 bp occurred in exons 10 and 11 respectively. Both were somatic heterozygous in frame mutations, not involving any cysteine residue. Moreover, the expression of a full length RET cDNA carrying one of the two deletions demonstrated a strong transforming capacity in NIH3T3 cells.

The physical map of the human RET proto-oncogene.

The RET proto-oncogene, a transmembrane tyrosine kinase receptor, is involved in the development of at least five different disease phenotypes. RET is activated through somatic rearrangements in a number of cases of papillary thyroid carcinoma while germ-line point mutations are associated with three inherited cancer syndromes MEN 2A, MEN 2B and FMTC. Moreover, point mutations or heterozygous deletions of RET are found in the dominant form of Hirschsprung disease or congenital colonic aganglionosis. We cloned the entire RET genomic sequence in a contig of cosmids encompassing 150 kb, from the CA repeat sTCL-2 to the region upstream the RET promoter, and established the position of the 20 exons of the RET gene with respect to a detailed restriction map based on eight endonucleases. A new highly polymorphic CA repeat sequence was identified within intron 5 of RET (RET-INT5). Finally the orientation of RET on chromosome 10q11.2 made it possible to orientate three other genes rearranged with RET in papillary thyroid carcinomas, namely H4/D10S170 on 10q21, R1 alpha on 17q23 and RFG2/Ele1 on 10q11.2.

Interferon-induced depression: prevalence and management.

BACKGROUND: Interferon-induced depression ranges from 0 to 50%. Interferon schedule and a history of psychiatric illnesses are not enough to predict who will develop symptoms and who will not. AIMS: To assess the prevalence of depression during interferon therapy; to test whether Minnesota Multiphasic Personality Inventory is useful in clinical practice for the early identification of patients at risk of depression; whether and how the depression can be cured. PATIENTS: One hundred and eighty-five patients treated with interferon and ribavirin for chronic hepatitis C. METHODS: Before therapy, all patients underwent a Minnesota Multiphasic Personality Inventory and a clinical examination, specifically for the identification of depressive symptoms. RESULTS: Thirty-one patients developed a psychiatric disorder, 11 of them requiring treatment with anti-depressant drugs. Among the 18 patients with Minnesota Multiphasic Personality Inventory positive tests, 16 developed a psychiatric disorder, 8 of them a severe disorder (sensitivity of 0.58; 0.73 for severe disorders). Among the 154 who did not develop psychiatric side effects, 152 had a negative Minnesota Multiphasic Personality Inventory (specificity: 0.99). Severe psychiatric disorders were successfully treated with anti-depressant drugs. CONCLUSIONS: Psychiatric side effects are easy to see during interferon therapy. A psychiatric evaluation should be considered on all patients before treatment. If depression develops, it should be treated aggressively, and selective serotonin re-uptake inhibitors are the anti-depressants of choice.

Central 5-HT(4) receptors and drinking behavior.

The aim of the present study was to investigate the effect of acute third ventricle injections of two different 5-HT(4) receptor antagonists, GR 113808 and SB 204070, on water intake in different situations. Injections of 80 nmol/rat of both GR 113808 and SB 204070 were unable to modify water intake in normohydrated rats. Pretreatment with GR 113808 (40 and 80 nmol/rat) and SB 204070 (80 and 160 nmol/rat) blunted water intake after third ventricle injections of angiotensin II (9.6 pmol/rat) compared to saline-pretreated controls. Pretreatment with 80 nmol/rat of both antagonists potentiated drinking induced by third ventricle injections of carbachol (11.0 nmol/rat) compared to saline-pretreated control. In all doses employed, none of the compounds was able to modify water intake in dehydrated rats. A separate control test using one-bottle taste aversion paradigm indicated that the reduction in water intake observed in some of the present experiments could not be attributed to a drug-induced malaise. It is suggested that central 5-HT(4) receptors exert a dualistic role on the control of water intake potentiating angiotensin II-induced drinking and inhibiting thirst induced by central cholinergic activation

Composite osteoarthrotenocutaneous free flap from the foot for reconstruction of an unusual hand wound.

A case of a single-stage reconstruction of the left hand of a 32-year-old right-handed construction worker with a shotgun wound by means of a composite osteoarthrotenocutaneous free flap from the foot is presented. The tissue loss caused by the injury included the cutaneous coverage of the dorsum of the left hand, extensor tendons of the second, third, fourth and fifth digits, metacarpals of the same fingers, and the second and third metacarpophalangeal joints. After 8 years of evolution, we have been able to verify a valuable degree of functional capability of the reconstructed hand.

cDNA sequence and genomic structure of the rat RET proto-oncogene.

The RET proto-oncogene, a member of the Receptor Tyrosine Kinase family, plays a crucial role during the development of the excretory system and the enteric nervous system, as demonstrated by in vivo animal studies and by its involvement in the pathogenesis of several human neurocristopathies like Hirschsprung disease and Multiple Endocrine Neoplasia type 2. Using a multistep RT-PCR approach we have isolated and sequenced the cDNA of the whole rat RET proto-oncogene, reporting the deduced amino acid sequence in comparison with the human and mouse counterparts. Moreover, two different isoforms (RET9 and RET51) have been confirmed in the rat, while a third RET isoform demonstrated in human (RET43) has not resulted to be conserved in this species. Finally, we have determined the genomic structure of the rat RET proto-oncogene comparing the exon-intron boundaries and intron sizes with the known structure of the human homologous gene. Our findings will facilitate the molecular study of appropriate rat models of RET related human diseases.

A constructed surface flow wetland for treating agricultural waste waters.

A study was conducted between December 1997 and December 1998 in NE Italy on a 3,200 m2 surface flow vegetated wetland receiving agricultural drainage water from a cultivated field of about 6 ha and occasional applications of organic wastes. The study aimed at evaluating: 1) biomass and seasonal nitrogen dynamics in above- and below-ground biomass of Phragmites australis Cav. (Trin.) and Typha latifolia (L.) grown in separate zones; 2) the effectiveness of the wetland in removing nutrients and sediments coming from the fields; 3) the possibility that wetland could treat occasional applications of organic wastes and 4) to collect some general information on whether the wetland can receive heavy loads coming from storm water runoff. Monthly observations showed that, in both species, aboveground biomass, nitrogen concentration and nitrogen content reached maximum values in summer and minimum values in winter. The contrary occurred in below-ground biomass. The total input of water in the wetland was 66,000 m3 ha(-1), of which 7,700 were drained. Total nitrogen input was 526 kg ha(-1), of which 58 were discharged out of the wetland.

[The gastrointestinal concealment of illegal drugs]. / Ocultación gastrointestinal de drogas ilegales.

The clinical, radiological and analytical aspects, and the complications observed in 16 cases of swallowing or insertion into the rectum of illicit drugs ("body-packing") are described. The drugs detected were heroin (6 cases), cocaine (5 cases) and cannabis (5 cases). In 15 cases abdominal plain X-rays were useful in the detection of the drug packages, their position and progression in the gastrointestinal tract and the presence of complications. The most valuable finding for radiologic diagnosis was the presence of a radiolucent halo surrounding the drug packages, or "double condom" sign, which was observed in 13/15 cases (87%). Urine analysis was positive for opiates or metabolites of cocaine in 7/9 cases (78%). One case presented acute heroin intoxication and three subjects gastric or intestinal obstruction requiring surgical treatment. In another case a packet, which had been retained in the stomach for five days, was extracted by upper gastrointestinal endoscopy using a Dormia basket with no complications.

[Accessory spleen: ultrasonographic and tomographic characteristics]. / Bazo accesorio: características ultrasonográficas y tomográficas.

The failure of fusion of splenic tissue results in the formation of accessory spleens. This entity normally appears in post-mortem examinations. The purpose of this work was to determine the incidence of the accessory spleen and to compare the ultrasonographic and tomographic features of the accessory spleen and the main spleen in a group of one thousand patients affected with several abdominal pathologies. Five hundred of these patients were studied by ultrasonography and five hundred patients by computed tomography. The ultrasonographic and tomographic features of the accessory and main spleen were similar. Its diagnosis is specially important in certain groups of patients with hematologic disease or abdominal trauma with splenic tear. This is due to the fact that the hypertrophy of the accessory spleen can produce a relapse of the disease.