Overwhelming genetic heterogeneity and exhausting molecular diagnostic process in chronic and progressive ataxias: facing it up with an algorithm, a gene, a panel at a time.

Ataxias are one of the most frequent complaints in Neurogenetics units worldwide. Currently, more than 50 subtypes of spinocerebellar ataxias and more than 60 recessive ataxias are recognized. We conducted an 11-year prospective, observational, analytical study in order to estimate the frequency of pediatric and adult genetic ataxias in Argentina, to describe the phenotypes of this cohort and evaluate the diagnostic yield of the algorithm used in our unit. We included 334 ataxic patients. Our diagnostic approach was successful in one-third of the cohort. A final molecular diagnosis was reached in 113 subjects. This rate is significantly higher in the subgroup of patients with a positive family history, where the diagnostic yield increased to 55%. The most prevalent dominant and recessive ataxias in Argentina were SCA-2 (36% of dominant ataxias) and FA (62% of recessive ataxias), respectively. Next generation sequencing-based assays were diagnostic in the 65% of the patients requiring these tests. These results provide relevant epidemiological information, bringing a comprehensive knowledge of the most prevalent subtypes of genetic ataxias and their phenotypes in our territory and laying the groundwork for rationally implementing genetic diagnostic programs for these disorders in our country.

Expert Elicitation Provides a Rapid Alternative to Formal Case-Control Study of an H7N9 Avian Influenza Outbreak in the United States.

An expert elicitation was staged to rapidly decipher plausible routes and risks of pathogen transmission in the 2017 H7N9 avian influenza (AI) outbreak in the four-state region of Tennessee, Alabama, Georgia, and Kentucky. The process included the identification of risk factors found in a preponderance of commercial broiler breeder case farms over matched controls and an opinion-based weighting of risks and mitigations perceived influential to this outbreak. Although the two highly pathogenic AI case farms had general location and company ownership in common, obvious connections were lacking for the remainder of H7N9-infected (all low pathogenicity) commercial farms. Expert elicitation of differences between known cases and controls suggested a key role for environmental rather than lateral (business network) pathways in the distribution of low pathogenicity AI across commercial broiler breeder operations. Factors with greatest strength as predictors of disease, whether or not they were causal, included mesopredator or rodent incursions, enclosure defects, and habitat disturbance that might attract wildlife to the farm (e.g., feed spills and vacating of neighboring properties). Business affiliations that may have facilitated farm-to-farm transfer, in contrast, were limited. Biosecurity standards varied across this study group but were no more or less stringent among cases over controls. However, results from a parallel hypothetical scenario staged to address field data gaps suggest that uniformity and consistency in the implementation of biosecurity practices may impact risk of disease introduction. Importantly, this study was conducted within a few weeks and with little disruption to emergency response activities. As such, the approach offers an alternative model for interim field investigation of new or emerging high-consequence diseases with immediate decision support needs.

Temporal changes in soil water repellency after a forest fire in a Mediterranean calcareous soil: Influence of ash and different vegetation type.

Forest fires usually modify soil water repellency (SWR), and its persistence and intensity show a high variability both in space and time. This research studies the evolution of SWR in a Mediterranean calcareous soil affected by a forest fire, which occurred in Gorga (SE Spain) in July 2011, comparing the effect of the main vegetation cover between pine (Pinus halepensis) and shrubs species (Quercus coccifera, Rosmarinus officinalis, Cistus albidus, Erica arborea and Brachypodium retusum) and the relationship with soil moisture content (SMC). Also the study analyzed the effect of ash on SWR dynamics under field conditions. Six plots were established on the fire-affected area and the unburned-control-adjacent area to monitoring SWR with the water drop penetration time (WDPT) test, SMC through moist sensors (5cm depth) and three different ash treatments: ash presence, ash absence and incorporation of ash into the soil. An immediate increase of SWR was observed in the fire-affected area, mainly in pine plots. SWR changes in control (unburned) plots were quite similar between different types of vegetation influence, despite higher SWR values being observed on pine plots during the study period. A noticeable decrease of SWR was observed during the first months after fire in the affected areas, especially after the first rainy period, both in pine and shrubs plots. SWR increase was registered in all plots, and the highest levels were in March 2012 in burned pine plots. SWR decrease was higher in plots where ash was removed. Fire-affected soils became wettable 1year and a half after the fire.

Selected Lactobacillus strains isolated from sugary and milk kefir reduce Salmonella infection of epithelial cells in vitro.

The isolation of potentially probiotic strains and the subsequent study of their properties are very important steps to gain insight in the health benefits ascribed to sugary and milk kefir. The aim of the present study was to characterise fifteen Lactobacillus strains isolated from these beverages by determining some surface properties and their ability to antagonise enterocyte cell damage after Salmonella infection in vitro. Lactobacillus surface properties were determined by hydrophobicity, autoaggregation, and coaggregation assays with Salmonella. In addition, lactobacilli adhesion to Caco-2/TC-7 cells and the effect on Salmonella invasion were evaluated. Finally, the disassembly of F-actin cytoskeleton on intestinal epithelial cells was assayed in vitro when Salmonella infection was performed in the presence of selected Lactobacillus strains. Ten out of the 15 strains showed a high adhesion capacity to Caco-2/TC-7 cells. Most of the strains were hydrophilic and non-autoaggregating. Strains isolated from sugary kefir were non-coaggregating with Salmonella, while strains Lactobacillus paracasei CIDCA 83120, 83121, 83123, 83124, 8339, 83102 isolated from milk kefir were able to coaggregate after 1 h. L. paracasei CIDCA 8339 and Lactobacillus kefiri CIDCA 83102 were able to diminish Salmonella invasion to the enterocytes. An antagonistic effect on cytoskeleton disruption elicited by the pathogen was also demonstrated. Our results suggest that both strains isolated from milk kefir could be considered as appropriate probiotic candidates.

Hydrocephalus and intraspinal tumor.

Hydrocephalus with spinal subarachnoid obstruction is rare, and its cause is obscure. Two such patients are presented. The pathophysiology is reviewed. Spinal absorptive pathways for cerebrospinal fluid are postulated to play a critical role in such cases.

The effect of furosemide on intracranial pressure and hemorrhage in preterm rabbits.

The hypothesis that intracranial hypotension due to excessive postnatal fluid loss places the premature infant at risk for germinal matrix and intraventricular hemorrhage (GM-IVH) was tested in preterm rabbits delivered at 28 and 29 days of gestation (term 32 days). Furosemide administered to newborn pups induced a diuresis that resulted in a 11% to 22% loss in body weight and a concomitant decline in muscle water (13% to 16%) and sodium (18% to 21%). Paradoxically, no change occurred in the water or electrolyte content of the brain even though cerebrospinal fluid and brain tissue pressure, but not blood pressure, declined. These changes were absent in littermates treated with saline. Microscopic examination of brain sections revealed a greater incidence of intracranial hemorrhage, particularly in the germinal matrix and choroid plexus, in furosemide-treated than in saline-treated preterm rabbit pups. These results are consistent with the hypothesis that intracranial hypotension promotes the incidence of GH-IVH in preterm animals.

Lack of interaction between avian leukosis virus subgroup J and fowl adenovirus (FAV) in FAV-antibody-positive chickens.

Unfounded field speculation has suggested that avian leukosis virus subgroup J (ALV-J) predisposes young meat-type chickens to inclusion body hepatitis caused by fowl adenovirus (FAV). To address this hypothesis, we infected 1-day-old grandparent meat-type chickens carrying maternal antibodies against FAV with a field isolate of FAV associated with inclusion body hepatitis in broilers, ALV-J, or both FAV and ALV-J. We examined the effects of FAV alone or in combination with ALV-J on the basis of clinical signs, overall mortality, growth rate, and gross and microscopic lesions. With such criteria for evaluating possible interactions, we found no significant differences in the dually infected birds in comparison with chickens that received a monovalent challenge with either FAV or ALV-J.

Dynamics of Salmonella contamination in a commercial quail operation.

Control of carcass contamination requires knowledge of the source and dynamics of spread of Salmonella in commercial poultry production. We examined Salmonella contamination at a U.S. commercial quail operation. Pulsed-field gel electrophoresis (PFGE) was used to type isolates in order to trace Salmonella throughout this production environment. During a 6-mo survey, Salmonella serotypes hadar, typhimurium, typhimurium variant Copenhagen, and paratyphi were encountered within this poultry operation. Ninety-four percent of the Salmonella isolated from breeder and production houses and from carcass rinses belonged to Salmonella serotypes typhimurium variant Copenhagen and hadar. There were six distinct S. typhimurium variant Copenhagen genetic types, as identified by PFGE, present within this particular poultry operation. Seventy-nine percent of S. typhimurium variant Copenhagen identified from the environment of the breeder and production houses produced the same PFGE pattern. Thirty-eight percent of S. typhimurium Copenhagen isolated from carcass rinses and the breeder house shared the same PFGE DNA pattern. This study demonstrates the transmission of salmonellae throughout this production environment, from the breeders to their progeny and to the birds ultimately processed for human consumption.

Effect of exenatide on gastric emptying and graft survival in islet allograft recipients.

OBJECTIVE: To evaluate the effect of exenatide on gastric emptying and long-term metabolic control. METHODS: Ten islet allograft recipients treated with exenatide up to 4 years. Data from a mixed meal test with (MMT+) versus without (MMT-) administration of exenatide before boost ingestion were analyzed at 6, 12, 24, 36, or 48 months after initiation of exenatide treatment. None of the subjects were symptomatic for gastroparesis before or during the study. The c-peptide, acetaminophen absorption and glucose responses to MMT were analyzed by Student t test and analysis of variance. RESULTS: Average exenatide dose was 12.75 ± 9.46 µg/dL. The MMT subjects included two groups those with acetaminophen peak ≤120 minutes ("good gastric emptying; n = 4") versus those with an acetaminophen peak ≥180 minutes ("delayed gastric emptying"). Among the MMT+, acetaminophen absorption was the same in both groups (P = .27). Up to 48 months exenatide delayed time to peak of glucose, c-peptide, and acetaminophen as well as suppressed the glucagon response to MMT mean peak: 70.89 ± 12.45 versus 43.24 ± 4.67. The mean values of c-peptide and glucose responses to MMT were not significantly different. CONCLUSIONS: Long-term exenatide administration up to 4 years was safe in islet transplant recipients, even in the presence of delayed gastric emptying. The effects of exenatide were acute and reversible when the agent was withdrawn. The main difficulty with the use of exenatide in islet transplant subjects is their poor tolerability, although the physiological effects are clearly evident even at low doses. Approximately 63% of total subjects under exenatide treatment discontinued the drug due to nausea and vomiting. The use of new GLP1 analogs with longer half lives and fewer side effects may help to attain higher GLP1 levels, therefore improving islet function and survival.

Changes in land cover and vegetation carbon stocks in Andalusia, Southern Spain (1956-2007).

Land use has significantly changed during the recent decades at global and local scale, while the importance of ecosystems as sources/sinks of C has been highlighted, emphasizing the global impact of land use changes. Land use changes can increase C loss rates which are extremely difficult to reverse, in the short term, opposite to organic carbon (OC) which accumulates in soil in the long-term. The aim of this research is to improve and test methodologies to assess land cover change (LCC) dynamics and temporal and spatial variability in C stored in vegetation at a wide scale. LCCs between 1956 and 2007 in Andalusia (Southern Spain) were selected for this pilot study, assessed by comparison of spatial data from 1956 to 2007 and were reclassified following land cover flows (LCFs) reported in major areas in Europe. Carbon vegetation densities were related to land cover, and C vegetation stocks for 1956 and 2007 were calculated by multiplying C density for each land cover class with land cover areas. The study area has supported important changes during the studied period with significant consequences for vegetation C stocks, mainly due to afforestation and intensification of agriculture, resulting in a total vegetation C stock of 156.08Tg in 2007, with an increase of 17.24Tg since 1956. This study demonstrates the importance of LCC for C sequestration in vegetation from Mediterranean areas, highlighting possible directions for management policies in order to mitigate climate change as well as promoting land conservation. The methodologies and information generated in this project will be a useful basis for designing land management strategies helpful for decision makers.

Buschke-Löwenstein tumor in childhood: a case report.

Buschke-Löwenstein tumor or giant condyloma is a warty verrucous lesion, characterized by slow growth, locally infiltrating and disfiguring lesions. Despite its benign histological appearance and low risk of metastasis, Buschke-Löwenstein tumor is an intermediate lesion between condyloma acuminatum and verrucous carcinoma. It has been linked to human papilloma virus, mainly subtypes 6 and 11. Other factors implicated in this disease include poor hygiene, chronic irritation, promiscuity, and cellular immunocompromised states. It rarely occurs in children. The first line of treatment is radical surgical excision with or without adjuvant chemotherapy. We report the case of a 12-year-old girl with a giant perianal condyloma that was treated with surgical excision and a 6-week course of 5-fluorouracil beginning 6 weeks after surgery, with excellent functional and cosmetic results.

Brain tissue pressure measurements in perinatal and adult rabbits.

Brain tissue pressure (BTP) in pre- and post-natal anesthetized rabbits, held in a stereotactic head holder, was measured with a fluid filled 23 gauge open-ended cannula connected distally to a pressure transducer. By advancing the cannula step wise through a hole in the cranium it was possible to sequentially measure pressure from the cranial subarachnoid space, cortex, ventricle and basal ganglia. Separate cannulas and transducers were used to measure CSFP from the cisterna magna and arterial and/or venous pressure. Pressure recordings obtained when the tip of the BTP cannula was located in the cranial subarachnoid space or ventricle exhibited respiratory and blood pressure pulsations equivalent to and in phase with CSF pulsations recorded from the cisterna magna. When the tip was advanced into brain parenchymal sites such pulsations were suppressed or non-detectable unless communication with a CSF compartment had been established inadvertently. Although CSF pressures in the three spinal fluid compartments were equivalent, in most animals BTP was higher than CSFP. However, after momentary venting of the system BTP equilibrated at a pressure below that of CSFP. We speculate that venting of the low compliance system (1.20 x 10(-5) ml/mmHg) relieves the isometric pressure build-up due to insertion of the cannula into brain parenchyma. Under these conditions, and at all ages examined, BTP in the rabbit is consistently lower than CSFP and, as with CSFP, it increases as the animal matures.

Furosemide lowers intracranial pressure by inhibiting CSF production.

Furosemide administration effectively lowers intracranial pressure in newborn preterm and term rabbit pups. This effect may be due to the diuretic action of the drug, its ability to inhibit cerebrospinal fluid production or to a combination of both. To test these possibilities newborn rabbits were either injected with furosemide and left unmolested for 6 hours, or anaesthetized and subjected to ventriculocisternal perfusions. During the 6 hour postnatal period the decrease in body weight was 8 times greater in furosemide than in saline treated pups. However, no difference was noted between the average brain weights of these two groups. Secondary effects of the diuretic were noted in blood (12.5% increase in the haematocrit over control value) and in muscle in which tissue water content and NA+ concentration were decreased while K+ concentration was increased. The fact that these parameters remained unchanged in brain suggests that the lowering of intracranial pressure was not attributable to the secondary effects of the diuretic agent. However, the marked reduction in cerebrospinal production noted following furosemide administration indicates that in newborn rabbits this may represent the primary mechanism by which furosemide lowers intracranial pressure.

[In vitro effects of argon laser radiation the human healthy and atherosclerotic aorta]. / Efectos in vitro de la radiación del laser de argón en aorta sana y aterosclerosa.

Argon laser exposures in vitro were done on human aortas. The laser energy applied on a fresh aorta section (A) was from 100mw to 1000mw. A second aorta section (B), formalin fixed, was irradiated under saline solution by a fiberoptic system. Laser energy was from 400mw to 720mw. The time exposures were all different in both sections. A and B histologic findings of thermal damage were similar Three zones of tissue injury were observed: I) crater because of tissue vaporization; II) coagulative necrosis surrounding it; and III) multiple vacuoles in the adjacent tissue produced by acoustic or shock injury. Tissue damage was related directly with total energy delivered: less than or equal to 500mw showed inner vascular wall necrosis, and at greater than or equal to 720mw it was perforated. Atherosclerotic tissue was more resistant to laser thermal injury than normal tissue. We could not find time relation with thermal damage. This preliminary information is an early step for the possible use of Argon laser on cardiovascular area.

La Oxitocina media la natriuresis inducida por la angiotensina II administrada centralmente / The half oxitocin the induce natriuresis by the angiotensin II centrally administered

El sistema renina-angiotensina cerebral es uno de los sistemas más importantes que participan en la regulación del balance hidromineral. La administración central de renina o angiotensina II (Ang II) induce dipsogenia, apetito por la sal, aumento de presión arterial, natriuresis, liberación de oxitocina y vasopresina desde el núcleo paraventricular hipotalámico. La evidencia indica que la oxitocina es una hormona natriurética. Por ello, estudiamos el papel de la oxitocina como posible efector humoral de la natriuresis inducida por la administración intracerebroventricular (ICV) de Ang II en ratas euvolémicas, mediante el uso del atosiban (AT), un antagonista selectivo de los receptores de oxitocina. La administración central de renina o Ang II produjo un efecto antidiurético a la primera hora y un aumento en la excreción urinaria de sodio, de potasio y de GMPc a las 1, 3 y 6 horas. El AT potenció el efecto antidiurético e inhibió completamente la natriuresis, kaliuresis y aumento de la excreción de GMPc, inducidos por la Ang II. Los efectos renales de renina fueron independientes del óxido nítrico ya que el pretratamiento con L-NAME, un inhibidor de la sintasa del óxido nítrico, no alteró la respuesta renal inducida por la administración de renina-ICV. Nuestros resultados apoyan el papel de la oxitocina como efector de la acción natriurética mediada por el sistema renina angiotensina cerebral

Infarto del miocardio con coronarias permeables. Correlacion clinicopatologica. / Myocardial infarction with patent coronary arteries. Clinico-pathological correlations

De 259 enfermos que fallecieron por infarto agudo del miocardio y en los que se obtuvo estudio post-mortem, el 11,7% tuvo arterias coronarias permeables con minimos cambios de ateroesclerosis. La edad promedio fue de 43,5 anos, muy inferior a la de aquellos que fallecen con infarto del miocardio por dano coronario oclusivo por ateroesclerosis. Predomino el sexo masculino sobre el femenino en proporcion de 3:2.El factor de riesgo coronario mas frecuente (56,6%) fue el tabaquismo. El 30% no tuvo factor de riesgo demostrable.El 96,7% no presento prodromos de cardiopatia isquemica y se encontraba asintomatico previo al infarto. El 10% mostro evidencia de infarto antiguo asociado al infarto agudo del miocardio. El 53,3% fueron posteroinferiores, el 36,7% anteriores y en los restantes el infarto abarco todo el ventriculo izquierdo. 40% de los infartos fueron subendocardicos, 33% transmurales y 26,7% mixtos (subendocardicos y transmurales). El 23,3% se asocio a valvulopatia reumatica. Se discute la probable fisiopatologia de estos casos y se hace una revision de la literatura