Microbiome-Gut-Mucosal-Immune-Brain Axis and Autism Spectrum Disorder (ASD): A Novel Proposal of the Role of the Gut Microbiome in ASD Aetiology.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by deficits in social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome-gut-brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function and microbiota metabolites in ASD. However, a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity and the microbiome-gut-brain axis in the development of autistic symptoms severity and a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via the microbiome-gut-brain axis in a feedback circuit.

Synchronous colorectal cancer and abdominal aortic aneurysm treated simultaneously. Is a one-stage surgery a feasible treatment?

The finding of synchronous abdominal aortic aneurysm and colorectal cancer is rare. There is no consensus on which is the best surgical approach, so its management remains uncertain. A 64-year-old man was diagnosed with synchronous abdominal aortic aneurysm and rectal cancer. One-stage treatment was performed: He underwent endovascular aortic repair followed by simultaneous laparoscopic tumor resection. In our experience, one-stage minimally invasive surgery could be a safe and feasible treatment for concomitant abdominal aortic aneurysm and colorectal cancer.

Cosmovisión andina: principios éticos en aculturados, endoculturados y transculturalizados / Andean cosmovision: ethical principles in acculturated, endoculturated and transculturalized people / Cosmovisão andina: princípios éticos em povos aculturados, endoculturados e transculturalizados

Resumen Los cambios políticos sucedidos en Bolivia en los últimos 50 años llevaron a modificaciones en la participación de grupos subalternizados y en la apreciación ética de la vida. Este estudio pretende establecer las conductas bioéticas de la cosmovisión andina en aculturados, endoculturados y transculturizados en La Paz, Bolivia. Se trata de una investigación mixta, exploratoria, etnográfica, transversal, comparativa sincrónica, diacrónica y sistemática, en la cual se aplicó un cuestionario validado por expertos (alfa de Cronbach de 0,932) a 399 personas (5,3% aculturadas; 73,9%, endoculturadas y 20,8%, transculturalizadas). Los resultados contrastados por hermenéutica obtuvieron cinco categorías, de las cuales la categoría relacionalidad era independiente a la culturación (p=0,262); mientras que las categorías conciencia ecológica, complementariedad, reciprocidad, concepto de salud, modelo social y comunitario dependían entre sí (p=0,000). Se constató que los sujetos aculturados del área rural presentaban mayor conocimiento de la ética ancestral. Se recomienda la promoción de políticas educativas relacionadas a ética.

Abstract The political changes that have taken place in Bolivia in the last fifty years have led to modifications in the participation of subalternized groups and changes in the ethical appreciation of life. This study aims to establish the bioethical behaviors of the Andean cosmovision in acculturated, endoculturated and transculturated people in La Paz, Bolivia. It is a mixed, exploratory, ethnographic, cross-sectional, comparative, synchronic, diachronic and systematic research, in which a questionnaire validated by experts (Cronbach's alpha 0.932) was applied to 399 people (5.3% acculturated; 73.9%, endoculturated and 20.8%, transculturated). The results contrasted by hermeneutics obtained five categories, of which the category relationality was independent of acculturation (p=0.262); while the categories ecological awareness, complementarity, reciprocity, concept of health, social model and community depended on each other (p=0.000). It was found that the acculturated subjects from the rural area presented greater knowledge of ancestral ethics. The promotion of educational policies related to ethics is recommended.

Resumo As mudanças políticas que ocorreram na Bolívia nos últimos 50 anos levaram a mudanças na participação de grupos subalternizados e na apreciação ética da vida. Este estudo tem como objetivo estabelecer os comportamentos bioéticos da cosmovisão andina em pessoas aculturadas, endoculturadas e transculturadas em La Paz, Bolívia. Trata-se de uma pesquisa mista, exploratória, etnográfica, transversal, comparativa, sincrônica, diacrônica e sistemática, na qual um questionário validado por especialistas (alfa de Cronbach de 0,932) foi aplicado a 399 pessoas (5,3% aculturadas, 73,9% endoculturadas e 20,8% transculturadas). Os resultados contrastados pela hermenêutica produziram cinco categorias, das quais a categoria relacionalidade era independente da aculturação (p=0,262), enquanto as categorias consciência ecológica, complementaridade, reciprocidade, conceito de saúde, modelo social e comunidade dependiam umas das outras (p=0,000). Constatou-se que os indivíduos aculturados de áreas rurais tinham maior conhecimento da ética ancestral. Recomenda-se a promoção de políticas educacionais relacionadas à ética.

Increased Hepatitis C virus screening, diagnosis and linkage to care rates among people who use drugs through a patient-centered program from Italy.

BACKGROUND: Rates of Hepatitis C virus (HCV) testing and diagnosis are variable among people who use drugs (PWUD). In Puglia in 2018, of 871 subjects screened, 38% had HCV antibodies (HCVAb). Despite sustained virologic response at week 12 Sustained virologic response (SVR12) rates >95%, addiction centers in Italy are not allowed to prescribe direct-acting antivirals (DAA). AIM: To increase testing and linkage to care a dedicated program including "ad hoc" transportation and fast-track access to care was offered to PWUD from Puglia. METHODS: Over 12 months, 1,470 individuals seen at 15 Services for Dependence (SERDs) underwent screening. For HCVAb positive, a fast-track evaluation was offered at our Hepatology Unit. Patients were subsequently taken to their pharmacists to receive the prescribed DAA regimen. Treatment and adherence were supervised by SERDs physicians, SVR12 assessed at our unit. The scalability of the process was based on both, number of patients screened in our region in 2018, and number of PWUD diagnosed and treated at our center during 2018-2019. RESULTS: Of 1,470 individuals screened, 634 (43.1%) tested HCVAb positive. Overall, 231 were RNA positive, 54% of whom on opioid agonist therapy (OAT) and 32% with cirrhosis. Median interval between RNA assessment and treatment start was 22 days (0-300). Patients received 12-week sofosbuvir/velpatasvir regimen without Ribavirin; in 220 patients who completed treatment, SVR12 was 98.6%. Among GT3, SVR12 was 98%. No re-infection was observed. Improvements in screening, and linkage to care were registered. CONCLUSIONS: A PWUD-tailored service led to HCV care cascade improvement and high SVR12 rates. Despite history of drug addiction, social instability and logistic barriers, micro-elimination programs providing dedicated care are key drivers of success.

Aerobiología de polen del olivo en las ciudades de Tacna y Arica y su relación con las enfermedades alérgicas respiratorias / Olive pollen aerobiology in Tacna and Arica cities and it is relation with the allergic respiratory diseases

Medir la concentración del polen en la atmósfera se ha convertido en objeto de interés a nivel mundial debido al aumento de las enfermedades alérgicas, ya que en muchas personas es causa de polinosis. Objetivos: se centró en la elaboración de un calendario de polen del olivo, basado en medir su concentración en las ciudades de Tacna (desde 2015 al 2018) y Arica (periodo 2018), y determinar la prevalencia de resultados positivos para extracto alergénico de polen del olivo en pacientes con síntomas de rinitis y/o asma provenientes de las ciudades de Tacna y Arica (periodo 2015-2018). Métodos: Se midió la concentración de polen, mediante el método volumétrico tipo Hirst, según estándares establecidos por el comité de aerobiología de la Sociedad Española de Alergología e Inmunología Clínica (SEAIC). Se incluyó una muestra total de 350 sujetos con síntomas respiratorios (200 de Tacna y 150 de Arica). Resultados: En Tacna, en 2015, 2016, 2017 y 2018, la concentración máxima de polen de olivo fue de 246 granos/m3 ; 110 granos/m3 ; 78 granos/ m3 y 688 granos/m3 respectivamente. En Arica en 2018, la concentración máxima de polen del olivo fue de 318 granos/ m3 . Se encontró que un 34% (68/200) y un 28% (42/150) de sujetos con síntomas respiratorios estaban sensibilizados u obtuvieron pruebas positivas al extracto de polen del olivo en sujetos de las ciudades de Tacna y Arica respectivamente. Conclusión: En ambas ciudades las concentraciones máximas de polen del olivo se encontraron principalmente entre los meses de septiembre a noviembre, siendo octubre el mes de mayores conteos. Se identificó sujetos alérgicos por test cutáneo al polen del olivo en las ciudades de Tacna y Arica.

The measurement of the concentration of pollen in the atmosphere has become an object of interest worldwide for the increase of allergy diseases, since in many people it is the cause of pollinosis. Objectives: focused on the elaboration of a calendar of olive tree pollen based on the measurement of the pollen concentration in Tacna (since 2015 to 2018) and Arica (period 2018) cities, and to determine the prevalence of positive results for allergenic extract of olive pollen in patients with symptoms of rhinitis and / or asthma, who came from Tacna and Arica cities (period 2015 to 2018). Methods. The pollen concentration was measured using the volumetric method according to standards established by the Aerobiology Committee of the Spanish Society of Allergology and Clinical Immunology (SEAIC), we included 350 subjects (200 from Tacna and 150 from Arica). Results: In Tacna, in 2015, 2016, 2017 and 2018, the maximum concentration of olive pollen was 246 grains/m3; 110 grains/m3; 78 grains/m3 and 688 grains/m3 respectively. In Arica in 2018, the maximum concentration of olive pollen was 318 grains/m3. We found 34% (68/200) and 28% (42/150) were sensitized or results positive test to the olive pollen extract in subjects with respiratory symptoms from Tacna and Arica cities respectively. Conclusion: The olive pollen in the atmosphere of Tacna and Arica is mainly concentrated in the months of September to November, being October the month with higher count. Allergic subjects were identified by skin test to olive pollen in Tacna and Arica cities.

A randomized clinical trial of the effects of saphenous and perforating veins radiofrequency ablation on venous ulcer healing (VUERT trial).

OBJECTIVES: To investigate whether radiofrequency endovenous ablation (RFA) of saphenous and perforating veins increases venous leg ulcer (VLU) healing rates and prevents ulcer recurrence. METHOD: This prospective, open-label, randomized, controlled, single-center trial recruited 56 patients with VLU divided into: compression alone (CR, N = 29) and RFA plus compression (RF, N = 27). Primary endpoints were ulcer recurrence rate at 12 months; and ulcer healing rates at 6, 12, and 24 weeks. Secondary endpoints were ulcer healing velocity; and Venous Clinical Severity Score (VCSS). RESULTS: Recurrence was lower in the RF group (p < .001), as well as mean VCSS after treatment (p = .001). There were no significant between-group differences in healing rates. Healing velocity was faster in the RF group (p = 0.049). In the RF group, 2 participants had type 1 endovenous heat-induced thrombosis (EHIT). CONCLUSIONS: RFA plus compression is an excellent treatment for VLU because of its safety, effectiveness, and impact on ulcer recurrence reduction and clinical outcome.Registration: Clinicaltrials.gov, NCT03293836, clinicaltrials.gov.

Antagonist effect of probiotic bifidobacteria on biofilms of pathogens associated with periodontal disease.

The in vitro antagonist growth effect of bifidobacteria were evaluated on periodontal bacteria. Bifidobacterium longum, Bifidobacterium lactis and Bifidobacterium infantis biofilms were grown in single, double or triple combinations with putative periodontal pathogens P. gingivalis and F. nucleatum or beneficial bacteria S. oralis for 24, 72 and 168 h and the total counts were analyzed by checkerboard DNA-DNA hybridization. The results showed that B. infantis and B. lactis, as single species, demonstrated the best antagonist effect on F. nucleatum and P. gingivalis and no influence on S. oralis growth at 168 h. All the double combinations of bifidobacteria tested demonstrated an inhibitory effect on F. nucleatum (72 h) and P. gingivalis (168 h) and did not affect S. oralis counts at any time. In conclusion, B. lactis and B. infantis alone or in double combinations have antagonist effect on periodontopathogens biofilms, at different time points, and minimal influence on S. oralis growth.

Estimulación magnética transcraneal para síntomas negativos en la esquizofrenia: una revisión / The transcraneal magnetic stimulation for the negative symptoms in schizofrenia: a review

Schizophrenia is one of the most studied diseases in psychiatry and different dysfunctions of thinking, emotions, perception, movement, and behavior converge in it. These dysfunctions affect the quality of life of the patients in different ways. It is a disease that has been observed in the whole world, with a 0.5 to 1.5% prevalence among adults. Although the biological basis of schizophrenia is not clear enough, the dopaminergic hypothesis is preponderant in our understanding of the symptoms of the disease. A mesolimbic pathway hyperactivity is related to a positive symptomathology, while a prefrontal dopaminergic hypofunction relates to negative symptoms. It has been observed that using serotoninergic antagonists, which promote dopaminergic activity in the prefrontal cortex, translates in to a reduction of the intensity of negative symptoms. This negative syndrome includes a difficulty to initiate new activities (apathy), speech and creativity impoverishment (alogia), alterations in emotional expression, and a lack of capacity to experiment joy. Patients with negative symptoms present gray and white matter loss in left-sided cerebral structures, including temporal lobe, anterior cingulated, and medial frontal cortex. Such a loss seems to be more evident in prefrontal regions, such as the dorsolateral prefrontal region, which connects with anterior temporal structures. Persistent negative symptomathology is a concept proposed by Buchanan, which must fulfill the following criteria: symptoms are primary to the disease or secondary but have not responded to current treatment; interfere with the patient's capacity to accomplish normal functioning; persist during periods of clinical stability, and represent an unresolved therapeutic need. They must be measurable by clinical scales and persist, at least, six months. The Food and Drug Administration has recently considered negative symptoms as an investigation target or new treatments due to their prevalence and high negative impact in the life of the schizophrenic population. Nowadays, the current treatments available for such an entity are second generation antipshycotics and glutamatergic agents -such as d-cycloserine and glicine-, amisulpiride and seleginine, even though their efficacy is limited. Dysfunction of the human prefrontal cortex is considered to be implicated in the pathophisiology of negative symptoms. This cerebral region is essential in the regulation of emotions and cognition. Multiple neural networks begin in the prefrontal cortex and go towards other cortical association areas, to insular region, thalamic structures, basal ganglia and limbic system. It regulates dopaminergic mesencephalic activity through activating and inhibitory pathways, allowing a precise regulation of dopaminergic activity. This double modulation model of dopaminergic pathways has been recently sustained by studies which prove that extracellular dopaminergic concentration in nucleus accumbens increases or reduces after a high or low frequency stimulation of the prefrontal cortex, respectively. A prefrontal cortex lesion causes a syndrome similar to the negative symptomathology in schizophrenia. Transcraneal magnetic stimulation (TMS) could be effective in the treatment of negative symptoms by activating the prefrontal cortex, maybe by stimulating the liberation of dopamine in the mesolimbic and mesoestriatal pathways which have a crucial role in the pathogenesis of negative symptoms such as apathy and anhedonia. TMS was introduced in 1985 and since the early 90's its potential as a treatment has been tested in numerous neurological and psychiatric conditions. It is a noninvasive means of stimulating nervous cells in superficial areas of the brain. During a TMS procedure, an electrical current passes through a wire coil placed over the scalp. This induces a magnetic field that can produce a substantive electrical field in the brain. This electrical field produces in turn a depolarization of nervous cells resulting in the stimulation or disruption of brain activity. TMS may be applied as a single stimulus or repeated many times per second (repetitive TMS), with variations in the intensity, site, and orientation of the magnetic field. Most research and interest has focused on the potential application of repetitive TMS (rTMS) in the treatment of depression. In addition, in recent years an increasing number of open and double-blinded studies of rTMS were conducted in patients with schizophrenia. Most investigators have chosen to focus on the treatment of specific refractory symptoms or syndromes within the disorder such as refractory auditory hallucinations or persistent negative symptoms. TMS has become widely used in research, especially as a method to probe normal and abnormal brain function, motor cortical physiology, and cognition. Regarding negative symptoms in schizophrenia, eleven studies using TMS were carried out until 2006, with a total of 172 patients studied. These studies are difficult to compare because they used different stimulation parameters and the symptoms described were heterogenic. Six studies were blind and five were open, using high frequency TMS in all of them (frequencies above 1 Hz), which is the type of stimulation most commonly used in treatment studies. Six of these studies found a reduction in the severity of the symptoms, but the reduction was not significant in two of them. Ten were the maximum number of sessions included in every study, except for one, in which 20 sessions of TMS were given. In this study, the score of negative subscale of the PANSS was reduced in 33%, which is considered a significant response, and this result was sustained within the next month. In one of these studies, researchers compared 3- and 20-Hz stimulation with sham stimulation and stimulation provided at the patient's individual alpha frequency. Alpha-frequency stimulation was calculated as the patient's peak alpha frequency from five frontal EEG leads. Stimulation of alpha frequency resulted in a significantly greater reduction in negative symptoms than the other conditions. This finding could suggest that negative symptoms may specifically relate to alpha EEG oscillations, which is interesting and requires further exploration and confirmation. Another two studies were conducted in 2007; in the first one, no improvement in negative, positive of affective symptoms was found. The second one, which was a double-blinded clinical trial, found a significant reduction in the intensity of negative, positive, and general symptoms with the active TMS. We should remark that TMS produces changes in the cortical activity in ventral and dorsoestratial regions, but other cerebral regions could be stimulated too, since some activation abnormalities in the left globus palidus, bilateral caudate nucleus, prefrontal, and temporal right cortex have been found and are associated with the etiology of the negative syndrome. In addition, it will be interesting to see whether changes in subcortical dopamine release, which were shown with rTMS in normal volunteers, can be demonstrated in clinical populations, such as patients with schizophrenia, and how this may relate to response to treatment. There is still a need for a larger number of controlled studies, with larger samples, longer periods of evaluation, and constant stimulation parameters, so they can be compared between them and the exact efficacy of TMS as a treatment for negative symptoms can be established.

La estimulación magnética transcraneal (EMT) es un método no invasivo que utiliza campos magnéticos alternantes para inducir corrientes eléctricas en el tejido cortical en diferentes áreas cerebrales. Se considera una forma de tratamiento para diferentes trastornos psiquiátricos, especialmente en la depresión, adicciones y esquizofrenia. Está técnica terapéutica ofrece una vía innovadora para estudiar la excitabilidad de la corteza, la conectividad regional cortical, la plasticidad de las respuestas cerebrales y las funciones cognitivas en el estado del enfermo. Aunque se han documentado resultados positivos en la estimulación de la CPF izquierda y en la CPF derecha, se sugiere que puede ejercer su acción beneficiosa a través de diversos mecanismos de acción aún no comprendidos en su totalidad. La corteza prefrontal humana es esencial en el control e integración de las emociones, la cognición y la regulación del Sistema Nervioso Autónomo. Numerosas conexiones neuronales bidireccionales se originan en la CPF y se extienden al resto de las áreas de asociación cortical, región insular, sistema límbico y los ganglios basales. La CPF modula la actividad dopaminérgica mesencefálica mediante una vía activadora y otra inhibidora, lo que permite una regulación sumamente fina de la actividad dopaminérgica. La vía activadora funciona por medio de proyecciones glutamatérgicas directas e indirectas a las células dopaminérgicas. La vía inhibitoria hace lo propio mediante eferencias glutamatérgicas prefrontales a las interneuronas GABAérgicas mesencefálicas y a las neuronas GABAérgicas estriatomesencefálicas. El modelo de la doble modulación del sistema dopaminérgico mesolímbico demuestra que la concentración dopaminérgica extracelular en el núcleo accumbens disminuye o aumenta después de la estimulación de la corteza prefrontal a baja o alta frecuencia, respectivamente. Dentro de los estudios que utilizan la EMT en la esquizofrenia, se ha encontrado que, tras una EMT de alta frecuencia (>1Hz) o repetititiva (EMTr), hay un aumento de la excitabilidad en varias áreas cerebrales, mientras que la excitabilidad cortical disminuye tras una EMT de baja frecuencia (<1Hz). La excitabilidad cortical también depende de la intensidad y duración de la estimulación, lo que quiere decir que a intensidades más altas habrá mayor actividad cortical y a trenes prolongados habrá cambios duraderos en la excitabilidad cortical. Una gama de síntomas de difícil tratamiento en la esquizofrenia son los síntomas negativos persistentes, donde se ha demostrado una disminución de la actividad en la CPF, por lo que la EMT se ha utilizado para revertir dicha hipoactividad y disminuir los síntomas. De forma contraria, los síntomas positivos, como las alucinaciones, se asocian con una hiperactividad de las áreas témporo-parietales y por tanto debería resultar beneficiosa la aplicación de EMT de baja frecuencia en dichas áreas. La EMT de alta frecuencia también se ha utilizado para tratar a sujetos con síntomas catatónicos prominentes y se ha logrado una mejoría con el tratamiento. El objetivo de esta revisión es que se comprendan mejor la EMT y el uso que se le puede dar para tratar diversos síntomas en la esquizofrenia.

A practical protocol to measure common carotid artery intima-media thickness.

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3%) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26+/-0.6 mm (transversal), 1.17+/-0.54 mm (longitudinal anterolateral), and 1.18+/-0.58 mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

A practical protocol to measure common carotid artery intima-media thickness

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3 percent) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Purification, crystallization and preliminary X-ray analysis of the BseCI DNA methyltransferase from Bacillus stearothermophilus in complex with its cognate DNA.

The DNA methyltransferase M.BseCI from Bacillus stearothermophilus (EC 2.1.1.72), a 579-amino-acid enzyme, methylates the N6 atom of the 3' adenine in the sequence 5'-ATCGAT-3'. M.BseCI was crystallized in complex with its cognate DNA. The crystals were found to belong to the hexagonal space group P6, with unit-cell parameters a = b = 87.0, c = 156.1 A, beta = 120.0 degrees and one molecule in the asymmetric unit. Two complete data sets were collected at wavelengths of 1.1 and 2.0 A to 2.5 and 2.8 A resolution, respectively, using synchrotron radiation at 100 K.

An experimental model for the treatment of lethal bleeding injury to the juxtahepatic vena cava with stent graft.

BACKGROUND: Juxtahepatic vein injuries present a high mortality rate. Our objectives were to develop an experimental model of endovascular lethal injury of the juxtahepatic inferior vena cava (JHIVC) and to evaluate its hemodynamic alterations; to treat the lesion with volume replacement, and a stent graft (SG); and to follow the animals after treatment. METHODS: Twenty dogs were anesthetized and monitored [heart rate (HR), mean arterial pressure (MAP), vesical and peritoneal pressures], and submitted to a JHIVC endovascular injury. After volume replacement the dogs were divided into two groups: control (GI) and experimental (GII). GI was observed until death. GII was treated with SG and followed by Doppler ultrasound (DUS) and cavography for 4 (GIIA), and 8 weeks (GIIB), and then sacrificed and IVC and SG were analyzed. RESULTS: GI presented increased abdominal pressures, arterial hypotension, and death after 80 minutes. GII had a 100% survival rate till sacrifice, without clinical repercussions. At DUS and cavography all SG were patent, with monophasic pulsatile flow. On US, SG diameters after 2, 4, and 8 weeks did not show differences. On cavography IVC diameters presented no difference between groups GIIA and GIIB throughout the experiment. These data analyzed for the GII as a whole, showed statistically significant differences. Average lumen diameter reduction of SG was 27.43+/-20,00%. Pressure values in the IVC cranially, caudally to the SG, and inside the SG, did not show differences. In the IVC with the SG we observed a thicker neointima layer, and the injury in the media layer was covered with fibroconnective tissue. CONCLUSIONS: We developed an experimental dog model of endovascular lethal injury of the JHIVC with significant increase in abdominal pressures, and a mortality rate of 100%. The treatment of this lesion with SG resulted in a thickened neointima layer, and a 27% reduction in the JHIVC lumen diameter, without clinical repercussion, and with a 100% survival rate.

Parâmetros dopplervelocimétricos na avaliação da perviedade da anastomose portossistêmica intra-hepática transjugular (TIPS) / Dopplerflowmetric patterns for evaluation of transjugular intrahepatic portosystemic shunt patency

A anastomose portossistêmica intra-hepática transjugular (TIPS) é um procedimento intervencionista minimamente invasivo realizado pela introdução de prótese metálica auto-expansível no parênquima hepático, via transjugular. Tem por objetivo tratar as complicações da hipertensão portal, principalmente a hemorragia digestiva alta e a ascite refratária. A estenose é complicação freqüente, embora o procedimento seja eficaz e com baixo índice de insucesso. O diagnóstico precoce da estenose é de fundamental importância, pois interfere no tipo de tratamento a ser realizado e o reaparecimento dos sintomas pode ser grave. O ultra-som Doppler é então utilizado para o seguimento dos pacientes portadores do TIPS, e vários parâmetros são descritos na literatura para o diagnóstico de estenose, como: as velocidades mínima e máxima no interior da prótese, a velocidade na veia porta, o gradiente de velocidade entre dois pontos da prótese, e outros. Infelizmente não há consenso sobre qual parâmetro ou conjunto de parâmetros é mais eficaz no diagnóstico, porque os protocolos de avaliação variam de instituição para instituição. Os autores realizaram uma revisão dos parâmetros de estenose descritos na literatura e de outros aspectos de fundamental importância na compreensão do procedimento, como as indicações, as contra-indicações e a fisiopatologia da estenose.

Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive interventional procedure that consists of placement of an auto expandable metallic stent in the hepatic parenchyma via transjugular. It is used to treat the complications of portal hypertension, particularly digestive bleeding of gullet varices and refractory ascites. Although TIPS is an efficient procedure with low rate of failure some complications such as stenosis are frequent. Early diagnosis of stenosis is mandatory since it interferes with the type of treatment and the reappearing symptoms can be serious. Doppler sonography is used in the follow-up of this patients and many parameters indicating TIPS stenosis are described in the literature such as the minimum and maximum velocity flow inside the stent, the velocity flow in portal vein, the velocity gradient between different sites of the stent, among others. Unfortunately there is no consensus on which parameter or group of parameters is more efficient for diagnosis because the evaluation protocols varied among institutions. The authors reviewed the parameters of stenosis reported in literature and other important aspects for comprehension of this procedure including indications, contraindications and physiopathology of stenosis.

Biosynthesis and regulation of two vitellogenins in the fat body and ovaries of Ceratitis capitata (Diptera).

In adult female Ceratitis capitata both fat body and ovaries synthesize two vitellogenins (Vg-1 and Vg-2) with the same molecular masses as the respective vitellins of the eggs. Furthermore, both tissues contain two abundant mRNAs which yield, in a cell-free system, two previtellogenin polypeptides with molecular masses approximately 1,000 daltons higher than the mature Vgs. In vivo and in vitro studies during development suggested co-ordinate synthesis of Vg-1 and Vg-2 in each tissue. Also, at least in the fat body, Vg synthesis appears to be regulated at the level of transcription. Although both Vg-1 and Vg-2 are synthesized in the fat body and ovaries synchronously, their relative synthetic rates differ in the two tissues. The ratio of Vg-1 to Vg-2 synthesis in the fat body is approximately twice the respective ratio in the ovaries. Adult C. capitata males do not synthesize Vgs; however, they do so after treatment with 20-hydroxyecdysone.