Post-mortem culture of Balamuthia mandrillaris from the brain and cerebrospinal fluid of a case of granulomatous amoebic meningoencephalitis, using human brain microvascular endothelial cells

The first isolation in the UK of Balamuthia mandrillaris amoebae from a fatal case of granulomatous amoebic meningoencephalitis is reported. Using primary cultures of human brain microvascular endothelial cells (HBMECs), amoebae were isolated from the brain and cerebrospinal fluid (CSF). The cultures showed a cytopathic effect at 20–28 days, but morphologically identifiable B. mandrillaris amoebae were seen in cleared plaques in subcultures at 45 days. The identification of the organism was later confirmed using PCR on Chelex-treated extracts. Serum taken while the patient was still alive reacted strongly with slide antigen prepared from cultures of the post-mortem isolate, and also with those from a baboon B. mandrillaris strain at 1 : 10 000 in indirect immunofluorescence, but with Acanthamoeba castellanii (Neff) at 1 : 160, supporting B. mandrillaris to be the causative agent. If the presence of amoebae in the post-mortem CSF reflects the condition in life, PCR studies on CSF and on biopsies of cutaneous lesions may also be a valuable tool. The role of HBMECs in understanding the interactions of B. mandrillaris with the blood–brain barrier is discussed

Tutela y Curatela en derecho romano

En este trabajo se hace una revisión general de las instituciones tutelares romanas pensadas para hacer frente a la discapacidad en alguna de sus formas. Partiendo de la capacidad general de todo sujeto libre, ciudadano romano y sui iuris, los romanos idearon un sistema de protección y complemento de la capacidad para aquellos que la tuvieran limitada por distintos motivos (edad, sexo, enfermedad física y/o mental). En el ámbito de la menor edad optaron por la tutela, en el de la enfermedad mental por la curatela. Estas medidas coinciden con el modelo previsto en el Anteproyecto de ley de reforma del Código civil y de la Ley de Enjuiciamiento civil en materia de discapacidad de 2018, siguiendo las recomendaciones de la Convención de Naciones Unidas de los derechos de las personas con discapacidad, celebrada en Nueva York el 13 de diciembre de 2006 (Dicho anteproyecto ha entrado recientemente en el Congreso de los Diputados)

Hepatocellular carcinoma: updates in pathogenesis, detection and treatment

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the second most common cause of cancer mortality worldwide [1]. The prognosis of HCC patients is very poor. The rates of HCC incidence and mortality are almost equivalent [2] and have increased across most countries over the past three decades [3]. HCC development is closely associated with the presence of chronic liver disease and cirrhosis, albeit the risk factors underlying this condition vary geographically. Hepatitis B virus (HBV) infection and aflatoxin B1 exposure are predominant risk factors in Asia and Africa, while hepatitis C virus (HCV) infection and alcohol consumption are the main risk factors in Europe, the USA and Japan [3,4,5]. Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease worldwide, and approximately 60% of biopsied NAFLD patients have non-alcoholic steatohepatitis (NASH) [3]. Importantly, patients with NASH are at high risk of developing HCC even without presenting established cirrhosis [6]. With widespread HBV vaccination and the advent of direct-acting antiviral drugs for HCV infection, NAFLD and associated conditions such as diabetes and obesity are emerging as major global risk factors for HCC. In view of the dismal prognosis of HCC patients, implementing preventive strategies would be an ideal approach to quell the incidence of the disease. Obvious interventions include advocating HBV vaccination in endemic regions, achieving HCV eradication with direct-acting antivirals, promoting healthy nutrition and weight reduction, improving diabetes control, and avoiding excessive alcohol consumption. Still, the implementation of these measures is not always feasible

Magnetospectroscopy of epitaxial few-layer graphene

The inter-Landau level transitions observed in far-infrared transmission experiments on few-layer graphene samples show a behaviour characteristic of the linear dispersion expected in graphene. This behaviour persists in relatively thick samples, and is qualitatively different from that of thin samples of bulk graphite.Comment: Invited short review to appear in a special issue of Solid State Communication

A column-store meets the point clouds

Dealing with LIDAR data in the context of database management systems calls for a re-assessment of their functionality, performance, and storage/processing limitations. The territory for efficient and scalable processing of LIDAR repositories using GIS enabled database systems is still largely unexplored. Bringing together hard core database management experts and GIS application developers is a sine qua non to advance the state of the art. In particular to assess the relative merits of both traditional row-based database engines and the modern column-oriented database engines

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding the importance of the inheritance of these epigenetic marks

NO sensitizes rat hepatocytes to proliferation by modifying S-adenosylmethionine levels

BACKGROUND & AIMS: Liver regeneration is a fundamental response of this organ to injury. Hepatocyte proliferation is triggered by growth factors, such as hepatocyte growth factor. However, hepatocytes need to be primed to react to mitogenic signals. It is known that nitrous oxide (NO), generated after partial hepatectomy, plays an important role in hepatocyte growth. Nevertheless, the molecular mechanisms behind this priming event are not completely known. S-adenosylmethionine (AdoMet) synthesis by methionine adenosyltransferase is the first step in methionine metabolism, and NO regulates hepatocyte S-adenosylmethionine levels through specific inhibition of this enzyme. We have studied the modulation of hepatocyte growth factor-induced proliferation by NO through the regulation of S-adenosylmethionine levels. METHODS: Studies were conducted in cultured rat hepatocytes isolated by collagenase perfusion, which triggers NO synthesis. RESULTS: The mitogenic response to hepatocyte growth factor was blunted when inducible NO synthase was inhibited; this process was overcome by the addition of an NO donor. This effect was dependent on methionine concentration in culture medium and intracellular S-adenosylmethionine levels. Accordingly, we found that S-adenosylmethionine inhibits hepatocyte growth factor-induced cyclin D1 and D2 expression, activator protein 1 induction, and hepatocyte proliferation. CONCLUSIONS: Together our findings indicate that NO may switch hepatocytes into a hepatocyte growth factor-responsive state through the down-regulation of S-adenosylmethionine levels

Adiabatic quantum pump in the presence of external ac voltages

We investigate a quantum pump which in addition to its dynamic pump parameters is subject to oscillating external potentials applied to the contacts of the sample. Of interest is the rectification of the ac currents flowing through the mesoscopic scatterer and their interplay with the quantum pump effect. We calculate the adiabatic dc current arising under the simultaneous action of both the quantum pump effect and classical rectification. In addition to two known terms we find a third novel contribution which arises from the interference of the ac currents generated by the external potentials and the ac currents generated by the pump. The interference contribution renormalizes both the quantum pump effect and the ac rectification effect. Analysis of this interference effect requires a calculation of the Floquet scattering matrix beyond the adiabatic approximation based on the frozen scattering matrix alone. The results permit us to find the instantaneous current. In addition to the current generated by the oscillating potentials, and the ac current due to the variation of the charge of the frozen scatterer, there is a third contribution which represents the ac currents generated by an oscillating scatterer. We argue that the resulting pump effect can be viewed as a quantum rectification of the instantaneous ac currents generated by the oscillating scatterer. These instantaneous currents are an intrinsic property of a nonstationary scattering process.Comment: 11 pages, 1 figur

Benchmarking and improving point cloud data management in MonetDB

The popularity, availability and sizes of point cloud data sets are increasing, thus raising interesting data management and processing challenges. Various software solutions are available for the management of point cloud data. A benchmark for point cloud data management systems was defined and it was executed for several solutions. In this paper we focus on the solutions based on the column-store MonetDB, the generic out-of-the-box approach is compared with two alternative approaches that exploit the spatial coherence of the data to improve the data access and to minimize the storage requirement