A Microphysiological System for Studying Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD), which to date has no approved drug treatments. There is an urgent need for better understanding of the genetic and molecular pathways that underlie NAFLD/NASH, and currently available preclinical models, be they in vivo or in vitro, do not fully represent key aspects of the human disease state. We have developed a human in vitro co‐culture NASH model using primary human hepatocytes, Kupffer cells and hepatic stellate cells, which are cultured together as microtissues in a perfused three‐dimensional microphysiological system (MPS). The microtissues were cultured in medium containing free fatty acids for at least 2 weeks, to induce a NASH‐like phenotype. The co‐culture microtissues within the MPS display a NASH‐like phenotype, showing key features of the disease including hepatic fat accumulation, the production of an inflammatory milieu, and the expression of profibrotic markers. Addition of lipopolysaccharide resulted in a more pro‐inflammatory milieu. In the model, obeticholic acid ameliorated the NASH phenotype. Microtissues were formed from both wild‐type and patatin‐like phospholipase domain containing 3 (PNPLA3) I148M mutant hepatic stellate cells. Stellate cells carrying the mutation enhanced the overall disease state of the model and in particular produced a more pro‐inflammatory milieu. Conclusion: The MPS model displays a phenotype akin to advanced NAFLD or NASH and has utility as a tool for exploring mechanisms underlying the disease. Furthermore, we demonstrate that in co‐culture the PNPLA3 I148M mutation alone can cause hepatic stellate cells to enhance the overall NASH disease phenotype

Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II

BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. RESULTS: 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0–38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early

Analiza efektywności poszczególnych wariantów obsługi komunikacyjnej Gliwic przez transport zbiorowy

In the present times the high volume of traffic results in a particular emphasis on well-organized urban transport. According to the ideas concerning the sustainable development, city authorities are trying to eliminate congestion in the downtown area of large urban centers. The article attempts to analyze the economic efficiency of the bus and tram transport in Gliwice. This topic was chosen because of the decision of the city authorities abolish tram services. Consequently, tram lines have been replaced by the bus service. The article presents the carriers who perform services for the Transportation Association of the Municipal Upper Silesian Industrial District in Katowice (Komunikacyjny Związek Komunalny Górnośląskiego Okręgu Przemysłowego w Katowicach, KZK GOP), and particularly – their fleet. It offers a comparison of operating the city bus and tram lines based on the economic efficiency, and taking into account the external costs of air pollution.W dobie dużego natężenia ruchu samochodowego szczególny nacisk kładziony jest na dobrze zorganizowaną komunikację miejską. Kierując się ideami zrównoważonego rozwoju próbuje się wyeliminować kongestię z centrum dużych ośrodków miejskich. W artykule podjęto próbę ekonomicznej analizy efektywności transportu tramwajowego i autobusowego na terenie Gliwic. Temat ten został wybrany ze względu na decyzję władz miasta, w wyniku której zrezygnowano z usług komunikacji tramwajowej, na rzecz transportu autobusowego. W artykule przedstawiono przewoźników wykonujących usługi na zlecenie Komunikacyjnego Związku Komunalnego Górnośląskiego Okręgu Przemysłowego w Katowicach, a w szczególności wykorzystywany przez nich tabor. Dokonano porównania obsługujących miasto linii autobusowych i tramwajowych oraz analizy efektywności ekonomicznej z uwzględnieniem kosztów zewnętrznych związanych z zanieczyszczeniem powietrza

A case of hypomagnesaemia due to malabsorption, unresponsive to oral administration of magnesium glycerophosphate, but responsive to oral magnesium oxide supplementation

Full text of this article is not available in the repositoryOral and intravenous replacement of minerals such as magnesium and calcium are usually straightforward in clinical practice, the choice generally being governed by the preparation most readily available. There are very few data comparing efficacy and absorption profiles of different magnesium salts. This case report highlights the importance of considering alternative preparations of oral magnesium salts in patients who appear unresponsive to one preparation, rather than moving on to chronic intravenous therapy via a Hickman line. In the case of patients with small bowel shortening, the use of magnesium oxide should be considered.Peer reviewe