Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

Protodioscin levels in Brachiaria spp. in a sheep production system and a brief review of the literature of Brachiaria spp. poisoning in ruminants / Níveis de protodioscina em Brachiaria spp. em um sistema de produção de ovinos e uma breve revisão da literatura da intoxicação por Brachiaria spp. em ruminantes

Plants of the genus Brachiaria, used in several countries as forage, are poisonous to some livestock species. Their toxic principle is protodioscin, and the main form of clinical presentation of the toxicosis is hepatogenous photosensitization. Here we compare protodioscin levels in B. decumbens and B. brizantha and review the literature on the concentrations and methodologies of collection and analysis of the toxic principle in Brachiaria spp. and the risk of contamination of pastures by more toxic species that may facilitate poisoning by plants of this genus in sheep. The experiment was conducted in pastures originally formed by B. brizantha, with many B. decumbens invasion points. The occurrence of cases of poisoning by Brachiaria spp. was the criterion for confirming pasture toxicity. The forage samples were collected at ten random points every 28 days through manual grazing simulation. The samples were analyzed for protodioscin by high-performance liquid chromatography (HPLC) with light scattering by evaporation (ELSD) after being dried and crushed. In the flock of 69 sheep, five poisoning cases occurred, three sheep died, and two recovered. The protodioscin levels found in the evaluated pastures ranged from 0.70 to 0.45%; higher levels appeared in B. decumbens (7.09%) compared to 1.04% in B. brizantha. We suggest that Brachiaria spp. should be avoided in pastures where sheep are grazing.(AU)

Plantas do gênero Brachiaria, utilizadas em vários países como forragem, são tóxicas para várias espécies pecuárias. Seu princípio tóxico é a protodioscina, e a principal forma de apresentação clínica da toxicose é a fotossensibilização hepatógena. Este estudo teve como objetivo comparar os níveis de protodioscina em B. decumbens e B. brizantha e revisar a literatura sobre as concentrações e metodologias de coleta e análise do princípio tóxico em Brachiaria spp. e o risco de contaminação das pastagens por espécies mais tóxicas que podem facilitar a intoxicação por plantas desse gênero em ovinos. O experimento foi conduzido em pastagens originalmente formadas por B. brizantha, com diversos pontos de invasão por B. decumbens. Ocorrência de casos de intoxicação por Brachiaria spp. foi o critério para confirmação da toxicidade da pastagem. As amostras de forragem foram coletadas a cada 28 dias em dez pontos aleatórios por meio de simulação de pastejo manual. As amostras foram analisadas para protodioscina por cromatografia líquida de alta eficiência (HPLC) com dispersão de luz por evaporação (ELSD) após serem secadas e trituradas. No rebanho de 69 ovelhas, cinco desenvolveram a intoxicação, três morreram e duas se recuperaram. Os níveis de protodioscina encontrados nas pastagens avaliadas variaram de 0,70 a 0,45%; níveis mais elevados apareceram em B. decumbens (7,09%) em comparação com 1,04% em B. brizantha. Sugerimos que Brachiaria spp. deve ser evitada no pasto de ovelhas em pastejo.(AU)

Drug Discovery Insights from Medicinal Beetles in Traditional Chinese Medicine

Traditional Chinese medicine (TCM) was the primary source of medical treatment for the people inhabiting East Asia for thousands of years. These ancient practices have incorporated a wide variety of materia medica including plants, animals and minerals. As modern sciences, including natural products chemistry, emerged, there became increasing efforts to explore the chemistry of this materia medica to find molecules responsible for their traditional use. Insects, including beetles have played an important role in TCM. In our survey of texts and review articles on TCM materia medica, we found 48 species of beetles from 34 genera in 14 different families that are used in TCM. This review covers the chemistry known from the beetles used in TCM, or in cases where a species used in these practices has not been chemically studied, we discuss the chemistry of closely related beetles. We also found several documented uses of beetles in Traditional Korean Medicine (TKM), and included them where appropriate. There are 129 chemical constituents of beetles discussed.

Protodioscin levels in Brachiaria spp. in a sheep production system and a brief review of the literature of Brachiaria spp. poisoning in ruminants

ABSTRACT: Plants of the genus Brachiaria, used in several countries as forage, are poisonous to some livestock species. Their toxic principle is protodioscin, and the main form of clinical presentation of the toxicosis is hepatogenous photosensitization. Here we compare protodioscin levels in B. decumbens and B. brizantha and review the literature on the concentrations and methodologies of collection and analysis of the toxic principle in Brachiaria spp. and the risk of contamination of pastures by more toxic species that may facilitate poisoning by plants of this genus in sheep. The experiment was conducted in pastures originally formed by B. brizantha, with many B. decumbens invasion points. The occurrence of cases of poisoning by Brachiaria spp. was the criterion for confirming pasture toxicity. The forage samples were collected at ten random points every 28 days through manual grazing simulation. The samples were analyzed for protodioscin by high-performance liquid chromatography (HPLC) with light scattering by evaporation (ELSD) after being dried and crushed. In the flock of 69 sheep, five poisoning cases occurred, three sheep died, and two recovered. The protodioscin levels found in the evaluated pastures ranged from 0.70 to 0.45%; higher levels appeared in B. decumbens (7.09%) compared to 1.04% in B. brizantha. We suggest that Brachiaria spp. should be avoided in pastures where sheep are grazing.

RESUMO: Plantas do gênero Brachiaria, utilizadas em vários países como forragem, são tóxicas para várias espécies pecuárias. Seu princípio tóxico é a protodioscina, e a principal forma de apresentação clínica da toxicose é a fotossensibilização hepatógena. Este estudo teve como objetivo comparar os níveis de protodioscina em B. decumbens e B. brizantha e revisar a literatura sobre as concentrações e metodologias de coleta e análise do princípio tóxico em Brachiaria spp. e o risco de contaminação das pastagens por espécies mais tóxicas que podem facilitar a intoxicação por plantas desse gênero em ovinos. O experimento foi conduzido em pastagens originalmente formadas por B. brizantha, com diversos pontos de invasão por B. decumbens. Ocorrência de casos de intoxicação por Brachiaria spp. foi o critério para confirmação da toxicidade da pastagem. As amostras de forragem foram coletadas a cada 28 dias em dez pontos aleatórios por meio de simulação de pastejo manual. As amostras foram analisadas para protodioscina por cromatografia líquida de alta eficiência (HPLC) com dispersão de luz por evaporação (ELSD) após serem secadas e trituradas. No rebanho de 69 ovelhas, cinco desenvolveram a intoxicação, três morreram e duas se recuperaram. Os níveis de protodioscina encontrados nas pastagens avaliadas variaram de 0,70 a 0,45%; níveis mais elevados apareceram em B. decumbens (7,09%) em comparação com 1,04% em B. brizantha. Sugerimos que Brachiaria spp. deve ser evitada no pasto de ovelhas em pastejo.

Herbaspirillum seropedicae as a degrading bacterium of monofluoroacetate: effects of its inoculation in goats by ingesting Amorimia septentrionalis and the concentrations of this compound in plants sprayed with the bacterium / Herbaspirillum seropedicae como bactéria degradadora de monofluoroacetato de sódio: efeitos de sua inoculação em caprinos ingerindo Amorimia septentrionalis e nas concentrações deste composto em plantas pulverizadas com a bactéria

Herbaspirillum seropedicae is a nitrogen-fixing bacterium capable of using toxic compounds as a source of carbon. Bacteria with this capacity can be used to make animals resistant to plant poisoning containing monofluoroacetate (MFA), such as Amorimia septentrionalis. The aim of this study was to evaluate if H. seropedicae is efficient in the degradation of MFA present in A. septentrionalis and if the inoculation of this bacterium in goats confers protection to A. septentrionalis intoxication. Two experiments were performed: in the first experiment 12 goats were divided into 2 groups. Goats in Group 1 were orally administered a solution containing the H. seropedicae bacterium for 10 days. From day 10 onwards, they received a daily dose of 5g/kg of A. septentrionalis with the bacteriauntil clinical signs of intoxication were observed. Group 2 goats received only the plant at the same dose, also until the observation of clinical signs of intoxication. The amount of MFA found in A. septentrionalis used in the experiment with goats was 1.6±0.058μg/mg. The total plant dose ingested by all goats in Group 1 was 80.83±12.81g/kg (129.33±20.50mg/kg MFA), which were significantly greater ​​(p<0.05) than those of Group 2 goats (39.16±19.08g/kg plant and 62.66±30.53mg/kg MFA). Group 1 goats took an average of 16.16±2.56 days to develop clinical signs of intoxication, significantly longer (p=0.0012) than Group 2 goats (7.83±3.81 days). Two Group 2 goats died on the same day that they developed clinical signs of intoxication. At necropsy of these two animals, no significant changes were observed. In the second experiment, samples of A. septentrionalis were sprayed with a solution containing H. seropedicae. Before and eight days after spraying, the samples were pressed and dried for quantitation of MFA. The amount of MFA present in samples of A. septentrionalis 8 days after spraying with H. seropedicae was significantly lower (p=0.017) than that found prior to spraying. It can be concluded that administration of H. seropedicae in goats is capable of causing greater resistance to A. septentrionalis intoxication, and spraying the plant with this bacterium significantly reduces the amount of MFA in the plant.(AU)

Herbaspirillum seropedicae é uma bactéria fixadora de nitrogênio, capaz de utilizar compostos tóxicos como fonte de carbono. Bactérias com essa capacidade podem ser utilizadas para tornar os animais resistentes à intoxicação por plantas que contém monofluoroacetato (MFA), como Amorimia septentrionalis. O objetivo do presente estudo é avaliar se H. seropedicae é eficiente na degradação do MFA presente em A. septentrionalis e se a inoculação dessa bactéria, em caprinos, confere proteção à intoxicação por A. septentrionalis. Foram realizados dois experimentos: no primeiro experimento foram utilizados 12 caprinos, divididos em dois grupos. Os caprinos do Grupo 1 receberam diariamente, oralmente, uma solução contendo a bactéria H. seropedicae durante 10 dias. A partir do décimo dia passaram a receber, diariamente, além da solução com a bactéria 5g/kg de A. septentrionalis até a observação de sinal clínico de intoxicação. Os caprinos do Grupo 2 receberam apenas a planta na mesma dose, também até que a observação de sinais clínicos de intoxicação. A quantidade de MFA encontrada em A. septentrionalis utilizada no experimento com caprinos foi de 1,6± 0,058µg/mg de planta em média. A dose total de planta ingerida por todos os caprinos do Grupo 1 foi de 80,83±12,81g/kg (129,33±20,50mg/kg de MFA), valores significativamente maiores (p<0,05) do que os dos caprinos do Grupo 2 (39,16±19,08g/kg de planta e 62,66± 30,53mg/Kg de MFA). Os caprinos do Grupo 1 demoraram em média 16,16 ±2,56 dias para desenvolver sinais clínicos da intoxicação, período significativamente maior (p=0,0012) que os caprinos do Grupo 2 (7,83±3,81dias). Dois caprinos do Grupo 2 morreram no mesmo dia que desenvolveram sinais clínicos da intoxicação. Na necropsia desses dois animais não foram observadas alterações significativas. No segundo experimento, amostras de A. septentrionalis foram pulverizadas com uma solução contendo a bactéria H. seropedicae. Antes e oito dias após a pulverização, as amostras foram prensadas e secas para posterior quantificação do MFA. A quantidade de MFA presente nas amostras de A. septentrionalis oito dias após a pulverização com H. seropedicae foi significativamente menor (p=0,017) do que a encontrada antes da pulverização. Pode-se concluir que a administração de H. seropedicae em caprinos é capaz de causar uma maior resistência à intoxicação por A. septentrionalis, e a pulverização da planta com esta bactéria reduz significativamente a quantidade de MFA na planta.(AU)

Effect of Watermelon Rind (Citrullus lanatus) Addition on the Functional, Pasting and Microbiological Quality of Sorghum Based Mumu

The effect of watermelon rind powder addition on the functional, pasting and microbiological quality of Sorghum based mumu was evaluated. Sorghum-based mumu was prepared from composite flours of 85:15, 75:15, 70:15 and 65:15% roasted sorghum flour and roasted partially defatted groundnut flour respectively and included with 0, 10, 15 and 20% watermelon rind powder respectively which were known as sample A, B, C and D accordingly. Subsequently, the functional, pasting properties and microbial quality was assessed. Functional properties values; Bulk density (0.89 to 0.80mg/100g), reconstitution index (4.99 to 4.89) and swelling index (2.35 to 2.20) decreased significantly (p < 0.05) with increase in watermelon powder addition while water absorption (10.36 to 10.97g/g), oil absorption (10.33 to 10.79) and foam capacities (12.46 to 13.85%) increased with increase in watermelon rind powder. The pasting properties; peak (302.22 to 292.44 RVU), trough (156.44 to 150.00 RVU) and Final viscosities (412.69 to 400.76RVU), and breakdown (149.95 to 140.59RVU) decreased significantly (p < 0.05) with increased in watermelon rind powder while setback viscosity (101.05 to 115.59RVU), pasting temperature (59.32 to 62.02oC) and pasting time (4.93 to 5.13mins) increased. Microbial analysis revealed the following ranges: Total viable count, 0.5x102 to1.0x102 cfu/g, fungi count of 6.1x101- 9.9x101 cfu/g and no coliform was detected. Overall, addition of watermelon rind powder showed good functional, pasting and microbiological qualities of sorghum based mumu.

Trends in patients' overall satisfaction with healthcare delivery in Accra, Ghana

Background: Patient satisfaction represents a key marker for the quality of healthcare delivery and is critical for smooth functioning of the healthcare system. Aim: The aim of this study was to determine the levels of patient satisfaction with the quality of care they receive, and thus identify the key factors that influence patients' overall satisfaction with healthcare. Setting: The study was conducted across seven healthcare facilities in Greater Accra region. Methods: The study employed a cross-sectional design to obtain data from 417 respondents between 01 November 2017 and 31 January 2018. Patient satisfaction within the context and setting of this study refers to the extent to which patients are happy with the healthcare services they receive. Statistical analysis was performed using Statistical Package for the social Sciences (SPSS) version 23. Results: Female patients constituted 66.7% of the respondents, while 33.3% were male patients. Most of the participants had health insurance coverage (95.2%). Overall, 69.5% of the patients were satisfied with the level of care, 29.3% were somewhat satisfied and 1.2% were not satisfied. Female patients (86.0%) were more satisfied with the level of care they received compared to male patients (61.9%). Majority of the female patients (87.8%) indicated that they were treated with courtesy and respect. However, more than a half (51.8%) of male patients indicated they were not treated with courtesy and respect. Patient satisfaction negatively correlated with social status and age of the patients. Conclusion: Measurement of patients' satisfaction is important for healthcare delivery. It was clear from this study that there is still a gap in improving and managing patients' satisfaction and expectation. All stakeholders must get involved to ensure timely and satisfactory healthcare delivery to all patients

Intoxicação experimental por Niedenzuella stannea (Malpighiaceae) em ovinos / Experimental poisoning by Niedenzuella stannea (Malpighiaceae) in sheep

Niedenzuella stannea é uma planta que contém monofluoracetato de sódio e é incriminada como causa de morte súbita em bovinos na Região Sul do Estado de Mato Grosso. Este estudo descreve a toxidez e achados clínicos e patológicos da intoxicação experimental por N. stannea em ovinos. Foram utilizados no experimento, frutos, folhas maduras e folhas jovens de N. stannea coletadas em propriedades as margens de afluentes das bacias hidrográficas do Rio Araguaia onde havia histórico de morte súbita em bovinos. Folhas maduras em doses entre 10 e 40g/kg e frutos na dose de 10 g/kg não causaram alterações clínicas. Alterações clínicas foram observadas em ovinos que receberam a partir de 5g/kg de folhas jovens em dose única e a morte ocorreu nos que receberam a partir de 30g/kg. A toxicidade na dose de 30g/kg se manteve após a secagem da planta. Os principais sinais clínicos foram anorexia, apatia, dispneia, arritmia e taquicardia em evolução clínica que variou de 16 às 20h. Notou-se em uma fase terminal hiperaguda, com evolução de 13 a 20 min., relutância ao movimento, micção frequente, jugular ingurgitada, pulso venoso evidente, tremor muscular, decúbito esternal e decúbito lateral e morte. Na necropsia os principais achados foram ingurgitamento de grandes veias, das aurículas do coração e edema pulmonar. Microscopicamente a principal alteração ocorreu no rim e caracterizou-se por degeneração hidrópico-vacuolar no citoplasma de epitélio de túbulos contorcidos distais. Conclui-se que N. stannea na fase de brotação é tóxica para ovinos e que a intoxicação por esta planta deve ser incluída no diagnóstico diferencial das doenças com curso clínico hiperagudo ou morte súbita em ovinos em regiões onde a planta existe.(AU)

Niedenzuella stannea a sodium monofluoroacetate-containing plant cause sudden death in cattle in southern Mato Grosso State. This investigation describes the toxicity and clinical and pathological findings of experimental poisoning by N. stannea in sheep. Fruits, mature leaves and young leaves of the plant collected in properties near the margins of the Araguaia river basins with history of sudden death in cattle were used in the experiment. No clinical signs were observed in sheep ingesting doses between 10 and 40g/kg of mature leaves and 10g/kg of fruits. The animals had shown clinical signs when received young leaves of the plant orally in a single dose of 5, 10, 20g/kg, and death occurred in sheep receiving 30g/kg. The plant at the dose of 30g/kg of fresh leaves maintained its toxicity after being dried. The main clinical signs observed were anorexia, lethargy, dyspnea, tachycardia, and arrhythmia with a clinical course ranging 16-20 hours after the onset of clinical signs. In an hyperacute terminal phase the animals showed reluctance to move, frequent urination, engorged jugular, evident venous pulse, muscle tremor, sternal recumbence, lateral decubitus, and death. At necropsy engorgement of the atrium and large veins of the heart, and pulmonary edema were observed. Microscopically, the kidney had hydropic-vacuolar degeneration in the cytoplasm of the epithelial cells of the distal convoluted tubules. It is concluded that young leaves of N. stannea can cause intoxication in sheep and should be considered in the differential diagnosis of acute diseases or sudden death in sheep in regions where the plant exist.(AU)

Current understanding of the relationship between periodontal and systemic diseases

Periodontal disease [PD] is among the most common infectious diseases affecting humans. While the burden of periodontal disease on oral health has been extensively investigated, a possible specific relationship between the disease and systemic health is a relatively new area of interest. More recently it has been suggested that PD has an etiological role in the development of atherosclerotic cardiovascular disease, diabetes mellitus, and preterm low-birth weight, among others. In this review, we critically evaluate the current knowledge on the relation between PD and systemic diseases overall, and specifically with cardiovascular diseases. The best available evidence today suggests that the infection and inflammatory reaction associated with PD may contribute toward systemic disease. It is critical that dentists and physicians are well informed of the potential general health impact of periodontal disease so that they are in a position to knowledgeably counsel patients

Poisoning by Poiretia punctata in cattle and sheep / Intoxicação por Poiretia punctata em bovinos e ovinos

Poiretia punctata (Willd.) Desv. was associated with cattle and sheep poisoning on nine farms in the State of Sergipe, northeastern Brazil. The animals were found dead or died later after showing clinical signs for up to 18 hours. Two sheep that ingested 40g/kg body weight (g/kg) of fresh P. punctata died three and eight hours after ingestion, respectively. Another sheep that ingested 40g/kg five days after plant collection showed mild clinical signs and recovered after 24 hours. Two sheep that received 20g/kg and another that ingested three daily doses of 20g/kg showed clinical signs, but recovered. Two cattle that ingested 20g/kg of the fresh plant exhibited clinical signs and recovered. The clinical observations of poisoning were depression, ataxia, loss of equilibrium, broad-based stance, head down, falls, mandibular trismus, opisthotonous, nystagmus, and recumbence. Significant gross and histologic lesions were not observed. Samples of P. punctata were analyzed for nitrates, cyanogenic glycosides, and sodium monofluouracetate with negative results. It is concluded that P. punctata is a toxic plant that caused death in cattle and sheep in the State of Sergipe.

Poiretia punctata (Willd.) Desv. foi associada a intoxicações em bovinos e ovinos em nove fazendas no estado de Sergipe, nordeste do Brasil. Os animais eram encontrados mortos ou morreram após apresentar sinais clínicos com evolução de até 18 horas. Dois ovinos que ingeriram P. punctata, fresca, na dose de 40g/kg de peso corporal (g/kg) morreram após a ingestão da planta em três e oito horas, respectivamente. Outro ovino que ingeriu a planta coletada cinco dias antes de ser oferecida ao animal na dose de 40g/kg apresentou sinais clínicos leves e se recuperou depois de 24 horas. Dois ovinos que receberam 20g/kg e outro que ingeriu, durante três dias consecutivos, doses de 20g/kg apresentaram sinais clínicos leves e se recuperaram. Dois bovinos que ingeriram a planta fresca, na dose de 20g/kg apresentaram sinais clínicos e se recuperaram. As observações clínicas da intoxicação foram depressão, ataxia, perda de equilíbrio, postura de base ampla, cabeça baixa, quedas, trismo mandibular, opistótono, nistagmo e decúbito. Não foram observadas lesões macroscópicas nem histológicas de significância. Amostras de P. punctata foram analisadas para nitratos, glicosídeos cianogênicos, e monofluoracetato sódio com resultados negativos. Conclui-se que P. punctata é uma planta tóxica que causa morte de bovinos e ovinos no estado de Sergipe.

Fibrose cardíaca associada à intoxicação por Amorimia septentrionalis em bovinos / Cardiac fibrosis associated to the poisoning by Amorimia septentrionalis in cattle

Amorimia septentrionalis contém monofluoracetato de sódio e quando consumida por ruminantes provoca morte súbita. Este estudo teve o objetivo de relatar a epidemiologia, os sinais clínicos e patológicos de surtos de morte súbita em bovinos provocadas por Amorimia septentrionalis nos Estados de Pernambuco e Paraíba. Para isso, realizaram-se visitas técnicas em diversas propriedades nas Microrregiões do Médio Capibaribe/PE e Itabaiana/PB. Oito bovinos foram necropsiados. Coletaram-se tecidos das cavidades abdominal e torácica, além do encéfalo e medula espinhal. As alterações clínicas consistiram em lentidão, decúbito esternal prolongado, relutância em se movimentar quando em estação, cansaço, taquipneia, taquicardia e pulso venoso positivo. Os bovinos que foram forçados a se movimentar apresentaram instabilidade, tremores musculares e queda repentina seguida de vocalizações, movimentos de pedalagem e morte súbita em cerca de 5 a 7 minutos. As principais alterações macroscópicas consistiram em edema pulmonar, coração com aspecto globular com áreas esbranquiçadas, petéquias e equimoses no epicárdio, miocárdio e músculos papilares. À microscopia observou-se aumento da eosinofilia do citoplasma dos cardiomiócitos, núcleos picnóticos, cariorrexia, cariólise, perda das estriações, edema intersticial, infiltrado inflamatório intersticial mononuclear e áreas multifocais de fibrose cardíaca. Nos rins, constatou-se degeneração hidrópico vacuolar e necrose das células epiteliais em túbulos contorcidos. Os sinais clínicos foram semelhantes aos sinais clínicos já descritos em bovinos por plantas que contém MFA. As lesões macro e microscópicas descritas no coração e rins são de grande valor diagnóstico. A. septentrionalis é a principal planta tóxica de interesse pecuário nas microrregiões do Médio Capibaribe e Itabaiana devido às perdas econômicas diretas e indiretas que provoca na pecuária dessas regiões.

Amorimia (Mascagnia) septentrionalis contains sodium monofluoracetate and when consumed by ruminants cause outbreaks of sudden death. This study aimed to describe the epidemiology, clinical and pathological signs of outbreaks of sudden deaths in cattle caused by A. septentrionalis in the states of Pernambuco and Paraíba. For this, technical visits where made on various properties in the regions of Médio Capibaribe/PE and Itabaiana/PB. Eight cattle were necropsied. Tissues were collected from abdominal and thoracic cavities, besides brain and spinal cord. The clinical changes consisted in apathy, prolonged sternal recumbency, reluctance to move, fatigue, tachypnea, tachycardia and positive venous pulse. The animals that were forced to move showed instability, muscular tremors and then a single fall followed by vocalizations, paddling and death in 5-7 minutes. Macroscopic changes consisted in pulmonary edema, globular heart with whitish areas, petechiae and ecchymosis in the epicardium, myocardium and papillary muscles. Microscopically there was an increase of eosinophilia of cytoplasm of cardiomyocytes, picnosis, cariorrexia, karyolysis, loss of striations and multifocal areas of cardiac fibrosis. In the kidney, there was hydropic vacuolar degeneration and necrosis of epithelial cells in convoluted tubules. The clinical signs presented by the cattle poisoned were similar to those previously described by plants containing MFA. The macroscopic and microscopic lesions described in the heart and kidneys are of great diagnostic value. A septentrionalis is the main toxic plant of livestock interests in the studied regions due to direct and indirect economic losses in livestock that causes.

Antibacterial and antibiotic-potentiation activities of some Cameroonian food plants against multi-drug resistant gram-negative bacteria / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the in vitro antibacterial properties and the ability to potentiate some common antibiotics effects of the methanol extracts of 11 Cameroonian food plants on 29 Gram-negative bacteria expressing multidrug resistant (MDR) phenotypes.</p><p><b>METHODS</b>The antimicrobial activity of the extracts was performed using the broth microdilution method. The phytochemical screening of these extracts was also performed using standard methods.</p><p><b>RESULTS</b>Ocimum basilicum, Gnetum africanum and Eucalyptus robusta extracts possessed an antibacterial activity against all the 29 studied bacteria. The extracts from G. africanum and E. robusta were the most active with the lowest minimal inhibitory concentration of 64 μg/mL on Escherichia coli AG100A for both extracts and also against Klebsiella pneumoniae K24 for G. africanum. When tested in the presence of phenylalanine-arginine β-Naphtylamide (PAβN), an efflux pump inhibitor, the extract of Thymus vulgaris and E. Robusta showed the best activities on most tested strains. E. Robusta extract showed good synergistic effects, improving the activity of commonly used antibiotics in about 85% of cases.</p><p><b>CONCLUSION</b>The overall results obtained provide the baseline information for the use of the tested plants in the treatment of bacterial infections.</p>

Importância da intoxicação por Amorimia pubiflora (Malpighiaceae) em bovinos em Mato Grosso: reprodução experimental da intoxicação em ovinos e bovinos / The importance of poisoning by Amorimia pubiflora (Malpighiaceae) in cattle in Mato Grosso: experimental reproduction of the poisoning in sheep and cattle

No município de Colniza, Mato Grosso, a principal limitação para expansão pecuária é a ocorrência de "morte súbita" em bovinos, com registros de mortalidade próxima a 50% dos animais. Em visitas realizadas em áreas de ocorrência do problema, nos anos de 2004, 2011 e 2012, constatou-se que havia coincidência entre a ocorrência de "mortes súbitas" no rebanho e a presença de Amorimia pubiflora nas pastagens. As mortes ocorrem durante todo ano, porém acentuam-se no início do período das chuvas, quando há maior quantidade de brotação nas áreas de pastoreio. A intoxicação foi reproduzida em ovinos e bovinos através da administração de folhas jovens coletadas em dois períodos do ano, e, em ovinos, através de folhas maduras e dos frutos. Nos ovinos que morreram, as primeiras manifestações clínicas foram observadas entre 34min e 17h34min após a administração da planta e a evolução clínica foi de 3min a 15h20min, com uma fase final superaguda de 3 a 21min. As principais alterações clínicas encontradas foram taquicardia, evidenciação da jugular, tremores musculares, apatia e relutância à movimentação. Todos os sinais acentuavam-se após a movimentação. A fase final superaguda foi caracterizada por relutância para caminhar, cifose, tremores e contrações musculares generalizadas, principalmente de membros, cabeça e pescoço. Notou-se também taquipneia com respiração abdominal, decúbito esternal e rapidamente lateral ou quedas em decúbito lateral, opistótono, nistagmo e cianose de mucosa oral, seguidos de morte. As folhas jovens, independentemente do período da coleta, foram mais tóxicas; causaram a morte de ovinos a partir de 2g/kg e de um bovino que ingeriu 3g/kg. Já as folhas maduras revelaram-se tóxicas e causaram morte na dose de 20g/kg e os frutos ocasionaram a morte de um ovino que ingeriu 5g/kg. Concluímos que monofluoracetato de sódio (MFA), encontrado na concentração de 0,015% nas folhas em brotação de A. pubiflora, é o princípio tóxico responsável pela "morte súbita" causada por Amorimia pubiflora. Esse estudo mostra a importância de A. pubiflora para a região Centro-Oeste do Brasil, principalmente para a pecuária bovina do município de Colniza, MT. Essa planta é tóxica, também, para ovinos e o quadro clínico é similar ao descrito para bovinos.

In the county of Colniza, Mato Grosso, the main limitation for livestock production is the occurrence of "sudden death" in cattle, which affects in some farms up to 50% of the herd. In visits to some of the farms where the problem occurred, in 2004, 2011 and 2012, the presence of Amorimia pubiflora on the pastures was associated with the occurrence of "sudden deaths" in cattle. The deaths occurred throughout the year, however more frequently at beginning of the rainy season, when A. pubiflora sprouts in the grazing areas. The poisoning was experimentally reproduced in sheep and cattle by the administration of young leaves of the plant collected during two seasons, and in sheep by the administration of mature leaves and fruits. In the sheep that died, the first clinical signs were observed between 34min and 17h34min after the administration of the plant, and the clinical course varied from 3min to 15h20min, with a final peracute phase of 3 to 21 minutes. The main clinical signs were tachycardia, engorgement of the jugular veins, muscle trembling, apathy and reluctance to move, which were more evident when the animals were moved. The peracute final phase was characterized by generalized tremors and muscle contractions mainly of limbs, head and neck, respiratory distress and abdominal respiration, sternal and quick lateral recumbence or falling to the ground with peddling movements, opisthotonus, nystagmus, nystagmus and cyanosis of the oral mucosa, followed by death. The young leaves of A. pubiflora, independent of the collection period, were more toxic and caused death of sheep and cattle after ingestion of 2g/kg and 3g/kg respectively. Mature leaves caused death at the dose of 20g/kg, and the fruits at 5g/kg. The young leaves contained 0.015% of sodium monofluoracetate which is responsible for clinical signs of the "sudden death". These findings show the importance of Amorimia pubiflora for cattle raising in Midwestern Brazil. The plant is toxic also for sheep causing a clinical picture similar to that reported in cattle poisoned by monofluoracetate-containing plants.

Avaliação da exposição solar na intoxicação experimental por Brachiaria decumbens em ovinos / Evaluation of solar exposure in Brachiaria decumbens poisoning in sheep

Foram utilizados 26 ovinos, entre 3 e 4 meses de idade, divididos em 3 grupos, provenientes de rebanhos que nunca tiveram contato com pastos de Brachiaria spp.. Dois grupos receberam Brachiaria decumbens no cocho diariamente ad libitum, sendo que um deles permaneceu em área com exposição solar (GS) e o outro foi mantido em baias cobertas protegidos do sol (GSB). O grupo controle (GC) foi também mantido em local com exposição solar e alimentado com feno de Cynodon dactylon e capim Pennisetum purpureum triturado. Todos os grupos receberam alimentação em cochos e foram suplementados com 200g/dia/animal de ração comercial para ovinos. Foi realizada a avaliação clínica diária dos ovinos e colhidas amostras duas vezes por semana para dosagem sérica de AST e GGT. Os animais que morreram foram submetidos a necropsia e em todos os ovinos sobreviventes foi realizada biópsia hepática no final do experimento. Três animais do grupo GS adoeceram e dois morreram. Um ovino do grupo GSB adoeceu e morreu. Não houve alterações clínicas nos ovinos controles. Os principais sinais clínicos observados nos animais que adoeceram foram apatia, emagrecimento, fotofobia, hiperemia e secreção ocular e icterícia. Nenhum animal apresentou lesões cutâneas de fotossensibilização. O grupo que permaneceu no sol apresentou atividades séricas médias de AST e GGT significativamente maiores que a dos demais grupos (p<0,05) e os animais que permaneceram na sombra apresentaram níveis maiores de GGT (p<0,05) em comparação ao grupo controle. A histopatologia das amostras de fígados dos ovinos com sinais clínicos demonstrou tumefação e vacuolização de hepatócitos, necrose individual de hepatócitos, macrófagos espumosos com cristais birrefringentes intracitoplasmáticos e dentro de ductos biliares e infiltrado mononuclear periportal. Amostras do capim fornecidas aos cordeiros evidenciaram níveis médios de 0,94±0,80% da saponina protodioscina. As observações do presente experimento sugerem que ...

Twenty-six five-month-old lambs originated from flocks with no previous contact with Brachiaria spp. pastures were divided into three groups. Two groups (GS and GSB) were fed daily with fresh harvested Brachiaria decumbens ad libitum. GS was kept in an area with solar exposure and GSB was kept in stalls sheltered from solar exposure. Control group (GC) was also kept under solar exposure, but fed with Cynodon dactylon grass hay and Pennisetum purpureum fresh grass. All sheep from the three groups were supplemented with 200g daily of a commercial concentrated food. Evaluation of clinical signs was carried out daily and blood samples were collected twice a week to determine AST and GGT serum activities. Three out of nine lambs of GS presented clinical signs of Brachiaria spp. poisoning, and two died. One animal showed clinical signs and died in GSB. The main clinical signs observed were apathy, weight loss, photophobia, conjunctivitis, ocular mucous discharge and jaundice. Dermatitis due to photosensitization was not observed. Mean serum AST and GGT activities were significantly higher (p<0,05) in the group exposed to sun, than in the other two groups, and the GGT activities were significantly higher in the group sheltered than in the control group (p<0,05). All animals at the end of the experiment were submitted to liver biopsy and died lambs were necropsied. Histopathological evaluation of liver samples from sheep with clinical signs evidenced swelling and vacuolization of hepatocytes, individual hepatocytes necrosis, presence of foamy macrophages, crystal negative images within bile ducts and foamy macrophages, biliary duct hyperplasia and periportal mononuclear infiltration. These results suggest that sun exposure does not define intoxication, but exacerbates the toxicity of the grass.

Toward pluripotency by reprogramming: mechanisms and application

The somatic epigenome can be reprogrammed to a pluripotent state by a combination of transcription factors. Altering cell fate involves transcription factors cooperation, epigenetic reconfiguration, such as DNA methylation and histone modification, posttranscriptional regulation by microRNAs, and so on. Nevertheless, such reprogramming is inefficient. Evidence suggests that during the early stage of reprogramming, the process is stochastic, but by the late stage, it is deterministic. In addition to conventional reprogramming methods, dozens of small molecules have been identified that can functionally replace reprogramming factors and significantly improve induced pluripotent stem cell (iPSC) reprogramming. Indeed, iPS cells have been created recently using chemical compounds only. iPSCs are thought to display subtle genetic and epigenetic variability; this variability is not random, but occurs at hotspots across the genome. Here we discuss the progress and current perspectives in the field. Research into the reprogramming process today will pave the way for great advances in regenerative medicine in the future.

Hepatitis B: report of prevalence and access to healthcare among Chinese residents in sheffield UK

Overall prevalence of hepatitis B [HBV] in the UK is low. However, among migrants from endemic areas, prevalence has been shown to be high. Furthermore, timely diagnosis and/or referral are required prevent serious health consequences through early institution of treatment. We identified locations that would be familiar to Chinese members of the community with the objective of facilitating testing. Dried blood spot samples were collected from 229 Chinese subjects and tested for HBV and also for hepatitis C virus [HCV] infection - offering complete chronic viral hepatitis screening. HBsAg was positive in 20/229 [8.7%] participants, [10 F, 10 M]. Five women and one man were aware of their condition, but only one man and none of the women were under specialist care. The average length of residence in the UK for positive patients was 15 years [range 2-40]. Evidence of HBV past infection, HBcAb[+]/HBsAg[-], was seen in 28/229 participants [12.2%]. HCV antibody testing produced negative results in all participants. The methodology of testing was well accepted, 139/144 [95%] responded to a feedback questionnaire declaring no discomfort and 100% finding the information session useful. This model of outreach testing is helpful for addressing health inequalities afflicting the UK's Chinese community

Mechanisms of Asthma and Implications for Its Prevention and Treatment: A Personal Journey

My research career has focused on the causes of asthma and its treatment. After establishing the key role that mast cells play in the inflammatory response in asthma, attention was turned towards understanding disease chronicity and variability across the lifecourse. Through a combination of studies on airway biopsies and primary cell cultures we have established that asthma is primarily an epithelial disease driven by increased environmental susceptibility to injury and an altered repair response as depicted by sustained activation of the epithelial mesenchymal trophic unit (EMTU) that is invoked in foetal branching morphogenesis. Varied activation of the EMTU connects the origins of asthma to its progression over time with involvement of epithelial susceptibility through impaired barrier and innate immune functions and altered mesenchymal susceptibility as exemplified by polymorphisms of the metalloprotease gene, ADAM33. Taken together these observations have led to a fundamental re-evaluation of asthma pathogenesis. Rather than placing allergic inflammation as the prime abnormality, it is proposed that the airway epithelium lies at the center of asthma pathogenesis, and that in conjunction with the underlying mesenchyme, it is the principle orchestrator of both the induction of asthma and its evolution over the lifecourse. This concept has provided 'the basis for a new preventative and therapeutic approach focused more on increasing the airways resistance to environmental insults rather than suppressing downstream inflammation once it is established.

Mechanisms of Asthma and Implications for Its Prevention and Treatment: A Personal Journey

My research career has focused on the causes of asthma and its treatment. After establishing the key role that mast cells play in the inflammatory response in asthma, attention was turned towards understanding disease chronicity and variability across the lifecourse. Through a combination of studies on airway biopsies and primary cell cultures we have established that asthma is primarily an epithelial disease driven by increased environmental susceptibility to injury and an altered repair response as depicted by sustained activation of the epithelial mesenchymal trophic unit (EMTU) that is invoked in foetal branching morphogenesis. Varied activation of the EMTU connects the origins of asthma to its progression over time with involvement of epithelial susceptibility through impaired barrier and innate immune functions and altered mesenchymal susceptibility as exemplified by polymorphisms of the metalloprotease gene, ADAM33. Taken together these observations have led to a fundamental re-evaluation of asthma pathogenesis. Rather than placing allergic inflammation as the prime abnormality, it is proposed that the airway epithelium lies at the center of asthma pathogenesis, and that in conjunction with the underlying mesenchyme, it is the principle orchestrator of both the induction of asthma and its evolution over the lifecourse. This concept has provided 'the basis for a new preventative and therapeutic approach focused more on increasing the airways resistance to environmental insults rather than suppressing downstream inflammation once it is established.

A Brief History of Asthma and Its Mechanisms to Modern Concepts of Disease Pathogenesis

The original concept of asthma being primarily a disease of airways smooth muscle drove the development of bronchodilator drugs. However when it was realised that airway inflammation underpinned the disordered airway function, this gave way to the development of controller therapies such as inhaled cromones and corticosteroids. More recently the discovery of complex interconnecting cytokine and chemokine networks has stimulated the development of biologics with varying success. With the recognition that airway wall "remodelling" is present early in asthma inception and is in part driven by aberrant epithelial-mesenchymal communication both genetic and environmental factors beyond allergen exposure such as virus infection and air pollution are being seen as being increasingly important not only in asthma exacerbations but in the origins of asthma and its evolution into different sub-phenotypes. This brings us round full circle to once again considering that the origins of asthma lie in defects in the formed elements of the airway; the epithelium, smooth muscle, and vasculature. Over the last 25 years Professor You Young Kim has engaged in the exciting discovery science of allergy and asthma and has made an enormous contribution in bringing Korea to the forefront of disease management and research, a position that both he and his colleagues can justly be proud of.

Irreversible Electroporation: A Novel Image-Guided Cancer Therapy

Irreversible electroporation (IRE) is a novel tumor ablation technique using a non-thermal energy to create innumerable permanent nanopores in the cell membrane to disrupt cellular homeostasis. This disruption of cellular homeostasis initiates apoptosis which leads to permanent cell death. In our translational research, we have demonstrated that IRE can be a safe, fast and powerful method of tumor treatment. In this review, we present an overview of IRE ablation including a brief history of IRE, advantages and disadvantages of IRE and clinical and research implications of IRE.