133 research outputs found
Towards a sterile insect technique field release of <it>Anopheles arabiensis </it>mosquitoes in Sudan: Irradiation, transportation, and field cage experimentation
No full textAbstract Background The work described in this article forms part of a study to suppress a population of the malaria vector Anopheles arabiensis in Northern State, Sudan, with the Sterile Insect Technique. No data have previously been collected on the irradiation and transportation of anopheline mosquitoes in Africa, and the first series of attempts to do this in Sudan are reported here. In addition, experiments in a large field cage under near-natural conditions are described. Methods Mosquitoes were irradiated in Khartoum and transported as adults by air to the field site earmarked for future releases (400 km from the laboratory). The field cage was prepared for experiments by creating resting sites with favourable conditions. The mating and survival of (irradiated) laboratory males and field-collected males was studied in the field cage, and two small-scale competition experiments were performed. Results Minor problems were experienced with the irradiation of insects, mostly associated with the absence of a rearing facility in close proximity to the irradiation source. The small-scale transportation of adult mosquitoes to the release site resulted in minimal mortality ( Conclusion It is concluded that although conditions are challenging, there are no major obstacles associated with the small-scale irradiation and transportation of insects in the current setting. The field cage is suitable for experiments and studies to test the competitiveness of irradiated males can be pursued. The scaling up of procedures to accommodate much larger numbers of insects needed for a release is the next challenge and recommendations to further implementation of this genetic control strategy are presented.</p
Rational deployment of antimalarial drugs in Africa: should first-line combination drugs be reserved for paediatric malaria cases?
No full textArtemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the 'premier' combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistanc
Molecular subtyping of DCIS : heterogeneity of breast cancer reflected in pre-invasive disease
No full textBackground: Molecular profiling has identified at least four subtypes of invasive breast carcinoma, which exhibit distinct clinical behaviour. There is good evidence now that DCIS represents the non-obligate precursor to invasive breast cancer and therefore it should be possible to identify similar molecular subtypes at this stage. In addition to a limited five-marker system to identify molecular subtypes in invasive breast cancer, it is evident that other biological molecules may identify distinct tumour subsets, though this has not been formally evaluated in DCIS.
Methods: Tissue microarrays were constructed for 188 cases of DCIS. Immunohistochemistry was performed to examine the expression patterns of oestrogen receptor (ER), progesterone receptor (PR), Her2, EGFR, cytokeratin (CK) 5/6, CK14, CK17, CK18, β4-integrin, β6-integrin, p53, SMA, maspin, Bcl-2, topoisomerase IIα and P-cadherin. Hierarchical clustering analysis was undertaken to identify any natural groupings, and the findings were validated in an independent sample series.
Results: Each of the intrinsic molecular subtypes described for invasive breast cancer can be identified in DCIS, though there are differences in the relative frequency of subgroups, in particular, the triple negative and basal-like phenotype is very uncommon in DCIS. Hierarchical cluster analysis identified three main subtypes of DCIS determined largely by ER, PR, Her2 and Bcl-2, and this classification is related to conventional prognostic indicators. These subtypes were confirmed in an analysis on independent series of DCIS cases.
Conclusion: This study indicates that DCIS may be classified in a similar manner to invasive breast cancer, and determining the relative frequency of different subtypes in DCIS and invasive disease may shed light on factors determining disease progression. It also demonstrates a role for Bcl-2 in classifying DCIS, which has recently been identified in invasive breast cancer
Clinical study evaluating β-blockers use and fracture risk in patients with primary osteoporosis Running title: β-blockers and primary osteoporosis
No full textBackground and objectives: In osteoporosis, low bone mass and growing fragility are main symptoms. BB users had greater BMD and/or decreased fracture risk, according to observational studies. Other studies found no effect of BB on fracture risk and osteoporosis disease. In this study, the effect of selective and non-selective BB on fracture risk in osteoporotic individuals was studied. Methods: A total of fifty osteoporotic patients of both genders were included in this randomized controlled, parallel, and prospective trial. Osteoporotic subjects were divided into three groups: a control group (CG), a non-selective beta-blocker group (NSBB), and a cardio-selective beta-blocker group (CSBB). T-score, fracture risk (FR), bone mineral density (BMD), and bone turnover markers were studied as a result of this investigation. Results: After six months of follow-up, it was discovered that the T-score mean values of the three groups varied significantly. BMD was significantly higher in the group receiving non-selective beta-blockers (NSBB) than in the control group (CG). In the three categories of fracture risk region, the fracture risk was statistically decreased in both the NSBB and CSBB groups. Additionally, both the NSBB and CSBB groups demonstrated a decrease in bone turnover markers (BTM), as contrasted to the control group
Soro de leite como agente encapsulante de Bifidobacterium BB-12 por spray drying
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Agrárias. Programa de Pós-Graduação em Ciência dos Alimentos.O soro de leite e o principal subproduto da industria lactea. Apesar do seu elevado valor nutricional, o aproveitamento do soro de leite ainda e pequeno. Novas alternativas para utilizacao do soro sao necessarias a fim de reduzir seu desperdicio e a poluicao ambiental causada quando nao descartado adequadamente. O objetivo deste estudo foi avaliar o potencial do soro de leite liquido como agente encapsulante de Bifidobacterium BB-12 por spray drying, comparando-o com a goma arabica, a qual e tradicionalmente utilizada na tecnologia de microencapsulacao. O rendimento da microencapsulacao e a viabilidade das microcapsulas durante o armazenamento foram determinados. Quando o soro de leite foi utilizado como agente encapsulante, o rendimento da microencapsulacao foi maior e a viabilidade das celulas manteve-se elevada e constante durante doze semanas. A caracterizacao das microcapsulas foi realizada atraves da determinacao da microestrutura, umidade, atividade de agua, tempo para dissolucao em agua e em oleo e a cor. As microcapsulas obtidas com ambos agentes encapsulantes apresentaram diametros em torno de 11 um e formato esferico, com a presenca de concavidades, tipicas de produtos atomizados. O conteudo de agua residual e a Aw obtidos estao dentro dos limites para produtos atomizados e tambem dentro do recomendado para garantir a estabilidade microbiologica. O tempo para dissolucao em oleo foi menor do que em agua tanto para as microcapsulas produzidas com goma arabica quanto para as produzidas com soro. As microcapsulas elaboradas com soro de leite apresentaram dissolucao mais rapida tanto em agua quanto em oleo quando comparadas as microcapsulas com goma arabica. Ambas as microcapsulas apresentaram coloracao clara, sendo observada tonalidade mais vermelha e amarela nas elaboradas com soro do que nas obtidas com goma arabica. Em um segundo momento, foi avaliada a sobrevivencia em condicoes gastrointestinais simuladas, a tolerancia ao NaCl e a viabilidade durante o armazenamento das microcapsulas obtidas com soro de leite. Foi observada uma pequena reducao na viabilidade de Bifidobacterium microencapsulada em pH baixo. Quanto a exposicao a bile, a microencapsulação com soro de leite não protegeu as células probióticas, no entanto, a viabilidade das microcápsulas permaneceu > 6 log UFC/g mesmo após 24 horas de incubação na maior concentração de bile estudada. A microencapsulação não teve influência na suscetibilidade da cultura ao sal. Quando as microcápsulas foram adicionadas em sobremesa láctea, a população do probiótico manteve-se acima de 7 log UFC/g por 6 semanas. O soro de leite apresentou-se como um eficiente agente encapsulante de Bifidobacterium por spray drying.The whey is the main by-product of the dairy industry. Despite its high nutritional value, the use of the whey is still small. New alternatives of usage are required to reduce its waste and environmental pollution, which are caused if it is not disposed properly. The objective of this study was to evaluate the potential of liquid whey as the encapsulating agent Bifidobacterium BB-12 by spray drying, compared with arabic gum, which is typically used in microencapsulation technology. The microencapsulation yield and viability during storage were determined. When the whey was used as the encapsulating agent, the microencapsulation yield was higher, and cell viability remained high and steady for twelve weeks. The characterization of the microcapsules was performed by determining the microstructure, moisture, water activity, time for dissolution in water and in oil and by the color. The microcapsules obtained with both encapsulating agents had diameters of about 11 um and spherical shape, with the presence of dimples, which are typical in atomized product. The residual water content and Aw obtained are within the range for atomized products and also within the recommended range to ensure microbiological stability. The time for dissolution in oil was lower than in water, for the microcapsules made with gum arabic as much as for the ones which were produced with whey. Microcapsules prepared with whey had much more rapid dissolution in water and in oil, when compared to microcapsules with gum arabic. Both microcapsules showed clear color. It was observed more red and yellow shades in microcapsules made with whey than in those obtained with gum arabic. In a second step, it was evaluated the survival of microcapsules obtained with whey under simulated gastrointestinal conditions, their tolerance to NaCl and their viability during storage. The results showed a small decrease in the viability of microencapsulated Bifidobacterium at low pH. In relation to the exposure of Bifidobacterium to bile, microencapsulation with whey did not protect the probiotic cells; however, the viability of the microcapsules remained >6 log cfu/g, even after 24 h of incubation at the highest bile concentration analyzed. No growth was noted with either the free cells or the microencapsulated cells on MRS-LP with NaCl. The viability of the microcapsules stored at 4 °C remained high and constant for 12 weeks. When the microcapsules were added to a dairy dessert, the probiotic count remained above 7 log cfu/g for 6 weeks. The whey was shown to be an effective encapsulating agent of Bifidobacterium by spray drying
Follicular dendritic cell differentiation is associated with distinct synovial pathotype signatures in rheumatoid arthritis
No full textFollicular dendritic cells (FDCs) fundamentally contribute to the formation of synovial ectopic lymphoid-like structures in rheumatoid arthritis (RA) which is associated with poor clinical prognosis. Despite this critical role, regulation of FDC development in the RA synovium and its correlation with synovial pathotype differentiation remained largely unknown. Here, we demonstrate that CNA.42(+) FDCs distinctively express the pericyte/fibroblast-associated markers PDGFR-β, NG2, and Thy-1 in the synovial perivascular space but not in established follicles. In addition, synovial RNA-Seq analysis revealed that expression of the perivascular FDC markers was strongly correlated with PDGF-BB and fibroid synovitis, whereas TNF-α/LT-β was significantly associated with lymphoid synovitis and expression of CR1, CR2, and FcγRIIB characteristic of mature FDCs in lymphoid follicles. Moreover, PDGF-BB induced CNA.42(+) FDC differentiation and CXCL13 secretion from NG2(+) synovial pericytes, and together with TNF-α/LT-β conversely regulated early and late FDC differentiation genes in unsorted RA synovial fibroblasts (RASF) and this was confirmed in flow sorted stromal cell subsets. Furthermore, RASF TNF-αR expression was upregulated by TNF-α/LT-β and PDGF-BB; and TNF-α/LT-β-activated RASF retained ICs and induced B cell activation in in vitro germinal center reactions typical of FDCs. Additionally, FDCs trapped peptidyl citrulline, and strongly correlated with IL-6 expression, and plasma cell, B cell, and T cell infiltration of the RA synovium. Moreover, synovial FDCs were significantly associated with RA disease activity and radiographic features of tissue damage. To the best of our knowledge, this is the first report describing the reciprocal interaction between PDGF-BB and TNF-α/LT-β in synovial FDC development and evolution of RA histological pathotypes. Selective targeting of this interplay could inhibit FDC differentiation and potentially ameliorate RA in clinically severe and drug-resistant patients
Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.
No full textAdequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine
Probiotic Characteristics of Some Bifidobacteria and Leuconostoc Strains and Growth Behavior of the Selected Strains with Different Prebiotics
No full textABSTRACT The present study aims to evaluate the probiotic potential of some lactic acid bacteria and select the candidates to be used as probiotic bacteria with some prebiotics in the functional foods. Ten of Bifidobacteria and Leuconostoc strains (8 Bifidobacteria and 2 Leuconostoc) were screened for their probiotic potential. The in vitro tests included survival in simulated gastrointestinal tract conditions (low pH, pepsin, bile salts, and phenol), resistance to 6 antibiotics and antimicrobial activity (against Escherichia coli 0157: H7 ATCC 6933, Bacillus cereus ATCC 33018, Staphylococcus aureus ATCC 20231, Pseudomonas aeruginosa ATCC 9027, Salmonella typhimurium ATCC 14028 and Listeria monocytogenes V7 serotype 1). Five selected strains were B. adolescentis a-1, B. longum BB-536, B. longum b-1, B. bifidum Bb 12 and L. mesenteroides subsp. mesenteroides B-512f demonstrated the highest final population (≥ 8 log cfu/ml) after exposure to MRSc broth (pH 3) for 3 hrs or when grown in MRSc medium with 0.3% pepsin at pH 3 and after incubation for 24 hr in MRSc medium with 3% bile salts or incubation for 48 hr in MRSc medium with 0.3% phenol. All tested strains exhibited high resistance to four antibiotics (e. g. Amikacin, Norfloxacin, Cefadroxil and Cefoperazone). The other antibiotics, Rifampicin and Oxytetracycline inhibited all five selected strains. Leu. mesenteroides subsp. mesenteroides B-512f had the lowest sensitivity to both Oxytetracycline and Rifampicin compared to the other five selected strains. The cell free supernatant of B. adolescentis a-1 retarded growth of all pathogenic indicators whereas, B. longum b-1 and Leu. mesenteroides subsp. mesenteroides B-512f retarded growth of all pathogenic indicators except Staphylococcus aureus ATCC 20231 and Salmonella typhimurium ATCC 14028 respectively. B. bifidum Bb 12 retarded growths of all pathogenic indicators except Staphylococcus aureus ATCC 20231 and Salmonella typhimurium ATCC 14028 while B. longum BB-536 retarded growth Escherichia coli 0157: H7 ATCC 6933 and Listeria monocytogenes V7 serotype 1 only. The aforementioned five strains stimulated with Inulin and Fructooligosaccharide at 5% for each, while Lactulose was stimulant for B. adolescentis a-1 and Leu. subsp. mesenteroides B-512f without the others strains. Therefore, these strains could be selected for use as probiotics with Inulin or Fructooligosaccharide as prebiotics in functional foods
Data_Sheet_1_Follicular dendritic cell differentiation is associated with distinct synovial pathotype signatures in rheumatoid arthritis.PDF
No full textFollicular dendritic cells (FDCs) fundamentally contribute to the formation of synovial ectopic lymphoid-like structures in rheumatoid arthritis (RA) which is associated with poor clinical prognosis. Despite this critical role, regulation of FDC development in the RA synovium and its correlation with synovial pathotype differentiation remained largely unknown. Here, we demonstrate that CNA.42+ FDCs distinctively express the pericyte/fibroblast-associated markers PDGFR-β, NG2, and Thy-1 in the synovial perivascular space but not in established follicles. In addition, synovial RNA-Seq analysis revealed that expression of the perivascular FDC markers was strongly correlated with PDGF-BB and fibroid synovitis, whereas TNF-α/LT-β was significantly associated with lymphoid synovitis and expression of CR1, CR2, and FcγRIIB characteristic of mature FDCs in lymphoid follicles. Moreover, PDGF-BB induced CNA.42+ FDC differentiation and CXCL13 secretion from NG2+ synovial pericytes, and together with TNF-α/LT-β conversely regulated early and late FDC differentiation genes in unsorted RA synovial fibroblasts (RASF) and this was confirmed in flow sorted stromal cell subsets. Furthermore, RASF TNF-αR expression was upregulated by TNF-α/LT-β and PDGF-BB; and TNF-α/LT-β-activated RASF retained ICs and induced B cell activation in in vitro germinal center reactions typical of FDCs. Additionally, FDCs trapped peptidyl citrulline, and strongly correlated with IL-6 expression, and plasma cell, B cell, and T cell infiltration of the RA synovium. Moreover, synovial FDCs were significantly associated with RA disease activity and radiographic features of tissue damage. To the best of our knowledge, this is the first report describing the reciprocal interaction between PDGF-BB and TNF-α/LT-β in synovial FDC development and evolution of RA histological pathotypes. Selective targeting of this interplay could inhibit FDC differentiation and potentially ameliorate RA in clinically severe and drug-resistant patients.</p
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