Enteric coated spheres produced by extrusion/spheronization provide effective gastric protection and efficient release of live therapeutic bacteria

We present a novel but simple enteric coated sphere formulation containing probiotic bacteria (Lactobacillus casei). Oral delivery of live bacterial cells (LBC) requires live cells to survive firstly manufacturing processes and secondly GI microbicidal defenses including gastric acid. We incorporated live L. casei directly in the granulation liquid, followed by granulation, extrusion, spheronization, drying and spray coating to produce dried live probiotic spheres. A blend of MCC, calcium-crosslinked alginate, and lactose was developed that gave improved live cell survival during manufacturing, and gave excellent protection from gastric acid plus rapid release in intestinal conditions. No significant loss of viability was observed in all steps except drying, which resulted in approximately 1 log loss of viable cells. Eudragit coating was used to protect dried live cells from acid, and microcrystalline cellulose (MCC) was combined with sodium alginate to achieve efficient sphere disintegration leading to rapid and complete bacterial cell release in intestinal conditions. Viability and release of L. casei was evaluated in vitro in simulated GI conditions. Uncoated spheres gave partial acid protection, but enteric coated spheres effectively protected dried probiotic LBC from acid for 2 h, and subsequently released all viable cells within 1h of transfer into simulated intestinal fluid.

Faith and protection: the construction of hope by parents of children with leukemia and their oncologists

Background. Oncologists are criticized for fostering unrealistic hope in patients and families, but criticisms reflect a perspective that is oversimplified and “expert” guidance that is ambiguous or impractical. Our aim was to understand how pediatric oncologists manage parents' hope in practice and to evaluate how they address parents' needs. Methods. Participants were 53 parents and 12 oncologists whom they consulted across six U.K. centers. We audio recorded consultations approximately 1–2, 6, and 12 months after diagnosis. Parents were interviewed after each consultation to elicit their perspectives on the consultation and clinical relationship. Transcripts of consultations and interviews were analyzed qualitatively. Results. Parents needed hope in order to function effectively in the face of despair, and all wanted the oncologists to help them be hopeful. Most parents focused hope on the short term. They therefore needed oncologists to be authoritative in taking responsibility for the child's long-term survival while cushioning parents from information about longer-term uncertainties and being positive in providing information about short-term progress. A few parents who could not fully trust their oncologist were unable to hope. Conclusion. Oncologists' pivotal role in sustaining hope was one that parents gave them. Most parents' “faith” in the oncologist allowed them to set aside, rather than deny, their fears about survival while investing their hopes in short-term milestones. Oncologists' behavior generally matched parents' needs, contradicting common criticisms of oncologists. Nevertheless, oncologists need to identify and address the difficulty that some parents have in fully trusting the oncologist and, consequently, being hopeful.

Blending systems thinking approaches for organisational analysis: reviewing child protection in England

This paper concerns the innovative use of a blend of systems thinking ideas in the ‘Munro Review of Child Protection’, a high-profile examination of child protection activities in England, conducted for the Department for Education. We go ‘behind the scenes’ to describe the OR methodologies and processes employed. The circumstances that led to the Review are outlined. Three specific contributions that systems thinking made to the Review are then described. First, the systems-based analysis and visualisation of how a ‘compliance culture’ had grown up. Second the creation of a large, complex systems map of current operations and the effects of past policies on them. Third, how the map gave shape to the range of issues the Review addressed and acted as an organising framework for the systemically coherent set of recommendations made. The paper closes with an outline of the main implementation steps taken so far to create a child protection system with the critically reflective properties of a learning organisation, and methodological reflections on the benefits of systems thinking to support organisational analysis.

An annotation-free method for evaluating privacy protection techniques in videos

While several privacy protection techniques are pre- sented in the literature, they are not complemented with an established objective evaluation method for their assess- ment and comparison. This paper proposes an annotation- free evaluation method that assesses the two key aspects of privacy protection that are privacy and utility. Unlike some existing methods, the proposed method does not rely on the use of subjective judgements and does not assume a spe- cific target type in the image data. The privacy aspect is quantified as an appearance similarity and the utility aspect is measured as a structural similarity between the original raw image data and the privacy-protected image data. We performed an extensive experimentation using six challeng- ing datasets (including two new ones) to demonstrate the effectiveness of the evaluation method by providing a per- formance comparison of four state-of-the-art privacy pro- tection techniques.

Papal power and protection in the Shebet Yehudah

The sixteenth-century Shebet Yehudah is an account of the persecutions of Jews in various countries and epochs, including their expulsion from Spain in the fifteenth century. It is not a medieval text and was written long after many of the events it describes. Yet although it cannot give us a contemporary medieval standpoint, it provides important insights into how later Jewish writers perceived Jewish–papal relations in the thirteenth, fourteenth, and fifteenth centuries. Although the extent to which Jewish communities came into contact either with the papacy as an institution or the actions of individual popes varied immensely, it is through analysis of Hebrew works such as the Shebet Yehudah that we are able to piece together a certain understanding of Jewish ideas about the medieval papacy as an institution and the policies of individual popes. This article argues that Jews knew only too well that papal protection was not unlimited, but always carefully circumscribed in accordance with Christian theology. It is hoped that it will be a scholarly contribution to our growing understanding of Jewish ideas about the papacy's spiritual and temporal power and authority in the Later Middle Ages and how this impacted on Jewish communities throughout medieval Europe.

The Léger ruling as another example of the ECJ’s disappointingly reticent approach to the protection of the rights of LGB persons under EU law

In the 1980s, in the midst of the AIDS epidemic, many countries introduced lifetime bans on blood donations by men who had sexual relations with men (MSM). These blanket bans have, recently, begun to be challenged and, as a result, many countries have either relaxed them or completely abolished them. The case under examination (Léger ) is another instance of questioning the legality of such a ban. In particular, in this case, the European Court of Justice was called on to rule on whether a measure such as the French lifetime exclusion from blood donation of the MSM population that was at issue before the referring court is contrary to EU law. The Court ruled that although discriminatory on the ground of sexual orientation, such a ban may be justified in certain circumstances, and left it to the national court to make the final decision. This article seeks to analyse the case and to explain why, in the author’s view, the Court can be accused of—once more—not going far enough in the protection of lesbian, gay and bisexual (LGB) rights.

PODOCARPUS SP.PL. REFUGIA IN BRAZIL`S ATLANTIC FOREST: ANALYSING THE PAST TO IMPROVE FUTURE PROTECTION

The Atlantic rainforest has the second highest biodiversity in Brazil. It has been shrinking rapidly in area as a result of intensive deforestation, and only 7% of the original cover now remains, as isolated patches or in ecological reserves. In order to obtain new information on the distribution of the Atlantic rainforest during the Quaternary, we examined herbarium data to locate relevant populations and extracted DNA from fresh leaves from 26 populations. The present-day distribution of endemic Podocarpus populations shows that they are widely dispersed across eastern Brazil, and that the expansion of Podocarpus recorded in single Amazonian pollen records may have originated from either western or eastern populations. Genetic analysis enabled us to determine the boundaries of their regional expansion: northern and central populations of P. sellowii appeared between 5 degrees and 15 degrees S some 16,000 years ago; populations of P lambertii or sellowii have appeared between 15 degrees and 23 degrees S at different times since the last glaciation at least; and P lambertii appeared between 23 degrees and 30 degrees S during the recent expansion of Araucaria forests. The combination of botanical, pollen, and molecular analyses proved to be a rapid means of inferring distribution boundaries for sparse populations and their regional evolution within tropical ecosystems. Today the rainforest refugia we identified have become hotspots that are crucial to the survival of the Atlantic forest under unfavourable climatic conditions and, as such, offer the only possible opportunity for this type of forest to expand in the event of future climate change.

Agribusiness Opportunity Costs and Environmental Legal Protection: Investigating Trade-Off on Hotspot Preservation in the State of So Paulo, Brazil

Prior to deforestation, So Paulo State had 79,000 km(2) covered by Cerrado (Brazilian savanna) physiognomies, but today less than 8.5% of this biodiversity hotspot remains, mostly in private lands. The global demand for agricultural goods has imposed strong pressure on natural areas, and the economic decisions of agribusiness managers are crucial to the fate of Cerrado domain remaining areas (CDRA) in Brazil. Our aim was to investigate the effectiveness of Brazilian private protected areas policy, and to propose a feasible alternative to promote CDRA protection. This article assessed the main agribusiness opportunity costs for natural areas preservation: the land use profitability and the arable land price. The CDRA percentage and the opportunity costs were estimated for 349 municipal districts of So Paulo State through secondary spatial data and profitability values of 38 main agricultural products. We found that Brazilian private protected areas policy fails to preserve CDRA, although the values of non-compliance fines were higher than average opportunity costs. The scenario with very restrictive laws on private protected areas and historical high interest rates allowed us to conceive a feasible cross compliance proposal to improve environmental and agricultural policies.

Strong quenching of chlorophyll fluorescence in the desiccated state in three poikilohydric and homoiochlorophyllous moss species indicates photo-oxidative protection on highly light-exposed rocks of a tropical inselberg

The three poikilophydric and homoiochlorophyllous moss species Campylopus savannarum (C. Muell.) Mitt., Racocarpus fontinaloides (C. Muell.) Par. and Ptychomitrium vaginatum Besch. grow on sun-exposed rocks of a tropical inselberg in Brazil subject to regular drying and wetting cycles. Effective photo-oxidative protection in the light-adapted desiccated state in all three species is achieved by a reduction of ground chlorophyll fluorescence, F, to almost zero. Upon rewatering, the kinetics of the recovery of F in air dry cushions to higher values is very fast in the first 5min, but more than 80min are needed until an equilibrium is reached gradually. The kinetics were not different between the three species. The three moss species, have a distinct niche occupation and form a characteristic zonation around soil vegetation islands on the rock outcrops, where C. savannarum and R. fontinaloides form an inner and outer belt, respectively, around vegetation islands and P vaginatum occurs as small isolated cushions on bare rock. However, they were not distinguished by the reduction of F in the dry state and the rewetting recovery kinetics and only slightly different in their photosynthetic capacity. Stable isotope ratios (delta C-13, delta N-15) indicate that liquid films of water limiting diffusion of CO2 are important in determining carbon acquisition and suggest that limitation of CO2 fixation by water films must be more pronounced over time in P vaginatum than in the latter species. This is determined by both the micro site occupied and the form of the moss cushions. (c) 2007 Elsevier GmbH. All rights reserved.

Poly(lactic acid-glycolic acid) nanoparticles markedly improve immunological protection provided by peptide P10 against murine paracoccidioidomycosis

Background and purpose: The present study reports on the preparation and testing of a sustained delivery system for the immunomodulatory peptide P10 aimed at reducing the in vivo degradation of the peptide and the amount required to elicit a protective immune response against paracoccidioidomycosis. Experimental approach: BALB/c mice were infected with the yeast Paracoccidioides brasiliensis to mimic the chronic form of paracoccidioidomycosis. The animals were treated daily with sulfamethoxazole/trimethoprim alone or combined with peptide P10, either emulsified in Freund`s adjuvant or entrapped in poly(lactic acid-glycolic acid) (PLGA) nanoparticles at different concentrations (1 mu g, 5 mu g, 10 mu g, 20 mu g or 40 mu g center dot 50 mu L-1). Therapeutic efficacy was assessed as fungal burden in tissues and the immune response by quantitative determination of cytokines. Key results: Animals given combined chemotherapy and P10 nanotherapy presented a marked reduction of fungal load in the lungs, compared with the non-treated animals. After 30 days of treatment, P10 entrapped within PLGA (1 mu g center dot 50 mu L-1) was more effective than `free` P10 emulsified in Freund`s adjuvant (20 mu g center dot 50 mu L-1), as an adjuvant to chemotherapy. After treatment for 90 days, the higher doses of P10 entrapped within PLGA (5 or 10 mu g center dot 50 mu L-1) were most effective. Treatment with P10 emulsified in Freund`s adjuvant (20 mu g center dot 50 mu L-1) or P10 entrapped within PLGA (1 mu g center dot 50 mu L-1) were accompanied by high levels of interferon-gamma in lung. Conclusions and implications: Combination of sulfamethoxazole/trimethoprim with the P10 peptide entrapped within PLGA demonstrated increased therapeutic efficacy against paracoccidioidomycosis. P10 incorporation into PLGA nanoparticles dramatically reduced the peptide amount necessary to elicit a protective effect.

Leishmania amazonensis META2 protein confers protection against heat shock and oxidative stress

The META cluster of Leishmania amazonensis contains both META1 and META2 genes, which are upregulated in metacyclic promastigotes and encode proteins containing the META domain. Previous studies defined META2 as a 48.0-kDa protein, which is conserved in other Leishmania species and in Trypanosoma brucei. In this work, we demonstrate that META2 protein expression is regulated during the Leishmania life cycle but constitutive in T. brucei. META2 protein is present in the cytoplasm and flagellum of L amazonensis promastigotes. Leishmania META2-null replacement mutants are more sensitive to oxidative stress and, upon heat shock, assume rounded morphology with shortened flagella. The increased susceptibility of null parasites to heat shock is reversed by extra-chromosomal expression of the META2 gene. Defective Leishmania promastigotes exhibit decreased ability to survive in macrophages. By contrast, META2 expression is decreased by 80% in RNAi-induced T. brucei bloodstream forms with no measurable effect on survival or resistance to heat shock. (C) 2010 Elsevier Inc. All rights reserved.

Protection against high-dose homologous infection in calves immunized with intestine or membrane extracts from Haemonchus placei

Control of Haemonchus placei, one of the most important cattle nematodes in Brazil, relies on the use of anthelmintics. However, there is a need for integrated control, which includes active immunization. The aim of this work was to assess the protection afforded to calves by immunization with adult H. placei extracts against a high-dose challenge infection, a condition frequently found in the tropics. Holstein calves aged 8-10 months were immunized four times with intestinal extracts (Group D) or with a Triton X-100-soluble fraction of adult H. placei (Group A), challenge-infected with 120,000 infective larvae and sacrificed 40 days later. Immunized animals had higher IgG titers than the controls against tested fractions after the 2nd immunization, peaking after the 4th. Sera from both immunized groups recognized bands of similar apparent mass in both antigenic preparations, some of which were similar in molecular weight to Haemonchus contortus antigens with known protective effect to sheep. Egg counts were 49% and 57% lower in Groups A and D than in controls, respectively. High levels of protection were observed in two of the four calves in Group D, as evidenced by very low worm numbers recovered at necropsy, absence of eggs in the uteri of the recovered females and reduced worm length. Group D animals also showed milder signs of anemia than the other infected animals. Results demonstrate that protection against homologous high-dose challenge can be achieved by immunizing calves with H. placei gut antigens. (C) 2007 Elsevier B.V. All rights reserved.