Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy.

Accumulating evidence suggests that polymorphisms in Toll-like receptors (TLRs) influence the pathogenesis of mycobacterial infections, including leprosy, a disease whose manifestations depend on host immune responses. Polymorphisms in TLR2 are associated with an increased risk of reversal reaction, but not susceptibility to leprosy itself. We examined whether polymorphisms in TLR4 are associated with susceptibility to leprosy in a cohort of 441 Ethiopian leprosy patients and 197 healthy controls. We found that two single nucleotide polymorphisms (SNPs) in TLR4 (896G>A [D299G] and 1196C>T [T399I]) were associated with a protective effect against the disease. The 896GG, GA and AA genotypes were found in 91.7, 7.8 and 0.5% of leprosy cases versus 79.9, 19.1 and 1.0% of controls, respectively (odds ratio [OR] = 0.34, 95% confidence interval [CI] 0.20-0.57, P < 0.001, additive model). Similarly, the 1196CC, CT and TT genotypes were found in 98.1, 1.9 and 0% of leprosy cases versus 91.8, 7.7 and 0.5% of controls, respectively (OR = 0.16, 95% CI 0.06--.40, P < 0.001, dominant model). We found that Mycobacterium leprae stimulation of monocytes partially inhibited their subsequent response to lipopolysaccharide (LPS) stimulation. Our data suggest that TLR4 polymorphisms are associated with susceptibility to leprosy and that this effect may be mediated at the cellular level by the modulation of TLR4 signalling by M. leprae.

Combined transesophageal and surface MRI provides optimal imaging in aortic atherosclerosis.

OBJECTIVE: Surface magnetic resonance imaging (MRI) for aortic plaque assessment is limited by the trade-off between penetration depth and signal-to-noise ratio (SNR). For imaging the deep seated aorta, a combined surface and transesophageal MRI (TEMRI) technique was developed 1) to determine the individual contribution of TEMRI and surface coils to the combined signal, 2) to measure the signal improvement of a combined surface and TEMRI over surface MRI, and 3) to assess for reproducibility of plaque dimension analysis. METHODS AND RESULTS: In 24 patients six black blood proton-density/T2-weighted fast-spin echo images were obtained using three surface and one TEMRI coil for SNR measurements. Reproducibility of plaque dimensions (combined surface and TEMRI) was measured in 10 patients. TEMRI contributed 68% of the signal in the aortic arch and descending aorta, whereas the overall signal gain using the combined technique was up to 225%. Plaque volume measurements had an intraclass correlation coefficient of as high as 0.97. CONCLUSION: Plaque volume measurements for the quantification of aortic plaque size are highly reproducible for combined surface and TEMRI. The TEMRI coil contributes considerably to the aortic MR signal. The combined surface and TEMRI approach improves aortic signal significantly as compared to surface coils alone. CONDENSED ABSTRACT: Conventional MRI aortic plaque visualization is limited by the penetration depth of MRI surface coils and may lead to suboptimal image quality with insufficient reproducibility. By combining a transesophageal MRI (TEMRI) with surface MRI coils we enhanced local and overall image SNR for improved image quality and reproducibility.

Immunization with H1, HASPB1 and MML Leishmania proteins in a vaccine trial against experimental canine leishmaniasis.

The protective capabilities of three Leishmania recombinant proteins - histone 1 (H1) and hydrophilic acylated surface protein B1 (HASPB1) immunized singly, or together as a protein cocktail vaccine with Montanide, and the polyprotein MML immunized with MPL-SE adjuvant - were assessed in beagle dogs. Clinical examination of the dogs was carried out periodically under blinded conditions and the condition of the dogs defined as asymptomatic or symptomatic. At the end of the trial, we were able to confirm that following infection with L. infantum promastigotes, five out of eight dogs immunized with H1 Montanide, and four out of eight dogs immunized with either the combination of HASPB1 with Montanide or the combination of H1+HASPB1 with Montanidetrade mark, remained free of clinical signs, compared with two out of seven dogs immunized with the polyprotein MML and adjuvant MPL-SE, and two out of eight dogs in the control group. The results demonstrate that HASPB1 and H1 antigens in combination with Montanide were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions.

Oligopotent stem cells are distributed throughout the mammalian ocular surface.

The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty-five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants, and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals. Identification of slow cycling cells (label-retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.

Variation of the Chlorophyll a Related to Sea Surface Temperature, Wind and Geostrophic Currents in the Cape Verde Region Using Satellite Data

We present a comparative analysis of satellite derived climatologies in the Cape Verde region (CV). In order to establish chlorophyll a variability, in relation to other oceanographic phenomena, a set of, relatively long (from five to eight years), time series of chlorophyll a, sea surface temperature, wind and geostrophic currents, were ensembled for the Eastern Central Atlantic (ECA). We studied seasonal and inter-annual variability of phytoplankton concentration, in relation to the rest of the variables, with a special focus in CV. We compared the situation within the archipelago with those of the surrounding marine environments, such as the North West African Upwelling (NWAU), North Atlantic Subtropical Gyre (NASTG), North Equatorial Counter Current (NECC) and Guinea Dome (GD). At the seasonal scale, CV region behaves partly as the surrounding areas, nevertheless, some autochthonous features were also found. The maximum peak of the pigment having a positive correlation with temperature is found at the end of the year for all the points in the archipelago; a less remarkable rise with negative correlation is also detected in February for points CV2 and CV4. This is behavior that none of the surrounding environments have shown. This enrichment was found to be preceded by a drastic drop in wind intensity (SW Monsoon) during summer months. The inter-annual analysis shows a tendency for decreasing of the chlorophyll a concentration.

Variation of the Chlorophyll a Related to Sea Surface Temperature, Wind and Geostrophic Currents in the Cape Verde Region Using Satellite Data

We present a comparative analysis of satellite derived climatologies in the Cape Verde region (CV). In order to establish chlorophyll a variability, in relation to other oceanographic phenomena, a set of, relatively long (from five to eight years), time series of chlorophyll a, sea surface temperature, wind and geostrophic currents, were ensembled for the Eastern Central Atlantic (ECA). We studied seasonal and inter-annual variability of phytoplankton concentration, in relation to the rest of the variables, with a special focus in CV. We compared the situation within the archipelago with those of the surrounding marine environments, such as the North West African Upwelling (NWAU), North Atlantic Subtropical Gyre (NASTG), North Equatorial Counter Current (NECC) and Guinea Dome (GD). At the seasonal scale, CV region behaves partly as the surrounding areas, nevertheless, some autochthonous features were also found. The maximum peak of the pigment having a positive correlation with temperature is found at the end of the year for all the points in the archipelago; a less remarkable rise with negative correlation is also detected in February for points CV2 and CV4. This is behavior that none of the surrounding environments have shown. This enrichment was found to be preceded by a drastic drop in wind intensity (SW Monsoon) during summer months. The inter-annual analysis shows a tendency for decreasing of the chlorophyll a concentration.

Érosion des sols au Cap Vert : étude des processus et quantification à l’échelle de trois bassins versants de l’île de Santiago

Erosão dos solos em Cabo Verde: estudo dos processos e quantificação à escala de três bacias hidrográficas O arquipélago de Cabo Verde é constituído por 10 ilhas vulcânicas pertence à zona do Sahel que se estende do Atlântico ao Mar Vermelho. Desde então, várias décadas, Cabo Verde é afectado pela desertificação causada principalmente pela recessão climatica e a erosão do solo. Esses fatores, aliados à alta pressão humana sobre os recursos, a topografia acidentada e chuvas tropicais por vezes torrenciais, causam sérios danos aos solos. No entanto, desde sua independência em 1975, o Governo realizou um amplo programa de arborização, recuperação de áreas degradadas e a correcção dos leitos das ribeiras. No entanto, a investigação, muito pouco foi realizada para avaliar as acções de protecção e conservação do solo e da água. Portanto, não há dados sobre o problema da degradação das terras nem balanços. Como parte deste trabalho, foram estudados vários factores que controlam a erosão do solo pela água. Especificamente, buscou-se diferenciar os efeitos das actividades humanas, incluindo a agricultura, os factores climáticos, como chuva e geração de escoamento. Também estabeleceu os primeiros balanços das exportações de matérias em suspensão e em solução no contexto do arquipélago de Cabo Verde. O estudo foi realizado em três bacias hidrográficas da ilha de Santiago, Cabo Verde. Estas três bacias hidrográficas (Longueira, Grande e Godim) estão localizadas na parte central da ilha de Santiago e representam os diversos tipos de uso da terra e as diferentes zonas bioclimaticas da ilha. Existe um gradiente climático entre as três bacias hidrográficas. Na verdade, Longueira que abrange uma área de 4,18 km2, tem um declive médio de 47 %, uma zona florestada de 69% e uma área agrícola de 17 %. Grande com uma área de 1,87 km2, é localizada numa zona sub humida com um declive médio de 50%, é essencialmente agrícola. Godim, com uma área de 2,0 km2, é localizado numa zona semi-árida com um declive médio de 32%, é particularmente uma zona agricola. Para estes três bacias hidrográficas, as cheias foram medidas e amostradas de 2004 a 2009. A bacia de Longueira teve um maior acompanhamento, nomeadamente em termos de amostragem e monitoramento dos escoamentos. Em cada amostra foram feitas a determinação da concentração de matérias em suspensão e a análise dos principais elementos quimicos. Os resultados mostram que a erosão mecânica nas três bacias hidrográficas é caracterizada por uma forte variabilidade espacial e temporal. Durante o período de 2005-2009, o balanço anual média para as bacias hidrográficas de Longueira, Grande e Godim é: 4266, 157 e 10,1 t.km2.an-1, respectivamente. A estação das chuvas de 2006 foi a mais erosiva para as três bacias, particularmente em Longueira, com 2 cheias excepcionais, que têm gerado uma concentração média de sólidos em suspensão superior a 100 g / l. Porém, as estações do ano de 2005 e 2008 foram de uma forma geral menos erosivas porque as concentrações médias não inferiores a 20 g / l. Além disso, não houve cheias para as temporadas 2005 e 2007 para a bacia do Godim. Na bacia de Longueira, o estudo dos fenómenos de histerese na caracterização das cheias mostrou que a evolução temporal das exportações de sólidos em suspensão durante a temporada é fortemente influenciada pelas atividades agrícolas. Na verdade, a primeira cheia causou uma exportação maciça de sedimento disponível e localizado no leito da ribeira. Assim, a segunda cheia exportou menos sedimentos. Um mês após as primeiras chuvas, a prática da monda que reduz a densidade da cobertura vegetal e destructura a camada superficial do solo, gerou uma grande quantidade de sedimento que novamente permitiu uma exportação muito forte de sedimentos durante a terceira forte cheia. Os resultados da erosão química na bacia de Longueira indicam que a taxa de erosão é de 45 t.km2.an-1 com uma forte variabilidade temporal. Na verdade, as temporadas de 2006 e 2007 são as mais erosivas, enquanto 2005 teve uma exportação de matérias disolvidas baixa. A utilização do modelo EMMA (End- Members Mixing Analysis) mostra que os escoamentos hipodermico e profundo, alimentandos os fluxos de elementos dissolvidos são os principais factores da erosão química. É mostrado que esses fluxos causam mais de 90% dos fluxos de erosão química. O escoamento superficial, que contribui com cerca de 70% na formação das cheias, é o maior factor da erosão mecânica do solo.

Staphylococcal biofilm formation on the surface of three different calcium phosphate bone grafts: a qualitative and quantitative in vivo analysis.

Differences in physico-chemical characteristics of bone grafts to fill bone defects have been demonstrated to influence in vitro bacterial biofilm formation. Aim of the study was to investigate in vivo staphylococcal biofilm formation on different calcium phosphate bone substitutes. A foreign-body guinea-pig infection model was used. Teflon cages prefilled with β-tricalcium phosphate, calcium-deficient hydroxyapatite, or dicalcium phosphate (DCP) scaffold were implanted subcutaneously. Scaffolds were infected with 2 × 10(3) colony-forming unit of Staphylococcus aureus (two strains) or S. epidermidis and explanted after 3, 24 or 72 h of biofilm formation. Quantitative and qualitative biofilm analysis was performed by sonication followed by viable counts, and microcalorimetry, respectively. Independently of the material, S. aureus formed increasing amounts of biofilm on the surface of all scaffolds over time as determined by both methods. For S. epidermidis, the biofilm amount decreased over time, and no biofilm was detected by microcalorimetry on the DCP scaffolds after 72 h of infection. However, when using a higher S. epidermidis inoculum, increasing amounts of biofilm were formed on all scaffolds as determined by microcalorimetry. No significant variation in staphylococcal in vivo biofilm formation was observed between the different materials tested. This study highlights the importance of in vivo studies, in addition to in vitro studies, when investigating biofilm formation of bone grafts.

High-dose sequential chemotherapy (ICE) under circulating progenitor cells (CPC) protection in patients with small cell lung carcinoma (SCLC). Preliminary report on a multicentric study

Starting in February 1994, 20 patients (pt) with a median age of 50 years(range 41-63) from 7 European centers have been included. Completedata were obtained in 16 patients so far. CPC were mobilized with chemo(Epirubicine 75 mg/m2 /d, 01 + 02) followed by G-CSF 5 p.gfkg/d for14 days. HD chemo consisted in 3 sequential courses of ICE regimen(UOs. 10 g/m2 , Carbo. 1200 mg/m2 and Etop. 1200 mg/m2 ) underCPC protection and G-CSF 5 p.g/kg/d. Out of the 16 pt, 12 completedfull program (3 cycles). One pt died of septic shock before receivingany ICE course. One pt died during the first ICE of renal insufficiency.Two pt had only 2 courses because of toxicity. Among the 16 pt, responserate (RR) was: 7 CR, 6 PR, 1 PO; 3 pt are not evaluable dueto early withdrawal (overall RR: 13/16 = 81 %). Thirty-nine cycles ofHD chemo were given with a median hematological recovery of 9 days(range 7-12) until neutro. counts> 1.0 x 109 /1 and 9 days (range 717)until thrombo. > 20 x 109 /1. No cumulative, hematological toxicitywas seen. Accrual of patients is still ongoing and updated results will bepresented.

OVERLAND FLOW AND SURFACE RUNOFF / Hydrological Science and Engineering

Cape Verde, off the coast of Senegal in western Africa, is a volcanic archipelago where soil and water conservation techniques play an important role in the overall subsistence of half a million inhabitants. In fact, the step slopes in the more agricultural islands due to it's volcanic origin, together with semi-arid and arid environments (the country is located in the Sahelian region), characterized by a very irregular wet season, with high intensity rainfall events, make life tough. The hard conditions lead during the first half of the XX century to frequent cycles of drought with severe implications on the local populations, with impressive numbers of deaths by famine, and a decrease of the number of local inhabitants by more than halve in some islands. Maintain the soil in place and the water inside the soil was there after a mater of survival, and the CapeVerdians implemented over the last half century a number of soil and water conservation techniques that cover all the landscape. In this work, we monitored a number of slope soil and water conservation techniques, such as terraces, half moons, live barriers, etc, together with two cultural strategies, used to plant corn and beans on one side and peanuts on the other, with a semi-quantitative methodology, to evaluate their effectiveness. A discussion is given on the costs and effectiveness of the techniques to reduce overland flow production and therefore erosion, and to promote rainfall infiltration.

Financial protection of patients through compensation of providers: the impact of health equity funds in Cambodia

Public providers have no financial incentive to respect their legal obligation to exempt the poor from user fees. Health Equity Funds (HEFs) aim to make exemptions effective by giving NGOs responsibility for assessing eligibility and compensating providers for lost revenue. We use the geographic spread of HEFs in Cambodia to identify their impact on out-of-pocket (OOP) payments. Among households with some OOP payment, HEFs reduce the amount by 29%, on average. The effect is larger for households that are poorer, mainly use public health care and live closer to a district hospital. HEFs are more effective in reducing OOP payments when they are operated by a NGO, rather than the government, and when they operate in conjunction with the contracting of public health services. HEFs reduce households' health-related debt by around 25%, on average. There is no significant impact on non-medical consumption and health care utilisation

Historic Alteration of Surface Hydrology on the Des Moines Lobe, 2001

Water fact sheet for Iowa Department of Natural Resources and the Geological Bureau.

Role of mTOR, Bad, and Survivin in RasGAP Fragment N-Mediated Cell Protection.

Partial cleavage of p120 RasGAP by caspase-3 in stressed cells generates an N-terminal fragment, called fragment N, which activates an anti-apoptotic Akt-dependent survival response. Akt regulates several effectors but which of these mediate fragment N-dependent cell protection has not been defined yet. Here we have investigated the role of mTORC1, Bad, and survivin in the capacity of fragment N to protect cells from apoptosis. Neither rapamycin, an inhibitor of mTORC1, nor silencing of raptor, a subunit of the mTORC1 complex, altered the ability of fragment N from inhibiting cisplatin- and Fas ligand-induced death. Cells lacking Bad, despite displaying a stronger resistance to apoptosis, were still protected by fragment N against cisplatin-induced death. Fragment N was also able to protect cells from Fas ligand-induced death in conditions where Bad plays no role in apoptosis regulation. Fragment N expression in cells did neither modulate survivin mRNA nor its protein expression. Moreover, the expression of cytoplasmic survivin, known to exert anti-apoptotic actions in cells, still occurred in UV-B-irradiated epidermis of mouse expressing a caspase-3-resistant RasGAP mutant that cannot produce fragment N. Additionally, survivin function in cell cycle progression was not affected by fragment N. These results indicate that, taken individually, mTOR, Bad, or Survivin are not required for fragment N to protect cells from cell death. We conclude that downstream targets of Akt other than mTORC1, Bad, or survivin mediate fragment N-induced protection or that several Akt effectors can compensate for each other to induce the pro-survival fragment N-dependent response.