Erosion of the Capital City Advantage in Child Survival and Reproductive, Maternal, Newborn, and Child Health Intervention Coverage in Sub-Saharan Africa.

The place of residence is a major determinant of RMNCH outcomes, with rural areas often lagging in sub-Saharan Africa. This long-held pattern may be changing given differential progress across areas and increasing urbanization. We assessed inequalities in child mortality and RMNCH coverage across capital cities and other urban and rural areas. We analyzed mortality data from 163 DHS and MICS in 39 countries with the most recent survey conducted between 1990 and 2020 and RMNCH coverage data from 39 countries. We assessed inequality trends in neonatal and under-five mortality and in RMNCH coverage using multilevel linear regression models. Under-five mortality rates and RMNCH service coverage inequalities by place of residence have reduced substantially in sub-Saharan Africa, with rural areas experiencing faster progress than other areas. The absolute gap in child mortality between rural areas and capital cities and that between rural and other urban areas reduced respectively from 41 and 26 deaths per 1000 live births in 2000 to 23 and 15 by 2015. Capital cities are losing their primacy in child survival and RMNCH coverage over other urban areas and rural areas, especially in Eastern Africa where under-five mortality gap between capital cities and rural areas closed almost completely by 2015. While child mortality and RMNCH coverage inequalities are closing rapidly by place of residence, slower trends in capital cities and urban areas suggest gradual erosion of capital city and urban health advantage. Monitoring child mortality and RMNCH coverage trends in urban areas, especially among the urban poor, and addressing factors of within urban inequalities are urgently needed.

Development and validation of a stability-indicating high performance liquid chromatographic assay for determination of cariprazine in bulk form and in drug product.

The aim of the present study is to develop a stability indicating high performance liquid chromatographic method for the determination of cariprazine in bulk substance and in drug product. The chromatographic separation was carried out using a Phenomenex Kinetex® C18 column (5µm, 250×4.6mm) and a mobile phase consisting of acetonitrile-potassium dihydrogen orthophosphate buffer (pH 4; 50mM) (30:70, v/v), at a flow rate of 1mlmin -1 and UV detection at 248nm. The column was maintained at 25°C and an injection volume of 20µL was used. Stress testing of cariprazine bulk substance and drug product was performed according to the International Conference on Harmonization (ICH) Q1A (R2) guideline. Various stress conditions were tested including acidic, alkaline and neutral hydrolysis, humidity, oxidation, dry heat and photolysis. A total of three degradation products (DPs) were formed. Among them two DPs were successfully characterized with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.

Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real-life.

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex® ) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real-life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2 mg/d in subcutaneous injection) and pegylated interferon (PEG-IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1 log10 and 3/3 of 2 log10 of HDV-VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV-VL relapse was notified 24 weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV-VL during the therapy (<100 IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV-VL by 1 log10 at 8 weeks and 1/1 by 2 log10 at 28 week on-treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long-term clinical benefit (fibrosis reversibility and reduction in hepato-cellular carcinoma [HCC]).

Measuring coverage of maternal and child health services using routine health facility data: a Sierra Leone case study.

BACKGROUND: There are limited existing approaches to generate estimates from Routine Health Information Systems (RHIS) data, despite the growing interest to these data. We calculated and assessed the consistency of maternal and child health service coverage estimates from RHIS data, using census-based and health service-based denominators in Sierra Leone. METHODS: We used Sierra Leone 2016 RHIS data to calculate coverage of first antenatal care contact (ANC1), institutional delivery and diphtheria-pertussis-tetanus 3 (DPT3) immunization service provision. For each indicator, national and district level coverages were calculated using denominators derived from two census-based and three health service-based methods. We compared the coverage estimates from RHIS data to estimates from MICS 2017. We considered the agreement adequate when estimates from RHIS fell within the 95% confidence interval of the survey estimate. RESULTS: We found an overall poor consistency of the coverage estimates calculated from the census-based methods. ANC1 and institutional delivery coverage estimates from these methods were greater than 100% in about half of the fourteen districts, and only 3 of the 14 districts had estimates consistent with the survey data. Health service-based methods generated better estimates. For institutional delivery coverage, five districts met the agreement criteria using BCG service-based method. We found better agreement for DPT3 coverage estimates using DPT1 service-based method as national coverage was close to survey data, and estimates were consistent for 8 out of 14 districts. DPT3 estimates were consistent in almost half of the districts (6/14) using ANC1 service-based method. CONCLUSION: The study highlighted the challenge in determining an appropriate denominator for RHIS-based coverage estimates. Systematic and transparent data quality check and correction, as well as rigorous approaches to determining denominators are key considerations to generate accurate coverage statistics using RHIS data.

Inequalities in early marriage, childbearing and sexual debut among adolescents in sub-Saharan Africa.

BACKGROUND: Adolescent sexual and reproductive health (ASRH) is a major public health concern in sub-Saharan Africa (SSA). However, inequalities in ASRH have received less attention than many other public health priority areas, in part due to limited data. In this study, we examine inequalities in key ASRH indicators. METHODS: We analyzed national household surveys from 37 countries in SSA, conducted during 1990-2018, to examine trends and inequalities in adolescent behaviors related to early marriage, childbearing and sexual debut among adolescents using data from respondents 15-24 years. Survival analyses were conducted on each survey to obtain estimates for the ASRH indicators. Multilevel linear regression modelling was used to obtain estimates for 2000 and 2015 in four subregions of SSA for all indicators, disaggregated by sex, age, household wealth, urban-rural residence and educational status (primary or less versus secondary or higher education). RESULTS: In 2015, 28% of adolescent girls in SSA were married before age 18, declined at an average annual rate of 1.5% during 2000-2015, while 47% of girls gave birth before age 20, declining at 0.6% per year. Child marriage was rare for boys (2.5%). About 54% and 43% of girls and boys, respectively, had their sexual debut before 18. The declines were greater for the indicators of early adolescence (10-14 years). Large differences in marriage and childbearing were observed between adolescent girls from rural versus urban areas and the poorest versus richest households, with much greater inequalities observed in West and Central Africa where the prevalence was highest. The urban-rural and wealth-related inequalities remained stagnant or widened during 2000-2015, as the decline was relatively slower among rural and the poorest compared to urban and the richest girls. The prevalence of the ASRH indicators did not decline or increase in either education categories. CONCLUSION: Early marriage, childbearing and sexual debut declined in SSA but the 2015 levels were still high, especially in Central and West Africa, and inequalities persisted or became larger. In particular, rural, less educated and poorest adolescent girls continued to face higher ASRH risks and vulnerabilities. Greater attention to disparities in ASRH is needed for better targeting of interventions and monitoring of progress.

[Analysis of preferences and behaviors towards dosing devices of liquid oral forms and study of the impact of a pharmaceutical education on the safety of their use]. / Analyse des préférences et des comportements envers les dispositifs d'administration des formes orales liquides et étude de l'impact d'une éducation pharmaceutique sur la sécurité de leur utilisation.

OBJECTIVES: The aim of this study was to analyze patients' preferences and behaviors towards dosing devices of oral liquid medication and the impact of pharmaceutical education on their handling practices. METHODS: A cross-sectional study was carried out at a pharmacy. Participants were asked to answer a pre-established questionnaire about their preferences and behaviors towards oral liquid administration devices. The impact of pharmaceutical education was assessed by simulating filling a 5mL dose using a metering device of their choice. The data collected was analyzed by SPSS 20.0. RESULTS: Preferences and behaviors regarding dosing devices were variable according to the characteristics of the population. Of the 396 participants, one third continued to use household spoons and only 54% of them chose calibrated dosing devices. Pharmaceutical education had a positive impact on administration practices. CONCLUSIONS: Particular attention should be carried to dosing devices of oral liquid forms. An inventory should be drawn up to assess the quality and safety of the marketed specialties.

Valorization of the Green Waste from Two Varieties of Fennel and Carrot Cultivated in Tunisia by Identification of the Phytochemical Profile and Evaluation of the Antimicrobial Activities of Their Essentials Oils.

The purpose of this study was to identify the chemical composition and the antibacterial activity of the essential oils (EOs) extracted from the green tops of Daucus carota L. subsp. sativus (Hoffm.) Arcang. plants producing yellow roots (DcsYR) and those producing orange roots (DcsOR) and from two varieties of Foeniculum vulgare subsp. vulgare cultivated in Tunisia. Analyses revealed that the EOs from the two D. carota varieties were rich in constituents belonging to sesquiterpenes. Phenylpropanoids and non-terpene derivatives were the most abundant classes of compounds in the EOs from the two varieties of F. vulgare, of which compositions were predominated by (E)-anethole and p-acetonylanisole. All the tested EOs were significantly more effective against Gram-negative bacteria, and that obtained from var. azoricum was more active against the yeast Candida albicans than the reference drug. The EOs obtained from these by-products showed indeed interesting potential to be promoted as natural antimicrobials in food preservation systems, as well as the possibility to be used in flavor industries.

Peritoneal Submesothelial Stromal Cells Support Hematopoiesis and Differentiate into Osteogenic and Adipogenic Cell Lineages.

The peritoneum is a thin membrane that covers most of the abdominal organs, composed of a monolayer of mesothelial cells and subjacent submesothelial loose connective tissue. Cells from the peritoneal wall are correlated with peritoneal fibrosis and epithelial-to-mesenchymal transition. However, the distinct involvement of mesothelial or submesothelial cells in such phenomena is still not clear. Here, we propose a new strategy to obtain stromal cells from anterior peritoneal wall explant cultures. These cells migrated from peritoneal tissues and proliferated in vitro for 4 weeks as adherent fibroblast-like cells. Optical and electronic microscopy analyses of the fragments revealed a significant submesothelial disorganization. The obtained cells were characterized as cytokeratin- vimentin+ laminin+ α-smooth muscle actin+, suggesting a connective tissue origin. Moreover, at the third passage, these stromal cells were CD90+CD73+CD29+Flk-1+CD45-, a phenotype normally attributed to cells of mesenchymal origin. These cells were able to support hematopoiesis, expressing genes involved in myelopoiesis (SCF, G-CSF, GM-CSF, IL-7 and CXCL-12), and differentiated into osteogenic and adipogenic cell lineages. The methodology demonstrated in this work can be considered an excellent experimental model to understand the physiology of the peritoneal wall in healthy and pathological processes. Moreover, this work shows for the first time that submesothelial stromal cells have properties similar to those of mesenchymal cells from other origins.

Conservation agriculture has no significant impact on sheep digestive parasitism.

Conservation agriculture (CONS A) is a sustainable agriculture system based on crop rotation with no tillage. It has various environmental advantages compared to conventional agriculture (CONV A): decreased water evaporation, erosion, and CO2 emissions. In this first study of its kind, we aim to evaluate the impact of this type of agriculture on sheep gastrointestinal parasites. Two lamb groups aged between 5 and 10 months were randomly included to graze separately on CONS A and CONV A pastures. Each group was composed of two batches of three lambs, and these were followed up for two rearing months. Liveweight, hematological parameter variation, and digestive parasites were studied. At the end of the study period, lambs were slaughtered the carcass yield was determined, and a helminthological autopsy was performed on the digestive tracts of the animals to estimate different parasitological indicators. There was no difference between lambs reared on CONS A and those reared on CONV A for all parasite indicators (infestation intensity, abundance, and prevalence). The same trend was also obtained for hematological parameters, liveweight evolution, and carcass yield. These results prove that there is no impact of CONS A on the sheep's digestive parasitism. Further studies are needed to support these findings on larger animal samples and to investigate the impact of conservation agriculture on other parasite species. Similar studies could also be conducted on ruminant species.

The bone marrow compartment is modified in the absence of galectin-3.

Galectin-3 (gal-3) is a ß-galactoside binding protein present in multivalent complexes with an extracellular matrix and with cell surface glycoconjugates. In this context, it can deliver a variety of intracellular signals to modulate cell activation, differentiation and survival. In the hematopoietic system, it was demonstrated that gal-3 is expressed in myeloid cells and surrounding stromal cells. Furthermore, exogenous and surface gal-3 drive the proliferation of myeloblasts in a granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent manner. Here, we investigated whether gal-3 regulates the formation of myeloid bone marrow compartments by studying galectin-3(-/-) mice (gal-3(-/-)) in the C57BL/6 background. The bone marrow histology of gal-3(-/-) mice was significantly modified and the myeloid compartments drastically disturbed, in comparison with wild-type (WT) animals. In the absence of gal-3, we found reduced cell density and diaphyseal disorders containing increased trabecular projections into the marrow cavity. Moreover, myeloid cells presented limited capacity to differentiate into mature myeloid cell populations in gal-3(-/-) mice and the number of hematopoietic multipotent progenitors was increased relative to WT animals. In addition, bone marrow stromal cells of these mice had reduced levels of GM-CSF gene expression. Taken together, our data suggest that gal-3 interferes with hematopoiesis, controlling both precursors and stromal cells and favors terminal differentiation of myeloid progenitors rather than proliferation.

Reorienting systematic conservation assessment for effective conservation planning.

Systematic conservation assessment (an information-gathering and prioritization process used to select the spatial foci of conservation initiatives) is often considered vital to conservation-planning efforts, yet published assessments have rarely resulted in conservation action. Conservation assessments may lead more directly to effective conservation action if they are reoriented to inform conservation decisions. Toward this goal, we evaluated the relative priority for conservation of 7 sites proposed for the first forest reserves in the Union of the Comoros, an area with high levels of endemism and rapidly changing land uses in the western Indian Ocean. Through the analysis of 30 indicator variables measured at forest sites and nearby villages, we assessed 3 prioritization criteria at each site: conservation value, threat to loss of biological diversity from human activity, and feasibility of reserve establishment. Our results indicated 2 sites, Yiméré and Hassera-Ndrengé, were priorities for conservation action. Our approach also informed the development of an implementation strategy and enabled an evaluation of previously unexplored relations among prioritization criteria. Our experience suggests that steps taken to ensure the closer involvement of practitioners, include a broader range of social data, encourage stakeholder participation, and consider the feasibility of conservation action can improve the relevance of assessments for conservation planning, strengthen the scientific basis for conservation decisions, and result in a more realistic evaluation of conservation alternatives.

Inequities in On-Time Childhood Vaccination: Evidence From Sub-Saharan Africa.

INTRODUCTION: Vaccination coverage has improved in the past decade, but inequalities persist: the poorest, least educated, and rural communities are left behind. Programming has focused on increasing coverage and reaching the hardest-to-reach children, but vaccination timeliness is equally important because delays leave children vulnerable to infections. This study examines the levels and inequities of on-time vaccination in the Sub-Saharan African region. METHODS: The most recent Demographic and Health Surveys or Multiple Indicator Clusters Surveys since 2000 from Sub-Saharan Africa were used to assess on-time vaccination and inequalities by household wealth, maternal education, and place of residence. Inequalities were quantified using slope index of inequality and concentration index. RESULTS: The analysis included 153,632 children aged 12-36 months from 40 Sub-Saharan Africa countries. Median on-time vaccination coverage was <50% in all the 4 subregions. Differences in on-time vaccination were observed by place of residence in the Southern (20.8 percentage points, 95% CI=0.8, 40.8), West (17.5 percentage points, 95% CI=5.1, 29.9), and Eastern (20.9 percentage points, 95% CI=6.5, 35.2) regions. Wealth-related inequities were observed in the Southern (22.6 percentage points, 95% CI=4.0, 41.2), Western (30.6 percentage points, 95% CI=19.1, 42.1), and Eastern (26.1 percentage points, 95% CI=8.2, 44.0) regions. Significant education-related differences in on-time vaccination were observed in the Western (20.7 percentage points, 95% CI=10.9, 30.5) and Eastern (21.2 percentage points, 95% CI=7.0, 35.4) regions. CONCLUSIONS: On-time vaccination coverage was low in all subregions and nearly all countries. Inequalities in on-time immunization by household wealth, place of residence, and education existed in most countries. Concrete strategies to improve levels of timeliness are needed. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Global Vaccination Equity, which is sponsored by the Global Institute for Vaccine Equity at the University of Michigan School of Public Health.

Adolescent sexual and reproductive health in sub-Saharan Africa: who is left behind?

Adolescent sexual and reproductive health (ASRH) continues to be a major public health challenge in sub-Saharan Africa where child marriage, adolescent childbearing, HIV transmission and low coverage of modern contraceptives are common in many countries. The evidence is still limited on inequalities in ASRH by gender, education, urban-rural residence and household wealth for many critical areas of sexual initiation, fertility, marriage, HIV, condom use and use of modern contraceptives for family planning. We conducted a review of published literature, a synthesis of national representative Demographic and Health Surveys data for 33 countries in sub-Saharan Africa, and analyses of recent trends of 10 countries with surveys in around 2004, 2010 and 2015. Our analysis demonstrates major inequalities and uneven progress in many key ASRH indicators within sub-Saharan Africa. Gender gaps are large with little evidence of change in gaps in age at sexual debut and first marriage, resulting in adolescent girls remaining particularly vulnerable to poor sexual health outcomes. There are also major and persistent inequalities in ASRH indicators by education, urban-rural residence and economic status of the household which need to be addressed to make progress towards the goal of equity as part of the sustainable development goals and universal health coverage. These persistent inequalities suggest the need for multisectoral approaches, which address the structural issues underlying poor ASRH, such as education, poverty, gender-based violence and lack of economic opportunity.

Assessing the long-term impact of conservation agriculture on wheat-based systems in Tunisia using APSIM simulations under a climate change context.

Several circulation models are forecasting climate changes in the Mediterranean region. Accordingly, it is expected that water scarcity in the region will be higher with drastic shifts of hydrological and erosive watershed responses. In Tunisia, wheat yields have been variable over the years and are lower than the potential yields. In response, the adoption of conservation agriculture (CA), introduced into Tunisia in 1999 to help adaptation to climate change, has resulted in a substantial reduction in agricultural productivity. CA areas increased from 52 ha in 1999 to 14,000 ha in 2015. Using a modelling approach, the present paper evaluates the potential of CA to adapt wheat-based-systems to climate change in Tunisia. The Agricultural Production Systems Simulator (APSIM) model was used to predict the effect of tillage (conventional tillage [CT] vs. zero-tillage [ZT] and soil residue retention [ZT-RR]) on wheat productivity and soil fertility. Two contrasting locations in Tunisia were studied; one semi-arid (Kef) and one sub-humid (Bizerte). Results showed that the sustainable production of durum wheat under climate change conditions in Tunisia is possible through the adoption of CA practices (ZT and ZT-RR) in both sub-humid and semi-arid areas. In fact, mulching (residue retention) is more effective than CT (under semi-arid and sub-humid conditions) in enhancing wheat yield (15%), water use efficiency (18% and 13%) and soil organic carbon accumulation (0.13 t ha-1 year-1 and 0.18 t ha-1 year-1). It is also more effective for soil resilience - preventing water erosion (1.7 t ha-1 year-1 and 4.6 t ha-1 year-1 of soil loss). The present study allowed identification of 260,000 ha as priority areas for CA adoption; this represent one-third of the total cereal area in Tunisia. Appropriate evaluation of the benefits of CA on sustainable agricultural intensification would provide more arguments for effectively supporting CA adoption in Tunisia.

Galectin-3 orchestrates the histology of mesentery and protects liver during lupus-like syndrome induced by pristane.

Galectin-3 (Gal-3) controls intercellular and cell-extracellular matrix interactions during immunological responses. In chronic inflammation, Gal-3 is associated with fibrotic events, regulates B cell differentiation and delays lupus progression. Gal-3 deficient mice (Lgals3-/-) have intense germinal center formation and atypical plasma cell generation correlated to high levels IgG, IgE, and IgA. Here, we used pristane (2,6,10,14-tetramethylpentadecane) to induce lupus-like syndrome in Lgals3-/- and Lgals3+/+ BALB/c mice. Mesentery and peritoneal cells were monitored because promptly react to pristane injected in the peritoneal cavity. For the first time, mesenteric tissues have been associated to the pathogenesis of experimental lupus-like syndrome. In Lgals3+/+ pristane-induced mice, mesentery was hallmarked by intense fibrogranulomatous reaction restricted to submesothelial regions and organized niches containing macrophages and B lymphocytes and plasma cells. In contrast, Lgals3-/- pristane-treated mice had diffuse mesenteric fibrosis affecting submesothelium and peripheral tissues, atypical M1/M2 macrophage polarization and significant DLL1+ cells expansion, suggesting possible involvement of Notch/Delta pathways in the disease. Early inflammatory reaction to pristane was characterized by significant disturbances on monocyte recruitment, macrophage differentiation and dendritic cell (DC) responses in the peritoneal cavity of pristane-induced Lgals3-/- mice. A correlative analysis showed that mesenteric damages in the absence of Gal-3 were directly associated with severe portal inflammation and hepatitis. In conclusion, it has suggested that Gal-3 orchestrates histological organization in the mesentery and prevents lupoid hepatitis in experimental lupus-like syndrome by controlling macrophage polarization, Notch signaling pathways and DC differentiation in mesenteric structures.

Kinetics of mobilization and differentiation of lymphohematopoietic cells during experimental murine schistosomiasis in galectin-3 -/- mice.

Galectin-3 (gal-3), a beta-galactoside-binding animal lectin, plays a role in cell-cell and cell-extracellular matrix interactions. Extracellular gal-3 modulates cell migration and adhesion in several physiological and pathological processes. Gal-3 is highly expressed in activated macrophages. Schistosoma mansoni eggs display a large amount of gal-3 ligands on their surface and elicit a well-characterized, macrophage-dependent, granulomatous, inflammatory reaction. Here, we have investigated the acute and chronic phases of S. mansoni infection in wild-type and gal-3(-/-) mice. In the absence of gal-3, chronic-phase granulomas were smaller in diameter, displaying thinner collagen fibers with a loose orientation. Schistosoma-infected gal-3(-/-) mice had remarkable changes in the monocyte/macrophage, eosinophil, and B lymphocyte subpopulations as compared with the infected wild-type mice. We observed a reduction of macrophage number, an increase in eosinophil absolute number, and a decrease in B lymphocyte subpopulation (B220(+/high) cells) in the periphery during the evolution of the disease in gal-3(-/-) mice. B lymphopenia was followed by an increase of plasma cell number in bone marrow, spleen, and mesenteric lymph nodes of the infected gal-3(-/-) mice. The plasma IgG and IgE levels also increased in these mice. Gal-3 plays a role in the organization, collagen distribution, and mobilization of inflammatory cells to chronic-phase granulomas, niches for extramedullary myelopoiesis, besides interfering with monocyte-to-macrophage and B cell-to-plasma cell differentiation.

Probing the role of the covalent linkage of ferrocene into a chloroquine template.

A new therapeutic approach to malaria led to the discovery of ferroquine (FQ, SR97276). To assess the importance of the linkage of the ferrocenyl group to a 4-aminoquinoline scaffold, two series of 4-aminoquinolines, structurally related to FQ, were synthesized. Evaluation of antimalarial activity, physicochemical parameters, and the beta-hematin inhibition property indicate that the ferrocene moiety has to be covalently flanked by a 4-aminoquinoline and an alkylamine. Current data reinforced our choice of FQ as a drug candidate.

Focal liver hyperplasia in a patient with Alagille syndrome: Diagnostic difficulties. A case report.

INTRODUCTION: Alagille syndrome is a multisystem autosomal disorder. The main clinical features are chronic cholestasis due to paucity of intrahepatic bile ducts, which can progress to cirrhosis and liver failure. PRESENTATION OF CASE: A 15 year-old girl with Alagille syndrome was referred for liver transplantation. She developed severe cirrhosis with refractory ascites. In the pre-transplant evaluation, imaging studies disclosed liver atrophy with a high density pseudotumor in the segment 4, raising the possibility of a hepatocellular carcinoma. However, behavior of the lesion was highly suggestive of focal compensatory hyperplasia surrounded by an atrophic liver. The patient was registered on the waiting list. DISCUSSION: Hepatic lesions have been described in Alagille syndrome in isolated case reports, and most of these have been reported to be hepatocellular carcinoma. However, they can be related to an area of focal compensatory hyperplasia in severe cirrhosis. These findings may also explain why progression of liver disease occurs only in 15% of patients. CONCLUSION: The presence of a large hepatic nodule Alagille syndrome can be benign in these patients also predisposed to hepatocellular carcinoma. Therefore, cautious evaluation with magnetic resonance imaging study before liver transplantation is mandatory.

IgE expression on the surface of B1 and B2 lymphocytes in experimental murine schistosomiasis.

In a previous study we monitored the distribution and phenotype expression of B1 cells during the evolution of experimental murine schistosomiasis mansoni and we proposed that the B1 cells were heterogeneous: a fraction which originated in the spleen and followed the migratory pathway to mesenteric ganglia, while the other was the resident peritoneal B1-cell pool. In the present study, we have addressed the question of whether these two B1-lymphocyte populations are involved in the production of the late Ig isotype IgE, which is present in high levels in schistosomal infection. Lymphocyte expression of surface markers and immunoglobulins were monitored by immunofluorescence flow cytometry. Both in the spleen and mesenteric ganglia, the B1 and B2 cells were induced to switch from IgM to IgE in the early Th2-dominated phase of the disease, with an increase of IgE in its later phases. Conversely, peritoneal B1-IgM+ switched to the remaining IgE+ present in high numbers in the peritoneal cavity throughout the disease. We correlated the efficient induction of the expression of late Ig isotypes by B1 cells with high levels of inflammatory cytokines due to the intense host response to the presence of worms and their eggs in the abdominal cavity. In conclusion, B1 cells have a different switch behavior from IgM to IgE indicating that these cell sub-populations depend on the microenvironment.