Xylo-oligosaccharide-based prebiotics upregulate the proteins of the Sus-like system in caecal Bacteroidetes of the chicken: evidence of stimbiotic mechanism.

The present study was conducted to investigate the stimbiotic mechanism of xylo-oligosaccharide (XOS) in degrading the complex polysaccharides by the caecal bacteria of the chicken, by applying a proteomic approach. A total of 800 as-hatched Ross 308 broiler chicks were equally divided into 4 experimental pens (200 chicks per pen) at a commercial poultry barn, allocating 2 pens per treatment. Birds were fed ad libitum with 2 dietary treatments; CON (without XOS) and XOS (with 0.1g XOS/kg diet) from d 0 to 35. From each pen, 60 Individual birds were weighed weekly whereas caecal content was obtained from 5 birds cervically dislocated on d 35. The caecal bacteria were lysed and their proteins were quantified using label-free quantitative proteomic mass spectrometry. The results showed that XOS significantly increased (P < 0.05) bird weight on d 7, 14, 21, and 28, and body weight gain on d 7, 14, 21, and 35 compared to CON. However, no difference (P > 0.05) in body weight gain was observed from d 0 to 35 between CON and XOS. The proteomic analysis of caecal bacteria revealed that 29 proteins were expressed differently between the CON and the XOS group. Out of 29, 20 proteins were significantly increased in the XOS group compared to CON and 9 of those proteins belonged to the starch-utilizing system (Sus)-like system of the gram-negative Bacteroidetes. Bacteroides thetaiotaomicron (Bt) is a significant constituent of the human gut microbiota, known for its remarkable ability to hydrolyze most glycosidic bonds of polysaccharides. This microorganism possesses a 5-protein complex in its outer membrane, named the starch utilization system (Sus), responsible for adhering to, breaking down, and transporting starch into the cell. Sus serves as an exemplar system for numerous polysaccharide utilization loci that target glycans found in Bt and other members of the Bacteroidetes phylum. The proteins of the Sus-like system are involved in the degradation of complex polysaccharides and transportation of the oligosaccharides into the periplasm of the caecal bacteria where they are further broken down into smaller units. These smaller units are then transported into the cytoplasm of the cell where they are utilized in metabolic pathways leading to potential generation of short-chain fatty acids, thus improving the nutritive value of residual feed. In conclusion, XOS supplementation upregulates the expression of the proteins of the Sus-like system indicating its role as a stimbiotic.

Parasitoses intestinais no nordeste entre 2012 e 2021: uma revisão integrativa de literatura / Intestinal parasitosis in the northeast between 2012 and 2021: an integrative literature review / Parasitosis intestinales en el noreste entre 2012 y 2021: una revisión bibliográfica integradora

As parasitoses intestinais ainda constituem um problema de saúde pública no Brasil, especialmente nas regiões onde o saneamento básico e condições socioeconômicas são frágeis, como na região Nordeste. São um conjunto de doenças causadas por parasitas helmínticos ou protozoários, que acometem o intestino humano, causando sintomas, como diarreia, dor abdominal, astenia, náuseas, vômitos, entre outros. Seu diagnóstico é feito pelo parasitológico de fezes e o tratamento é baseado no uso de anti-protozoários ou anti-helmínticos. Objetivo: analisar os principais aspectos das parasitoses intestinais presentes no Nordeste, identificando aquelas mais prevalentes e as populações de maiores riscos. Metodologia: o estudo foi do tipo descritivo, utilizando-se uma revisão integrativa de literatura do período de 2012 a 2021, nas bases de dados eletrônicas Scielo, BVS e Google Acadêmico. Para o processo de busca e análise dos artigos, foi utilizado o diagrama flow. Todos os dados da pesquisa foram analisados no Microsoft Word e, posteriormente os resultados foram transformados em quadros e tabelas para melhor organização e interpretação das informações colhidas. Resultados: observou-se, a partir da análise dos 10 artigos, uma variação de 26,00% a 92,85% na taxa de infecções por parasitas intestinais na região Nordeste, em diversas populações, desde pré-escolares, escolares e adultos. Os fatores de risco que estiveram associados ao desenvolvimento, foram: falta de higiene pessoal e dos alimentos, ausência ou precariedade dos serviços de saneamento básico, baixa escolaridade e renda dos pais, qualidade da água de beber e práticas de andar descalço por parte das crianças. Considerações finais: Os resultados apontam para a necessidade de medidas preventivas e tratamento das enteroparasitoses, como mudanças de hábitos de higiene e melhorias nas condições de vida, como o acesso à água tratada e saneamento básico adequado. Além disso, é importante que surjam mais estudos epidemiológicos para subsidiar medidas de controle e prevenção adequadas e eficazes.

Intestinal parasites are still a public health problem in Brazil, especially in regions where basic sanitation and socioeconomic conditions are fragile, as in the Northeast region. They are a set of diseases caused by helminthic or protozoan parasites, which affect the human intestine, causing symptoms such as diarrhea, abdominal pain, asthenia, nausea, vomiting, among others. Its diagnosis is made by fecal parasitology and treatment is based on the use of anti-protozoal or anthelmintic agents. Objective: to analyze the main aspects of intestinal parasites present in the Northeast, identifying the most prevalent ones and the populations at greatest risk. Methodology: the study was descriptive, using an integrative literature review from 2012 to 2021, in the electronic databases Scielo, BVS and Google Scholar. For the process of searching and analyzing the articles, the flow diagram was used. All survey data were analyzed in Microsoft Excel and, later, the results were transformed into graphs and tables for better interpretation of the collected information. RESULTS: from the analysis of the 10 articles, a variation from 26.00% to 92.85% was observed in the rate of infections by intestinal parasites in the Northeast region, in different populations, from preschoolers, schoolchildren and adults. The risk factors that were associated with development were: lack of personal hygiene and food, absence or precariousness of basic sanitation services, low parental education and income, quality of drinking water and practices of walking barefoot by children. Final Considerations: The results point to the need for preventive measures and treatment of intestinal parasites, such as changes in hygiene habits and improvements in living conditions, such as access to treated water and adequate basic sanitation. In addition, it is important that more epidemiological studies appear to support appropriate and effective control and prevention measures.

Las parasitosis intestinales siguen siendo un problema de salud pública en Brasil, especialmente en regiones donde el saneamiento básico y las condiciones socioeconómicas son frágiles, como en la región Nordeste. Son un conjunto de enfermedades causadas por parásitos helmínticos o protozoarios, que afectan el intestino humano, causando síntomas como diarrea, dolor abdominal, astenia, náuseas, vómitos, entre otros. Su diagnóstico se realiza mediante parasitología fecal y el tratamiento se basa en el uso de agentes antiprotozoarios o antihelmínticos. Objetivo: analizar los principales aspectos de los parásitos intestinales presentes en el Nordeste, identificando los más prevalentes y las poblaciones de mayor riesgo. Metodología: el estudio fue descriptivo, utilizando una revisión bibliográfica integradora de 2012 a 2021, en las bases de datos electrónicas Scielo, BVS y Google Scholar. Para el proceso de búsqueda y análisis de los artículos, se utilizó el diagrama de flujo. Todos los datos de la encuesta fueron analizados en Microsoft Excel y, posteriormente, los resultados fueron transformados en gráficos y tablas para una mejor interpretación de la información recogida. Resultados: a partir del análisis de los 10 artículos, se observó una variación de 26,00% a 92,85% en la tasa de infecciones por parásitos intestinales en la región Nordeste, en diferentes poblaciones, desde preescolares, escolares y adultos. Los factores de riesgo que se asociaron al desarrollo fueron: falta de higiene personal y alimentaria, ausencia o precariedad de servicios de saneamiento básico, baja escolaridad e ingresos de los padres, calidad del agua de consumo y prácticas de caminar descalzo por parte de los niños. Consideraciones Finales: Los resultados apuntan a la necesidad de medidas preventivas y de tratamiento de los parásitos intestinales, como cambios en los hábitos de higiene y mejoras en las condiciones de vida, como el acceso a agua tratada y a un saneamiento básico adecuado. Además, es importante que aparezcan más estudios epidemiológicos que respalden medidas de control y prevención adecuadas y eficaces.

BIM upregulation and ROS-dependent necroptosis mediate the antitumor effects of the HDACi Givinostat and Sorafenib in Hodgkin lymphoma cell line xenografts.

Relapsed/refractory Hodgkin's lymphoma (HL) is an unmet medical need requiring new therapeutic options. Interactions between the histone deacetylase inhibitor Givinostat and the RAF/MEK/ERK inhibitor Sorafenib were examined in HDLM-2 and L-540 HL cell lines. Exposure to Givinostat/Sorafenib induced a synergistic inhibition of cell growth (range, 70-80%) and a marked increase in cell death (up to 96%) due to increased H3 and H4 acetylation and strong mitochondrial injury. Gene expression profiling indicated that the synergistic effects of Givinostat/Sorafenib treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to Givinostat/Sorafenib resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented Givinostat/Sorafenib-induced ROS production, mitochondrial injury, activation of BH3-only protein BIM and cell death. Knockdown experiments identified BIM as a key signaling molecule that mediates Givinostat/Sorafenib-induced oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 50% reduction in tumor burden (P<0.0001), a 5- to 15-fold increase in BIM expression (P < 0.0001) and a fourfold increase in tumor necrosis in Givinostat/Sorafenib-treated animals compared with mice that received single agents. These results provide a rationale for exploring Givinostat/Sorafenib combination in relapsed/refractory HL.

Productive HIV-1 infection of human cervical tissue ex vivo is associated with the secretory phase of the menstrual cycle.

Cervical tissue explants (CTEs) from 22 HIV-1 seronegative women were exposed to R5 HIV-1 ex vivo. Eight CTEs were productively infected in terms of HIV-1 p24Gag release in culture supernatants, whereas 14 were not. Nonetheless, both accumulation of HIV-1gag DNA and of p24Gag(+) CD4(+) T cells and macrophages occurred in both productive and, at lower levels, in nonproductive CTEs. Nonproductive CTEs differed from productive CTEs for higher secretion of C-C motif chemokine ligand 3 (CCL3) and CCL5. A post-hoc analysis revealed that all productive CTEs were established from women in their secretory phase of the menstrual cycle, whereas nonproductive CTEs were derived from women either in their secretory (28%) or proliferative (36%) menstrual cycle phases or with an atrophic endometrium (36%). Thus, our results support the epidemiological observation that sexual HIV-1 transmission from males to women as well as from women to men is more efficient during their secretory phase of the menstrual cycle.

HIV-1 sexual transmission: early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model.

Infection and dissemination of human immunodeficiency virus (HIV)-1 through the female body after vaginal intercourse depends on the activation/differentiation status of mucosal CD4 T cells. In this study, we investigated this status and the susceptibility to HIV-1 infection of human cervico-vaginal tissue ex vivo. We found that virtually all T cells are of the effector memory phenotype with broad CC chemokine receptor 5 (CCR5) expression. As it does in vivo, human cervico-vaginal tissue ex vivo preferentially supports the productive infection of R5 HIV-1 rather than that of X4 HIV-1 in spite of the broad expression of CXC chemokine receptor 4 (CXCR4). X4 HIV-1 replicated only in the few tissues that were enriched in CD27(+)CD28(+) effector memory CD4 T cells. Productive infection of R5 HIV-1 occurred preferentially in activated CD38(+)CD4 T cells and was followed by a similar activation of HIV-1-uninfected (bystander) CD4 T cells that may amplify viral infection. These results provide new insights into the dependence of HIV-1 infection and dissemination on the activation/differentiation of cervico-vaginal lymphocytes.

Middle East and North Africa consensus on osteoporosis.

With the increasing life expectancy, osteoporosis is becoming a major worldwide health problem. The magnitude of the disease may become larger in developing countries, more particularly in the Middle East region where the prevalence of low bone mass is higher than in western countries. Although several local organizations and countries have developed guidelines for osteoporosis, no previous regional guidelines have been developed encompassing all Middle-Eastern and North African countries. The present document reviews all the regional published data on bone mineral density, risk factors, fracture prevalence and vitamin D status. It also gives simple recommendations applicable to all these countries. This document was endorsed by leading members of all the different regional countries including, Iran, Egypt, Tunisia, Jordan, Palestine, Syria, Iraq, Libya, Oman, Kuwait, Saudi Arabia and Bahrain.

Phylogeny and evolution of mating-type genes from Pyrenophora teres, the causal agent of barley "net blotch" disease.

The main aim of this study was to test the patterns of sequence divergence and haplotype structure at the MAT locus of Pyrenophora teres, the causal agent of barley 'net blotch' disease. P. teres is a heterothallic ascomycete that co-occurs in two symptomatological forms, the net form (NF) and the spot form (SF). The mating-type genes MAT1-1-1 and MAT1-2-1 were sequenced from 22 NF isolates (12 MAT1-1-1 and 10 MAT1-2-1 sequences) and 17 SF isolates (10 MAT1-1-1 and seven MAT1-2-1 sequences) collected from Sardinian barley landrace populations and worldwide. On the basis of a parsimony network analysis, the two forms of P. teres are phylogenetically separated. More than 85% of the total nucleotide variation was found between formae speciales. The two forms do not share any polymorphisms. Six diagnostic nucleotide polymorphisms were found in the MAT1-1-1 intron (1) and in the MAT1-1-1 (3) and MAT1-2-1 (2) exons. Three diagnostic non-synonymous mutations were found, one in MAT1-1-1 and two in MAT1-2-1. For comparison with P. teres sequence data, the mating-type genes from Pyrenophora graminea were also isolated and sequenced. Divergence between P. graminea and P. teres is of a similar magnitude to that between NF and SF of P. teres. The MAT genes of P. graminea were closer to those of SF than to NF, with the MAT1-2-1 SF peptide not different from the MAT1-2-1 peptide of P. graminea. Overall, these data suggest long genetic isolation between the two forms of P. teres and that hybridization is rare or absent under field conditions, with each form having some particular niche specialization. This indicates that research on resistance to P. teres should consider the two forms separately, as different species.

Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues.

Relatively few attempts have been made in the past to isolate and expand lymphatic endothelial cells (LECs). Recently this task has become feasible thanks to the identification of new lymphatic markers such as Podoplanin, Lyve-1, Prox-1 and D2-40. Using a two-step purification method based on the sorting of endothelial cells with Ulex Europaeus Agglutinin 1-coated beads followed by purification with monoclonal antibody D2-40, we were able to purify and in vitro expand human derived LECs from tissues such as lymph node, spleen, thymus, palatine tonsil and iliac lymphatic vessels. The isolated LECs were expanded on collagen type 1 and fibronectin coated flasks for up to 8-10 passages and then analyzed for phenotypic and functional properties. LECs were able to form a capillary like network, when seeded on Cultrex BME, indicating their capability to form lymphatic vessels in vitro. Comparative studies were performed, and we found that specific lymphatic and vascular markers were differentially expressed by LECs prepared from different sources, clearly demonstrating the phenotypic heterogeneity of LECs from different organs and different segments of the lymphatic vasculature. We here propose a new technique to make available ready sources of abundant well-characterized human LECs to examine normal profiles and behavior to compare with abnormal conditions.

Amplified fragment length polymorphism for genetic diversity assessment in globe artichoke.

Globe artichoke ( Cynara cardunculus L. var. scolymus L.) is a diploid (2 n=2 x=34), predominantly cross-pollinated plant native to the Mediterranean basin, and Italy contains the richest primary cultivated 'gene pool'. Commercial production is mainly based on perennial cultivation of vegetatively propagated clones that are highly heterozygous and segregate widely when progeny-tested. Analysis of the artichoke genome by means of molecular markers has been limited to a few studies; here we report on the genetic relatedness among 118 artichoke accessions, including clones belonging to the same varietal type, two accessions of cultivated cardoon ( C. cardunculus L. var. altilis DC.) and four accessions of wild cardoon [ C. cardunculus L. var. sylvestris (Lamk) Fiori] as measured by amplified fragment length polymorphism (AFLP). Eight primer combinations yielded a total of 667 bands, of which 519 were polymorphic. Genetic similarities among accessions were calculated according to Jaccard's Similarity Index and used to construct a dendrogram based on the unweighted pair group method using arithmetic averages. Our results demonstrate that AFLP markers can be useful in evaluating Cynara cardunculus genetic diversity and in classifying accessions to phylogenetic groups based on their genetic similarity values. Genetic variation among artichoke clones belonging to the same varietal type was in some cases higher than that found among accessions differently named and coming from different areas. The lowest Jaccard's Similarity Index found within a varietal type can be considered as a threshold for the identification of accessions which share an analogous genetic background. This will enable the selection of representatives in order to develop and manage a germplasm 'core collection' as well as the identification of suitable material for future artichoke breeding efforts.

Population genetic structure of Pyrenophora teres Drechs. the causal agent of net blotch in Sardinian landraces of barley (Hordeum vulgare L.).

Monoconidial cultures of Pyrenophora teres, the causal agent of barley net blotch, were isolated from leaves collected from six populations of the barley landrace "S'orgiu sardu" growing in five agro-ecological areas of Sardinia, Italy, and genotyped using AFLPs. The 150 isolates were from lesions of either the "net form" (P. teres f. sp. teres) or the "spot form" (P. teres f. sp. maculata) of the disease. Of 121 AFLP markers, 42%, were polymorphic. Cluster analysis resolved the isolates into two strongly divergent groups (F(ST) = 0.79), corresponding to the net (45% of the isolates) and the spot (55% of the isolates) forms (designated the NFR and SFR groups, respectively). The absence of intermediate genotypes and the low number of shared markers between the two groups indicated that hybridization between the two formae is rare or absent under the field condition of Sardinia. Five of the barley populations hosted both forms but in different proportions. The SFR populations were similar in overall polymorphism to the NFR populations. However, compared to the SFR form, the NFR occurred in all fields sampled and showed a higher population divergence (F(ST) = 0.43 versus F(ST) = 0.09 with all isolates; F(ST) = 0.37 versus F(ST) = 0.06 with clone corrected samples) probably due to a lower migration rate. AFLP fingerprints resolved 117 distinct genotypes among the 150 isolates sampled (78%), 87% in SFR and 68% in NFR isolates. Although the absolute numbers may be a function of the number of AFLP markers assayed, the relative difference suggests that clonality is more prevalent among the NFR isolates (with 11 of 46 haplotypes observed more than once), compared with SFR isolates (7 of 71 haplotypes). Both digenic and multilocus linkage disequilibrium analyses suggested that sexual reproduction occurs at significant levels within the NFR and SFR populations, and that the relative contribution of sexual and asexual reproduction varies among different environments.

Phase II study of carboplatin as a single drug for relapsed Wilms' tumor: experience of the Brazilian Wilms' Tumor Study Group.

A total of 15 patients with relapsed Wilms' tumor were treated with carboplatin as a single agent. There were six females and nine males, aged between 2 and 9 years (median:5). The treatment consisted of carboplatin given I.V. as a single agent at a dose of 550 mg/m2 over 1 hour every 3 weeks. There were four (26%) complete responses, four (26%) partial responses, one stable disease, and six with progressive disease. In all patients a total of 56 courses were given and the toxicities found were leukopenia and thrombocytopenia. The overall response rate was encouraging and the toxicity was acceptable and reversible.

The neurophysiological features of benign partial epilepsy with rolandic spikes.

SEPs were performed in 44 children with benign partial epilepsy with rolandic spikes (BERS). High-amplitude mid- or long-latency SEPs were recorded in 17 patients (38%). These giant responses showed normal latency values but reached an exceedingly high amplitude (up to 200 microV). They showed the same reactivity characteristic of normal long-latency SEPs. In a 3-year follow-up study, the giant responses were shown to disappear in some patients and to shift from side to side in others. Our study demonstrates that giant SEPs are relatively common in BERS and give further support to the concept of a functional nature of rolandic foci.