The impact of highly active antiretroviral therapy on the burden of bacterial lower respiratory tract infections in children

Background. Respiratory diseases are common and associated with significant morbidity and mortality in children.Objective. To evaluate the prevalence and outcome of bacterial lower respiratory tract infections (LRTIs) in HIV-infected and uninfected children at a primary level hospital.Methods. A cross-sectional descriptive study of children aged 6 months - 18 years was conducted. Recruitment included HIV-positive children who had been on highly active antiretroviral therapy (HAART) for at least 6 months. A comparator group of HIV-negative children admitted with bacterial pneumonia was included. Laboratory data collected included CD4+ T-cell counts, HIV viral load and C-reactive protein (CRP). Data collected in both groups included demographic data, immunisation status, zinc supplementation, previous LRTIs, environmental exposures and treatment.Results. Fifty-nine HIV-infected and 20 uninfected children were enrolled. The HIV-positive children were older, with a mean age of 107.2 (standard deviation 50.0) months v. 12.0 (5.8) months (p<0.005). The HIV-infected group had a mean CD4 percentage of 31.5%, and had had an average of 3.9 visits for bacterial LRTIs. All were treated with amoxicillin with no complications. In the HIV-uninfected group, cough and rapid breathing were the most common presenting symptoms, and the mean CRP level was 463.0 mg/L. The mean hospital stay was 4 days.Conclusion. HAART is effective in reducing the burden of LRTIs in HIV-positive children, even when the diagnosis is delayed. Cough and fast breathing are still the most reliable presenting symptoms of pneumonia. The majority of children still respond to amoxicillin as first-line therapy, with low complication rates

Benchmarking of human Y-chromosomal haplogroup classifiers with whole-genome and whole-exome sequence data

In anthropological, medical, and forensic studies, the nonrecombinant region of the human Y chromosome (NRY) enables accurate reconstruction of pedigree relationships and retrieval of ancestral information. Using high-throughput sequencing (HTS) data, we present a benchmarking analysis of command-line tools for NRY haplogroup classification. The evaluation was performed using paired Illumina data from whole-genome sequencing (WGS) and whole-exome sequencing (WES) experiments from 50 unrelated donors. Additionally, as a validation, we also used paired WGS/WES datasets of 54 individuals from the 1000 Genomes Project. Finally, we evaluated the tools on data from third-generation HTS obtained from a subset of donors and one reference sample. Our results show that WES, despite typically offering less genealogical resolution than WGS, is an effective method for determining the NRY haplogroup. Y-LineageTracker and Yleaf showed the highest accuracy for WGS data, classifying precisely 98% and 96% of the samples, respectively. Yleaf outperforms all benchmarked tools in the WES data, classifying approximately 90% of the samples. Yleaf, Y-LineageTracker, and pathPhynder can correctly classify most samples (88%) sequenced with third-generation HTS. As a result, Yleaf provides the best performance for applications that use WGS and WES. Overall, our study offers researchers with a guide that allows them to select the most appropriate tool to analyze the NRY region using both second- and third-generation HTS data

Chemical analysis of Greek pollen - Antioxidant, antimicrobial and proteasome activation properties

<p>Abstract</p> <p>Background</p> <p>Pollen is a bee-product known for its medical properties from ancient times. In our days is increasingly used as health food supplement and especially as a tonic primarily with appeal to the elderly to ameliorate the effects of ageing. In order to evaluate the chemical composition and the biological activity of Greek pollen which has never been studied before, one sample with identified botanical origin from sixteen different common plant taxa of Greece has been evaluated.</p> <p>Results</p> <p>Three different extracts of the studied sample of Greek pollen, have been tested, in whether could induce proteasome activities in human fibroblasts. The water extract was found to induce a highly proteasome activity, showing interesting antioxidant properties. Due to this activity the aqueous extract was further subjected to chemical analysis and seven flavonoids have been isolated and identified by modern spectral means. From the methanolic extract, sugars, lipid acids, phenolic acids and their esters have been also identified, which mainly participate to the biosynthetic pathway of pollen phenolics. The total phenolics were estimated with the Folin-Ciocalteau reagent and the total antioxidant activity was determined by the DPPH method while the extracts and the isolated compounds were also tested for their antimicrobial activity by the dilution technique.</p> <p>Conclusions</p> <p>The Greek pollen is rich in flavonoids and phenolic acids which indicate the observed free radical scavenging activity, the effects of pollen on human fibroblasts and the interesting antimicrobial profile.</p

Restored in vivo-like membrane lipidomics positively influence in vitro features of cultured mesenchymal stromal/stem cells derived from human placenta

BACKGROUND: The study of lipid metabolism in stem cell physiology has recently raised great interest. The role of lipids goes beyond the mere structural involvement in assembling extra- and intra-cellular compartments. Nevertheless, we are still far from understanding the impact of membrane lipidomics in stemness maintenance and differentiation patterns. In the last years, it has been reported how in vitro cell culturing can modify membrane lipidomics. The aim of the present work was to study the membrane fatty acid profile of mesenchymal stromal cells (MSCs) derived from human fetal membranes (hFM-MSCs) and to correlate this to specific biological properties by using chemically defined tailored lipid supplements (Refeed®). METHODS: Freshly isolated hFM-MSCs were characterized for their membrane fatty acid composition. hFM-MSCs were cultivated in vitro following a classical protocol and their membrane fatty acid profile at different passages was compared to the profile in vivo. A tailored Refeed® lipid supplement was developed with the aim of reducing the differences created by the in vitro cultivation and was tested on cultured hFM-MSCs. Cell morphology, viability, proliferation, angiogenic differentiation, and immunomodulatory properties after in vitro exposure to the tailored Refeed® lipid supplement were investigated. RESULTS: A significant modification of hFM-MSC membrane fatty acid composition occurred during in vitro culture. Using a tailored lipid supplement, the fatty acid composition of cultured cells remained more similar to their in vivo counterparts, being characterized by a higher polyunsaturated and omega-6 fatty acid content. These changes in membrane composition had no effect on cell morphology and viability, but were linked with increased cell proliferation rate, angiogenic differentiation, and immunomodulatory properties. In particular, Refeed®-supplemented hFM-MSCs showed greater ability to express fully functional cell membrane molecules. CONCLUSIONS: Culturing hFM-MSCs alters their fatty acid composition. A tailored lipid supplement is able to improve in vitro hFM-MSC functional properties by recreating a membrane environment more similar to the physiological counterpart. This approach should be considered in cell therapy applications in order to maintain a higher cell quality during in vitro passaging and to influence the outcome of cell-based therapeutic approaches when cells are administered to patients

Prediction of social structure and genetic relatedness in colonies of the facultative polygynous stingless bee Melipona bicolor (Hymenoptera, Apidae)

Stingless bee colonies typically consist of one single-mated mother queen and her worker offspring. The stingless bee Melipona bicolor (Hymenoptera: Apidae) shows facultative polygyny, which makes this species particularly suitable for testing theoretical expectations concerning social behavior. In this study, we investigated the social structure and genetic relatedness among workers from eight natural and six manipulated colonies of M. bicolor over a period of one year. The populations of M. bicolor contained monogynous and polygynous colonies. The estimated genetic relatedness among workers from monogynous and polygynous colonies was 0.75 ± 0.12 and 0.53 ± 0.16 (mean ± SEM), respectively. Although the parental genotypes had significant effects on genetic relatedness in monogynous and polygynous colonies, polygyny markedly decreased the relatedness among nestmate workers. Our findings also demonstrate that polygyny in M. bicolor may arise from the adoption of related or unrelated queens

Cells of the human intestinal tract mapped across space and time

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease