Bifidobacterial Dominance of the Gut in Early Life and Acquisition of Antimicrobial Resistance.

Bifidobacterium species are important commensals capable of dominating the infant gut microbiome, in part by producing acids that suppress growth of other taxa. Bifidobacterium species are less prone to possessing antimicrobial resistance (AMR) genes (ARGs) than other taxa that may colonize infants. Given that AMR is a growing public health crisis and ARGs are present in the gut microbiome of humans from early life, this study examines the correlation between a Bifidobacterium-dominated infant gut microbiome and AMR levels, measured by a culture-independent metagenomic approach both in early life and as infants become toddlers. In general, Bifidobacterium dominance is associated with a significant reduction in AMR in a Bangladeshi cohort, both in the number of acquired AMR genes present and in the abundance of AMR genes. However, by year 2, Bangladeshi infants had no significant differences in AMR related to their early-life Bifidobacterium levels. A generalized linear model including all infants in a previously published Swedish cohort found a significant negative association between log-transformed total AMR and Bifidobacterium levels, thus confirming the relationship between Bifidobacterium levels and AMR. In both cohorts, there was no change between early-life and later-life AMR abundance in high-Bifidobacterium infants but a significant reduction in AMR abundance in low-Bifidobacterium infants. These results support the hypothesis that early Bifidobacterium dominance of the infant gut microbiome may help reduce colonization by taxa containing ARGs.IMPORTANCE Infants are vulnerable to an array of infectious diseases, and as the gut microbiome may serve as a reservoir of AMR for pathogens, reducing the levels of AMR in infants is important to infant health. This study demonstrates that high levels of Bifidobacterium are associated with reduced levels of AMR in early life and suggests that probiotic interventions to increase infant Bifidobacterium levels have the potential to reduce AMR in infants. However, this effect is not sustained at year 2 of age in Bangladeshi infants, underscoring the need for more detailed studies of the biogeography and timing of infant AMR acquisition

Bifidobacterium longum subsp. infantis in experimental necrotizing enterocolitis: alterations in inflammation, innate immune response, and the microbiota.

BackgroundProbiotics decrease the risk of necrotizing enterocolitis (NEC). We sought to determine the impact of Bifidobacterium longum subsp. infantis (B. infantis) in the established rat model of NEC.MethodsRat pups delivered 1 d prior to term gestation were assigned to one of three groups: dam fed (DF), formula fed (FF), or fed with formula supplemented with 5 × 10(6) CFU B. infantis per day (FF+Binf). Experimental pups were exposed to hypoxia and cold stress. Ileal tissue was examined for pathology and expression of inflammatory mediators, antimicrobial peptides, and goblet-cell products. Ceca were assessed for bacterial composition by analysis of the 16S rRNA sequence.ResultsAdministration of B. infantis significantly reduced the incidence of NEC, decreased expression of Il6, Cxcl1, Tnfa, Il23, and iNOS, and decreased expression of the antimicrobial peptides Reg3b and Reg3g. There was significant microbial heterogeneity both within groups and between experiments. The cecal microbiota was not significantly different between the FF and FF+Binf groups. Bifidobacteria were not detected in the cecum in significant numbers.ConclusionIn the rat model, the inflammation associated with NEC was attenuated by administration of probiotic B. infantis. Dysbiosis was highly variable, precluding determination of the precise role of the microbiota in experimental NEC

Two-tier charging in Maputo Central Hospital: Costs, revenues and effects on equity of access to hospital services

<p>Abstract</p> <p>Background</p> <p>Special services within public hospitals are becoming increasingly common in low and middle income countries with the stated objective of providing higher comfort services to affluent customers and generating resources for under funded hospitals. In the present study expenditures, outputs and costs are analysed for the Maputo Central Hospital and its Special Clinic with the objective of identifying net resource flows between a system operating two-tier charging, and, ultimately, understanding whether public hospitals can somehow benefit from running Special Clinic operations.</p> <p>Methods</p> <p>A combination of step-down and bottom-up costing strategies were used to calculate recurrent as well as capital expenses, apportion them to identified cost centres and link costs to selected output measures.</p> <p>Results</p> <p>The results show that cost differences between main hospital and clinic are marked and significant, with the Special Clinic's cost per patient and cost per outpatient visit respectively over four times and over thirteen times their equivalent in the main hospital.</p> <p>Discussion</p> <p>While the main hospital cost structure appeared in line with those from similar studies, salary expenditures were found to drive costs in the Special Clinic (73% of total), where capital and drug costs were surprisingly low (2 and 4% respectively). We attributed low capital and drug costs to underestimation by our study owing to difficulties in attributing the use of shared resources and to the Special Clinic's outsourcing policy. The large staff expenditure would be explained by higher physician time commitment, economic rents and subsidies to hospital staff. On the whole it was observed that: (a) the flow of capital and human resources was not fully captured by the financial systems in place and stayed largely unaccounted for; (b) because of the little consideration given to capital costs, the main hospital is more likely to be subsidising its Special Clinic operations, rather than the other way around.</p> <p>Conclusion</p> <p>We conclude that the observed lack of transparency may create scope for an inequitable cross subsidy of private customers by public resources.</p

“What if There's Something Wrong with Her?”‐How Biomedical Technologies Contribute to Epistemic Injustice in Healthcare

While there is a steadily growing literature on epistemic injustice in healthcare, there are few discussions of the role that biomedical technologies play in harming patients in their capacity as knowers. Through an analysis of newborn and pediatric genetic and genomic sequencing technologies (GSTs), I argue that biomedical technologies can lead to epistemic injustice through two primary pathways: epistemic capture and value partitioning. I close by discussing the larger ethical and political context of critical analyses of GSTs and their broader implications for just and equitable healthcare delivery

High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype

The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior

The analysis of European lacquer : optimization of thermochemolysis temperature of natural resins

In order to optimize chromatographic analysis of European lacquer, thermochemolysis temperature was evaluated for the analysis of natural resins. Five main ingredients of lacquer were studied: sandarac, mastic, colophony, Manila copal and Congo copal. For each, five temperature programs were tested: four fixed temperatures (350, 480, 550, 650 degrees C) and one ultrafast thermal desorption (UFD), in which the temperature rises from 350 to 660 degrees C in 1 min. In total, the integrated signals of 27 molecules, partially characterizing the five resins, were monitored to compare the different methods. A compromise between detection of compounds released at low temperatures and compounds formed at high temperatures was searched. 650 degrees C is too high for both groups, 350 degrees C is best for the first, and 550 degrees C for the second. Fixed temperatures of 480 degrees C or UFD proved to be a consensus in order to detect most marker molecules. UFD was slightly better for the molecules released at low temperatures, while 480 degrees C showed best compounds formed at high temperatures

PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival

Background: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced by growth factor receptor hyperactivation in many cell types. We aimed to identify molecules that critically regulate IGF-1-induced anchorage-independent survival. Methods and Results: We conducted a high-throughput siRNA screen and identified PTK6 as a critical component of IGF-1 receptor (IGF-1R)-induced anchorage-independent survival of mammary epithelial cells. PTK6 downregulation induces apoptosis of breast and ovarian cancer cells deprived of matrix attachment, whereas its overexpression enhances survival. Reverse-phase protein arrays and subsequent analyses revealed that PTK6 forms a complex with IGF-1R and the adaptor protein IRS-1, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. PTK6 is highly expressed not only in the previously reported Her2$^+$ breast cancer subtype, but also in high grade ER$^+$, Luminal B tumors and high expression is associated with adverse outcomes. Conclusions: These findings highlight PTK6 as a critical regulator of anchorage-independent survival of breast and ovarian tumor cells via modulation of IGF-1 receptor signaling, thus supporting PTK6 as a potential therapeutic target for multiple tumor types. The combined genomic and proteomic approaches in this report provide an effective strategy for identifying oncogenes and their mechanism of action