Home Parenteral Nutrition in Patients with Advanced Cancer: A Systematic Review and Meta-Analysis

The use of home parenteral nutrition (HPN) in patients with incurable cancer remains controversial with significant variation worldwide. We aimed to systematically evaluate the literature from 1960 to 2018 examining the use of HPN in advanced cancer patients for all intestinal failure indications and assess the potential benefits/burdens of HPN in this cohort of patients. The primary end point was survival and secondary end points were quality of life and nutritional/performance status. Meta-analysis was performed with a random effects model, where suitable. Of 493 studies retrieved, 22 met the quality inclusion criteria. Studies were mainly conducted in Western countries (Italy, USA, Canada, Germany), including a total of 3564 patients (mean age 57.8 years). Mean duration for HPN was 5.0 mo. Mean overall survival was 7.3 mo. Patients with improved performance status survived for longer on HPN. Quality of life was sparsely reported though there was no observed negative impact of PN. HPN-related complications were reported in eight studies only and were mainly catheter-related blood stream infections. In conclusion, HPN is used for several indications in advanced cancer, though there is significant heterogeneity of results. Disparities in geographical distribution of the studies may reflect variation in accessing HPN

Chytridiomycosis outbreak in a Chilean giant frog (Calyptocephalella gayi) captive breeding program: genomic characterization and pathological findings

Emerging infectious diseases in wildlife are increasingly associated with animal mortality and species declines, but their source and genetic characterization often remains elusive. Amphibian chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has been associated with catastrophic and well-documented amphibian population declines and extinctions at the global scale. We used histology and whole-genome sequencing to describe the lesions caused by, and the genetic variability of, two Bd isolates obtained from a mass mortality event in a captive population of the threatened Chilean giant frog (Calyptocephalella gayi). This was the first time an association between Bd and high mortality had been detected in this charismatic and declining frog species. Pathological examinations revealed that 30 dead metamorphosed frogs presented agnathia or brachygnathia, a condition that is reported for the first time in association with chytridiomycosis. Phylogenomic analyses revealed that Bd isolates (PA1 and PA2) from captive C. gayi group with other Bd isolates (AVS2, AVS4, and AVS7) forming a single highly supported Chilean Bd clade within the global panzootic lineage of Bd (BdGPL). These findings are important to inform the strengthening of biosecurity measures to prevent the impacts of chytridiomycosis in captive breeding programs elsewhere

In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide

<p>Abstract</p> <p>Background</p> <p>Hydrogen peroxide (H₂O₂) produced by vaginal lactobacilli is generally believed to protect against bacteria associated with bacterial vaginosis (BV), and strains of lactobacilli that can produce H₂O₂are being developed as vaginal probiotics. However, evidence that led to this belief was based in part on non-physiological conditions, antioxidant-free aerobic conditions selected to maximize both production and microbicidal activity of H₂O₂. Here we used conditions more like those <it>in vivo </it>to compare the effects of physiologically plausible concentrations of H₂O₂and lactic acid on a broad range of BV-associated bacteria and vaginal lactobacilli.</p> <p>Methods</p> <p>Anaerobic cultures of seventeen species of BV-associated bacteria and four species of vaginal lactobacilli were exposed to H₂O₂, lactic acid, or acetic acid at pH 7.0 and pH 4.5. After two hours, the remaining viable bacteria were enumerated by growth on agar media plates. The effect of vaginal fluid (VF) on the microbicidal activities of H₂O₂and lactic acid was also measured.</p> <p>Results</p> <p>Physiological concentrations of H₂O₂(< 100 μM) failed to inactivate any of the BV-associated bacteria tested, even in the presence of human myeloperoxidase (MPO) that increases the microbicidal activity of H₂O₂. At 10 mM, H₂O₂inactivated all four species of vaginal lactobacilli but only one of seventeen species of BV-associated bacteria. Moreover, the addition of just 1% vaginal fluid (VF) blocked the microbicidal activity of 1 M H₂O₂. In contrast, lactic acid at physiological concentrations (55-111 mM) and pH (4.5) inactivated all the BV-associated bacteria tested, and had no detectable effect on the vaginal lactobacilli. Also, the addition of 10% VF did not block the microbicidal activity of lactic acid.</p> <p>Conclusions</p> <p>Under optimal, anaerobic growth conditions, physiological concentrations of lactic acid inactivated BV-associated bacteria without affecting vaginal lactobacilli, whereas physiological concentrations of H₂O₂produced no detectable inactivation of either BV-associated bacteria or vaginal lactobacilli. Moreover, at very high concentrations, H₂O₂was more toxic to vaginal lactobacilli than to BV-associated bacteria. On the basis of these <it>in vitro </it>observations, we conclude that lactic acid, not H₂O₂, is likely to suppress BV-associated bacteria <it>in vivo</it>.</p

Identifying co-endemic areas for major filarial infections in sub-Saharan Africa: seeking synergies and preventing severe adverse events during mass drug administration campaigns

BACKGROUND: Onchocerciasis and lymphatic filariasis (LF) are major filarial infections targeted for elimination in most endemic sub-Saharan Africa (SSA) countries by 2020/2025. The current control strategies are built upon community-directed mass administration of ivermectin (CDTI) for onchocerciasis, and ivermectin plus albendazole for LF, with evidence pointing towards the potential for novel drug regimens. When distributing microfilaricides however, considerable care is needed to minimise the risk of severe adverse events (SAEs) in areas that are co-endemic for onchocerciasis or LF and loiasis. This work aims to combine previously published predictive risk maps for onchocerciasis, LF and loiasis to (i) explore the scale of spatial heterogeneity in co-distributions, (ii) delineate target populations for different treatment strategies, and (iii) quantify populations at risk of SAEs across the continent. METHODS: Geographical co-endemicity of filarial infections prior to the implementation of large-scale mass treatment interventions was analysed by combining a contemporary LF endemicity map with predictive prevalence maps of onchocerciasis and loiasis. Potential treatment strategies were geographically delineated according to the level of co-endemicity and estimated transmission intensity. RESULTS: In total, an estimated 251 million people live in areas of LF and/or onchocerciasis transmission in SSA, based on 2015 population estimates. Of these, 96 million live in areas co-endemic for both LF and onchocerciasis, providing opportunities for integrated control programmes, and 83 million live in LF-monoendemic areas potentially targetable for the novel ivermectin-diethylcarbamazine-albendazole (IDA) triple therapy. Only 4% of the at-risk population live in areas co-endemic with high loiasis transmission, representing up to 1.2 million individuals at high risk of experiencing SAEs if treated with ivermectin. In these areas, alternative treatment strategies should be explored, including biannual albendazole monotherapy for LF (1.4 million individuals) and 'test-and-treat' strategies (8.7 million individuals) for onchocerciasis. CONCLUSIONS: These maps are intended to initiate discussion around the potential for tailored treatment strategies, and highlight populations at risk of SAEs. Further work is required to test and refine strategies in programmatic settings, providing the empirical evidence needed to guide efforts towards the 2020/2025 goals and beyond

Genomic epidemiology of the emerging pathogen Batrachochytrium dendrobatidis from native and invasive amphibian species in Chile

Emerging fungal diseases represent a threat to food security, animal and human health worldwide. Amphibian chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has been associated with catastrophic and well-documented amphibian population declines and extinctions. For the first time, Bd was cultured from native and non-native wild amphibians in Chile. Phylogenomic analyses revealed that Chilean isolates AVS2, AVS4 and AVS7 group within the global panzootic lineage of Bd (BdGPL) in a single highly supported clade that includes a genotype previously isolated from the United Kingdom. Our results extend the known distribution of BdGPL in South America and suggest a single and relatively recent introduction of BdGPL into the country, providing additional support to the role of anthropogenic activity in the global spread of this panzootic lineage

Comparison of Storage Conditions for Human Vaginal Microbiome Studies

BACKGROUND: The effect of storage conditions on the microbiome and metabolite composition of human biological samples has not been thoroughly investigated as a potential source of bias. We evaluated the effect of two common storage conditions used in clinical trials on the bacterial and metabolite composition of the vaginal microbiota using pyrosequencing of barcoded 16S rRNA gene sequencing and (1)H-NMR analyses. METHODOLOGY/PRINCIPAL FINDINGS: Eight women were enrolled and four mid-vaginal swabs were collected by a physician from each woman. The samples were either processed immediately, stored at -80°C for 4 weeks or at -20°C for 1 week followed by transfer to -80°C for another 4 weeks prior to analysis. Statistical methods, including Kolmogorovo-Smirnov and Wilcoxon tests, were performed to evaluate the differences in vaginal bacterial community composition and metabolites between samples stored under different conditions. The results showed that there were no significant differences between samples processed immediately after collection or stored for varying durations. (1)H-NMR analysis of the small molecule metabolites in vaginal secretions indicated that high levels of lactic acid were associated with Lactobacillus-dominated communities. Relative abundance of lactic acid did not appear to correlate with relative abundance of individual Lactobacillus sp. in this limited sample, although lower levels of lactic acid were observed when L. gasseri was dominant, indicating differences in metabolic output of seemingly similar communities. CONCLUSIONS/SIGNIFICANCE: These findings benefit large-scale, field-based microbiome and metabolomic studies of the vaginal microbiota

Recent Asian origin of chytrid fungi causing global amphibian declines

Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide

Search for rare decays of D0 mesons into two muons

A search for the very rare D 0 → μ + μ − decay is performed using data collected by the LHCb experiment in proton-proton collisions at √ s = 7 , 8, and 13 TeV, corresponding to an integrated luminosity of 9     fb − 1 . The search is optimized for D 0 mesons from D * + → D 0 π + decays but is also sensitive to D 0 mesons from other sources. No evidence for an excess of events over the expected background is observed. An upper limit on the branching fraction of this decay is set at B ( D 0 → μ + μ − ) &lt; 3.1 × 10 − 9 at a 90% C.L. This represents the world’s most stringent limit, constraining models of physics beyond the standard model

Recent Asian origin of chytrid fungi causing global amphibian declines

Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide