Intravenous ferric carboxymaltose and ferric derisomaltose alter the intestinal microbiome in female iron-deficient anemic mice.

Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron stores, either by oral or intravenous (IV) supplementation. There is a complex bidirectional interplay between the gut microbiota, the host's iron status, and dietary iron availability. Dietary iron deficiency and supplementation can influence the gut microbiome; however, the effect of IV iron on the gut microbiome is unknown. We studied how commonly used IV iron preparations, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), affected the gut microbiome in female iron-deficient anemic mice. At the phylum level, vehicle-treated mice showed an expansion in Verrucomicrobia, mostly because of the increased abundance of Akkermansia muciniphila, along with contraction in Firmicutes, resulting in a lower Firmicutes/Bacteroidetes ratio (indicator of dysbiosis). Treatment with either FCM or FDI restored the microbiome such that Firmicutes and Bacteroidetes were the dominant phyla. Interestingly, the phyla Proteobacteria and several members of Bacteroidetes (e.g., Alistipes) were expanded in mice treated with FCM compared with those treated with FDI. In contrast, several Clostridia class members were expanded in mice treated with FDI compared with FCM (e.g., Dorea spp., Eubacterium). Our data demonstrate that IV iron increases gut microbiome diversity independently of the iron preparation used; however, differences exist between FCM and FDI treatments. In conclusion, replenishing iron stores with IV iron preparations in clinical conditions, such as inflammatory bowel disease or chronic kidney disease, could affect gut microbiome composition and consequently contribute to an altered disease outcome.

Aerial remote sensing of sub-sea dispersant injection effects during the Deepwater Horizon (MC-252) oil spill.

During the Deepwater Horizon oil spill in 2010, subsea dispersant injection (SSDI) was utilized for the first time in an effort to reduce the amount of oil reaching the sea surface and thus potentially decrease its environmental impact and enhance responders' safety. Since then, controversy has developed about SSDI's effectiveness. Most of the analysis is based on modeling, with some models concluding SSDI significantly reduced surfacing oil volumes, and others predicting that processes unrelated to the dispersant caused most of the subsurface oil retention. This study utilized a multispectral aerial sensor image time series to correlate the surface area covered by freshly upwelled oil with changes in SSDI rates, accounting for an approximate 4 hour oil rise time lag. A significant negative correlation was found between oil-covered surface area and SSDI rates, providing direct observation support that the technique did reduce the amount of surfacing oil around the wellhead.

Investigation of some endophytic fungi from five medicinal plants with growth promoting ability on maize (Zea mays L.).

AIMS: This study aimed to identify endophytic fungi from Anthemis altissima, Matricaria parthenium, Cichorium intybus, Achillea millefolium, and A. filipendulina with plant-promoting ability on the ZP684 maize hybrid-cultivar. METHODS AND RESULTS: Plants were collected from northeast-Iran and endophytic fungi were isolated and identified using partial large subunit nrDNA, internal transcribed spacer, translation elongation factor, and ß-tubulin genetic markers. Endophytic fungi that improved seed germination were studied under greenhouse conditions. Ninety-seven endophytic fungi were identified. Preussia africana, Bjerkandera adusta, Schizophyllum commune, Alternaria embellisia, Trichaptum biforme, Septoria malagutii, A. consortiale, Verticillium dahliae, Fusarium avenacearum, and Trametes versicolor significantly improved seed-germination. Alternaria consortiale produced the highest level of indole-3-acetic acid-like compounds and maize growth-promoting. CONCLUSIONS: Plant fungal colonization frequency increased with orthometric height. Sampling location Chahar Bagh at 2230 m contained the most endophytic fungi. Fusarium and Alternaria were the most frequently isolated endophytic genera. Therefore, medicinal plants are potential hosts for endophytic fungi that may be suitable biofertilizer agents in agriculture. SIGNIFICANCE AND IMPACT OF THE STUDY: This study helps to better understand the ecosystem functions by investigating of endophytic fungi distribution under different ecological conditions. Finding effective isolates among these microorganisms with a suitable plant-promoting ability on crops may help to reduce the use of chemical fertilizers in an agroecosystem.

Women's knowledge, attitudes and views of preconception health and intervention delivery methods: a cross-sectional survey.

BACKGROUND: Several preconception exposures have been associated with adverse pregnancy, birth and postpartum outcomes. However, few studies have investigated women's knowledge of and attitudes towards preconception health, and the acceptability of potential intervention methods. METHODS: Seven primary care centres in the West of England posted questionnaires to 4330 female patients aged 18 to 48 years. Without providing examples, we asked women to list maternal preconception exposures that might affect infant and maternal outcomes, and assessed their knowledge of nine literature-derived risk factors. Attitudes towards preconception health (interest, intentions, self-efficacy and perceived awareness and importance) and the acceptability of intervention delivery methods were also assessed. Multivariable multilevel regression examined participant characteristics associated with these outcomes. RESULTS: Of those who received questionnaires, 835 (19.3%) responded. Women were most aware of the preconception risk factors of diet (86.0%) and physical activity (79.2%). Few were aware of weight (40.1%), folic acid (32.9%), abuse (6.3%), advanced age (5.9%) and interpregnancy intervals (0.2%), and none mentioned interpregnancy weight change or excess iron intake. After adjusting for demographic and reproductive covariates, women aged 18-24-years (compared to 40-48-year-olds) and nulligravid women were less aware of the benefit of preconception folic acid supplementation (adjusted odds ratios (aOR) for age: 4.30 [2.10-8.80], gravidity: aOR 2.48 [1.70-3.62]). Younger women were more interested in learning more about preconception health (aOR 0.37 [0.21-0.63]) but nulligravid women were less interested in this (aOR 1.79 [1.30-2.46]). Women with the lowest household incomes (versus the highest) were less aware of preconception weight as a risk factor (aOR: 3.11 [1.65-5.84]) and rated the importance of preconception health lower (aOR 3.38 [1.90-6.00]). The most acceptable information delivery methods were websites/apps (99.5%), printed healthcare materials (98.6%), family/partners (96.3%), schools (94.4%), television (91.9%), pregnancy tests (91.0%) and doctors, midwives and nurses (86.8-97.0%). Dentists (23.9%) and hairdressers/beauticians (18.1%) were the least acceptable. CONCLUSIONS: Our findings demonstrate a need to promote awareness of preconception risk factors and motivation for preconception health changes, particularly amongst younger and nulligravid women and women with lower incomes. Interventions to improve preconception health should focus on communication from healthcare professionals, schools, family members, and digital media.

Evaluation of colonization and mutualistic endophytic symbiosis of Escherichia coli with tomato and Bermuda grass seedlings.

Escherichia coli is generally considered a bacterium associated with animal microbiomes. However, we present evidence that E. coli may also mutualistically colonize roots of plant species, even to the extent that it may become endophytic in plants. In this study we used GFP tagged E. coli to observe its colonization and effects on tomato (Solanum lycopersicum) and Bermuda grass (Cynodon dactylon) seedling development and growth. Inoculation with the bacterium significantly improved root development of both seedlings tested. Treatment also increased the photosynthetic pigments in Bermuda grass seedlings. However, effects on shoot length in both seedlings were not significant. This bacterium was found to produce indole acetic acid (IAA) up to 8.68 ± 0.43 µg ml-1 in the broth medium amended with tryptophan. Effects on seedling root growth could, in part, be explained by IAA production. Bacteria successfully colonized the root surfaces and interiors of both seedlings. Tagged bacteria expressing the GFP were observed in the vascular tissues of Bermuda grass seedling roots. Seedlings with bacteria showed greater survival and were healthier than seedlings without bacteria, indicating that E. coli set up a successful mutualistic symbiosis with seedlings. E. coli is not commonly considered to be a plant endophyte but is more generally considered to be a crop contaminant. In this study we show that E. coli may also be an endophyte in plant tissues.

The effect of mindfulness-based stress reduction on the urinary microbiome in interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the impact of mindfulness-based stress reduction therapy on the urinary microbiome of patients with interstitial cystitis/bladder pain syndrome. METHODS: In this Institutional Review Board-approved prospective cohort study, patients with interstitial cystitis/bladder pain syndrome were recruited to attend an 8-week mindfulness-based stress reduction course involving yoga and meditation. Eligible participants were English-speaking women aged 18 or older with interstitial cystitis/bladder pain syndrome. All participants had a negative urinalysis within 2 months of enrollment and were currently undergoing first- or second-line treatment at the time of recruitment. The mindfulness-based stress reduction course met weekly for 1 h. A straight-catheter urine sample was obtained prior to and following the mindfulness-based stress reduction series. DNA from urine samples underwent bacterial 16S ribosomal gene sequencing at Johns Hopkins University Laboratories followed by taxonomic abundance and diversity analysis by Resphera Biosciences Laboratory. Participants completed validated symptom questionnaires pre- and post-intervention. RESULTS: A total of 12 participants completed the 8-week course and were included in the analysis. The average age was 59 and the majority identified as white. Patient symptoms, measured by the Urogenital Distress Inventory Short Form and Interstitial Cystitis Symptom and Pain Indices, improved significantly (all p < 0.05). Overall composition of the urinary microbiome changed significantly (p < 0.01) and demonstrated an increase in diversity following the intervention. CONCLUSIONS: Mindfulness-based stress reduction therapy improves patient symptoms and was associated with significant changes in the urinary microbiome in patients with interstitial cystitis/bladder pain syndrome.

Fungal Endophytes as Efficient Sources of Plant-Derived Bioactive Compounds and Their Prospective Applications in Natural Product Drug Discovery: Insights, Avenues, and Challenges.

Fungal endophytes are well-established sources of biologically active natural compounds with many producing pharmacologically valuable specific plant-derived products. This review details typical plant-derived medicinal compounds of several classes, including alkaloids, coumarins, flavonoids, glycosides, lignans, phenylpropanoids, quinones, saponins, terpenoids, and xanthones that are produced by endophytic fungi. This review covers the studies carried out since the first report of taxol biosynthesis by endophytic Taxomyces andreanae in 1993 up to mid-2020. The article also highlights the prospects of endophyte-dependent biosynthesis of such plant-derived pharmacologically active compounds and the bottlenecks in the commercialization of this novel approach in the area of drug discovery. After recent updates in the field of 'omics' and 'one strain many compounds' (OSMAC) approach, fungal endophytes have emerged as strong unconventional source of such prized products.

Isolation and identification of L-asparaginase-producing endophytic fungi from the Asteraceae family plant species of Iran.

L-asparaginase is an important anticancer enzyme that is used in the first line treatment of acute lymphoblastic leukemia. This study was conducted to isolate L-asparaginase-producing endophytic fungi from medicinal plants of family Asteraceae. Seven healthy medicinal plants from family Asteraceae were selected for the isolation of endophytic fungi using standard surface sterilization techniques. A total of 837 isolates belonging to 84 species were comprised of the stem (55.6%), leaf (31.1%), root (10.6%) and flower (2.7%). Initial screening of L-asparaginase-producing endophytes was performed by qualitative plate assay on modified Czapex dox's agar medium. L-asparaginase activity of fungal endophytes was quantified by the nesslerization method. Identification of endophytic fungi was performed using both morphological characteristics and phylogenetic analyses of DNA sequence data including ribosomal DNA regions of ITS (Internal transcribed spacer) and LSU (partial large subunit rDNA), TEF1 (Translation Elongation Factor) and TUB (ß-tubulin). Of the 84 isolates, 38 were able to produce L-asparaginase and their L-asparaginase activities were between 0.019 and 0.492 unit/mL with Fusarium proliferatum being the most potent. L-asparaginase-producing endophytes were identified as species of Plectosphaerella, Fusarium, Stemphylium, Septoria, Alternaria, Didymella, Phoma, Chaetosphaeronema, Sarocladium, Nemania, Epicoccum, Ulocladium and Cladosporium. This study showed that endophytic fungi from Asteraceae members have a high L-asparaginase-producing potential and they can be used as an alternative source for production of anticancer enzymes.

LC-MS based identification of stylosin and tschimgine from fungal endophytes associated with Ferula ovina.

OBJECTIVES: Ferula ovina is an Iranian medicinal plant. Tschimgine and stylosin are two of its major monoterpene derivatives. In this study, we proceeded to investigate some fungal endophytes from F. ovina that can produce plant secondary metabolites. MATERIALS AND METHODS: The isolated endophytic fungi were fermented in potato dextrose broth (PDB) medium and their extracts were screened for the presence of the plant compounds by liquid chromatography-tandem mass spectrometry (LC-MS). Endophytes identification was performed by morphological and molecular methods. Three markers (ITS, LSU, and TEF1) were used for accurate molecular identification. RESULTS: Forty isolates from 9 different genera of endophytic fungi were identified, of which two recently reported species of O. ferulica and Pithoascus persicus were able to produce tschimgine and stylosin. CONCLUSION: These fungi can be used as a substitute for the production of plant's medicinal compounds independent of wild populations of the source plant.

Interlaboratory trial for the measurement of total cobalt in equine urine and plasma by ICP-MS.

Cobalt is an essential mineral micronutrient and is regularly present in equine nutritional and feed supplements. Therefore, cobalt is naturally present at low concentrations in biological samples. The administration of cobalt chloride is considered to be blood doping and is thus prohibited. To control the misuse of cobalt, it was mandatory to establish an international threshold for cobalt in plasma and/or in urine. To achieve this goal, an international collaboration, consisting of an interlaboratory comparison between 5 laboratories for the urine study and 8 laboratories for the plasma study, has been undertaken. Quantification of cobalt in the biological samples was performed by inductively coupled plasma-mass spectrometry (ICP-MS). Ring tests were based on the analysis of 5 urine samples supplemented at concentrations ranging from 5 up to 500 ng/mL and 5 plasma samples spiked at concentrations ranging from 0.5 up to 25 ng/mL. The results obtained from the different laboratories were collected, compiled, and compared to assess the reproducibility and robustness of cobalt quantification measurements. The statistical approach for the ring test for total cobalt in urine was based on the determination of percentage deviations from the calculated means, while robust statistics based on the calculated median were applied to the ring test for total cobalt in plasma. The inter-laboratory comparisons in urine and in plasma were successful so that 97.6% of the urine samples and 97.5% of the plasma samples gave satisfactory results. Threshold values for cobalt in plasma and urine were established from data only obtained by laboratories involved in the ring test. Copyright © 2017 John Wiley & Sons, Ltd.

Upward revision of global fossil fuel methane emissions based on isotope database.

Methane has the second-largest global radiative forcing impact of anthropogenic greenhouse gases after carbon dioxide, but our understanding of the global atmospheric methane budget is incomplete. The global fossil fuel industry (production and usage of natural gas, oil and coal) is thought to contribute 15 to 22 per cent of methane emissions to the total atmospheric methane budget. However, questions remain regarding methane emission trends as a result of fossil fuel industrial activity and the contribution to total methane emissions of sources from the fossil fuel industry and from natural geological seepage, which are often co-located. Here we re-evaluate the global methane budget and the contribution of the fossil fuel industry to methane emissions based on long-term global methane and methane carbon isotope records. We compile the largest isotopic methane source signature database so far, including fossil fuel, microbial and biomass-burning methane emission sources. We find that total fossil fuel methane emissions (fossil fuel industry plus natural geological seepage) are not increasing over time, but are 60 to 110 per cent greater than current estimates owing to large revisions in isotope source signatures. We show that this is consistent with the observed global latitudinal methane gradient. After accounting for natural geological methane seepage, we find that methane emissions from natural gas, oil and coal production and their usage are 20 to 60 per cent greater than inventories. Our findings imply a greater potential for the fossil fuel industry to mitigate anthropogenic climate forcing, but we also find that methane emissions from natural gas as a fraction of production have declined from approximately 8 per cent to approximately 2 per cent over the past three decades.

Synergistic effect of exogeneous and endogeneous electrostimulation on osteogenic differentiation of human mesenchymal stem cells seeded on silk scaffolds.

Bioelectrical regulation of bone fracture healing is important for many cellular events such as proliferation, migration, and differentiation. The aim of this study was to investigate the osteogenic differentiation potential of human mesenchymal stem cells (hMSCs) cultivated on silk scaffolds in response to different modes of electrostimulation (e.g., exogeneous and/or endogeneous). Endogeneous electrophysiology was altered through the use of monensin (10 nM) and glibenclamide (10 µM), along with external electrostimulation (60 kHz; 100-500 mV). Monensin enhanced the expression of early osteogenic markers such as alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX-2). When exogeneous electrostimulation was combined with glibenclamide, more mature osteogenic marker upregulation based on bone sialoprotein expression (BSP) and mineralization was found. These results suggest the potential to exploit both exogeneous and endogeneous biophysical control of cell functions towards tissue-specific goals.

Centennial-scale changes in the global carbon cycle during the last deglaciation.

Global climate and the concentration of atmospheric carbon dioxide (CO2) are correlated over recent glacial cycles. The combination of processes responsible for a rise in atmospheric CO2 at the last glacial termination (23,000 to 9,000 years ago), however, remains uncertain. Establishing the timing and rate of CO2 changes in the past provides critical insight into the mechanisms that influence the carbon cycle and helps put present and future anthropogenic emissions in context. Here we present CO2 and methane (CH4) records of the last deglaciation from a new high-accumulation West Antarctic ice core with unprecedented temporal resolution and precise chronology. We show that although low-frequency CO2 variations parallel changes in Antarctic temperature, abrupt CO2 changes occur that have a clear relationship with abrupt climate changes in the Northern Hemisphere. A significant proportion of the direct radiative forcing associated with the rise in atmospheric CO2 occurred in three sudden steps, each of 10 to 15 parts per million. Every step took place in less than two centuries and was followed by no notable change in atmospheric CO2 for about 1,000 to 1,500 years. Slow, millennial-scale ventilation of Southern Ocean CO2-rich, deep-ocean water masses is thought to have been fundamental to the rise in atmospheric CO2 associated with the glacial termination, given the strong covariance of CO2 levels and Antarctic temperatures. Our data establish a contribution from an abrupt, centennial-scale mode of CO2 variability that is not directly related to Antarctic temperature. We suggest that processes operating on centennial timescales, probably involving the Atlantic meridional overturning circulation, seem to be influencing global carbon-cycle dynamics and are at present not widely considered in Earth system models.

Biased generalization of newly learned phonological alternations by 12-month-old infants.

Previous work has suggested that learners are sensitive to phonetic similarity when learning phonological patterns (e.g., Steriade, 2001/2008; White, 2014). We tested 12-month-old infants to see if their willingness to generalize newly learned phonological alternations depended on the phonetic similarity of the sounds involved. Infants were exposed to words in an artificial language whose distributions provided evidence for a phonological alternation between two relatively dissimilar sounds ([p∼v] or [t∼z]). Sounds at one place of articulation (labials or coronals) alternated whereas sounds at the other place of articulation were contrastive. At test, infants generalized the alternation learned during exposure to pairs of sounds that were more similar ([b∼v] or [d∼z]). Infants in a control group instead learned an alternation between similar sounds ([b∼v] or [d∼z]). When tested on dissimilar pairs of sounds ([p∼v] or [t∼z]), the control group did not generalize their learning to the novel sounds. The results are consistent with a learning bias favoring alternations between similar sounds over alternations between dissimilar sounds.

Preanalytical treatment of EDTA-anticoagulated blood to ensure stabilization of the mean platelet volume and component measured with the ADVIA counters.

The mean platelet component (MPC) parameter calculated by the ADVIA blood cell analyzers provides direct information on density, or granularity, of platelets and could become a useful biomarker to detect in vivo platelet activation. Unfortunately, it is largely affected by time and storage conditions in standard anticoagulants based on EDTA. The present study was designed to improve the stability of the MPC in blood specimens to facilitate a more standardized use in different laboratories. Blood from healthy controls was collected into EDTA plus additives, and stored at different conditions. MPC and the mean platelet volume (MPV) were assessed at 30 min and at 1, 3, 6 and 24hours after blood drawing on the ADVIA 2120 system. Flow cytometry was used to evaluate platelet-activation proteins. Ultrastructural morphology of platelets was assessed using electron microscopy. Storage in EDTA increased MPV, decreased MPC, reduced the number of alpha-granules, and induced changes in the phosphorylation patterns of platelet proteins. A solution based on EDTA containing wortmanin and tyrphostin (ED-WORTY), both inhibitors of signaling pathways, provided good stability for most of the parameters tested up to 6 hours at room temperature. Storage at lower temperatures produced more favorable results. ED-WORTY solutions preserved adequate morphology and had minimal influence on other parameters provided by the ADVIA 2120 system. Thus, the additives included in ED-WORTY may be useful for maintaining the stability of MPC for prolonged periods and to facilitate the transport and exchange of samples among institutions and laboratories.

Faithfully fit forever: a holistic exercise and wellness program for faith communities.

Older adults are at risk for numerous acute and chronic health conditions. Many of these conditions can be prevented or better managed by participation in health promotion and wellness programming. The social support found through involvement in a faith community makes this setting an ideal place for offering health promotion and wellness programming. This article includes a description of an innovative, faith-based, community-based wellness program titled Faithfully Fit Forever (FFF). The Cardiac Rehabilitation and Parish Nursing Departments at MeritCare Health System, Fargo, North Dakota, developed FFF in 2000. FFF is a holistic health improvement program that embraces the interconnection between mind, body, and spirit. It is led by laypeople (many are parish nurses) who are members of the individual religious community. The program includes 30 to 40 minutes of exercise, health education time, and devotional time promoting spiritual and emotional health.

Developing a systemwide approach to patient safety: the first year.

BACKGROUND: Health care organizations face an imperative to ensure that care is provided to patients in the safest manner possible. In 2000 INTEGRIS Health, an Oklahoma City-based health system including ten acute care organizations, developed a patient safety framework that was built on the foundation of a culture of patient safety and began implementation in January 2001. IMPORTANCE OF LEADERSHIP IN PATIENT SAFETY: The first step in establishing a culture of safety was to ensure that leadership and the entire organization understand the rationale for a focus on patient safety. The traditional blaming approach will not prevent human error; staff need to speak freely, to talk about errors that happen and those that almost happen, and to identify where mistakes are likely and where systems allow mistakes to get through. Systems and processes should make it difficult for staff to make mistakes and easy for them to do things correctly. EXPERIENCE TO DATE: Since our efforts began, staff have helped identify multiple accidents waiting to happen. For example, an anesthesiologist, the service chief at one of our large hospitals, prepared a list of safety issues immediately after hearing a presentation to the Medical Executive Committee. Many system flaws have been identified as a result of our discussions; some of the solutions are easy and some much more complex. CHALLENGES: Challenges include keeping patient safety highly visible and demonstrating progress in our implementation, developing effective mechanisms for communicating safety solutions and ensuring that they are implemented in all the facilities, and figuring out how to measure success in a meaningful way.