Removal of hydrophilic, hydrophobic, and charged xenobiotic organic compounds from greywater using green wall media.

Green walls offer a novel on-site approach for greywater treatment and reuse in densely build urban environments. However, they need to be engineered for effective removal of a wide range of emerging contaminants such as xenobiotic organic compounds (XOCs), which may be present in greywater due to extensive use of personal care products and household chemicals. This study used laboratory column design and batch experiments to investigate the performance of three lightweight green wall media (coco coir, zeolite, and perlite) and their mixture in three different combinations for the removal of twelve XOCs, covering wide range of hydrophilic, hydrophobic, and charged pollutants in greywater. The experiments were designed to assess the removal of targeted XOCs under different operational condition (i.e., hydraulic loading, infiltration rate, drying) and uncover the dominant mechanisms of their removal. Results showed excellent removal (>90%) of all XOCs in coco coir and media mix columns at the start of the experiment (i.e., fresh media and initial 2 pore volume (PV) of greywater dosing). The removal of highly hydrophobic and positively charged XOCs remained high (>90%) under all operational conditions, while hydrophilic and negatively charged XOCs exhibited significant reduction in removal after 25 PV and 50 PV, possibly due to their low adsorption affinity and electrostatic repulsion from negatively charged media. The effect of infiltration rate on the removal of XOCs was not significant; however, higher removal was achieved after 2-weeks of drying in coco coir and media mix columns. The dominant removal mechanism for most XOCs was found to be adsorption, however, a few hydrophilic XOCs (i.e., acetaminophen and atrazine) exhibited both adsorption and biodegradation removal processes. While findings showed promising prospects of unvegetated media for removing XOCs from greywater, long term studies on vegetated green wall systems are needed to understand any synergetic contribution of plants and media in removing these XOCs.

A randomised controlled study shows supplementation of overweight and obese adults with lactobacilli and bifidobacteria reduces bodyweight and improves well-being.

In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years old) with BMI 25-34.9 kg/m2 received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p < 0.0001), BMI (0.045 kg/m2, p < 0.0001), WC (0.94 cm, p < 0.0001) and WtHR (0.006, p < 0.0001) were in favour of the probiotic. Stratification identified greater body weight reductions in overweight subjects (1.88%, p < 0.0001) and in females (1.62%, p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (-2.5%, p < 0.0001) alongside a significant between group reduction in small dense LDL-cholesterol (0.2 mmol/L, p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p < 0.0001) were recorded for the probiotic group. No adverse events were recorded. Six months supplementation with Lab4P probiotic resulted in significant weight reduction and improved small dense low-density lipoprotein-cholesterol (sdLDL-C) profiles, QoL and URTI incidence outcomes in overweight/obese individuals.

Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease.

BACKGROUND AND AIMS: Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease. METHODS: Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. RESULTS: Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease. CONCLUSIONS: This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Infection and pubertal timing: a systematic review.

The decline in age of pubertal timing has serious public health implications ranging from psychosocial adjustment problems to a possible increase in reproductive cancers. One biologically plausible explanation for the decline is a decrease in exposures to infections. To systematically review studies that assess the role of infection in pubertal timing, Medline, Web of Science and EMBASE were systematically searched and retrieved studies were reviewed for eligibility. Eligible studies examined the association between infections, including microbial exposures, and physical pubertal characteristics (breast, genitalia and pubic hair development) or age at menarche. We excluded studies that were published in a language other than English, focused on precocious puberty, were case studies, and/or included youth with autoimmune diseases. We report on study design, population characteristics, measurement of infection and puberty and the main effects of infection on pubertal development. Based on our search terms we identified 1372 unique articles, of which only 15 human and five animal studies met our eligibility criteria. Not all studies examined all outcomes. Infection was associated with later breast development (4/4 human studies), with less consistent evidence for genitalia and pubic hair development. Seven studies assessed age at menarche with inconsistent findings (three supporting later, four no association). We conclude that a small but consistent literature supports that infection is associated with later breast development; the evidence for other pubertal events and age at menarche is less clear. Where fewer childhood infections coincide with the rise in incidence of hormone-related cancers.

Chemical monitoring strategy for the assessment of advanced water treatment plant performance.

A pilot-scale plant was employed to validate the performance of a proposed full-scale advanced water treatment plant (AWTP) in Sydney, Australia. The primary aim of this study was to develop a chemical monitoring program that can demonstrate proper plant operation resulting in the removal of priority chemical constituents in the product water. The feed water quality to the pilot plant was tertiary-treated effluent from a wastewater treatment plant. The unit processes of the AWTP were comprised of an integrated membrane system (ultrafiltration, reverse osmosis) followed by final chlorination generating a water quality that does not present a source of human or environmental health concern. The chemical monitoring program was undertaken over 6 weeks during pilot plant operation and involved the quantitative analysis of pharmaceuticals and personal care products, steroidal hormones, industrial chemicals, pesticides, N-nitrosamines and halomethanes. The first phase consisted of baseline monitoring of target compounds to quantify influent concentrations in feed waters to the plant. This was followed by a period of validation monitoring utilising indicator chemicals and surrogate measures suitable to assess proper process performance at various stages of the AWTP. This effort was supported by challenge testing experiments to further validate removal of a series of indicator chemicals by reverse osmosis. This pilot-scale study demonstrated a simplified analytical approach that can be employed to assure proper operation of advanced water treatment processes and the absence of trace organic chemicals.

Quantifying human exposure to contaminants for multiple-barrier water reuse systems.

Reliance upon advanced water treatment processes to provide safe drinking water from relatively compromised sources is rapidly increasing in Australia and other parts of the world. Advanced treatment processes such as reverse osmosis have the ability to provide very effective treatment for a wide range of chemicals when operated under optimal conditions. However, techniques are required to comprehensively validate the performance of these treatment processes in the field. This paper provides a discussion and demonstration of some effective statistical techniques for the assessment and description of advanced water treatment plant performance. New data is provided, focusing on disinfection byproducts including trihalomethanes and N-nitrosamines from a recent comprehensive quantitative exposure assessment for an advanced water recycling scheme in Australia.

Decontamination of uranium-contaminated steel surfaces by hydroxycarboxylic acid with uranium recovery.

We developed a simple, safe method to remove uranium from contaminated metallic surfaces so that the materials can be recycled or disposed of as low-level radioactive or nonradioactive waste. Surface analysis of rusted uranium-contaminated plain carbon-steel coupons by X-ray photoelectron spectroscopy and Rutherford backscattering spectroscopy showed that uranium was predominantly associated with ferrihydrite, lepidocrocite, and magnetite, or occluded in the matrix of the corrosion product as uranyl hydroxide and schoepite (UO3 x 2H2O). Citric acid formulations, consisting of oxalic acid-hydrogen peroxidecitric acid (OPC) or citric acid-hydrogen peroxidecitric acid (CPC), were used to remove uranium from the coupons. The efficiency of uranium removal varied from 68% to 94% depending on the extent of corrosion, the association of uranium with the iron oxide matrix, and the accessibility of the occluded contaminant. Decontaminated coupons clearly showed evidence of the extensive removal of rust and uranium. The waste solutions containing uranium and iron from decontamination by OPC and CPC were treated first by subjecting them to biodegradation followed by photodegradation. Biodegradation of a CPC solution by Pseudomonas fluorescens resulted in the degradation of the citric acid with concomitant precipitation of Fe (>96%), whereas U that remained in solution was recovered (>99%) by photodegradation as schoepite. In contrast, in an OPC solution citric acid was biodegraded but not oxalic acid, and both Fe and U remained in solution. Photodegradation of this OPC solution resulted in the precipitation of iron as ferrihydrite and uranium as uranyl hydroxide.

Stem-loop SL4 of the HIV-1 psi RNA packaging signal exhibits weak affinity for the nucleocapsid protein. structural studies and implications for genome recognition.

Encapsidation of the genome of the human immunodeficiency virus type-1 (HIV-1) during retrovirus assembly is mediated by interactions between the nucleocapsid (NC) domains of assembling Gag polyproteins and a approximately 110 nucleotide segment of the genome known as the Psi-site. The HIV-1 Psi-site contains four stem-loops (SL1 through SL4), all of which are important for genome packaging. Recent isothermal titration calorimetry (ITC) studies have demonstrated that SL2 and SL3 are capable of binding NC with high affinity (K(d) approximately 140 nM), consistent with proposals for protein-interactive functions during packaging. To determine if SL4 may have a similar function, NC-interactive studies were conducted by NMR and gel-shift methods. In contrast to previous reports, we find that SL4 binds weakly to NC (K(d)=(+/-14 microM), suggesting an alternative function. NMR studies indicate that the GAGA tetraloop of SL4 adopts a classical GNRA-type fold (R=purine, N=G, C, A or U), a motif that stabilizes RNA tertiary structures in other systems. In combination with previously reported gel mobility studies of Psi-site deletion mutants, these findings suggest that SL4 functions in genome recognition not by binding to Gag, but by stabilizing the structure of the Psi-site. Differences in the affinities of NC for SL2, SL3 and SL4 stem-loops can now be rationalized in terms of the different structural properties of stem loops that contain GGNG (SL2 and SL3) and GNRA (SL4) sequences.

Codon optimization markedly improves doxycycline regulated gene expression in the mouse heart.

Tetracycline regulated gene expression in transgenic animals is potentially a very powerful technique (Furth et al., 1994; Gossen & Bujard 1992). We have utilized this system in an attempt to overcome the perinatal lethality resulting from constitutive transgenic expression in the heart (Valencik & McDonald, Am J Physiol Heart Circ Physiol 280: H361-H367). We found that compound hemizygous animals created by mating selected reverse tetracycline transactivator (rtTA) and transresponder (TR) lines display tightly regulated TR expression in the heart. However, we identified two fundamental problems. First, codon usage bias appeared to severely limit the expression of the rtTA driven by the cardiac alpha-myosin heavy chain promoter. Second, co-injection of rtTA and TR transgenes led to compound hemizygous animals that exhibited unregulated TR gene expression. Codon optimization of the rtTA construct leads to marked improvement (increasing the average induction from 20-fold to 832-fold) in cardiac myocyte expression. The resulting opt-rtTA lines can be bred to homozygosity, facilitating rapid screening of F0 TR animals for doxycycline regulated transgene expression.

A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects.

Normal cardiovascular development is exquisitely dependent on the correct dosage of the angiogenic growth factor and vascular morphogen vascular endothelial growth factor (VEGF). However, cardiac expression of VEGF is also robustly augmented during hypoxic insults, potentially mediating the well-established teratogenic effects of hypoxia on heart development. We report that during normal heart morphogenesis VEGF is specifically upregulated in the atrioventricular (AV) field of the heart tube soon after the onset of endocardial cushion formation (i.e. the endocardium-derived structures that build the heart septa and valves). To model hypoxia-dependent induction of VEGF in vivo, we conditionally induced VEGF expression in the myocardium using a tetracycline-regulated transgenic system. Premature induction of myocardial VEGF in E9.5 embryos to levels comparable with those induced by hypoxia prevented formation of endocardial cushions. When added to explanted embryonic AV tissue, VEGF fully inhibited endocardial-to-mesenchymal transformation. Transformation was also abrogated in AV explants subjected to experimental hypoxia but fully restored in the presence of an inhibitory soluble VEGF receptor 1 chimeric protein. Together, these results suggest a novel developmental role for VEGF as a negative regulator of endocardial-to-mesenchymal transformation that underlies the formation of endocardial cushions. Moreover, ischemia-induced VEGF may be the molecular link between hypoxia and congenital defects in heart septation.

Cardiac expression of a gain-of-function alpha(5)-integrin results in perinatal lethality.

Communication between the extracellular matrix and the intracellular signal transduction and cytoskeletal system is mediated by integrin receptors. alpha(5)beta(1)-Integrin and its cognate ligand fibronectin are essential in development of mesodermal structures, myocyte differentiation, and normal cardiac development. To begin to explore the potential roles of alpha(5)beta(1)-integrin specifically in cardiomyocytes, we used a transgenic expression strategy. We overexpressed two forms of the human alpha(5)-integrin in cardiomyocytes: the full-length wild-type alpha(5)-integrin and a putative gain-of-function mutation created by truncating the cytoplasmic domain, designated alpha(5-1)-integrin. Overexpression of the wild-type alpha(5)-integrin has no detectable adverse effects in the mouse, whereas expression of alpha(5-1)-integrin caused electrocardiographic abnormalities, fibrotic changes in the ventricle, and perinatal lethality. Thus physiological regulation of integrin function appears essential for maintenance of normal cardiomyocyte structure and function. This strengthens the role of inside-out signaling in regulation of integrins in vivo and suggests that integrins and associated signaling molecules are important in cardiomyocyte function.

Regulation of cardiac cushion development by hyaluronan.

Hyaluronan is an extracellular matrix component implicated in expansion of the extracellular space, organization of supramolecular architecture, cell motility, proliferation, tumour metastases and wound healing. Hyaluronan is highly expressed in the developing heart but it is only a minor component of the mature heart. The loss of hyaluronan synthase-2 (Has2) results in embryonic lethality with a phenotype remarkably similar to that of the versican-deficient heart defect mouse. Has2-deficient embryos lack hyaluronan-containing cardiac jelly, and at embryonic day 9.5 show arrested development, with an apparent absence of the right ventricle and underdevelopment of the conustruncus segment, and pericardial effusion consistent with heart failure. Cardiac cushions are totally absent, and endocardial cell migration over collagen gels is not detectable in Has2-deficient atrioventricular (AV) canal explants. Endothelial to mesenchymal transformation is also defective in AV explants from Has2-null embryos. The normal phenotype is restored in AV canal explants from Has2-deficient embryos by co-culture with wild type AV canal explants, with conditioned media from wild type AV explants or with exogenous hyaluronan. These results provide evidence for a direct role for hyaluronan during endocardial cushion and AV canal morphogenesis.

Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme.

We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA) during embryonic development, and we used gene targeting to study its function in vivo. Has2(-/-) embryos lack HA, exhibit severe cardiac and vascular abnormalities, and die during midgestation (E9.5-10). Heart explants from Has2(-/-) embryos lack the characteristic transformation of cardiac endothelial cells into mesenchyme, an essential developmental event that depends on receptor-mediated intracellular signaling. This defect is reproduced by expression of a dominant-negative Ras in wild-type heart explants, and is reversed in Has2(-/-) explants by gene rescue, by administering exogenous HA, or by expressing activated Ras. Conversely, transformation in Has2(-/-) explants mediated by exogenous HA is inhibited by dominant-negative Ras. Collectively, our results demonstrate the importance of HA in mammalian embryogenesis and the pivotal role of Has2 during mammalian development. They also reveal a previously unrecognized pathway for cell migration and invasion that is HA-dependent and involves Ras activation.

Sensory neuropathy in the prodromal phase of hepatitis A and review of the literature.

We report an unrecognized clinical presentation of hepatitis A with unilateral peripheral acute sensory loss in the prodromal phase of the illness. Although rare, focal neurological signs are known to occur in hepatitis A before, during and after the icteric phase; a pure peripheral sensory neuropathy is distinctly uncommon. Possible lesions could include radiculopathy of the lower thoraco-lumbo-sacral dorsal nerve roots or a partial transverse myelitis of Brown-Séquad like distribution. The signs and symptoms lasted only a few days and the patient had an uneventful recovery.

Prognostic factors in early-onset epithelial ovarian cancer: a population-based study.

OBJECTIVE: To investigate the clinical prognostic factors that influence ovarian cancer survival in women with early-onset epithelial ovarian cancer using population-based data. METHODS: Subjects in the current study were from a population-based series of 197 patients with invasive ovarian cancer and 60 patients with ovarian cancer of low malignant potential who were identified from the Cancer and Steroid Hormone study. All subjects were between 20 and 54 years of age at diagnosis for ovarian cancer. Epidemiologic data were obtained from each participant. Immunohistochemical staining was performed to assess p53 expression in paraffin-embedded ovarian cancers. Univariate and multivariate analyses for survival were conducted using the proportional hazards model to test the prognostic significance of several clinicopathologic factors among subjects. RESULTS: Among women with invasive tumors, the proportional hazards model revealed that advanced stage at diagnosis [hazard ratio = 4.1, 95% confidence interval (CI) = 2.5, 6.6], age at diagnosis 46-54 (hazard ratio = 2.0, 95% CI = 1.3, 3.0), and overexpression of p53 (hazard ratio = 1.5, 95% CI = 1.1, 2.3) were significantly associated with decreased survival. CONCLUSION: These results provide evidence that stage, age, and p53 overexpression are independent predictors of decreased survival in women with invasive ovarian cancer diagnosed younger than age 55. Further investigation of the effect of age at diagnosis on the relationship between p53 overexpression and ovarian cancer survival is warranted.