Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial–connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, "ECTI contour," is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo. Cancer Res; 76(16); 4637–47. ©2016 AACR.
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 14 Αυγούστου 2016
Altered Epithelial-Connective Tissue Interface in Dysplasia
ICOS Costimulation of Tregs in Follicular Lymphoma
The prognosis of follicular lymphoma (FL) patients is suspected to be influenced by tumor-infiltrating regulatory T cells (Treg). The mechanism of Treg enrichment in FL and their impact on malignant FL B cells remains to be elucidated. We analyzed 46 fresh lymph node biopsy samples, including FL (n = 20), diffuse large B-cell lymphoma (n = 10), classical Hodgkin lymphoma (n = 9), and reactive lymphadenitis (n = 7). Using multicolor flow cytometry and cell sorting, we observed an accumulation of CD25highCD127low/neg Tregs in FL tissues. These Tregs comprised activated ICOS+ Tregs that were able to suppress not only conventional T cells, but also FL B cells. These FL B cells were able to express ICOSL in vitro and to generate CD25highFoxP3high Tregs expressing ICOS. Treg generation was associated with ICOS/ICOSL engagement and was abrogated by antagonist anti-ICOS and anti-ICOSL antibodies. Interactions between Tregs and FL B cells resulted in ICOSL downregulation on FL B cells. Our results highlight a key role for Tregs in FL pathogenesis and suggest that targeting the ICOS/ICOSL pathway may be a promising immunotherapy for FL treatment. Cancer Res; 76(16); 4648–60. ©2016 AACR.
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HER2-Mediated Tumorigenesis Requires mTORC2
HER2 overexpression drives Akt signaling and cell survival and HER2-enriched breast tumors have a poor outcome when Akt is upregulated. Akt is activated by phosphorylation at T308 via PI3K and S473 via mTORC2. The importance of PI3K-activated Akt signaling is well documented in HER2-amplified breast cancer models, but the significance of mTORC2-activated Akt signaling in this setting remains uncertain. We report here that the mTORC2 obligate cofactor Rictor is enriched in HER2-amplified samples, correlating with increased phosphorylation at S473 on Akt. In invasive breast cancer specimens, Rictor expression was upregulated significantly compared with nonmalignant tissues. In a HER2/Neu mouse model of breast cancer, genetic ablation of Rictor decreased cell survival and phosphorylation at S473 on Akt, delaying tumor latency, penetrance, and burden. In HER2-amplified cells, exposure to an mTORC1/2 dual kinase inhibitor decreased Akt-dependent cell survival, including in cells resistant to lapatinib, where cytotoxicity could be restored. We replicated these findings by silencing Rictor in breast cancer cell lines, but not silencing the mTORC1 cofactor Raptor (RPTOR). Taken together, our findings establish that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. Cancer Res; 76(16); 4752–64. ©2016 AACR.
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Therapeutic Efficacy of CSC Vaccine in the Adjuvant Setting
Dendritic cell (DC)-based vaccine strategies aimed at targeting cancer stem–like cells (CSC) may be most efficacious if deployed in the adjuvant setting. In this study, we offer preclinical evidence that this is the case for a CSC-DC vaccine as tested in murine models of SCC7 squamous cell cancer and D5 melanoma. Vaccination of mice with an ALDHhigh SCC7 CSC-DC vaccine after surgical excision of established SCC7 tumors reduced local tumor relapse and prolonged host survival. This effect was augmented significantly by simultaneous administration of anti-PD-L1, an immune checkpoint inhibitor. In the minimal disease setting of D5 melanoma, treatment of mice with ALDHhigh CSC-DC vaccination inhibited primary tumor growth, reduced spontaneous lung metastases, and increased host survival. In this setting, CCR10 and its ligands were downregulated on ALDHhigh D5 CSCs and in lung tissues, respectively, after vaccination with ALDHhigh D5 CSC-DC. RNAi-mediated attenuation of CCR10 blocked tumor cell migration in vitro and metastasis in vivo. T cells harvested from mice vaccinated with ALDHhigh D5 CSC-DC selectively killed ALDHhigh D5 CSCs, with additional evidence of humoral immunologic engagement and a reduction in ALDHhigh cells in residual tumors. Overall, our results offered a preclinical proof of concept for the use of ALDHhigh CSC-DC vaccines in the adjuvant setting to more effectively limit local tumor recurrence and spontaneous pulmonary metastasis, as compared with traditional DC vaccines, with increased host survival further accentuated by simultaneous PD-L1 blockade. Cancer Res; 76(16); 4661–72. ©2016 AACR.
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Paclitaxel Halts S100A4-Driven Metastasis in CCA
Nuclear expression of the calcium-binding protein S100A4 is a biomarker of increased invasiveness in cholangiocarcinoma, a primary liver cancer with scarce treatment opportunities and dismal prognosis. In this study, we provide evidence that targeting S100A4 nuclear import by low-dose paclitaxel, a microtubule-stabilizing agent, inhibits cholangiocarcinoma invasiveness and metastatic spread. Administration of low-dose paclitaxel to established (EGI-1) and primary (CCA-TV3) cholangiocarcinoma cell lines expressing nuclear S100A4 triggered a marked reduction in nuclear expression of S100A4 without modifying its cytoplasmic levels, an effect associated with a significant decrease in cell migration and invasiveness. While low-dose paclitaxel did not affect cellular proliferation, apoptosis, or cytoskeletal integrity, it significantly reduced SUMOylation of S100A4, a critical posttranslational modification that directs its trafficking to the nucleus. This effect of low-dose paclitaxel was reproduced by ginkolic acid, a specific SUMOylation inhibitor. Downregulation of nuclear S100A4 by low-dose paclitaxel was associated with a strong reduction in RhoA and Cdc42 GTPase activity, MT1-MMP expression, and MMP-9 secretion. In an SCID mouse xenograft model, low-dose metronomic paclitaxel treatment decreased lung dissemination of EGI-1 cells without significantly affecting their local tumor growth. In the tumor mass, nuclear S100A4 expression by cholangiocarcinoma cells was significantly reduced, whereas rates of proliferation and apoptosis were unchanged. Overall, our findings highlight nuclear S100A4 as a candidate therapeutic target in cholangiocarcinoma and establish a mechanistic rationale for the use of low-dose paclitaxel in blocking metastatic progression of cholangiocarcinoma. Cancer Res; 76(16); 4775–84. ©2016 AACR.
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Prolonged measurement improves the assessment of the barrier function of the esophago-gastric junction by high-resolution manometry
Abstract
Background
Etiology of gastro-esophageal reflux disease (GERD) is multifactorial, but incompetence of the esophago-gastric junction (EGJ) appears to be of crucial importance. Established manometric parameters for assessment of EGJ barrier function are sub-optimal, potentially because they reflect only a very brief (up to 30 seconds), not necessarily representative period. This prospective, case–control study tested the performance of novel, high-resolution manometry (HRM) parameters of EGJ function in the assessment of GERD.
Methods
Patients with reflux symptoms and healthy controls (HC) underwent standard HRM and 24-hour pH±impedance measurements. EGJ morphology, lower esophageal sphincter pressure integral (LES-PI), EGJ contractile integral (EGJ-CI) were compared with total-EGJ-CI, a novel parameter summarizing EGJ barrier function during the entire HRM protocol. Esophageal acid exposure ≥4.2%/24 h (A-Reflux-pos) or ≥73 reflux episodes in 24 hours (V-Reflux-pos) were considered pathological.
Key Results
Sixty five HC and 452 patients completed HRM, 380 (84%) patients underwent ambulatory reflux-monitoring. LES-PI, EGJ-CI and total-EGJ-CI correlated with EGJ morphology subtypes (all P<.00001). Only total-EGJ-CI was consistently lower in A-Reflux-pos and V-Reflux-pos subjects compared with HC and patients without GERD. Total-EGJ-CI was also the single best parameter for prediction of pathological reflux (optimal cut-off 47 mmHg cm, AUC 0.746, P<.0001). This cut-off value, approximately 1 SD below the mean normal value, showed modest sensitivity 54% and positive predictive value 46%, but good specificity 85% and negative predictive value 89% for GERD diagnosis.
Conclusion & Inferences
Total EGJ-CI, a new metric that summarizes EGJ contractility over time, allows an improved assessment of EGJ barrier function. Pathological reflux is unlikely if this metric is within the upper two-thirds of the normal range.
Total-esophagogastric junction contractile integral (EGJ-CI), a new metric summarizing EGJ contractility over the entire length of standard HRM, was tested in 65 healthy controls and 452 GERD patients and proved to be superior over conventional metrics and other HRM metrics for prediction of pathological reflux. In particular, the negative predictive value approached 90% if total-EGJ-CI was within the upper two-thirds of the normal range. These findings suggest that GERD is highly unlikely if the EGJ can maintain normal contractility over several minutes.
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Interplay of brain structure and function in neonatal congenital heart disease
Abstract
Objective
To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity.
Methods
We studied a prospective cohort of 20 neonates with CHD who underwent continuous EEG monitoring before surgery to assess functional brain maturation and network connectivity, structural magnetic resonance imaging (MRI) to determine the presence of brain injury and structural brain development, and diffusion tensor MRI to assess brain microstructural development.
Results
Neonates with MRI brain injury and delayed structural and microstructural brain development demonstrated significantly stronger high-frequency (beta and gamma frequency band) connectivity. Furthermore, neonates with delayed microstructural brain development demonstrated significantly weaker low-frequency (delta, theta, alpha frequency band) connectivity. Neonates with brain injury also displayed delayed functional maturation of EEG background activity, characterized by greater background discontinuity.
Interpretation
These data provide new evidence that early structural and microstructural developmental brain abnormalities can have immediate functional consequences that manifest as characteristic alterations of neuronal network connectivity. Such early perturbations of developing neuronal networks, if sustained, may be responsible for the persistent neurocognitive impairment prevalent in adolescent survivors of CHD. These foundational insights into the complex interplay between evolving brain structure and function may have relevance for a wide spectrum of neurological disorders manifesting early developmental brain injury.
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Influence of Nonenzymatic Glycation in Dentinal Collagen on Dental Caries
Advanced glycation end-products (AGEs) are generated via nonenzymatic glycation of dentinal collagen, resulting in accumulation of AGEs in dentin tissue. Since accumulated AGEs cause crosslinking between amino acid polypeptides in the collagen molecule and modify mechanical properties of dentinal collagen, the authors assumed that there would be a significant interaction between the generation of AGEs and progression of caries in dentin. To confirm such an interaction, spectroscopic imaging analyses (i.e., nanosecond fluorescence lifetime imaging and second harmonic generation light imaging) were performed in addition to biochemical and electron microscopic analyses in the present study. Seven carious human teeth were fixed in paraformaldehyde and cut longitudinally into 1-mm sections using a low-speed diamond saw for the following analyses. In transmission electron microscopy (TEM) analysis, nondecalcified specimens were embedded in epoxy resin and sliced into thin sections for observation. For the immunohistochemical analysis, the specimens were paraffin embedded after decalcification for 2 wk and sectioned with a microtome. Resultant sections were stained with anti-AGE and anticollagen antibodies. The demineralized specimens were used for spectroscopic analyses without additional treatment. For Western blotting analysis, specimens were separated into carious and sound dentin. Each specimen was homogenized with a bead crusher and an ultrasonic homogenizer and then treated with hydrochloric acid. In carious dentin, the collagen fibers showed an amorphous structure in the TEM image, and the AGEs were localized in the areas of bacterial invasion in the immunostaining image. The total amount of AGEs in carious dentin was higher than in sound dentin in Western blotting. The ultrastructure of type I collagen and total amount of AGEs varied markedly in the dentinal caries region. The fluorescence lifetime was shorter in the carious area than that in the sound areas, indicating an increase of AGEs in the carious area. The increase of AGEs could influence the progression of dentinal caries.
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Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss
Characteristic features of Alzheimer's disease are memory loss, plaques resulting from abnormal processing of amyloid precursor protein (APP), and presence of neurofibrillary tangles and dystrophic neurites containing hyperphosphorylated tau. Currently, it is not known what links these abnormalities together. Cytoplasmic FMR1 interacting protein 2 (CYFIP2) has been suggested to regulate mRNA translation at synapses and this may include local synthesis of APP and alpha-calcium/calmodulin-dependent kinase II, a kinase that can phosphorylate tau. Further, CYFIP2 is part of the Wiskott-Aldrich syndrome protein-family verprolin-homologous protein complex, which has been implicated in actin polymerization at synapses, a process thought to be required for memory formation. Our previous studies on p25 dysregulation put forward the hypothesis that CYFIP2 expression is reduced in Alzheimer's disease and that this contributes to memory impairment, abnormal APP processing and tau hyperphosphorylation. Here, we tested this hypothesis. First, in post-mortem tissue CYFIP2 expression was reduced by ~50% in severe Alzheimer's hippocampus and superior temporal gyrus when normalized to expression of a neuronal or synaptic marker protein. Interestingly, there was also a trend for decreased expression in mild Alzheimer's disease hippocampus. Second, CYFIP2 expression was reduced in old but not in young Tg2576 mice, a model of familial Alzheimer's disease. Finally, we tested the direct impact of reduced CYFIP2 expression in heterozygous null mutant mice. We found that in hippocampus this reduced expression causes an increase in APP and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) protein, but not mRNA expression, and elevates production of amyloid-β42. Reduced CYFIP2 expression also increases alpha-calcium/calmodulin-dependent kinase II protein expression, and this is associated with hyperphosphorylation of tau at serine-214. The reduced expression also impairs spine maturity without affecting spine density in apical dendrites of CA1 pyramidal neurons. Furthermore, the reduced expression prevents retention of spatial memory in the water maze. Taken together, our findings indicate that reduced CYFIP2 expression triggers a cascade of change towards Alzheimer's disease, including amyloid production, tau hyperphosphorylation and memory loss. We therefore suggest that CYFIP2 could be a potential hub for targeting treatment of the disease.
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Ventral tegmental area deep brain stimulation in refractory short-lasting unilateral neuralgiform headache attacks
Short-lasting unilateral neuralgiform headache attacks are primary headache disorders characterized by short-lasting attacks of unilateral pain accompanied by autonomic features. A small minority are refractory to medical treatment. Neuroimaging studies have suggested a role of the posterior hypothalamic region in their pathogenesis. Previous case reports on deep brain stimulation of this region, now understood to be the ventral tegmental area, for this disorder are limited to a total of three patients. We present a case series of 11 new patients treated with ventral tegmental area deep brain stimulation in an uncontrolled, open-label prospective observational study. Eleven patients with refractory short-lasting unilateral neuralgiform headache attacks underwent ipsilateral ventral tegmental area deep brain stimulation in a specialist unit. All patients had failed, or been denied access to, occipital nerve stimulation within the UK's National Health Service. Primary endpoint was change in mean daily attack frequency at final follow-up. Secondary outcomes included attack severity, attack duration, headache load (a composite score of attack frequency, severity and duration), quality of life measures, disability and affective scores. Information was also collected on adverse events. Eleven patients (six male) with a median age of 50 years (range 26–67) were implanted between 2009 and 2014. Median follow-up was 29 months (range 7–63). At final follow-up the median improvement in daily attack frequency was 78% (interquartile range 33%). Response rate (defined as at least a 50% improvement in daily attack frequency) was 82% and four patients were rendered pain-free for prolonged periods of time. Headache load improved by 99% (interquartile range 52%). Improvements were observed in a number of quality of life, disability and affect measures. Adverse events included mild incision site pain, subcutaneous displacement of the implantable pulse generator, transient oscillopsia and minor wound infection. One patient required removal of the system due to wound infection. Ventral tegmental area deep brain stimulation may be an effective treatment option for refractory short-lasting unilateral neuralgiform headache attack patients who have failed other therapies.
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Table top Bacillus
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Pituitary stalk thickening: the role of an innovative MRI imaging analysis which may assist in determining clinical management
Context
Disease processes that affect the pituitary stalk are broad; the diagnosis and management of these lesions remains unclear.
ObjectiveThe aim was to assess the clinical, biochemical and histopathological characteristics of pituitary stalk lesions and their association with specific MRI features in order to provide diagnostic and prognostic guidance.
Design and methodsRetrospective observational study of 36 patients (mean age 37years, range: 4–83) with pituitary stalk thickening evaluated at a university hospital in Oxford, UK, 2007–2015. We reviewed morphology, signal intensity, enhancement and texture appearance at MRI (evaluated with the ImageJ programme), along with clinical, biochemical, histopathological and long-term follow-up data.
ResultsDiagnosis was considered certain for 22 patients: 46% neoplastic, 32% inflammatory and 22% congenital lesions. In the remaining 14 patients, a diagnosis of a non-neoplastic disorder was assumed on the basis of long-term follow-up (mean 41.3months, range: 12–84). Diabetes insipidus and headache were common features in 47 and 42% at presentation, with secondary hypogonadism the most frequent anterior pituitary defect. Neoplasia was suggested on size criteria or progression with 30% sensitivity. However, textural analysis of MRI scans revealed a significant correlation between the tumour pathology and pituitary stalk heterogeneity in pre- and post-gadolinium T1-weighted images (sensitivity: 88.9%, specificity: 91.7%).
ConclusionsNew techniques of MRI imaging analysis may identify clinically significant neoplastic lesions, thus directing future therapy. We propose possible textural heterogeneity criteria of the pituitary stalk on pre- and post-gadolinium T1 images with the aim of differentiating between neoplastic and non-neoplastic lesions with a high degree of accuracy.
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Ectopic adrenocortical carcinoma located in the ovary
Aim
Ovarian corticosteroid-producing tumors are exquisitely rare. Our aim was to describe the first case observed in our practice.
Case historyA 34-year-old female was referred for Cushing's syndrome (CS) occurring in the postpartum period. Clinical examination showed severe CS with diabetes mellitus, hypertension, and a large mass in the right lower abdomen. Biochemistry demonstrated corticotropin (ACTH)-independent CS (cortisol=1900ng/mL (n=50–250), ACTH<10pg/mL (n=20–46)) with estradiol and testosterone overproduction.
InvestigationsAbdomen CT scan revealed a 14cm right ovarian mass and small adrenal glands. Surgical exploration found the ovarian tumor with hemoperitoneum and enlarged lymph nodes. Histological study confirmed adrenocortical tumor located in the ovary with a Weiss score >5, associated with peritoneal and lymph node metastases. Immunohistochemical staining was positive for inhibin-α, melan-A, and SF1, demonstrating tissue of adrenal origin. After surgery, plasma glucose level spontaneously returned to normal. However, the patient died on the second post-surgical day due to catastrophic pulmonary embolism.
ConclusionIn this reported case, clinical, hormonal, histological, and immunohistochemical findings confirmed a cortisol and sex hormone-producing ovarian tumor with peritoneal and lymph node metastases, a very rare but important condition to recognize.
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MANAGEMENT OF ENDOCRINE DISEASE: Recurrence or new tumors after complete resection of pheochromocytomas and paragangliomas: a systematic review and meta-analysis
Objectives
To systematically review the incidence and factors associated with recurrences or new tumors after apparent complete resection of pheochromocytoma or thoraco–abdomino–pelvic paraganglioma.
DesignA systematic review and meta-analysis of published literature was performed.
MethodsPubmed and Embase from 1980 to 2012 were searched for studies published in English on patients with non-metastatic pheochromocytoma or thoraco–abdomino–pelvic paraganglioma, complete tumor resection, postoperative follow-up exceeding 1 month, and recurrence or new tumor documented by pathology, hormonal dosages, or imaging tests. Incidence rates of new events after curative surgery were calculated for each study that had sufficient information and pooled using random-effect meta-analysis.
ResultsIn total, 38 studies were selected from 3518 references, of which 36 reported retrospective cohorts from the USA, Europe, and Asia. Patient follow-up was neither standardized nor exhaustive in the included studies. A clear description of patient retrieval methods was available for nine studies and the follow-up protocol and patient flow for four studies. Only two studies used multivariable methods to assess potential predictors of postoperative events.
The overall rate of recurrent disease from 34 studies was 0.98 events/100 person-years (95% confidence interval 0.71, 1.25). Syndromic diseases and paragangliomas were consistently associated with a higher risk of a new event in individual studies and in meta-regression analysis.
ConclusionsThe risk of recurrent disease after complete resection of pheochromocytoma may be lower than that previously estimated, corresponding to five events for 100 patients followed up for 5 years after complete resection. Risk stratification is required to tailor the follow-up protocol after complete resection of a pheochromocytoma or paraganglioma. Large multicenter studies are needed to this end.
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The relationship between estimated glomerular filtration rate trajectory and all-cause mortality in type 2 diabetes: the Fremantle Diabetes Study
Objective
To investigate the association between estimated GFR (eGFR) and all-cause mortality, including the contribution of temporal eGFR changes, in well-characterised community-based patients with type 2 diabetes.
DesignLongitudinal observational study.
MethodsParticipants from the Fremantle Diabetes Study Phase 1 were assessed between 1993 and 1996 and followed until end-December 2012. Cox proportional hazards modelling was used to assess the relationship between baseline eGFR category (Stage 1–5) and all-cause death, and between eGFR trajectories assigned by semiparametric group-based modelling (GBM) and all-cause death in patients with five post-baseline annual eGFR measurements.
ResultsIn the full cohort (1296 patients; mean±s.d. age 64.1±11.3years, 48.6% males), 738 (56.9%) died during 12.9±6.1years of follow-up. There was a U-shaped relationship between all-cause death and eGFR category. With Stage 3 (45–59mL/min/1.73m2) as reference, the strongest association was for eGFR ≥90mL/min/1.73m2 (hazard ratio (95% CI) 2.01 (1.52–2.66); P<0.001). GBM identified four linear trajectories ('low', 'medium', 'high', 'high/declining') in 532 patients with serial eGFR measurements. With medium trajectory as reference, eGFR trajectory displaced baseline eGFR category as an independent predictor of death, with low and high/declining trajectories associated with more than double the risk (2.03 (1.30–3.18) and 2.24 (1.31–3.83) respectively, P≤0.003) and associated median reductions in survival of 6.5 and 8.7years respectively.
ConclusionThere is a nonlinear relationship between eGFR and death in type 2 diabetes, which is at least partially explained by a sub-group of patients with an initially high but then rapidly declining eGFR.
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MANAGEMENT OF ENDOCRINE DISEASE: Acromegaly and cancer: an old debate revisited
Based on experimental and animal models, epidemiological data from non-acromegaly populations, and longitudinal and cross-sectional cohorts of patients with acromegaly, a potential association between acromegaly and cancer has long been hypothesized, in particular colorectal cancer, and, to a lesser extent, breast, thyroid and prostate cancers. The exact mechanisms underlying this potential association have not been fully elucidated. Results from studies examining cancer incidence and mortality in acromegaly have been inconsistent, with some demonstrating increased risk, whereas others show no increase. This article reviews the existing data relating to cancer risk and mortality in acromegaly, exploring the limitations of study designs and the impact of changes in disease control and patient outcomes over time.
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The relation between changes in thyroid function and anthropometric indices during long-term follow-up of euthyroid subjects: the Tehran Thyroid Study (TTS)
Objective
Uncertainties exist regarding the causal relationship between thyroid function tests (TFT) within the euthyroid range and anthropometric measures. This longitudinal cohort is aimed to examine the relationship between the two conditions.
Subjects and methodsEuthyroid participants of Tehran Thyroid Study (TTS) attending phase I (1999–2001) were included in this study and were followed up to phase IV (2008–2011). TSH and free T4 (fT4) levels as well as weight (Wt), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR) were measured at both phases.
Results971 women and 784 men were included in the analysis. During 9.7years of follow-up, increases in TSH levels, Wt and WHR as well as a decrease in fT4 level were observed. Multivariable regression analysis showed a significant relationship between TSH changes and alterations in WC in women (β=0.69, P=0.021) and men (β=0.61, P=0.038). Moreover, a significant negative association of fT4 with changes in weight was documented (β=–0.49, P=0.001 in women and β=–0.56, P<0.001 in men). Additionally, we found a negative relationship between fT4 and HC in men (β=–0.36, P=0.001).
ConclusionIn both genders, there was a positive relationship between changes in TSH and waist circumference and conversely a negative association of changes of fT4 levels with weight over time.
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MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects
PCOS is a clinical heterogeneous entity of female androgen excess diagnosed by exclusion of other disorders responsible for androgen excess. The concept of secondary PCOS implies that there is a primary well-defined cause leading to the PCOS phenotype with underlying androgen overproduction, regardless of the origin. In these cases, we presume the term of 'secondary PCOS' could be used. In all these conditions, the potential complete recovery of the hyperandrogenemic state as well as the remission of the PCOS phenotype should follow the removal of the cause. If accepted, these concepts could help clinicians to perform in-depth investigations of the potential factors or disorders responsible for the development of these specific forms of secondary PCOS. Additionally, this could contribute to develop further research on factors and mechanisms involved in the development of the classic and the nonclassic PCOS phenotypes.
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Cross-sectional area of the median nerve is increased in primary autoimmune hypothyroidism and decreases upon treatment with thyroxine
Background
The purpose of this study was to assess changes in the cross-sectional area (CSA) of nervus medianus by ultrasound in newly diagnosed primary hypothyroid patients after thyroxine replacement treatment.
Patients and methodsThe cohort comprised 30 patients with newly diagnosed primary autoimmune hypothyroidism. These were subsequently compared with 30 controls, matched for sex, BMI and age. Ultrasound evaluation, including measurement of CSA at the level of the pisiform bone or tunnel inlet was performed at baseline and after 3months. A CSA threshold of more than 10mm2 was considered pathological.
ResultsCSA was increased in patients compared with controls (9.8±0.7mm2 vs 7.2±1.1mm2; P<0.001). Thyroxin substitution increased fT4 levels (baseline, 11.0±0.6pmol/L vs 15.5±0.4pmol/L; P<0.001) and decreased TSH (baseline, 23.9±6.0mIU/L vs 2.7±0.2mIU/L; P<0.001). Thyroxine treatment decreased CSA to 8.4mm2±0.3mm2 (P=0.033). Before treatment, four patients experienced distal paresthesia in the median nerve distribution area. Increased CSA pathognomonic for carpal tunnel syndrome found in two symptomatic patients normalized after 3months. No clinical symptoms were observed after 3months. A positive correlation was found between TSH and CSA (R=0.155, P=0.05) before treatment.
ConclusionOur study demonstrates that increase in median nerve CSA caused by primary autoimmune hypothyroidism can be fully reversible after achieving target levels of TSH and fT4.
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Treatment with high doses of pegvisomant in 56 patients with acromegaly: experience from ACROSTUDY
Objective
To investigate the characteristics of patients who need more or less pegvisomant (PEGV) to normalize serum IGF-I.
DesignACROSTUDY is a global noninterventional safety surveillance study of long-term treatment outcomes in patients treated with PEGV. As of June, 2014, ACROSTUDY included data on 2016 patients. All patients treated for at least 6weeks at a dose above 30mg/day and who had two consecutive normal serum IGF-I values were included in the 'high'-dose group (H; n=56; mean daily dose 44±12.5; median dose 40, 35–60 (10–90%)). Patients with two consecutive normal IGF-I values and who never received a PEGV dose above 10mg/day were included in the 'low'-dose group (L; n=368; mean daily dose 7.5±2.5; median dose 8.6, 4.3–10 (10–90%)).
ResultsPatients in the H group were significantly younger (median 47 vs 52years) and had a significantly higher BMI (median 31.8 vs 26.5kg/m2). They had more diabetes (55% vs 21%), sleep apnea (25% vs 14 %) and more hypertension (61% vs 43%). The incidence of (serious) adverse events was low and was not different between the groups.
ConclusionsPatients who need more PEGV to normalize IGF-I have more aggressive disease, as they are younger, have higher baseline IGF-I levels, more hypertension, more sleep apnea and diabetes and are more overweight. A better understanding of this dose-efficacy relationship of PEGV might avoid inappropriate dosing and prevent serum IGF-I levels from remaining unnecessarily uncontrolled.
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Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria
Objective
An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this.
DesignTwo hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy.
MethodsCumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan–Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance.
ResultsTwenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up.
ConclusionsThe proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study.
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Optimization and validation of moving average quality control procedures using bias detection curves and moving average validation charts
Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print
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Mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) in severe aortic valve stenosis: association with outcome after transcatheter aortic valve implantation (TAVI)
Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print
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Looking beyond linear regression and Bland-Altman plots: a comparison of the clinical performance of 25-hydroxyvitamin D tests
Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print
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Lactic acidosis: an update
Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print
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Identification of 5-fluorocytosine as a new interfering compound in serum capillary zone electrophoresis
Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print
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Factor VIIa-antithrombin complex: a possible new biomarker for activated coagulation
Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print
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A systems approach to renal inflammation in SLE
Publication date: Available online 14 August 2016
Source:Clinical Immunology
Author(s): Celine C. Berthier, Matthias Kretzler, Anne Davidson
Lupus disease and its complications including lupus nephritis (LN) are very disabling and significantly impact the quality of life and longevity of patients. Broadly immunosuppressive treatments do not always provide the expected clinical benefits and have significant side effects that contribute to patient morbidity. In the era of systems biology, new strategies are being deployed integrating diverse sources of information (molecular and clinical) so as to identify individual disease specificities and select less aggressive treatments. In this review, we summarize integrative approaches linking molecular disease profiles (mainly tissue transcriptomics) and clinical phenotypes. The main goals are to better understand the pathogenesis of lupus nephritis, to identify the risk factors for renal flare and to find the predictors of both short and long-term clinical outcome. Identification of common key drivers and additional patient-specific key drivers can open the door to improved and individualized therapy to prevent and treat LN.
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An Effort to Develop an Algorithm to Target Abdominal CT Scans for Patients After Gastric Bypass
Abstract
Abdominal CT (abdCT) scans are frequently ordered for Roux-en-Y gastric bypass (RYGB) patients presenting to the emergency department (ED) with abdominal pain, but often do not reveal intra-abdominal pathology. We aimed to develop an algorithm for rational ordering of abdCTs. We retrospectively reviewed our institution's RYGB patients presenting acutely with abdominal pain, documenting clinical and laboratory data, and scan results. Associations of clinical parameters to abdCT results were examined for outcome predictors. Of 1643 RYGB patients who had surgery between 2005 and 2015, 355 underwent 387 abdCT scans. Based on abdCT, 48 (12 %) patients required surgery and 86 (22 %) another intervention. No clinical or laboratory parameter predicted imaging results. Imaging decisions for RYGB patients do not appear to be amenable to a simple algorithm, and patient work-up should be based on astute clinical judgment.
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hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR
Abstract
Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA). Our data support a model in which hsa-miR-135-1 acts as a potential tumor suppressor in metastatic prostate cancer. First, its downregulation was positively correlated with late TNM stage, high Gleason score, and adverse prognosis. Second, cell growth, cell cycle progression, cell migration and invasion, and xenograft tumor formation were dramatically inhibited by miR-135a overexpression. Third, in the microarray gene expression data analysis using Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, Ingenuity Pathway Analysis (IPA), and Oncomine concept analysis, we showed that miR-135a targets multiple oncogenic pathways including epidermal growth factor receptor (EGFR), which we verified using functional experimental assays. These results help advance our understanding of the function of miRNAs in metastatic prostate cancer and provide a basis for further clinical investigation.
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In vitro Xanthine Oxidase (XO) and Albumin Denaturation Inhibition Assay of Barringtonia racemosa L. and Total Phenolic Content Analysis for Potential Anti-Inflammatory Use in Gouty Arthritis
2016-08-14T14-35-21Z
Source: Journal of Intercultural Ethnopharmacology
Nurul Izzati Osman, Norrizah Jaafar Sidik, Asmah Awal, Nurul Athirah Mohamad Adam, Nur Inani Rezali.
Aim: The present study was conducted to evaluate the in vitro anti-inflammatory activities and total phenolic content (TPC) of methanolic extracts of infloresence axes, endosperms, leaves and pericarps of Barringtonia racemosa L. Methods: The anti-inflammatory study was carried out by assessing the potential through xanthine oxidase (XO) and albumin denaturation inhibition assays. Meanwhile, the total phenolic content (TPC) in the extracts were assessed by Folin Ciocalteu assay. Results: In the XO inhibition assay, the infloresence axes extract was found to exert the highest inhibition capacity at 0.1% (v/v) with 59.54% ± 0.001 inhibition followed by leaves (58.82% ± 0.001), pericarps (57.99% ± 0.003) and endosperms (57.20% ± 0.003) extracts. Similarly in the albumin denaturation inhibition assay, the infloresence axes extract had shown the greatest inhibition capacity with 70.58% ± 0.004 inhibition followed by endosperms (66.80% ± 0.024), leaves (65.29% ± 0.006) and pericarps extracts (43.33% ± 0.002). Meanwhile, for TPC analysis, leaves extract was found to have the highest phenolic content (53.94 ± 0.000 mg GAE/g DW) followed by infloresence axes (31.54 ± 0.001 mg GAE/g DW), endosperms (22.63 ± 0.001 mg GAE/g DW) and the least was found in pericarps (15.54 ± 0.001 mg GAE/g DW). Conclusion: The results indeed verified the in vitro anti-inflammatory activities of B. racemosa and supported its potential to be used in alleviating gouty arthritis and XO-related diseases.
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In vitro Antileishmanial and Antimalarial Activity of Selected Plants of Nepal
2016-08-14T14-35-21Z
Source: Journal of Intercultural Ethnopharmacology
Bishnu Joshi, Sarah Hendrickx, Lila Magar, Niranjan Parajuli, Pierre Dorny, Louis Maes.
Ethnopharmacological relevance: Nepal is rich in biodiversity and no extensive effort has yet been carried out to screen plants that are used by traditional healers against parasitic diseases. The aim of this study was to evaluate the in vitro antileishmanial and antimalarial activity of crude methanolic or ethanolic extracts of 30 selected plant species. Materials and methods: Crude extracts of leaves, twigs, aerial parts and/or roots were evaluated for in vitro inhibitory activity against intracellular amastigotes of Leishmania infantum and against erythrocytic stages of Plasmodium falciparum. To determine the selectivity index (SI), cytotoxicity was assessed on MRC5 cells in parallel. Results: Three plant species revealed antiprotozoal activity, namely Phragmites vallatoria, Ampelocissus tomentosa for which no antiprotozoal activity has previously been reported, and Terminalia chebula. The extract of A. tomentosa exhibited moderate activity against L. infantum with an IC50 of 13.2 ± 4.3 µg/ml and SI >3 while T. chebula exhibited fairly good antiplasmodial activity with IC50 values of 4.5 ± 2.4 µg/ml and SI values >5. Conclusion: In countries like Nepal where the current health system is unable to combat the burden of endemic parasitic diseases, evaluation of local plants as a potential source of drug will help in expanding the treatment options. The extent of untapped resources available in these countries provides an opportunity for future bioprospecting. Keywords: Leishmania, Plasmodium, crude plant extracts, in vitro, Nepal
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Evaluation of the synergistic effect of Allium sativum, Eugenia jambolana, Momordica charantia, Ocimum sanctum and Psidium guajav on hepatic and intestinal drug metabolizing enzymes in rats
2016-08-14T14-35-21Z
Source: Journal of Intercultural Ethnopharmacology
Devendra Kumar, Neerja Trivedi, Rakesh K Dixit.
Aims/Background: Present study investigated the synergistic effect of polyherbal formulations (PHF) of Allium sativum L Eugenia jambolana Lam., Momordica charantia L., Ocimum sanctum Linn and Psidium guajava L. in the inhibition/induction of hepatic and intestinal CYPs and Phase-II conjugated drug metabolizing enzymes. Consumption of these herbal remedy has been extensively documented for diabetes treatment in Auyureda. Methodology: PHF of these five herbs was prepared and different doses were orally administered to Sprague Dawley rats of different groups except control group. Expression of mRNA and activity of drug metabolizing enzymes were examined by RT-PCR and HPLC in isolated liver and intestine microsomes in PHF pretreated rats. Results: Activities of hepatic and intestinal Phase-II enzyme levels increased along with mRNA levels except CYP3A mRNA level. PHF administration increases the activity of hepatic and intestinal UDPGT and GST in response to dose and time; however, activity of hepatic SULT increased at higher doses. Conclusions: CYPs and Phase-II conjugated enzymes levels can be modulated in dose and time dependent manner. Observations suggest that poly herbal formulation might be a possible cause of herb-drug interaction, due to changes in pharmacokinetic of crucial CYPs and Phase-II substrate drug.
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Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps
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Strategic Endothelial Cell Tube Formation Assay: Comparing Extracellular Matrix and Growth Factor Reduced Extracellular Matrix
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Attenuation of phenanthrene and pyrene adsorption by sewage sludge-derived biochar in biochar-amended soils
Abstract
The aim of this study was to evaluate the effect of soils on the sorption of phenanthrene (PHE) and pyrene (PYR) by sewage sludge-derived biochars (SS-derived biochars). The SS-derived biochars were added to soils with varying properties as well as with a different degree and source of polycyclic aromatic hydrocarbons (PAHs) contamination. The biochars (BCs) were produced from sewage sludge during pyrolysis at temperatures of 500 °C (BC500) and 700 °C (BC700). The addition of biochars to the soils (5 %, w/w) increased the sorption of PHE from 8.3 to 20.3 % and PYR from 14.5 to 31.7 % by amended soil. BC700 biochar was characterized by better sorption capacity than BC500 biochar. Nevertheless, the presence of soil reduces the effectiveness of biochars in binding the compounds studied. The sorption capacity of the biochars decreased several times after they had been mixed with the soil compared to pure biochars. The study found dissolved organic carbon (DOC) and clay minerals present in the soils to have a significant effect on reducing the efficiency of PHE and PYR sorption by biochar. A greater impact of fouling was observed in the case of BC500 biochar characterized by lower porosity than BC700 biochar.
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Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120
Abstract
In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.
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Analysis of baseline and alternative air quality scenarios for Pakistan: an integrated approach
Abstract
This study aims to assess the current and future air pollution and associated health impacts in Pakistan. In this study, the Pakistan Integrated Energy Model (Pak-IEM) is used to assess current and future energy consumption in Pakistan. To assess air pollution levels and associated health impacts, we used the Greenhouse gas and Air pollution INteractions and Synergies (GAINS) model. A linkage has been established between both the models to feed the energy outputs from Pak-IEM into GAINS for exploring different scenarios. Mainly, the emissions of three air pollutants (SO2, NOx, and PM2.5) as well as the associated health impacts of increased emissions are assessed. Baseline emission scenario (BES) shows a growth in emissions of SO2, NOx, and PM2.5 by a factor of 2.4, 2.2, and 2.5 between 2007 and 2030. In terms of health impacts, by 2030, annual mean concentrations of fine particles (PM2.5) would increase to more than 150 μg/m3 in some parts of Punjab region of Pakistan, for which loss in statistical life expectancy is calculated to increase from 30 to 60 months in 2007 up to 60–100 months in 2030 on average.
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Enhanced photo-Fenton-like process over Z-scheme CoFe 2 O 4 /g-C 3 N 4 Heterostructures under natural indoor light
Abstract
Low-cost catalysts with high activity and stability toward producing strongly oxidative species are extremely desirable, but their development still remains a big challenge. Here, we report a novel strategy for the synthesis of a magnetic CoFe2O4/C3N4 hybrid via a simple self-assembly method. The CoFe2O4/C3N4 was utilized as a photo-Fenton-like catalyst for degradation of organic dyes in the presence of H2O2 under natural indoor light irradiation, a green and energy-saving approach for environmental cleaning. It was found the CoFe2O4/C3N4 hybrid with a CoFe2O4: g-C3N4 mass ratio of 2:1 can completely degrade Rhodamine B nearly 100 % within 210 min under room-light irradiation. The effects of the amount of H2O2 (0.01–0.5 M), initial dye concentration (5–20 mg/L), solution pH (3.08-10.09), fulvic acid concentration (5–50 mg/L), different dyes and catalyst stability on the organic dye degradation were investigated. The introduction of CoFe2O4 on g-C3N4 produced an enhanced separation efficiency of photogenerated electron − hole pairs by a Z-scheme mechanism between the interfaces of g-C3N4 and CoFe2O4, leading to an excellent activity as compared with either g-C3N4 or CoFe2O4 and their mixture. This study demonstrates an efficient way to construct the low-cost magnetic CoFe2O4/C3N4 heterojunction as a typical Z-scheme system in environmental remediation.
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Changes in subcellular distribution and antioxidant compounds involved in Pb accumulation and detoxification in Neyraudia reynaudiana
Abstract
The effects of increasing concentrations of lead (Pb) on Pb accumulation, subcellular distribution, ultrastructure, photosynthetic characteristics, antioxidative enzyme activity, malondialdehyde content, and phytochelatin contents were investigated in Neyraudia reynaudiana seedlings after a 21-day exposure. A Pb analysis at the subcellular level showed that the majority of Pb in the roots was associated with the cell wall fraction, followed by the soluble fraction. In contrast, the majority of the Pb in the leaves was located in the soluble fraction based on transmission electron microscopy and energy dispersive X-ray analyses. Furthermore, high Pb concentrations adversely affected N. reynaudiana cellular structure. The changes in enzyme activity suggested that the antioxidant system plays an important role in eliminating or alleviating Pb toxicity, both in the roots and leaves of N. reynaudiana. Additionally, the phytochelatin contents in the roots and leaves differed significantly between Pb-spiked treatments and control plants. Our results provide strong evidence that cell walls restrict Pb uptake into the protoplasm and establish an important protective barrier. Subsequent vacuolar compartmentalization in leaves could isolate Pb from other substances in the cell and minimize Pb toxicity in other organelles over time. These results also demonstrated that the levels of antioxidant enzymes and phytochelatin in leaves and roots are correlated with Pb toxicity. These detoxification mechanisms promote Pb tolerance in N. reynaudiana.
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Green and sustainable remediation (GSR) evaluation: framework, standards, and tool. A case study in Taiwan
Abstract
Taiwan has a large number of poorly managed contaminated sites in need of remediation. This study proposes a framework, a set of standards, and a spreadsheet-based evaluation tool for implementing green and sustainable principles into remediation projects and evaluating the projects from this perspective. We performed a case study to understand how the framework would be applied. For the case study, we used a spreadsheet-based evaluation tool (SEFA) and performed field scale cultivation tests on a site contaminated with total petroleum hydrocarbons (TPHs). The site was divided into two lots: one treated by chemical oxidation and the other by bioremediation. We evaluated five core elements of green and sustainable remediation (GSR): energy, air, water resources, materials and wastes, and land and ecosystem. The proposed evaluation tool and field scale cultivation test were found to efficiently assess the effectiveness of the two remediation alternatives. The framework and related tools proposed herein can potentially be used to support decisions about the remediation of contaminated sites taking into account engineering management, cost effectiveness, and social reconciliation.
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The patterns of bacterial community and relationships between sulfate-reducing bacteria and hydrochemistry in sulfate-polluted groundwater of Baogang rare earth tailings
Abstract
Microorganisms are the primary agents responsible for the modification, degradation, and/or detoxification of pollutants, and thus, they play a major role in their natural attenuation; yet, little is known about the structure and diversity of the subsurface community and relationships between microbial community and groundwater hydrochemistry. In this study, denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism (T-RFLP) allowed a comparative microbial community analysis of sulfate-contaminated groundwater samples from nine different wells in the region of Baogang rare earth tailings. Using real-time PCR, the abundance of total bacteria and the sulfate-reducing genes of aprA and dsrB were quantified. Statistical analyses showed a clear distinction of the microbial community diversity between the contaminated and uncontaminated samples, with Proteobacteria being the most dominant members of the microbial community. SO42− concentrations exerted a significant effect on the variation of the bacterial community (P < 0.05), with higher concentrations of sulfate reducing the microbial diversity (H′ index), indicating that human activity (e.g., mining industries) was a possible factor disturbing the structure of the bacterial community. Quantitative analysis of the functional genes showed that the proportions of dsrB to total bacteria were 0.002–2.85 %, and the sulfate-reducing bacteria (SRB) were predominant within the prokaryotic community in the groundwater. The uncontaminated groundwater with low sulfate concentration harbored higher abundance of SRB than that in the polluted samples, while no significant correlation was observed between sulfate concentrations and SRB abundances in this study, suggesting other environmental factors possibly contributed to different distributions and abundances of SRB in the different sites. The results should facilitate expanded studies to identify robust microbe-environment interactions and provide a strong foundation for qualitative exploration of the bacterial diversity in rare earth tailings groundwater that might ultimately be incorporated into the remediation of environmental contamination.
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Functionalized iron oxide/SBA-15 sorbent: investigation of adsorption performance towards glyphosate herbicide
Abstract
Glyphosate is a worldwide-used herbicide occurring in many monitoring campaigns. Efficient technologies are currently unavailable for glyphosate removal from waters. In this work, a SBA-15 mesoporous silica-based material (Fe-NH2-SBA-15) was synthesized and studied for the adsorption of glyphosate from waters. In order to promote specific interactions between the sorbent and glyphosate via phosphoric group, iron oxide nanoparticles were encapsulated and a surface functionalization with (3-aminopropyl)triethoxysilane was accomplished. The adsorption of glyphosate on Fe-NH2-SBA-15 was investigated as a function of (i) pH, (ii) ionic strength (I), and (iii) adsorbate to adsorbent ratio (C), using a two-level, three-factor experimental design. The experimental design allowed for understanding the effect of the abovementioned variables and for proposing experimental conditions for quantitative removal (pH = 2.1, I = 1⋅10−2 M and C = 0.35) under both batch and dynamic conditions. Interaction mechanism between glyphosate and Fe-NH2-SBA-15 sorbent was elucidated by studying the adsorption behavior of sorbents derived from the intermediate stages of synthesis and by desorption tests. Fe-NH2-SBA-15 sorbent can be quantitatively regenerated by 12.5 mM NaOH, and can be reused at least for five adsorption/desorption cycles. Quantitative removal of glyphosate from inlet and effluent wastewaters from a wastewater treatment plant is shown.
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Assessment of plant growth promoting bacterial populations in the rhizosphere of metallophytes from the Kettara mine, Marrakech
Abstract
Soil heavy metal contamination resulting from mining activities constitutes a major environmental problem worldwide. The spread of heavy metals is often facilitated by scarce vegetation cover, so there is an urgent need to improve plant survival and establishment in these metalliferous areas. This study is aimed at the isolation and analysis of the phylogenetic relationship of culturable bacteria from the rhizosphere of metallophyte plants growing in the Kettara mine, in Marrakech, in order to select plant growth-promoting rhizobacteria (PGPR), which could be used in assisted-phytoremediation. Bacterial isolates were grouped by random amplified polymorphic DNA analysis and identified by 16S rRNA gene sequencing. Strains were further characterized for the production of plant growth-promoting (PGP) substances, such as NH3, siderophores, indol-3-acetic acid (IAA), hydrogen cyanide, and extracellular enzymes, for ACC-deaminase activity, their capacity to solubilize phosphate, and for their tolerance to heavy metals and acidic pH. Rhizosphere soils were highly contaminated with Cu and Zn and presented low fertility. Phylogenetic analysis showed that the rhizobacteria were affiliated to three major groups: γ-Proteobacteria (48 %), β-Proteobacteria (17 %), and Bacilli (17 %). The most represented genera were Pseudomonas (38 %), Bacillus (10 %), Streptomyces (10 %), and Tetrathiobacter (10 %). Overall, rhizobacterial strains showed an ability to produce multiple, important PGP traits, which may be helpful when applied as plant growth promoter agents in contaminated soils. PGPR were also able to withstand high levels of metals (up to 2615.2 mg Zn l−1, 953.29 mg Cu l−1, and 1124.6 mg Cd l−1) and the order of metal toxicity was Cd > Cu > Zn. The rhizobacterial strains isolated in the present study have the potential to be used as efficient bioinoculants in phytoremediation strategies for the recovery of Kettara mine soils.
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Synergistic effect of photocatalysis and adsorption of nano-TiO 2 self-assembled onto sulfanyl/activated carbon composite
Abstract
We report a significant synergistic effect of photocatalysis and adsorption by depositing 3–6 nm TiO2 particles onto sulfanyl (HS)/activated carbon composite using molecular self-assemble method in low-temperature aqueous system. The synergistic effect was studied by comparing pure TiO2 and TiO2/sulfanyl/activated carbon composite to photocatalytic degrade methylene blue (MB) in a quartz glass reactor. The results showed that the photocatalytic activity of the TiO2/HS/AC composite compared to pure TiO2 has been greatly enhanced calculated from a simulated first-order kinetics model. The synergistic enhancement at low MB concentration was significantly stronger than that at high concentration, and the synergistic effect calculated from the model at initial concentration of 1 mg/L was approximately 64 times than at initial concentration of 15 mg/L. This is because when the adsorption rate was much faster than the photocatalytic degradation rate, strong adsorption of MB molecules may inhibit subsequent photocatalytic degradation reaction. The enhancement was found mainly due to the strong synergistic effect of the adsorption of MB of sulfanyl/activated carbon substrate and the photocatalysis of TiO2 nanoparticles.
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Hydrogen-based membrane biofilm reactor for tetracycline removal: biodegradation, transformation products, and microbial community
Abstract
Tetracycline (TC) in aqueous environment could be reductively degraded by using a hydrogen-based membrane biofilm reactor (H2-MBfR) under denitrifying conditions as it provides an appropriate environment for the antibiotic-degrading bacteria in biofilm communities. This study evaluates the performance of H2-MBfR for simultaneous removal of nitrate and TC, formation of degradation products of TC, and community analysis of the biofilm grown on the gas-permeable hollow fiber membranes. Hence, a H2-MBfR receiving approximately 20 mg N/l nitrate and 0.5 mg/l TC was operated under different H2 pressures, hydraulic retention times (HRTs), and influent TC concentrations in order to provide various nitrate and TC loadings. The results showed that H2-MBfR accomplished successfully the degradation of TC, and it reached TC removal of 80–95 % at 10 h of HRT and 6 psi (0.41 atm) of H2 gas pressure. TC degradation took placed at increased HRT and H2 pressures while nitrate was the preferred electron acceptor for most of the electrons generated from H2 oxidation used for denitrification. The transformation products of TC were found at part per billion levels through all the experiments, and the concentrations decreased with the increasing HRT regardless of H2 pressure. Analyses from clone library showed that the microbial diversity at the optimal conditions was higher than that at the other periods. The dominant species were revealed to be Betaproteobacteria, Acidovorax caeni, and Alicycliphilus denitrificans.
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Simultaneous analysis 26 mineral element contents from highly consumed cultured chicken overexposed to arsenic trioxide by inductively coupled plasma mass spectrometry
Abstract
This study assessed the impacts of dietary arsenic trioxide (As2O3) on 26 mineral element contents in the liver and kidney of chicken. A total of 100 male Hy-line cocks were randomly divided into 2 groups (50 chickens in each group), including an arsenic-treated group (basic diet supplemented with As2O3 at 30 mg/kg) and a control group (basal diet). The feeding experiment lasted for 90 days and the experimental animals were given free access to feed and water. We determined 26 mineral elements in the liver and kidney by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that nine element levels (Al, Mn, Co, Cu, Zn, Se, Cd, Ba, and Pb) were significantly decreased (P < 0.05) in the liver of chickens exposed to As2O3 compared to the control chickens where three element levels (Ni, As, and Hg) increased significantly (P < 0.05). The results in the kidney showed that nine element levels (Al, K, Ca, Cr, Mn, Ni, Sb, Ba, and Pb) were significantly decreased (P < 0.05) in the chickens exposed to As2O3 compared to the control chickens where four element levels (Mo, As, Cd, and Hg) increased significantly (P < 0.05). These results suggest that supplementation of high levels of arsenic affected trace mineral levels in the liver and kidney of chicken, and the effects vary from organ to organ. The aim of this study is to provide references for further study of heavy metal poisoning by detecting the contents of minerals induced by arsenic in chicken.
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Influence of metals on rhinosinusal polyposis in Sardinian population (Italy)
Abstract
Metals have strong toxic effects in humans and can act as immunoregulatory factors. The purpose of our study was to determine whether the concentrations of metals are associated with the clinical course of nasal polyposis (NP). We measured the concentrations of 10 metals and non-metal (Zn, Mn, Se, Fe, Cr, Ni, Pb, Al, Cd, and Cu) in 58 patients with NP, and 29 controls with a healthy nasal mucosa. We used electron microscopy to compare the ultrastructural features of the nasal mucosa between NP patients and healthy controls. Concentrations of metals in nasal polyps and healthy mucosa were determined by mass spectrometry. Transmission electron microscopic (TEM) and scanning electron microscopic (SEM) images of the nasal mucosa were obtained. The mean tissue concentrations of all 10 metals and non-metal were significantly lower in NP patients than in healthy controls (P < 0.05).TEM and SEM revealed changes in the mucosal ultrastructure in NP with progressive fibrosis, devascularisation, and inflammation. Tissue concentrations of metals were lower in NP patients than in healthy controls, and this was particularly evident in massive polyposis.
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Evaluation of estrogenic activity in the Pearl River by using effect-directed analysis
Abstract
This study investigated estrogenic activity of water, sediment, and fish bile of the Pearl River in southern China by effect-directed analysis based on in vitro yeast screen assay and chemical analysis. Results showed higher estradiol equivalents (EEQ) for surface water in dry season than in wet season. Simple risk assessment suggested that high estrogenic risk would be expected in Shima River and Danshui River receiving discharge of effluents from cities in the region. Fractionation and effect-directed analysis showed that estrogenic activity mainly occurred in relatively polar fractions of surface water. Seven target estrogenic compounds (bisphenol A, 4-nonylphenol, 4-tert-octylphenol, 17α-ethynyl estradiol, estrone, diethylstilbestrol, and 17β-estradiol) only accounted for part of the measured estrogenic activity, with the rest contributions from other potential estrogenic chemicals such as phenols. Findings from this study suggest that fish in the river could be affected by those estrogenic chemicals. Proper measures should be taken to reduce the estrogenic activity in wastewaters before they are discharged into the riverine system in order to protect aquatic organisms.
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