Anti-angiogenic treatment for breast cancer?

Publication date: Available online 9 March 2017
Source:Cancer Treatment Reviews
Author(s): Johannes Pieter van Netten, Stephen Hoption Cann, Ian Thornton, Rory P. Finegan, Chris Maxwell




http://ift.tt/2m6xQCw

The role of drug-drug interactions in prostate cancer treatment: focus on abiraterone acetate/prednisone and enzalutamide

Publication date: Available online 9 March 2017
Source:Cancer Treatment Reviews
Author(s): Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications. Therefore, abiraterone may increase plasma levels of CYP2D6 substrates, including amitriptyline, oxycodone and risperidone, as well as of CYP2C8 substrates including amiodarone and carbamazepine. Since enzalutamide is extensively metabolized by CYP2C8, its plasma levels are likely to be raised if coadministered with strong CYP2C8 inhibitors such as gemfibrozil or pioglitazone. Inducers of CYP2C8 (i.e., rifampin) may reduce the effectiveness of enzalutamide and hence should be avoided. Enzalutamide may decrease plasma levels of CYP3A4, 2C9 and 2C19 substrates including disopiramide, quetiapine, quinidine and warfarin. Growing awareness of the importance of DDIs in cancer patients is now reflected in the variety of web-based sources offering information and guidance. However, the evaluation of the clinical relevance of DDIs is the result of a comprehensive evaluation of many factors, including therapeutic index, amplitude of therapeutic range and presence of comorbidities, requiring a specific expertise in clinical pharmacology.

Graphical abstract

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Incidental Findings on Pediatric Abdominal Magnetic Resonance Angiography

Publication date: Available online 9 March 2017
Source:Academic Radiology
Author(s): Nattinee Leelakanok, Matthew A. Zapala, Emily A. Edwards, Andrew S. Phelps, John D. Mackenzie, Jesse Courtier
Rationale and ObjectivesAbdominal magnetic resonance angiography (MRA) has gained favor in pediatric patients owing to its lack of ionizing radiation and noninvasive nature. Reports exist regarding incidental findings on body MRA in adult patients. However, the incidental findings in pediatric abdominal MRA have not been previously reported. Our study aims to determine the frequencies, characteristics, and categories of incidental findings in pediatric patients undergoing abdominal MRA.Materials and MethodsRetrospective study was performed in 78 consecutive contrast-enhanced abdominal MRA of patients between ages 0 and 20 years over a 7-year time period. The presence of incidental vascular and extravascular findings was noted. Reports were categorized in consensus by two radiologists as no incidental finding (group A), normal or normal variants or nonsignificant incidental common findings (group B), or abnormal incidental findings (group C). Group C was reviewed to determine whether additional management was performed.ResultsA total of 40 boys and 38 girls (51%:49%) were reported, with a mean age of 12.3 years (standard deviation ±5.6 years, range 7 days to 20 years). Three most common indications for MRA were renal artery stenosis (24.4%), vasculitis (21.8%), and suspected intra-abdominal venous thrombosis (14.1%). We identified a total of 92 incidental findings in 50 of 78 patients; 60 findings in 29 patients in group B, and 32 findings in 21 patients in group C. Atelectasis at the lung bases was the most common incidental finding in group B (14 of 78 patients). The most common findings in group C were ascites, scoliosis, and splenomegaly. There were three abnormal incidental findings that led to causative workup and/or further management (moderate ascites, pericardial and pleural effusion, and venous malformation). The remaining cases with abnormal findings received treatment of their primary conditions only.ConclusionsPediatric abdominal MRA revealed a large number of incidental findings. The large majority were findings without clinical significance. Basal lung atelectasis was the most common overall incidental and nonsignificant finding, whereas ascites was the most common abnormal incidental finding. Although not all abnormal incidental findings affected management, appropriate identification and communication of relevant findings would improve patient care.



http://ift.tt/2mHrKwc

Dosimetric Analysis of Liver Toxicity Post Liver Metastasis Stereotactic Body Radiotherapy

Publication date: Available online 9 March 2017
Source:Practical Radiation Oncology
Author(s): A. Barry, A. McPartlin, P. Lindsay, L. Wang, J Brierley, J Kim, J Ringash, R Wong, R Dinniwell, T. Craig, L.A. Dawson
PurposeThe aim of this study is to describe the incidence and type of liver toxicity seen following liver metastases stereotactic body radiotherapy (SBRT) and the corresponding clinical and dosimetric factors associated with toxicity.Methods and MaterialsBetween 2002 and 2009, 81 evaluable patients with liver metastases were treated on two prospective studies assessing SBRT, with prescription doses based on the effective liver volume irradiated evaluated. Toxicity was defined as grade≥2 classic or non-classic radiation induced liver disease (RILD). Specific toxicity endpoints evaluated were worsening transaminases and albumin levels, within 3months of SBRT.ResultsSeventy percent of patients had colorectal carcinoma, 55% had extra-hepatic disease, 1 patient had Hepatitis B and 54% had received prior chemotherapy. Baseline transaminases were elevated at CTCAE V4.0 grade 1, 2 and 3 levels in 33 (41%), 2 (2%) and 0 (0%) of patients. The mean prescription dose was 43Gy (27.7 – 60Gy) in 6 fractions. The mean liver (minus GTV) dose (MLD) was 16Gy (3–25.6Gy) in 6 fractions. No classic or non-classical ≥ grade 2 RILD was observed. Within 3months of SBRT, 49 (61%) patients had worsening of grade of transaminase and 23 (28%) patients had a reduction in albumin, all transient (majority grade≤2 toxicity) without subsequent clinical toxicity. Seventeen patients exceeded QUANTEC MLD guidelines (≤20Gy), 13 (76%) of whom had worsening of transaminase grade. On multivariate analysis, worsening of liver enzymes was more likely in patients with higher doses to the spared 700cc of liver (p=0.026), and reduction of albumin was more likely with higher effective liver volume (OR 1.53 (1.08, 2.16)) p=0.016).ConclusionLiver metastases SBRT is safe with a low risk of transient biochemical liver toxicity, more likely in patients with a higher effective liver volume and higher doses to the spared uninvolved liver volume.



http://ift.tt/2m6cSE0

Outcomes and Toxicity following High-Dose Radiation Therapy in 15 Fractions for Non-Small Cell Lung Cancer

Publication date: Available online 9 March 2017
Source:Practical Radiation Oncology
Author(s): Penny Fang, Cameron W. Swanick, Todd A. Pezzi, Zhongxing Liao, James Welsh, Steven H. Lin, Daniel R. Gomez
Background and PurposeAccelerated hypofractionated radiation therapy (AHRT) is increasingly used for select lung cancer patients. We evaluated clinical outcomes and predictors of pulmonary/esophageal toxicity in patients treated with ≥52.5Gy in 15 fractions.Material and MethodsWe evaluated 229 patients treated with RT doses ≥52.5Gy in 15 fractions for non-small cell lung cancer from January 2009–January 2016. Toxicity was scored using Common Terminology Criteria for Adverse Events, v4.0. Univariate and multivariate logistic regression was used to identify predictors of toxicity. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using Kaplan–Meier method. Predictors of clinical outcome were modeled using Cox proportional hazards regression.ResultsMedian follow-up was 7months. Forty-two patients (19%) developed grade≥2 pneumonitis, and nine (4%) grade≥3 esophagitis. In multivariate analysis, age>75years (OR2.56, 95%CI 1.24–5.25, P=0.01) and lung V10≥32% were associated with grade≥2 pneumonitis (OR2.79, 95%CI 1.39–5.79, P=0.005). On univariate analysis, esophagus mean dose ≥17Gy (OR10.14, 95%CI 1.82–189.8, P=0.006), GTV size ≥71cm3 (P=0.002) and PTV size ≥409cm3 (P=0.02) were associated with development of grade≥3 esophagitis. In patients with stage II/III disease (n=73), median LC was not reached, median OS 14months, and median PFS 6months.ConclusionsAHRT in 15 fractions can be safe and effective. Consideration for using AHRT with immunotherapy and sequential chemotherapy for improved out-of-radiation field and distant control is warranted.



http://ift.tt/2mO0ehl

Persistent nasal carriers of Acinetobacter baumannii in long-term-care facilities

Publication date: Available online 9 March 2017
Source:American Journal of Infection Control
Author(s): Ming-Li Liou, Kuan-Hsueh Chen, Hui-Ling Yeh, Chun-Yi Lai, Chang-Hua Chen
BackgroundAcinetobacter baumannii and Staphylococcus aureus have persisted as 2 major pathogens worldwide.AimWe designed a prevalence study to investigate the prevalence of nasal carriage of S aureus and A baumannii in long-term-care facilities (LCTFs) and their collaborative community hospitals. In addition, we aimed to clarify persistent or nonpersistent carriage of the 2 organisms among residents of LTCFs.MethodsWe performed a prevalence study concerning nasal carriers of A baumannii and S aureus in 3 LTCFs and 1 collaborative community hospital.ResultsSeventy subjects were enrolled and clustered into 3 groups: the elderly sick group (n = 24), the elderly healthy group (n = 33), and the healthy health care worker group (n = 13). Nasal samples were collected, and the nuc and mecA genes of S aureus and the blaOXA gene of A baumannii were analyzed by polymerase chain reaction. Among the 3 groups, the rate of nasal carriage of S aureus was approximately 0%-15%. However, the rate for A baumannii was approximately 54%-92%. Notably, the persistent carrier rate of A baumannii in the elderly sick group was 83.3% (20 out of 24) despite a 12.5% (3 out of 24) rate of carbapenem-resistant A baumannii.ConclusionsWe emphasized that the persistent nasal carriage of A baumannii in LTCFs could be another portal of exit to cause A baumannii infection in Taiwan.



http://ift.tt/2m99Teu

A New Keystone Flap “Plus” Design: Case Series and Analysis of Follow-Up

The original keystone island flap, originally described by Behan (1), is a surgical technique used after the removal of skin cancer in order to close skin defects. It is essentially two end-to-side V-Y flaps based on fasciocutaneous perforators, offering both the robust vascularity of perforator flaps and the relative ease and speed of local tissue rearrangement (2). Some authors (3, 4) highlight the advantages of this technique. Other authors applied their own modifications improving the technique (5).

http://ift.tt/2m99Jnt

Failure to Diagnose an Incompetent Cervix,Premature Birth Lawsuits,Universal Cervical Length Screening,καθ' έξιν αποβολές, ανεπάρκεια τραχήλου,. πρόωρος τοκετός ... νομικό πλαίσιο−αστική−ποινική ευθύνη στη μαιευτική− γυναικολογία

http://emergencymedicinesfakianakis.blogspot.com/2017/03/premature-birth-lawsuitsuniversal.html

Every expectant mother hopes that her pregnancy will go full-term and that she will have a healthy baby to take home from the hospital. The unborn baby continues to grow throughout the entire pregnancy, and it has the best chance at being healthy when born after 37 weeks of pregnancy.

Unfortunately, 1 out of every 10 births in the U.S.—or an estimated 380,000 babies each year – are delivered too soon, often with devastating, life-changing results.

There are many factors that can contribute to a baby being born prematurely, and some are simply unavoidable in nature. However, there are some premature births that can be prevented, and may in fact be caused by a doctor's deviation from the accepted standard of care.

Some of our many multi-million-dollar recoveries have involved:

Injuries from premature delivery due to the failure to place a cervical cerclage for cervical incompetence or insufficiency

The failure to properly manage preeclampsia and delayed delivery, resulting in placental abruption and fetal bradycardia

Injuries suffered as a result of medication errors in neonatal intensive care units, or NICUs

Injuries from the failure to address non-reassuring fetal heart tracings

There are numerous causes for a premature birth, and doctors must be aware of them in order to appropriately care for expectant mothers. These are just some of the causes:

Women with a history of a second trimester miscarriage or a previous premature delivery

Women who are found to have a short cervix (a condition where the cervix is not the length that it should be) during a routine sonogram

Women with recurrent urinary tract infections

Women with diabetes – gestational or pre-gestational

Women with hypertension, which can result in preeclampsia

African American women, who, regardless of age or other conditions, are naturally at greater risk for delivering premature babies

Women with vaginal infections or sexually transmitted diseases

Because there are many things that can cause a baby to be born early, a doctor needs to ask the right questions of the expectant mother. Failure of the doctor to recognize, properly monitor and/or treat any of the factors mentioned can certainly rise to the level of negligence and malpractice. If this has occured to your baby, you should speak with an experienced premature birth attorney.

Expectant mothers should give their doctors as much information as they can about their medical history, but they may not be aware of all of the things that can contribute to premature birth. Consequently, a doctor must be prepared to ask pertinent questions to have all of the information needed to lower the chances of an early birth. If a doctor neglects to ask thorough questions and fails to act appropriately once the information is obtained and a baby is born premature as a result, it could be a case of malpractice and the mother may have grounds for a premature birth lawsuit.

When a premature birth does occur, there are many medical complications that can affect the child, and there is a higher risk of serious disability or death the earlier the baby is born. Some problems that a baby born too early may face include:

Breathing problems

Difficulty feeding

Increased risk of severe infection

Neurological problems

Cerebral palsy

Delayed development

Vision and hearing impairment

Determining whether or not a premature birth could have been prevented can be complicated, so it is imperative that you have both legal and medical experts to help and support you. 

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Permanent prostate brachytherapy pubic arch evaluation with diagnostic MRI

Publication date: Available online 9 March 2017
Source:Brachytherapy
Author(s): Geoffrey V. Martin, Thomas J. Pugh, Usama Mahmood, Rajat J. Kudchadker, Jihong Wang, Teresa L. Bruno, Tharakeswara Bathala, Steven J. Frank
PurposePubic arch interference (PAI), when it occurs, is often a limiting factor for patients pursuing brachytherapy treatment of prostate cancer. Pre-brachytherapy pubic arch evaluation is often performed by CT or transrectal ultrasound (TRUS), but MRI has increasingly replaced these modalities for prostate cancer evaluation. The purpose of this study was to determine if staging MRI could be used to evaluate PAI and compare it with these other imaging methods.Methods and MaterialsForty-one consecutive patients undergoing brachytherapy evaluation had pelvic MRI-, CT-, and TRUS-based brachytherapy simulation. Pubic arch overlap on T2-weighted MRI and CT was determined by contouring the prostate gland on its largest axial slice and superimposing this contour onto the pubic arch bones. The largest degree of overlap of the prostate gland on MRI and CT was used to predict the existence of PAI as determined by TRUS-based simulation. The correlation between prostate contour overlap was also compared between MRI and CT.ResultsNineteen patients (48%) exhibited PAI on TRUS brachytherapy simulation evaluation. The average (±standard error) amount of prostate contour overlap on the pubic arch on CT was 2.9 ± 0.6 mm and on MRI was 2.0 ± 0.6 mm (linear correlation, R, of 0.783, p < 0.001). CT and MRI were equally predictive of PAI on TRUS evaluation (area under the curve = 0.75).ConclusionPre-brachytherapy pubic arch assessment with diagnostic MRI provides similar predictability of PAI compared with CT, potentially obviating the need for additional pre-brachytherapy CT in the setting of staging MRI.



http://ift.tt/2mrUybu

Assessment of clinical and radiologic differences between small and large adrenal pheochromocytomas

Publication date: Available online 10 March 2017
Source:Clinical Imaging
Author(s): Dong Won Kim, Seong Kuk Yoon, Sang Hyeon Kim, Eun Ju Kang, Hee Jin Kwon
ObjectiveTo evaluate differences in clinical and radiologic features of small and large pheochromocytomas.Materials and methodsThis study included 39 patients with adrenal pheochromocytomas. Several clinical and radiologic features were statistically analyzed and compared between small and large pheochromocytomas.ResultsNo significant differences were found in clinical features between them. Small pheochromocytomas had more relatively homogeneous attenuation although large pheochromocytomas had more cystic or necrotic changes.ConclusionsPheochromocytomas tend to have different CT imaging features mimicking other tumors according to the size of the tumors. However, clinical features, CT imaging characteristics, and radioisotope activity are not different between small and large pheochromocytomas.



http://ift.tt/2m6lwlB

Use of hepatobiliary phase images in Gd-EOB-DTPA-enhanced MRI of breast cancer hepatic metastasis to predict response to chemotherapy

Publication date: Available online 9 March 2017
Source:Clinical Imaging
Author(s): Hyun Ji Lee, Chang Hee Lee, Jeong Woo Kim, Yang Shin Park, Jongmee Lee, Kyeong Ah Kim
ObjectivesTo determine the prognostic value of Gd-EOB-DTPA MRI findings of liver metastasis from breast cancer.Methods29 metastatic lesions from 12 breast cancer patients who received chemotherapy were retrospectively reviewed. We evaluated hepatobiliary phase of the lesions and classified them as a "target" or "non-target" appearance. The relationship of appearance or SI ratio with tumor response was analyzed.ResultsA non-target appearance was more frequent in disease control group than in non-control group [14/18 (77.8%) vs. 4/18 (22.2%)], and it was associated with a better response [p=0.048].ConclusionHBP analysis may be useful to predict the response to chemotherapy and survival.



http://ift.tt/2mNGHxb

Unusual ultrasound appearance of small bowel intussusception and secondary bowel obstruction in a child with Peutz-Jeghers syndrome

Publication date: Available online 9 March 2017
Source:Clinical Imaging
Author(s): Lei Wu, Ramesh S. Iyer, George T. Drugas, A. Luana Stanescu
Small bowel intussusception (SBI) in pediatric patients resolves spontaneously in the majority of cases. Pathologic small bowel intussusception with a lead point is rare in children. Ultrasound (US) is the preferred initial imaging study for the diagnosis of intussusception. We report a case of long-segment SBI and secondary bowel obstruction caused by a large hamartomatous polyp.This case emphasizes unique, atypical ultrasound findings that may be encountered in small bowel intussusception, with correlative radiographic, CT (computed tomography) and intra-operative findings. Increased awareness of these atypical imaging features can lead to early diagnosis and decrease the risk of potential complications including mesenteric venous thrombosis, bowel ischemia and necrosis.



http://ift.tt/2m67joS

Contrast-enhanced ultrasound and computed tomography findings of granulomatosis with polyangiitis presenting with multiple intrarenal microaneurysms: A case report

Publication date: Available online 9 March 2017
Source:Clinical Imaging
Author(s): Youe Ree Kim, Young Hwan Lee, Jong-Ho Lee, Kwon-Ha Yoon
Granulomatosis with polyangiitis (GPA) is a systemic disorder that affects small- and medium- sized vessels in many organs. Although the kidneys are the second most commonly involved organ in patients with GPA, its manifestation as multiple intrarenal aneurysms is rare. We report an unusual manifestation of GPA with multiple intrarenal microaneurysms, as demonstrated by contrast-enhanced ultrasound and computed tomography.



http://ift.tt/2mNSjjW

Neocortical and hippocampal TREM2 protein levels during the progression of Alzheimer’s disease

Publication date: Available online 9 March 2017
Source:Neurobiology of Aging
Author(s): Sylvia E. Perez, Muhammad Nadeem, Bin He, Jennifer C. Miguel, Michael H. Malek-Ahmadi, Kewei Chen, Elliott J. Mufson
Heterozygous TREM2 mutations are an Alzheimer's disease (AD) risk factor. Non-mutated TREM2 dysregulation occurs in AD brain. Whether TREM2 is altered in prodromal AD remains unknown. Western blotting was used to determine levels of TREM2 (∼ 25 kDa) and Iba1 in the frontal cortex and TREM2 in the hippocampus from people who died with an ante-mortem clinical diagnosis of non- and mild-cognitive impairment, mild/moderate AD (mAD) and severe AD (sAD). Immunohistochemistry defined the relationship between amyloid and Iba1 profiles. PCR analysis revealed that all subjects did not carry the most common R47H TREM2 variant. TREM2 was significantly upregulated in sAD frontal cortex, but stable in hippocampus. Frontal TREM2 mRNA and protein level patterns were similar, but not significantly different. Iba1 immunopositive microglia counts increased significantly in frontal cortex containing plaques in sAD. TREM2 and Iba1 levels were not associated with plaques, tangles, neuropathological criteria or cognitive performance. Frontal cortex TREM2 upregulation is a late event and may not play a major role early in the pathogenesis of the disease.



http://ift.tt/2m90L9I

Engineering intravaginal vaccines to overcome mucosal and epithelial barriers

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Zhonghua Ji, Zhaolu Xie, Zhirong Zhang, Tao Gong, Xun Sun
The mucosal surface of the vagina is a primary human immunodeficiency virus (HIV) entry portal, making it an attractive site for HIV vaccination. However, HIV vaccines based on recombinant adenovirus (rAd) do not efficiently cross the mucus layers or underlying epithelium of the vagina. Here we designed nanocomplexes of rAd particles coated with (1) the polyethylene glycol derivative APS to provide a hydrophilic surface that would prevent entrapment in the hydrophobic mucus, and (2) the cell-penetrating peptide TAT to improve transduction efficiency. The optimized rAd-TAT-APS nanocomplexes could achieve the balance of effective mucus-penetrating and cellular transduction. Intravaginal delivery of rAd-TAT-APS encoding HIVgag p24 into mice strongly enhanced HIVgag-specific systemic and mucosal immune responses. This rAd-TAT-APS system may allow effective vaginal delivery of vaccines against HIV and other infectious agents.



http://ift.tt/2nc9c5h

Islet encapsulation with polyphenol coatings decreases pro-inflammatory chemokine synthesis and T cell trafficking

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Dana Pham-Hua, Lindsey E. Padgett, Bing Xue, Brian Anderson, Michael Zeiger, Jessie M. Barra, Maigen Bethea, Chad S. Hunter, Veronika Kozlovskaya, Eugenia Kharlampieva, Hubert M. Tse
Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of islet-infiltrating leukocytes involved in pancreatic β-cell lysis. One promising treatment for T1D is islet transplantation; however, clinical application is constrained due to limited islet availability, adverse effects of immunosuppressants, and declining graft survival. Islet encapsulation may provide an immunoprotective barrier to preserve islet function and prevent immune-mediated rejection after transplantation. We previously demonstrated that a novel cytoprotective nanothin multilayer coating for islet encapsulation consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), was efficacious in dampening in vitro immune responses involved in transplant rejection and preserving in vitro islet function. However, the ability of (PVPON/TA) to maintain islet function in vivo and reverse diabetes has not been tested. Recent evidence has demonstrated that modulation of redox status can affect pro-inflammatory immune responses. Therefore, we hypothesized that transplanted (PVPON/TA)-encapsulated islets can restore euglycemia to diabetic mice and provide an immunoprotective barrier. Our results demonstrate that (PVPON/TA) nanothin coatings can significantly decrease in vitro chemokine synthesis and diabetogenic T cell migration. Importantly, (PVPON/TA)-encapsulated islets restored euglycemia after transplantation into diabetic mice. Our results demonstrate that (PVPON/TA)-encapsulated islets may suppress immune responses and enhance islet allograft acceptance in patients with T1D.



http://ift.tt/2mHapnh

Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Jaya Arya, Sebastien Henry, Haripriya Kalluri, Devin V. McAllister, Winston P. Pewin, Mark R. Prausnitz
To support translation of microneedle patches from pre-clinical development into clinical trials, this study examined the effect of microneedle patch application on local skin reactions, reliability of use and acceptability to patients. Placebo patches containing dissolving microneedles were administered to fifteen human participants. Microneedle patches were well tolerated in the skin with no pain or swelling and only mild erythema localized to the site of patch administration that resolved fully within seven days. Microneedle patches could be administered by hand without the need of an applicator and delivery efficiencies were similar for investigator-administration and self-administration. Microneedle patch administration was not considered painful and the large majority of subjects were somewhat or fully confident that they self-administered patches correctly. Microneedle patches were overwhelmingly preferred over conventional needle and syringe injection. Altogether, these results demonstrate that dissolving microneedle patches were well tolerated, easily usable and strongly accepted by human subjects, which will facilitate further clinical translation of this technology.



http://ift.tt/2n5sMmU

The Transient Receptor Potential Melastatin 7 Channel Regulates Pancreatic Cancer Cell Invasion through the Hsp90α/uPA/MMP2 pathway

Publication date: April 2017
Source:Neoplasia, Volume 19, Issue 4
Author(s): Pierre Rybarczyk, Alison Vanlaeys, Bertrand Brassart, Isabelle Dhennin-Duthille, Denis Chatelain, Henri Sevestre, Halima Ouadid-Ahidouch, Mathieu Gautier
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a very poor prognosis. There is an urgent need to better understand the molecular mechanisms that regulate PDAC cell aggressiveness. The transient receptor potential melastatin 7 (TRPM7) is a nonselective cationic channel that mainly conducts Ca²⁺ and Mg²⁺. TRPM7 is overexpressed in numerous malignancies including PDAC. In the present study, we used the PANC-1 and MIA PaCa-2 cell lines to specifically assess the role of TRPM7 in cell invasion and matrix metalloproteinase secretion. We show that TRPM7 regulates Mg²⁺ homeostasis and constitutive cation entry in both PDAC cell lines. Moreover, cell invasion is strongly reduced by TRPM7 silencing without affecting the cell viability. Conditioned media were further studied, by gel zymography, to detect matrix metalloproteinase (MMP) secretion in PDAC cells. Our results show that MMP-2, urokinase plasminogen activator (uPA), and heat-shock protein 90α (Hsp90α) secretions are significantly decreased in TRPM7-deficient PDAC cells. Moreover, TRPM7 expression in human PDAC lymph node metastasis is correlated to the channel expression in primary tumor. Taken together, our results show that TRPM7 is involved in PDAC cell invasion through regulation of Hsp90α/uPA/MMP-2 proteolytic axis, confirming that this channel could be a promising biomarker and possibly a target for PDAC metastasis therapy.



http://ift.tt/2nccaGG

Reactivating p53 and Inducing Tumor Apoptosis (RITA) Enhances the Response of RITA-Sensitive Colorectal Cancer Cells to Chemotherapeutic Agents 5-Fluorouracil and Oxaliplatin

Publication date: April 2017
Source:Neoplasia, Volume 19, Issue 4
Author(s): Armin Wiegering, Niels Matthes, Bettina Mühling, Monika Koospal, Anne Quenzer, Stephanie Peter, Christoph-Thomas Germer, Michael Linnebacher, Christoph Otto
Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death. Additionally, it has been shown that RITA can induce DNA damage signaling. It is expected that the therapeutic benefits of 5FU and oxaliplatin can be increased by enhancing DNA damage signaling pathways. Therefore, we highlighted the antiproliferative response of RITA alone and in combination with 5FU or oxaliplatin in human CRC cells. A panel of long-term established CRC cell lines (n=9) including p53 wild-type, p53 mutant, and p53 null and primary patient-derived, low-passage cell lines (n=5) with different p53 protein status were used for this study. A substantial number of CRC cells with pronounced sensitivity to RITA (IC50<3.0 μmol/l) were identified within established (4/9) and primary patient-derived (2/5) CRC cell lines harboring wild-type or mutant p53 protein. Sensitivity to RITA appeared independent of p53 status and was associated with an increase in antiproliferative response to 5FU and oxaliplatin, a transcriptional increase of p53 targets p21 and NOXA, and a decrease in MYC mRNA. The effect of RITA as an inducer of DNA damage was shown by a strong elevation of phosphorylated histone variant H2A.X, which was restricted to RITA-sensitive cells. Our data underline the primary effect of RITA, inducing DNA damage, and demonstrate the differential antiproliferative effect of RITA to CRC cells independent of p53 protein status. We found a substantial number of RITA-sensitive CRC cells within both panels of established CRC cell lines and primary patient-derived CRC cell lines (6/14) that provide a rationale for combining RITA with 5FU or oxaliplatin to enhance the antiproliferative response to both chemotherapeutic agents.



http://ift.tt/2n5I0rT

Noninvasive Bioluminescence Imaging of AKT Kinase Activity in Subcutaneous and Orthotopic NSCLC Xenografts: Correlation of AKT Activity with Tumor Growth Kinetics

Publication date: April 2017
Source:Neoplasia, Volume 19, Issue 4
Author(s): Karina Suchowski, Thomas Pöschinger, Alnawaz Rehemtulla, Michael Stürzl, Werner Scheuer
Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung cancer therapy. A549 non–small cell lung cancer cell line, engineered to express BAR, enabled the evaluation of compounds targeting the EGFR/PI3K/AKT pathway in vitro as well as in mouse models. We found that erlotinib treatment of resistant A549 subcutaneous and orthotopic xenografts resulted in significant AKT inhibition as determined by an 8- to 13-fold (P < .0001) increase in reporter activity 3 hours after erlotinib (100 mg/kg) administration compared to the control. This was confirmed by a 25% (P < .0001) decrease in pAKT ex vivo and a decrease in tumor growth. Treatment of the orthotopic xenograft with varying doses of erlotinib (25, 50, and 100 mg/kg) revealed a dose- and time-dependent increase in reporter activity (10-, 12-, and 23-fold). Correspondingly, a decrease in phospho-AKT levels (0%, 16%, and 28%, respectively) and a decrease in the AKT dependent proliferation marker PCNA (0%, 50%, and 50%) were observed. We applied μ-CT imaging for noninvasive longitudinal quantification of lung tumor load which revealed a corresponding decrease in tumor growth in a dose-dependent manner. These findings demonstrate the utility of BAR to noninvasively monitor AKT activity in preclinical studies in response to AKT modulating agents. These results also demonstrate that BAR can be applied to study drug dosing, drug combinations, and treatment efficacy in orthotopic mouse lung tumor models.



http://ift.tt/2ncfaDj

Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma

Publication date: Available online 9 March 2017
Source:Cell Stem Cell
Author(s): Demeng Chen, Mansi Wu, Yang Li, Insoon Chang, Quan Yuan, Mari Ekimyan-Salvo, Peng Deng, Bo Yu, Yongxin Yu, Jiaqiang Dong, John M. Szymanski, Sivakumar Ramadoss, Jiong Li, Cun-Yu Wang
Squamous cell carcinoma in the head and neck (HNSCC) is a common yet poorly understood cancer, with adverse clinical outcomes due to treatment resistance, recurrence, and metastasis. Putative cancer stem cells (CSCs) have been identified in HNSCC, and BMI1 expression has been linked to these phenotypes, but optimal treatment strategies to overcome chemotherapeutic resistance and eliminate metastases have not yet been identified. Here we show through lineage tracing and genetic ablation that BMI1⁺ CSCs mediate invasive growth and cervical lymph node metastasis in a mouse model of HNSCC. This model and primary human HNSCC samples contain highly tumorigenic, invasive, and cisplatin-resistant BMI1⁺ CSCs, which exhibit increased AP-1 activity that drives invasive growth and metastasis of HNSCC. Inhibiting AP-1 or BMI1 sensitized tumors to cisplatin-based chemotherapy, and it eliminated lymph node metastases by targeting CSCs and the tumor bulk, suggesting potential regimens to overcome resistance to treatments and eradicate HNSCC metastasis.

Graphical abstract

Teaser

Chen et al. show that BMI1⁺ CSCs drive invasive growth and cervical lymph node metastasis in squamous cell carcinoma. BMI1⁺ CSCs have increased AP-1 activity and are chemotherapy resistant, and combination therapy that targets BMI1⁺ CSCs and the tumor bulk yields better outcomes and effectively eliminates metastasis.


http://ift.tt/2mpjoqZ

PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation

Publication date: Available online 9 March 2017
Source:Cell Stem Cell
Author(s): Sara Cruz-Molina, Patricia Respuela, Christina Tebartz, Petros Kolovos, Milos Nikolic, Raquel Fueyo, Wilfred F.J. van Ijcken, Frank Grosveld, Peter Frommolt, Hisham Bazzi, Alvaro Rada-Iglesias
Poised enhancers marked by H3K27me3 in pluripotent stem cells have been implicated in the establishment of somatic expression programs during embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Using CRISPR/Cas9 technology to engineer precise genetic deletions, we demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Interestingly, circularized chromosome conformation capture sequencing (4C-seq) shows that poised enhancers already establish physical interactions with their target genes in ESCs in a polycomb repressive complex 2 (PRC2)-dependent manner. Loss of PRC2 does not activate poised enhancers or induce their putative target genes in undifferentiated ESCs; however, loss of PRC2 in differentiating ESCs severely and specifically compromises the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates an unexpected function for polycomb proteins in facilitating neural induction by endowing major anterior neural loci with a permissive regulatory topology.

Graphical abstract

Teaser

Cruz-Molina et al. demonstrate that pluripotent-associated poised enhancers are necessary for the induction of anterior neural genes. Poised enhancers physically interact with their target genes in embryonic stem cells in a PRC2-dependent manner. Thus, polycomb proteins might facilitate neural induction by providing anterior neural loci with a permissive regulatory topology.


http://ift.tt/2mpuX1q

Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells

Publication date: Available online 9 March 2017
Source:Cell Stem Cell
Author(s): Francisco M. Barriga, Elisa Montagni, Miyeko Mana, Maria Mendez-Lago, Xavier Hernando-Momblona, Marta Sevillano, Amy Guillaumet-Adkins, Gustavo Rodriguez-Esteban, Simon J.A. Buczacki, Marta Gut, Holger Heyn, Douglas J. Winton, Omer H. Yilmaz, Camille Stephan-Otto Attolini, Ivo Gut, Eduard Batlle
Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes. During homeostasis, Mex3a+ cells continually shift into the rapidly dividing, self-renewing ISC pool. Chemotherapy and radiation preferentially target rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, helping to promote regeneration of the intestinal epithelium following toxic insults. Thus, Mex3a defines a reserve-like ISC population within the Lgr5+ compartment.

Graphical abstract

Teaser

Lgr5+ intestinal stem cells are considered to be a homogeneous and rapidly proliferating population. Barriga et al. show that the RNA binding protein Mex3a defines a subset of slowly proliferating Lgr5+ cells that contribute to all intestinal lineages with slow kinetics, are resistant to chemotherapy, and support intestinal regeneration.


http://ift.tt/2mpl7wz

Stimuli-responsive shell cross-linked micelles from amphiphilic four-arm star copolymers as potential nanocarriers for “pH/redox-triggered” anticancer drug release

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Di Xiong, Na Yao, Huawei Gu, Jufang Wang, Lijuan Zhang
A novel amphiphilic four-arm star copolymer [poly(ε-caprolactone)-b-poly(poly(ethylene glycol) methyl ether methacrylate-co-p-(2-methacryloxyethoxy) benzaldehyde)]4 [4-AS-PCL-P(PEGMA-co-MAEBA)] was designed and synthesized by a combination of ring-opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). Stimuli-responsive cross-linked micelles (SCMs) were prepared by crosslinking the shell structure of the self-assembled micelles from star copolymers. The SCMs could be de-cross-linked under low pH and redox conditions. After loading with the anticancer drug camptothecin (CPT), the SCMs displayed a good stability against extensive dilution and a slow sustained drug release at pH 7.4 with 15% in 24 h, while a fast release (54%) was observed at pH 5.0 and 10 mM DTT. Confocal microscopy studies and MTT assays revealed that the CPT-loaded SCMs showed a good uptake property and a high cytotoxicity against HepG2 tumor cells. The pH/redox dual stimuli-responsive cross-linked micelles are proposed to be a highly promising platform for the intracellular delivery of insoluble chemotherapeutics for cancer therapy.

Graphical abstract

http://ift.tt/2nl4aTf

Novel endodontic sealers induce cell cytotoxicity and apoptosis in a dose-dependent behavior and favorable response in mice subcutaneous tissue

Abstract

Objectives

The objective of the present study is to evaluate the in vitro cytotoxicity and in vivo biocompatibility of two novel endodontic sealers: RealSeal XT1 and Sealapex Xpress on the subcutaneous connective tissue of mice.

Materials and methods

The cytotoxicity was assessed by cell viability using the MTT assay (one-way ANOVA), trypan blue test (Mann-Whitney) and cell apoptosis by flow cytometer. For the subcutaneous study, polyethylene tubes filled with the sealers were implanted in 70 BALB/c mice: 6 experimental groups (n = 10/group) and 2 control groups with empty tubes (n = 5/group). At the end of experimental periods (7, 21, and 63 days), the tissue was removed and histotechnically processed. Angioblastic proliferation and edema (Fisher's exact test) were evaluated, besides thickness measurement (μm) of the reactionary granulomatous tissue and neutrophil counts (Kruskal-Wallis and Dunn's post test; Mann-Whitney) (α = 0.05).

Results

MTT assay, trypan blue, and analysis of apoptotic cells showed a dose-dependent direct effect: the more diluted the sealer, the less cytotoxic. Regarding the angioblastic proliferation and edema, difference between the sealers at 7 and 63 days occurred (p < 0.05). Both endodontic sealers initially promoted perimaterial tissue reaction as a foreign body granuloma and thus stimulated favorable tissue responses.

Conclusions

Both sealers showed a dose-dependent effect and promoted satisfactory subcutaneous tissue response; the sealer Sealapex Xpress was less cytotoxic and more biocompatible than RealSeal XT.

Clinical relevance

The step of root canal filling during endodontic treatment is highly important for the preservation of the periapical tissue integrity. Subcutaneous reaction to endodontic sealers enables scientific basis for clinical use.

http://ift.tt/2m5Ttmv

Root canal morphology and variations in mandibular second molar teeth of an Indian population: an in vivo cone-beam computed tomography analysis

Abstract

Objectives

This study aims to investigate the root canal morphology of permanent mandibular second molars of an Indian population in vivo using cone-beam computed tomography (CBCT) images.

Methods

CBCT images (n = 983; males = 489, females = 494) of untreated, completely developed permanent mandibular second molar teeth were examined. CBCT scans were acquired as part of diagnosis and treatment planning for treatments unrelated to the present study. The number of roots and root canals were recorded. Canal configuration was classified based on Vertucci's and Fan's classifications.

Results

The most common configuration was two-root (79.35%) and three-root canals (53.50%). The incidence of three-rooted molars was 7.53%, whereas 13.12% of the studied teeth studied have fused roots with C-shaped canals. The predominant canal morphology in the mesial roots was Vertucci's type IV (45.17%), followed by type II (32.55%), type I (7.23%), type V (1.02%), and type III (0.91%). The distal root in contrast showed type I (61.14%) as the predominant canal configuration, followed by type II (18.21%) and type IV (7.53%). The incidence of three-rooted molars was higher in males (n = 55; 5.59%) than in females (n = 19; 1.94%) (p < 0.01). The canals in the extra roots exhibited type I (100%) root canal morphology. In teeth with C-shaped root canal (13.12%), the variations in the coronal, middle, and apical third ranged from C1 to C4.

Conclusions

Root canal systems of the mesial roots of mandibular second molars of the study population demonstrated a high degree of variability. While three roots were rare, there was a sexual predisposition. Fused roots with C-shaped canals were rare and demonstrated significant variations from the coronal to apical third.

Clinical relevance

Root canal morphology can demonstrate variations based on race and sex of patients. Clinicians must always consider the possible variations to ensure successful endodontic treatment.

http://ift.tt/2mNoH6s

Lipid parameters in obese and normal weight patients with or without chronic periodontitis

Abstract

Objective

The aim of this study was to evaluate the serum levels of lipids in patients with normal weight (NW) or obesity with or without chronic periodontitis (ChP).

Materials and methods

One hundred and sixty non-smoking patients without history of diabetes and/or cardiovascular events were allocated into one of the following groups: NW patients with periodontal health (NWH; n = 40), NW patients with ChP (NWChP; n = 40), obese patients with periodontal health (ObH; n = 40), and obese patients with ChP (ObChP; n = 40). Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TRG) were estimated.

Results

After adjustments for gender and age, both NW groups presented lower levels of TRG than both obese groups (p < 0.05). The NWH group presented lower levels of LDL than both periodontitis groups (p < 0.05) and the lowest TC/HDL ratio when compared to the other groups (p < 0.05). Females from the NWH group exhibited higher levels of HDL and lower LDL/HDL ratio than females from the ObChP group (p < 0.05). Furthermore, individuals from the ObChP group were more likely to have levels of LDL ≥130 mg/dl and HDL ≤40 mg/dl, compared to those from the NWH group (p < 0.05).

Conclusions

ChP and obesity, jointly or individually, are associated with undesirable pro-atherogenic lipid profiles.

Clinical relevance

There is interest in identifying clinical conditions associated with dyslipidemia to improve preventive and treatment strategies. This study demonstrated that ChP, obesity, and the association of both conditions might be related to pro-atherogenic lipid profiles.

http://ift.tt/2m5Rwq4

Odontogenic differentiation potential of human dental pulp cells cultured on a calcium-aluminate enriched chitosan-collagen scaffold

Abstract

Objective

The study aims to evaluate the odontogenic potential of human dental pulp cells (HDPCs) in contact with an experimental porous chitosan-collagen scaffold (CHC) enriched or not with a mineral phase of calcium-aluminate (CHC-CA).

Material and methods

To assess the chemotactic effect of the materials, we placed HDPCs seeded on transwell membranes in intimate contact with the CHC or CHC-CA surface, and the cell migration was monitored for 48 h. Additionally, cells were seeded onto the material surface, and the viability and proliferation were evaluated at several time points. To assess the odontoblastic differentiation, we evaluated ALP activity, DSPP/DMP-1 gene expression, and mineralized matrix deposition. HDPCs cultured onto a polystyrene surface (monolayer) were used as negative control group.

Results

The experimental CHC-CA scaffold induced intense migration of HDPCs through transwell membranes, with cells attaching to and spreading on the material surface after 24-h incubation. Also, the HDPCs seeded onto the CHC-CA scaffold were capable of migrating inside it, remaining viable and featuring a proliferative rate more rapid than that of CHC and control groups at 7 and 14 days of cell culture. At long-term culture, cells in the CHC-CA scaffold featured the highest deposition of mineralized matrix and expression of odontoblastic markers (ALP activity and DSPP/DMP-1 gene expression).

Conclusions

According to the results, the CHC-CA scaffold is a bioactive and cytocompatible material capable of increasing the odontogenic potential of human pulp cells. Based on analysis of the positive data obtained in this study, one can suggest that the CHC-CA scaffold is an interesting future candidate for the treatment of exposed pulps.

Clinical relevance

The experimental scaffold composed by a chitosan-collagen matrix mineralized with calcium aluminate seems to be an interesting candidate for in vivo application as a cell-free approach to dentin tissue engineering, which may open a new perspective for the treatment of exposed pulp tissue.

http://ift.tt/2mNoG2o

Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation

Publication date: Available online 9 March 2017
Source:Immunity
Author(s): Haiyan Tan, Kai Yang, Yuxin Li, Timothy I. Shaw, Yanyan Wang, Daniel Bastardo Blanco, Xusheng Wang, Ji-Hoon Cho, Hong Wang, Sherri Rankin, Cliff Guy, Junmin Peng, Hongbo Chi
The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early dynamics of phosphorylation and delayed ribosome biogenesis and mitochondrial activation. Systems biology analyses identified multiple functional modules, active kinases, transcription factors and connectivity between them, and mitochondrial pathways including mitoribosomes and complex IV. Genetic perturbation revealed physiological roles for mitochondrial enzyme COX10-mediated oxidative phosphorylation in T cell quiescence exit. Our multi-layer proteomics profiling, integrative network analysis, and functional studies define landscapes of the T cell proteome and phosphoproteome and reveal signaling and bioenergetics pathways that mediate lymphocyte exit from quiescence.

Graphical abstract

Teaser

Tan et al. apply multi-layer proteomic profiling and systems biology approaches to define T cell proteome and phosphoproteome landscapes, and they identify signaling networks and bioenergetics pathways that mediate T cell quiescence exit. These data establish the function and mechanisms of oxidative phosphorylation and mitochondrial activation in antigen-induced T cell responses.


http://ift.tt/2mGLAI3

Concentration-dependent alterations in gene expression induced by cadmium in Solanum lycopersicum

Abstract

Cadmium (Cd) toxicity in agricultural soil has received significant attention because of its higher transformation in the food chain and toxicity to humans. The aim of the present study was to develop sensitive and specific biomarkers for Cd stress. Therefore, transcriptional analyses were performed to investigate concentration-response characteristics of Cd responsive genes identified from a Solanum lycopersicum microarray. The results showed that the lowest observable adverse effect concentrations (LOAECs) of Cd to S. lycopersicum were 1 mg/kg for seed germination, 8 mg/kg for root dry weight, 8 mg/kg for root elongation, and 8 mg/kg for root morphology. Furthermore, the genes were differentially expressed even at the lowest Cd concentrations (0.5 mg/kg), indicating that the detection of Cd in soil at the molecular level is a highly sensitive method. Cd in soil was positively correlated with the expression of the F-box protein PP2-B15 (r = 0.809, p < 0.01) and zinc transporter 4 (r = 0.643, p < 0.01), indicating that these two genes could be selected as indicators of soil Cd contamination.

http://ift.tt/2mrGVt0

Precipitation and air temperature control the variations of dissolved organic matter along an altitudinal forest gradient, Gongga Mountains, China

Abstract

Dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) contribute significantly to C and N cycling in forest ecosystems. Little information is available on the variations in the DOC and DON concentrations and depositions in bulk and stand precipitation within forests along an altitudinal gradient. To determine the temporal variations in the DOC and DON concentrations and depositions in different forests and the spatial variations along the elevation gradient, the DOC and DON concentrations and depositions were measured in bulk precipitation, throughfall, and stemflow within three forest types, i.e., broadleaf forest (BLF), broadleaf-coniferous forest (BCF), and coniferous forest (CF), during the wet season (May to October) on Gongga Mountain, China, in 2015. The concentrations of bulk precipitation in BLF, BCF, and CF were 3.92, 4.04, and 2.65 mg L⁻¹, respectively, for DOC and were 0.38, 0.26, and 0.29 mg L⁻¹, respectively, for DON. BCF had the highest DOC deposition both in bulk precipitation (45.12 kg ha⁻¹) and stand precipitation (98.52 kg ha⁻¹), whereas the highest DON deposition was in BLF (3.62 kg ha⁻¹ bulk precipitation and 4.11 kg ha⁻¹ stand precipitation) during the study period. The meteorological conditions of precipitation and air temperature significantly influenced the dissolved organic matter (DOM) depositions along the elevation gradient. The leaf area index did not show any correlation with DOM depositions during the growing season.

http://ift.tt/2mppCat

Amelioration of boron toxicity in sweet pepper as affected by calcium management under an elevated CO 2 concentration

Abstract

We investigated B tolerance in sweet pepper plants (Capsicum annuun L.) under an elevated CO₂ concentration, combined with the application of calcium as a nutrient management amelioration technique. The data show that high B affected the roots more than the aerial parts, since there was an increase in the shoot/root ratio, when plants were grown with high B levels; however, the impact was lessened when the plants were grown at elevated CO₂, since the root FW reduction caused by excess B was less marked at the high CO₂ concentration (30.9% less). Additionally, the high B concentration affected the membrane permeability of roots, which increased from 39 to 54% at ambient CO₂ concentration, and from 38 to 51% at elevated CO₂ concentration, producing a cation imbalance in plants, which was differentially affected by the CO₂ supply. The Ca surplus in the nutrient solution reduced the nutritional imbalance in sweet pepper plants produced by the high B concentration, at both CO₂ concentrations. The medium B concentration treatment (toxic according to the literature) did not result in any toxic effect. Hence, there is a need to review the literature on critical and toxic B levels taking into account increases in atmospheric CO₂.

http://ift.tt/2mrDuTb

Slow-release formulations of the herbicide picloram by using Fe–Al pillared montmorillonite

Abstract

Slow-release formulations of the herbicide picloram (PCM, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid) were designed based on its adsorption on pillared clays (pillared clays (PILCs)) for reducing the water-polluting risk derived from its use in conventional formulations. Fe–Al PILCs were synthesized by the reaction of Na⁺-montmorillonite (SWy-2) with base-hydrolyzed solutions of Fe and Al. The Fe/(Fe + Al) ratios used were 0.15 and 0.50. The PCM adsorption isotherms on Fe–Al PILCs were well fitted to Langmuir and Freundlich models. The PCM adsorption capacity depended on the Fe content in the PILCs. Slow-release formulations were prepared by enhanced adsorption of the herbicide from PCM-cyclodextrin (CD) complexes in solution. CDs were able to enhance up to 2.5-fold the solubility of PCM by the formation of inclusion complexes where the ring moiety of the herbicide was partially trapped within the CD cavity. Competitive adsorption of anions such as sulfate, phosphate, and chloride as well as the FTIR analysis of PCM-PILC complexes provided evidence of formation of inner sphere complexes of PCM-CD on Fe–Al PILCs. Release of the herbicide in a sandy soil was lower from Fe–Al PILC formulations relative to a PCM commercial formulation.

http://ift.tt/2mrIs2c

Iron-based adsorbent prepared from Litchi peel biomass via pyrolysis process for the removal of pharmaceutical pollutant from synthetic aqueous solution

Abstract

A porous iron-based adsorbent obtained from litchi peel via pyrolysis process was prepared in this work, in order to evaluate its adsorptive potential for the removal of a pharmaceutical dye (amaranth) from aqueous solution. The material was characterized by X-ray diffraction, nitrogen adsorption–desorption isotherms, and scanning electron microscopy. Several isotherm and kinetic models were tested aiming to represent the amaranth dye adsorption. The prepared sample presented magnetic property, and a mesoporous texture constituted of graphite and three iron-based phases. The adsorption kinetics of amaranth on the adsorbent followed the pseudo-second-order model, whereas the equilibrium data were in good agreement with the BET isotherm, being represented by a sigmoid-shaped adsorption isotherm. The maximum adsorption capacity for the amaranth dye was found to be 44.87 mg g⁻¹, demonstrating that the material prepared in this work showed to be a promising adsorbent for the removal of amaranth from aqueous solution.

http://ift.tt/2mppZl7

Effect of foliar application of plant growth regulators on nitrous oxide (N 2 O) emission and grain yield in wheat

Abstract

Agricultural soils are the major source of global nitrous oxide (N₂O) emission, and more than two thirds of N₂O emission originate from soil. Recent studies have identified that green plants contribute to transport of N₂O to the atmosphere. We investigated the effects of foliar application of plant growth regulators (PGRs) and growth stimulating chemicals on N₂O emission and wheat grain yield for 2 years. The PGRs' abscisic acid (ABA) and cytozyme (20 mg L⁻¹), kinetin (10 and 20 mg L⁻¹) and wet tea extract (1:20 w/w) along with distilled water as control were sprayed on wheat canopy at the tillering and panicle initiation stages. Our results showed that cytozyme and tea extract enhanced the plant dry biomass over control. Kinetin (10 and 20 mg L⁻¹) and cytozyme increased the plant photosynthetic rate and photosynthate partitioning towards the developing grain. ABA (20 mg L⁻¹) and kinetin (10 and 20 mg L⁻¹) reduced the N₂O emission over control primarily through regulation of leaf growth, stomatal density and xylem vessel size. Leaf area, stomatal density and xylem vessel size were found to be associated with N₂O transport and emission. We concluded that use of ABA and kinetin can reduce N₂O emissions without any impact on wheat grain yield.

http://ift.tt/2mpoQu0

Withered on the stem: is bamboo a seasonally limiting resource for giant pandas?

Abstract

In response to seasonal variation in quality and quantity of available plant biomass, herbivorous foragers may alternate among different plant resources to meet nutritional requirements. Giant pandas (Ailuropoda melanoleuca) are reliant almost exclusively on bamboo which appears omnipresent in most occupied habitat, but subtle temporal variation in bamboo quality may still govern foraging strategies, with population-level effects. In this paper, we investigated the possibility that temporal variation in the quality of this resource is involved in population regulation and examined pandas' adaptive foraging strategies in response to temporal variation in bamboo quality. Giant pandas in late winter and early spring consumed a less optimal diet in Foping Nature Reserve, as the availability of the most nutritious and preferred components and age classes of Bashania fargesii declined, suggesting that bamboo may be a seasonally limiting resource. Most panda mortalities and rescues occurred during the same period of seasonal food limitation. Our findings raised the possibility that while total bamboo biomass may not be a limiting factor, carrying capacity may be influenced by subtle seasonal variation in bamboo quality. We recommend that managers and policy-makers should consider more than just the quantity of bamboo in the understory and that carrying capacity estimates should be revised downward to reflect the fact that all bamboos are not equal.

http://ift.tt/2mrHYcn

Frequencies of erythrocyte nuclear abnormalities and of leucocytes in the fish Barbus peloponnesius correlate with a pollution gradient in the River Bregalnica (Macedonia)

Abstract

Integrated chemical and biomarker approaches were performed to estimate if there is ongoing toxicity in the River Bregalnica, namely connected with the presence of metals. The study was performed in water, sediment, and barbel (Barbus peloponnesius), collected in two seasons, from two suspected polluted and one reference zones. The water analyses revealed higher mean values in polluted sites for most of the examined physicochemical parameters. Metal concentrations (Zn, Cu, Cd, Mn, Pb, and Fe) in water were more or less constant, whereas in sediment, they were higher at the two polluted locations. Condition factor (CF), as a general health indicator, revealed better overall condition in barbel from the reference site. In general, blood parameters revealed higher values in the polluted localities. Irrespective of sex and/or season, the frequency of micronuclei (MN) and vacuolated nuclei (VN) were with higher rates in polluted sites. Similarly, the frequencies of the leucocytes (Le), binuclei (BN), and irregularly shaped nuclei (ISN) were also significantly increased in the polluted localities, but they seemed prone to be influenced by sex and/or season. However, strong positive correlations between blood biomarkers and most water physicochemical parameters and metal in sediment were estimated. Our data support that the River Bregalnica's lower course receives significant genotoxic pollution, likely via metal industry effluents, agricultural runoff, and domestic sewage, and reinforced the utility of MN and other nuclear abnormalities as sensitive and suitable biomarkers for genotoxicity when used in monitoring studies.

http://ift.tt/2mpipar

Using early life stages of marine animals to screen the toxicity of priority hazardous and noxious substances

Abstract

This study provides toxicity values for early life stages (ELS) of two phylogenetically distinct marine animal taxa, the sea urchin (Paracentrotus lividus), a deuterostome invertebrate, and the turbot (Scophthalmus maximus), a vertebrate (teleost), when challenged by six hazardous and noxious substances (HNS): aniline, butyl acrylate, m-cresol, cyclohexylbenzene, hexane and trichloroethylene. The aim of the study was to provide preliminary information on toxic effects of representative and relevant priority HNS to assess the risk posed by spills to marine habitats and therefore improve preparedness and the response at the operational level. Selection criteria to include each compound in the study were (1) inclusion in the HASREP (2005) list; (2) presence on the priority list established by Neuparth et al. (2011); (3) paucity of toxicological data (TOXnet and ECOTOX) for marine organisms; (4) behaviour in the water according to the categories defined by the European Behaviour classification system (GESAMP 2002), by selecting compounds with different behaviours in water; and (5) physicochemical and toxicological properties, where available, in order to anticipate the most toxic compounds. Aniline and m-cresol were the most toxic compounds with no observed apical effect concentration (NOAEC) values for sea urchin ranging between 0.01 and 0.1 mg/L, followed by butyl acrylate and cyclohexylbenzene with NOAECs ranging between 0.1 and 1.0 mg/L and trichloroethylene with NOAEC values that were in the range between 1 and 10 mg/L, reflecting their behaviour in water, mostly vapour pressure, but also solubility and log Kow. Hexane was toxic only for turbot embryos, due to its neurotoxic effects, and not for sea urchin larvae, at concentrations in the range between 1 and 10 mg/L. The concentrations tested were of the same order of magnitude for both species, and it was observed that sea urchin embryos (length of the longest arm) are more sensitive than turbot eggs larvae (hatching and cumulative mortality rates) to the HNS tested (except hexane). For this specific compound, concentrations up to 70 mg/L were tested in sea urchin larvae and no effects were observed on the length of the larvae. Both tests were found to be complementary depending on behaviour in water and toxicity target of the compounds analysed.

http://ift.tt/2mrIwis

Toxic effect of nonylphenol on the marine macroalgae Gracilaria lemaneiformis (Gracilariales, Rhodophyta): antioxidant system and antitumor activity

Abstract

The objective of the present work was to evaluate the toxic effect of nonylphenol (NP) on the antioxidant response and antitumor activity of Gracilaria lemaneiformis. An obvious oxidative damage was observed in this study. The thallus exposed to NP showed 1.2–2.0-fold increase in lipid peroxide and displayed a maximum level of 16.58 μmol g⁻¹ Fw on 0.6 mg L⁻¹ for 15-day exposure. The activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) enhanced significantly by 1.1–3.2-fold and subsequently diminished at the high concentrations and prolonged exposure. The results of DNA damage in comet assay also supported that NP was obviously toxic on G. lemaneiformis with increasing the percentage of tail DNA in a dose-dependent manner. Furthermore, the ethanol extract of G. lemaneiformis (EEGL) did exhibit antitumor potential against HepG-2 cells. While decreased in cell inhibition, ROS generation, apoptosis, and caspase-3 in HepG-2 cells treated with the EEGL were observed when G. lemaneiformis was exposed to NP for 15 days, and which were related to exposure concentration of NP. These suggested that NP has strongly toxic effect on the antitumor activity of G. lemaneiformis. The results revealed in this study imply that macroalgae can be useful biomarkers to evaluate marine pollutions.

http://ift.tt/2mpdiqB

Unique characteristics of algal dissolved organic matter and their association with membrane fouling behavior: a review

Abstract

Over the last several decades, the frequent occurrence of algal bloom in drinking water supplies, driven by increasing anthropogenic input and climate change, has posed serious problems for membrane filtration processes, resulting in reduced membrane permeability and increased energy consumption. It is essential to comprehensively understand the characteristics of algal dissolved organic matter (DOM) and the subsequent effects on the filtration processes for better insight into membrane fouling mitigation. Many studies have revealed that algal DOM has displayed unique characteristics distinguished from other sources of DOM with respect to the chemical composition, the structures, and the molecular weight distributions. Algal DOM is considered to be a major obstacle in understanding membrane fouling due to its complicated interactions among dissimilar algal DOM constituents as well as between algal DOM and membrane material matrices. The present review article summarizes (1) recent characterizing methods for algal DOM, (2) environmental factors affecting the characteristics of algal DOM, (3) the discrepancies between algal DOM and other sources of aquatic DOM, particularly terrestrial sources, and (4) potential fouling effects of algal DOM on membrane filtration processes and their associations with algal DOM characteristics. A broad understanding of algal DOM-driven membrane fouling can lead to breakthroughs in efficient membrane filtration processes to treat algal bloom water sources.

http://ift.tt/2mrGWNA

The death of the circulatory system diseases in China: provincial socioeconomic and environmental perspective

Abstract

Few studies have explored the association between circulatory system diseases (CSDs) and provincial socioeconomic and environmental factors from spatial perspective, although large literature have focused on CSD. The numbers of death of hypertension disease (HD), ischemic heart disease (IHD), and cerebrovascular disease (CVD) are investigated, and 14 representative socioeconomic and environmental factors are collected. Stepwise regression model (SRM) and geographically weighted regression model (GWRM) are applied to determine the spatial correlation between the number of death of those diseases and selected factors. The results are the following: (1) diseases exhibit a pattern of zonal distribution. Higher HD is mostly distributed in south district, whereas higher IHD and CVD are observed in the north area. (2) SO₂ emission amount (SO₂ EA) is significantly positively related with HD, while coal consumption (CC) and PM_2.5 are notably positively correlated with IHD and CVD. (3) A 10,000 tons increase in SO₂ EA results in three increases in the numbers of death of HD. For every 100 ten thousand tons (TTTs) increase in CC, the death of IHD and CVD increases by 11.1 and 15.7, while for every 1 μg/m³ increase in ambient PM_2.5 concentration, the numbers of death of IHD and CVD increase by 34.773 and 43.222, respectively. (4) Our findings show that there exist spatial differences for SO₂ EA, CC, and PM_2.5 influencing HD, IHD, and CVD. This study is expected to provide a reference for HD, IHD, and CVD control in different regions.

http://ift.tt/2mpoFyK

Migration of nitrate, nitrite, and ammonia through the municipal solid waste incinerator bottom ash layer in the simulated landfill

Abstract

Simulated landfill was operated for 508 days to investigate the effect of municipal solid waste incinerator (MSWI) bottom ash layer on the migration of nitrate, nitrite, and ammonia when it was used as the intermediate layer in the landfill. The result suggested that the MSWI bottom ash layer could capture the nitrate, nitrite, and ammonia from the leachate. The adsorption of the nitrate, nitrite, and ammonia on the MSWI bottom ash layer was saturated at the days 396, 34, and 97, respectively. Afterwards, the nitrogen species were desorbed from the MSWI bottom ash layer. Finally, the adsorption and desorption could reach the equilibrium. The amounts of adsorbed nitrate and nitrite on the MSWI bottom ash layer were 1685.09 and 7.48 mg, respectively, and the amount of the adsorbed and transformed ammonia was 13,773.19 mg, which was much higher than the desorbed. The water leaching test and synthetic precipitation leaching procedure (SPLP) results showed that the leachable nitrate, nitrite, and ammonia in the MSWI bottom ash were greatly increased after the landfill operation, suggesting that the adsorbed nitrogen could be finally leached out. Besides, the results also showed that MSWI bottom ash layer could affect the release of nitrate and ammonia at the initial stage of the landfill. However, it had little effect on the release of nitrite.

http://ift.tt/2mphRkF

Investigations of temperature and pH variations on metal trophic transfer in turbot ( Scophthalmus maximus )

Abstract

Studying dietary metal transfer kinetics is essential to gain a better understanding in global metal accumulation rates and its impacts in marine fish. While there exists a solid understanding on the influence of various biotic factors on this transfer, metal assimilation in fish might be also affected by abiotic factors, as has been observed in marine invertebrates. The present study therefore aims to understand the potential effects of two climate-related master variables, temperature and pH, on the assimilation efficiency (AE) of essential (Co and Zn) and non-essential (Ag) metals in the turbot Scophthalmus maximus using radiotracer tools. Juvenile turbots were acclimated for 8 weeks at two temperatures (17 and 20 °C) and pH (7.5 and 8.0) regimes, under controlled laboratory conditions, and then fed with radiolabelled shrimp (⁵⁷Co, ⁶⁵Zn and ^110mAg). Assimilation efficiencies of Co and Ag in juvenile turbot, determined after a 21-day depuration period, were not affected by pre-exposition to the different environmental conditions. In contrast, temperature did significantly influence Zn AE (p < 0.05), while pH variations did not affect the assimilation of any of the metals studied. In fact, temperature is known to affect gut physiology, specifically the membrane properties of anterior intestine cells where Zn is adsorbed and assimilated from the ingested food. These results are relevant to accurately assess the influence of abiotic factors in AEs of metals in fish as they are highly element-dependent and also modulated by metabolic processes.

http://ift.tt/2ms1mpN

Enhancing filterability of activated sludge from landfill leachate treatment plant by applying electrical field ineffective on bacterial life

Abstract

The aim of this study is to investigate filterability enhancement of activated sludge supplied form a full-scale leachate treatment plant by applying DC electric field while keeping the biological operational conditions in desirable range. The activated sludge samples were received from the nitrification tank in the leachate treatment plant of Istanbul's Odayeri Sanitary Landfill Site. Experimental sets were conducted as laboratory-scale batch studies and were duplicated for 1A, 2A, 3A, 4A, and 5A of electrical currents and 2, 5, 10, 15, and 30 min of exposure times under continuous aeration. Physicochemical parameters such as temperature, pH, and oxidation reduction potential in the mixture right after each experimental set and biochemical parameters such as chemical oxygen demand, total phosphorus, and ammonia nitrogen in supernatant were analyzed to define the sets that remain in the range of ideal biological operational conditions. Later on, sludge filterability properties such as capillary suction time, specific resistance to filtration, zeta potential, and particle size were measured for remaining harmless sets. Additionally, cost analyses were conducted in respect to energy and electrode consumptions. Application of 2A DC electric field and 15-min exposure time was found to be the most favorable conditions to enhance filterability of the landfill leachate-activated sludge.

http://ift.tt/2mpeV7N

Enhanced heterogeneous photo-Fenton process modified by magnetite and EDDS: BPA degradation

Abstract

In this research, magnetite and ethylenediamine-N,N′-disuccinic acid (EDDS) are used in a heterogeneous photo-Fenton system in order to find a new way to remove organic contaminants from water. Influence of different parameters including magnetite dosage, EDDS concentration, H₂O₂ concentration, and pH value were evaluated. The effect of different radical species including HO^· and HO₂^·/O₂^·− was investigated by addition of different scavengers into the system. The addition of EDDS improved the heterogeneous photo-Fenton degradation of bisphenol A (BPA) through the formation of photochemically efficient Fe-EDDS complex. This effect is dependent on the H₂O₂ and EDDS concentrations and pH value. The high performance observed at pH 6.2 could be explained by the ability of O₂^·− to generate Fe(II) from Fe(III) species reduction. GC-MS analysis suggested that the cleavage of the two benzene rings is the first degradation step followed by oxidation leading to the formation of the benzene derivatives. Then, the benzene ring was opened due to the attack of HO^· radicals producing short-chain organic compounds of low molecular weight like glycerol and ethylene glycol. These findings regarding the capability of EDDS/magnetite system to promote heterogeneous photo-Fenton oxidation have important practical implications for water treatment technologies.

http://ift.tt/2mrFY3L

Characterization of ferromagnetic sludge-based activated carbon and its application in catalytic ozonation of p -chlorobenzoic acid

Abstract

In order to solve the separation problem of powdered sludge-based activated carbon (SAC), a series of novel ferromagnetic sludge-based activated carbons (FMSACs, with different iron content 2.3, 4.3, and 9.5 wt%) with a good magnetic separation ability were prepared through co-precipitation method in this study. The structure and physicochemical properties of FMSACs and their catalytic ozonation performance on the removal of p-chlorobenzoic acid (p-CBA) were investigated. The saturation magnetization (Ms) of FMSACs was determined in the range of 0.3674–5.7992 emu g⁻¹, and experiments confirmed that these FMSACs could be easily separated by magnetic fields. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis indicated that magnetite and maghemite were the main magnetic phases in FMSACs. Comparing with ozonation alone and SAC catalytic ozonation, the presence of 2.3 wt% – FMSAC improved the degradation of p-CBA during catalytic ozonation from 44 and 70 to 80%. The tertiary butanol inhibition experiment indicated that FMSACs catalytic ozonation process followed hydroxyl radical reaction mechanism. Furthermore, after six repetitive catalytic ozonation runs, 2.3 wt% – FMSAC still showed relatively high catalytic activity for the removal of p-CBA. Consequently, the novel FMSACs with magnetic separation ability and catalytic performance provide a practical pathway for the sludge utilization.

http://ift.tt/2mpdBlu

High contribution of the particulate uptake pathway to metal bioaccumulation in the tropical marine clam Gafrarium pectinatum

Abstract

The clam Gafrarium pectinatum was investigated to assess its usefulness as a bioindicator species of metal mining contamination in the New Caledonia lagoon. The uptake and depuration kinetics of Ag, Cd, Co, Cr, and Zn were determined following exposures via seawater, sediment, and food using highly sensitive radiotracer techniques (^110mAg, ¹⁰⁹Cd, ⁵¹Cr, ⁵⁷Co, and ⁶⁵Zn). When the clams were exposed to dissolved metals, Co, Zn, and Ag were readily incorporated in their tissues (concentration factors (CF) ranging from 181 to 4982 after 28 days of exposure) and all metals were strongly retained (biological half-lives always >2 months). The estimated transfer factor (TF) in clam tissues after a 35-day sediment exposure was 1 to 4 orders of magnitude lower than the estimated CF, indicating a lower bioavailability of sediment-bound metals than dissolved ones. Once incorporated, metals taken up from sediment and seawater were retained longer than metals ingested with food, indicating that the uptake pathway influences the storage processes of metals in clam tissues. Compilation of our data into a global bioaccumulation model indicated that, except for Ag that essentially originated from food (92%), sediment was the main source of metal bioaccumulation in the clam (more than 80%). These results highlight that bioaccumulation processes strongly depend from one metal to the other. The overall efficient bioaccumulation and retention capacities of the clam G. pectinatum confirm its usefulness as a bioindicator species that can provide time-integrated information about ambient contamination levels in the tropical marine coastal environment.

http://ift.tt/2mrPpk1

Estimation of decrease in cancer risk by biodegradation of PAHs content from an urban traffic soil

Abstract

The role of preferential biodegradation in the reduction of cancer risk caused by polycyclic aromatic hydrocarbons (PAHs) has been studied. A consortium of microorganisms isolated from aged oil refinery exposed soil was used to degrade 13 PAHs content extracted from an urban traffic site soil. The biodegradation arranged in a batch process with a mineral salt broth, where PAHs were the sole carbon source. 70.46% biodegradation of the total PAHs occurred in an incubation period of 25 days. Sequential or preferential biodegradation took place as the lower molecular weight (LMW) PAHs were more prone to biodegradation than that of the higher molecular weight (HMW) PAHs. Microorganisms from the isolated consortia preferred the simpler carbon sources first. The relatively higher carcinogenicity of the HMW PAHs than that of the LMW PAHs leads to only 40.26% decrement in cancer risk. Initial cancer risk for children was 1.60E−05, which was decreased to 9.47E−06, whereas, for the adults, the risk decreased to 1.01E−05 from an initial value of 1.71E−05. The relative skin adherence factor for soil (AF) turned out to be the most influential parameter with 54.2% contributions to variance in total cancer risk followed by the exposure duration (ED) for children. For the adults, most contributions to the variance in total cancer risk were 58.5% by ED and followed by AF.

http://ift.tt/2mppQ13

Methyl acrylate modified apple pomace as promising adsorbent for the removal of divalent metal ion from industrial wastewater

Abstract

Polymerized apple pomace (PoAP) surface was evaluated as adsorbent for the removal of Pb⁺², Cd⁺², and Ni⁺² ions from aqueous solution. PoAP was characterized by FTIR, SEM, EDS, XRD, and BET surface area analyzer. Furthermore, the adsorption influencing parameters such as dose, pH, time, concentration, and temperature were optimized for maximum removal of metal ions from aqueous solution. The maximum monolayer adsorption capacity of PoAP was found to be 106, 34.12, and 19.45 mg g⁻¹, for Pb⁺², Cd⁺², and Ni⁺² ions respectively, using the Langmuir isotherm model. The rate of adsorption was evaluated using pseudo-second order kinetics and intra-particle diffusion. The adsorption data followed pseudo-second order kinetic with the correlation coefficient (r ²) from 0.99–1 at all concentration. Thermodynamic study revealed endothermic nature of Pb⁺² and Cd⁺² adsorption and exothermic for Ni⁺² ions. The rate of adsorption for binary and tertiary mixtures of Pb⁺², Ni⁺², and Cd⁺² metal ion was studied using the ideal adsorbed solution theory. The regeneration study revealed that PoAP could be re-utilized up to 4 cycles for Pb⁺² and 2 cycles for Cd⁺² and Ni⁺² ions. PoAP was successfully applied to real industrial wastewater for the removal of Pb⁺², Cd⁺², and Ni⁺² ions.

http://ift.tt/2mrzi5Y

Editorial Board

Publication date: 22 March 2017
Source:Journal of Proteomics, Volume 157





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Identification of novel autoantigens via mass spectroscopy-based antibody-mediated identification of autoantigens (MS-AMIDA) using immune thrombocytopenic purpura (ITP) as a model disease

Publication date: 22 March 2017
Source:Journal of Proteomics, Volume 157
Author(s): Julian Kamhieh-Milz, Viktor Sterzer, Hatice Celik, Omid Khorramshahi, Reham Fadl Hassan Moftah, Abdulgabar Salama
Immune thrombocytopenic purpura (ITP) is one of the best characterized autoimmune diseases. Autoantibodies (AABs) against platelet antigens are considered as the diagnostic hallmark of ITP, but are detectable in only 50% of patients. We designed and applied a novel proteomic approach termed Mass Spectroscopy-based Antibody-Mediated Identification of Autoantigens (MS-AMIDA) for platelet antigens. Patients were separated into patients with classical AABs [ITP(+)] and patients without AABs [ITP(−)]. Altogether, 181 potential AAGs were found in ITP(+) and 135 AAGs in ITP(−), with 34 and 23 AAGs reproducibly found in two runs of MS-AMIDA. After subtracting identifiers from the controls, 57 AAGs in ITP(+) and 29 AAGs in ITP(+) remained, with 16 AAGs commonly found in ITP(+) and ITP(−) patients. Label-free quantification (LFQ) revealed 15 potential AAGs that are quantitatively stronger in ITP. Dot blot validation was performed on hexokinase 1 (HK1), E1 pyruvate dehydrogenase (E1-PDH), coagulation factor XIII, filamin A (FLNA), non-muscle myosin 9. Eleven patients were found to have anti-HK1 AABs, one patient had anti-E1-PDH AABs, and two patients had anti-FLNA AABs. Most antigens were of intracellular origin with significant association with actin-cytoskeleton and regulation of programmed cell death. In conclusion, novel AAGs for ITP were identified using MS-AMIDA.

Graphical abstract

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Synaptic proteome changes in the hypothalamus of mother rats

Publication date: Available online 9 March 2017
Source:Journal of Proteomics
Author(s): Edina Brigitta Udvari, Katalin Völgyi, Péter Gulyássy, Diána Dimén, Viktor Kis, János Barna, Éva Rebeka Szabó, Gert Lubec, Gábor Juhász, Katalin Adrienna Kékesi, Árpád Dobolyi
To establish synaptic proteome changes associated with motherhood, we isolated synaptosome fractions from the hypothalamus of mother rats and non-maternal control females at the 11th postpartum day. Proteomic analysis by two-dimensional differential gel electrophoresis combined with mass spectrometric protein identification established 26 significant proteins, 7 increasing and 19 decreasing protein levels in the dams. The altered proteins are mainly involved in energy homeostasis, protein folding, and metabolic processes suggesting the involvement of these cellular processes in maternal adaptations. The decrease in a significantly altered protein, complement component 1q subcomponent-binding protein (C1qbp) was validated with Western blotting. Furthermore, immunohistochemistry showed its presence in hypothalamic fibers and terminals in agreement with its presence in synaptosomes. We also found the expression of C1qbp in different hypothalamic nuclei including the preoptic area and the paraventricular hypothalamic nucleus at the protein and at the mRNA level using immunohistochemistry and in situ hybridization histochemistry, respectively. Bioinformatical network analysis revealed that cytokines, growth factors, and protein kinases are common regulators, which indicates a complex regulation of the proteome change in mothers. The results suggest that maternal responsiveness is associated with synaptic proteins level changes in the hypothalamus, and that growth factors and cytokines may govern these alterations.Biological significanceThe period of motherhood is accompanied with several behavioral, neuroendocrine, emotional and metabolic adaptations in the brain. Although it is established that various hypothalamic networks participate in the maternal adaptations of the rodent brain, our knowledge on the molecular background of these alterations remains seriously limited. In the present study, we first determined that the functional alterations of the maternal brain can be detected at the level of the synaptic proteome in the hypothalamus. Independent confirmation of synaptic localization, and also the established decrease in the level of C1qbp protein suggest the validity of the data. Common regulators of altered proteins belonging to the growth factor and cytokine family suggest that the synaptic adaptation is governed by these extracellular signals and future studies should focus on their specific roles. Our study was also the first to describe the expression pattern of C1qbp in the hypothalamus, a protein potentially involved in mitochondrial and neuroimmunological regulations of synaptic plasticity. Its presence in the preoptic area responsible for maternal behaviors and also in the paraventricular hypothalamic and arcuate nuclei regulating hormonal levels suggests that the same proteins may be involved in different aspects of maternal adaptations. The conclusions of the present work contribute to establishing the molecular alterations that determine different maternal adaptations in the brain. Since maternal changes are models of neuronal plasticity in all social interactions, the reported results can affect a wide field of molecular and behavioral neuroscience.

Graphical abstract

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Earwax: A neglected body secretion or a step ahead in clinical diagnosis? A pilot study

Publication date: Available online 9 March 2017
Source:Journal of Proteomics
Author(s): Engy Shokry, Anselmo Elcana de Oliveira, Melissa Ameloti Gomes Avelino, Mariana Moreira de Deus, Nelson Roberto Antoniosi Filho
This work combines the advantages of volatile metabolites profiling as a young growing research field with a non-invasive sampling technique using earwax "a neglected body secretion" for detection and monitoring of biomarkers for diabetes mellitus (types 1 and 2). Earwax samples were collected from 26 diabetic patients of both types, analyzed by headspace gas chromatography mass spectrometry and confronted to the volatile earwax composition of 33 healthy individuals. Data mining analysis was conducted using different models to discriminate the healthy individuals from the diabetic patients and to discriminate between both types of diabetes as well. The model with the best discriminating ability was found to be partial least squares discriminant analysis (PLS-DA) after variable selection. The 6 most important biomarkers were ethanol, acetone, methoxyacetone, hydroxyurea, isobutyraldehyde, and acetic acid. The multivariate model constructed was validated using a test data set and was able to correctly predict all the samples. The receiver operating characteristic (ROC) curves were built for the 6 variables for diabetes types 1 and 2 diagnoses. Among the 6 variables selected, methoxyacetone was the only biomarker able solely to perfectly discriminate between diabetes types 1 and 2. The method is simple, non-invasive, accurate, and highly accepted by patients.SignificanceOur method involves a volatolomic approach by headspace gas chromatography coupled with mass spectrometry as a single analytical technique combined with multivariate data analysis to detect biomarkers of diabetes in earwax samples. Our method was able to discriminate with high accuracy between 33 healthy controls and 26 diabetic patients as well as its types (1 and 2). Our method employing earwax, a "neglected biological matrix" not only has the advantage of non-invasive sampling but also overcomes the limitations of the applied procedures in other biological samples, involving no or minimum sample pretreatment, no external contamination and utilizing a simple sample collection technique.

Graphical abstract

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Broken Heart Syndrome – An intra operative complication

Publication date: Available online 9 March 2017
Source:Alexandria Journal of Medicine
Author(s): Zara Wani, Meenaxi Sharma
We report a case of Broken Heart Syndrome in a 56year old Postmenopausal woman suffered while undergoing simple biopsy procedure for vocal cord polyp that lead to physical, mental and financial burden both for the patient as well as the doctors. A team of cardiologists based on clinical and echocardiographic findings made the diagnosis of this case.



http://ift.tt/2m86rRG

Hypofractionated radiotherapy in older patients with non-melanoma skin cancer: Less is better

Abstract

Radiotherapy is a non-surgical option for patients with non-melanoma skin cancer. Lesions in middle-aged to older patients with good performance status are typically prescribed 4–5 weeks of outpatient weekday treatment. Daily radiotherapy fraction sizes of 2–3 Gy are recommended to decrease the late cutaneous consequences such as in-field hypopigmentation and telangiectasia. In elderly, often unwell patients, these concerns are less of an issue and larger fraction sizes (5–7 Gy), referred to as hypofractionation, can be delivered over a shorter time yet still achieve excellent in-field control and improve a patient's quality of life and avoid the need for surgery. The three case studies presented illustrate this approach along with a review of the evidence to support this.

http://ift.tt/2n5kkE3

Engineering intravaginal vaccines to overcome mucosal and epithelial barriers

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Zhonghua Ji, Zhaolu Xie, Zhirong Zhang, Tao Gong, Xun Sun
The mucosal surface of the vagina is a primary human immunodeficiency virus (HIV) entry portal, making it an attractive site for HIV vaccination. However, HIV vaccines based on recombinant adenovirus (rAd) do not efficiently cross the mucus layers or underlying epithelium of the vagina. Here we designed nanocomplexes of rAd particles coated with (1) the polyethylene glycol derivative APS to provide a hydrophilic surface that would prevent entrapment in the hydrophobic mucus, and (2) the cell-penetrating peptide TAT to improve transduction efficiency. The optimized rAd-TAT-APS nanocomplexes could achieve the balance of effective mucus-penetrating and cellular transduction. Intravaginal delivery of rAd-TAT-APS encoding HIVgag p24 into mice strongly enhanced HIVgag-specific systemic and mucosal immune responses. This rAd-TAT-APS system may allow effective vaginal delivery of vaccines against HIV and other infectious agents.



http://ift.tt/2nc9c5h

G protein-coupled calcium-sensing receptor is a crucial mediator of MTA-induced biological activities

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Jin Man Kim, Seulki Choi, Kyu Hwan Kwack, Sun-Young Kim, Hyeon-Woo Lee, Kyungpyo Park
Mineral trioxide aggregate (MTA) is a calcium silicate-based bioactive material that has been extensively used in dentistry. MTA has been highlighted in its diverse biological functions and excellent clinical outcomes. However, limited insight into the intracellular signaling pathways has been provided to explain the biological activities of MTA. Here, we firstly elucidate that the extracellular calcium-sensing receptor (CaSR) is a major signaling mediator of MTA-induced biological reactions through versatile live imaging techniques of human dental pulp cells (hDPCs). We found that MTA activates diverse CaSR downstream pathways; notably, CaSR activation essentially requires dual modulation of extracellular Ca²⁺ and pH via MTA. Among the CaSR downstream pathways, Ca²⁺ mobilization from intracellular stores by the phospholipase C pathway plays an important role in osteogenic differentiation of hDPCs by regulating transcriptional activity. Our findings shed light on the signal transduction mechanism of MTA, thus providing a crucial molecular basis for the use of MTA in regenerative dental therapy.



http://ift.tt/2m1wSaP

Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Jaya Arya, Sebastien Henry, Haripriya Kalluri, Devin V. McAllister, Winston P. Pewin, Mark R. Prausnitz
To support translation of microneedle patches from pre-clinical development into clinical trials, this study examined the effect of microneedle patch application on local skin reactions, reliability of use and acceptability to patients. Placebo patches containing dissolving microneedles were administered to fifteen human participants. Microneedle patches were well tolerated in the skin with no pain or swelling and only mild erythema localized to the site of patch administration that resolved fully within seven days. Microneedle patches could be administered by hand without the need of an applicator and delivery efficiencies were similar for investigator-administration and self-administration. Microneedle patch administration was not considered painful and the large majority of subjects were somewhat or fully confident that they self-administered patches correctly. Microneedle patches were overwhelmingly preferred over conventional needle and syringe injection. Altogether, these results demonstrate that dissolving microneedle patches were well tolerated, easily usable and strongly accepted by human subjects, which will facilitate further clinical translation of this technology.



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Surface engineering of semiconducting polymer nanoparticles for amplified photoacoustic imaging

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Xu Zhen, Xiaohua Feng, Chen Xie, Yuanjin Zheng, Kanyi Pu
Despite the deeper tissue penetration of photoacoustic (PA) imaging, its sensitivity is generally lower than optical imaging. This fact partially restricts the applications of PA imaging and greatly stimulates the development of sensitive PA imaging agents. We herein report that the surface coating of semiconducting polymer nanoparticles (SPNs) with the silica layer can simultaneously amplify fluorescence and PA brightness while maintaining their photothermal conversion efficiency nearly unchanged. As compared with the bare SPNs, the silica-coated SPNs (SPNs-SiO2) have higher photothermal heating rate in the initial stage of laser irradiation due to the higher interfacial thermal conductance between the silica layer and water relative to that between the SP and water. Such an interfacial effect consequently results in sharp temperature increase and in turn amplified PA brightness for SPNs-SiO2. By conjugating poly(ethylene glycol) (PEG) and cyclic-RGD onto SPNs-SiO2, targeted PA imaging of tumor in living mice is demonstrated after systemic administration, showing a high signal to background ratio. Our study provides a surface engineering approach to amplify the PA signals of organic nanoparticles for molecular imaging.

Graphical abstract

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Proximal upper limb jerking: important clinical sign to diagnose epilepsy with myoclonic absences

Publication date: Available online 9 March 2017
Source:Pediatric Neurology
Author(s): Rajesh Shankar Iyer




http://ift.tt/2mNdouY

Graphene oxide functionalized long period grating for ultrasensitive label-free immunosensing

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Chen Liu, Qi Cai, Baojian Xu, Weidong Zhu, Lin Zhang, Jianlong Zhao, Xianfeng Chen
We explore graphene oxide (GO) nanosheets functionalized dual-peak long period grating (dLPG) based biosensor for ultrasensitive label-free antibody-antigen immunosensing. The GO linking layer provides a remarkable analytical platform for bioaffinity binding interface due to its favorable combination of exceptionally high surface-to-volume ratio and excellent optical and biochemical properties. A new GO deposition technique based on chemical-bonding in conjunction with physical-adsorption was proposed to offer the advantages of a strong bonding between GO and fiber device surface and a homogeneous GO overlay with desirable stability, repeatability and durability. The surface morphology of GO overlay was characterized by Atomic force microscopy, Scanning electron microscope, and Raman spectroscopy. By depositing the GO with a thickness of 49.2nm, the sensitivity in refractive index (RI) of dLPG was increased to 2538nm/RIU, 200% that of non-coated dLPG, in low RI region (1.333–1.347) where bioassays and biological events were usually carried out. The IgG was covalently immobilized on GO-dLPG via EDC/NHS heterobifunctional cross-linking chemistry leaving the binding sites free for target analyte recognition. The performance of immunosensing was evaluated by monitoring the kinetic bioaffinity binding between IgG and specific anti-IgG in real-time. The GO-dLPG based biosensor demonstrates an ultrahigh sensitivity with limit of detection of 7ng/mL, which is 10-fold better than non-coated dLPG biosensor and 100-fold greater than LPG-based immunosensor. Moreover, the reusability of GO-dLPG biosensor has been facilitated by a simple regeneration procedure based on stripping off bound anti-IgG treatment. The proposed ultrasensitive biosensor can be further adapted as biophotonic platform opening up the potential for food safety, environmental monitoring, clinical diagnostics and medical applications.



http://ift.tt/2m5I85S