Anti-inflammatory effect of glucose-lysine Maillard reaction products on intestinal inflammation model in vivo

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Chung-Oui Hong, Chae Hong Rhee, Min Cheol Pyo, Kwang-Won Lee
Inflammatory bowel diseases (IBDs) are chronic disorders that are characterized by intestinal epithelial inflammation and injury. Currently, the most employed therapies are antibiotics and anti-inflammatory drugs; however, the side effects limit long-term effectiveness. We evaluated the impact of glucose-lysine Maillard reaction products (Glc-Lys MRPs) on colitis, induced in rats by an administration of 5% dextran sulfate sodium (DSS) in drinking water. Glc-Lys MRPs ameliorate DSS-induced colitis, as determined by a decrease in disease index activity, colon weight/length ratio, nitric oxide levels in serum, recovery of body weight loss, colon length and serum lysozyme levels. Furthermore, Glc-Lys MRPs increase the glutathione content and the activity of glutathione peroxidase, superoxide dismutase and catalase, and inhibit lipid peroxidation and myeloperoxidase activity in colon tissues. In particular, Glc-Lys MRPs suppress the mRNA level of the inflammatory cytokines and nuclear factor-κB in colon tissues. This study suggests the potential of Glc-Lys MRPs in preventing or treating IBDs.



http://ift.tt/2xUjJKw

Low-dose combined exposure of nanoparticles and heavy metal compared with PM 2.5 in human myocardial AC16 cells

Abstract

The co-exposure toxicity mechanism of ultrafine particles and pollutants on human cardiovascular system are still unclear. In this study, the combined effects of silica nanoparticles (SiNPs) and/or carbon black nanoparticles (CBNPs) with Pb(AC)₂ compared with particulate matter (PM)_2.5 were investigated in human myocardial cells (AC16). Our study detected three different combinations of SiNPs and Pb(AC)₂, CBNPs and Pb(AC)₂, and SiNPs and CBNPs compared with PM_2.5 at low-dose exposure. Using PM_2.5 as positive control, our results suggested that the combination of SiNPs and Pb(AC)₂/CBNPs could increase the production of reactive oxygen species (ROS), lactate dehydrogenase leakage (LDH), and malondialdehyde (MDA) and decrease the activities of superoxide dismutase (SOD) and glutathione (GSH); induce inflammation by the upregulation of protein CRP and TNF-α, and apoptosis by the upregulation of protein caspase-3, caspase-9, and Bax while the downregulation of protein Bcl-2; and trigger G2/M phase arrest by the upregulation of protein Chk2 and downregulation of protein Cdc2 and cyclin B1. In addition, the combination of CBNPs and Pb(AC)₂ induced a significant increase in MDA and reduced the activities of ROS, LDH, SOD, and GSH, with G1/S phase arrest via upregulation of Chk1 and downregulation of CDK6 and cyclin D1. Our data suggested that the additive interaction and synergistic interaction are the major interaction in co-exposure system, and PM_2.5 could trigger more severe oxidative stress, G2/M arrest, and apoptosis than either co-exposure or single exposure.

http://ift.tt/2xhg1uW

Erratum to: Sub-chronic exposure to low concentration of dibutyl phthalate affects anthropometric parameters and markers of obesity in rats

Abstract

The correct name of the 1st and corresponding Author is Khalid Abdul Majeed.

http://ift.tt/2fLGGoB

The Correlation of Allergic Rhinitis with ABO Phenotype

Abstract

The aim of study the correlation of ABO phenotypes in patients of allergic rhinitis and controls and to compare our study with the previous studies to analyse the association of above. 100 patients with symptoms of allergic rhinitis and 100 controls individual were selected from same geographical region and paired by gender and age were enrolled in the study. Detailed history, examination and relevant radiological and hematological investigations were done. ABO phenotypes were identified in red blood cells using hemagglutination technique. This clinic-based observational study was conducted among the patients presenting with signs and symptoms of allergic rhinitis. Maximum no. of cases were seen in ABO phenotype O (52%), followed by A, B and AB (33, 12 and 3% respectively) and it was found to be statistically significant (p = 0.001). Also more number of male patients were found in B and O blood group which was statistically significant (OR 5.33, p = 0.017 and OR 3.63, p = 0.006 respectively). Controls showed marginalized difference in distribution among the basis of different ABO phenotypes. The O blood group phenotype of ABO histo-blood group system is associated with AR. This study contributes to the better understanding of the pathophysiology and clinical variability of this disease and may help to improve strategies towards its prevention and diagnosis. Additionally, ABO histo-blood group phenotyping, an inexpensive and easy to perform assay could be used to identify individuals at risk of developing allergic rhinitis.

http://ift.tt/2xjfO5r

The Correlation of Allergic Rhinitis with ABO Phenotype

Abstract

The aim of study the correlation of ABO phenotypes in patients of allergic rhinitis and controls and to compare our study with the previous studies to analyse the association of above. 100 patients with symptoms of allergic rhinitis and 100 controls individual were selected from same geographical region and paired by gender and age were enrolled in the study. Detailed history, examination and relevant radiological and hematological investigations were done. ABO phenotypes were identified in red blood cells using hemagglutination technique. This clinic-based observational study was conducted among the patients presenting with signs and symptoms of allergic rhinitis. Maximum no. of cases were seen in ABO phenotype O (52%), followed by A, B and AB (33, 12 and 3% respectively) and it was found to be statistically significant (p = 0.001). Also more number of male patients were found in B and O blood group which was statistically significant (OR 5.33, p = 0.017 and OR 3.63, p = 0.006 respectively). Controls showed marginalized difference in distribution among the basis of different ABO phenotypes. The O blood group phenotype of ABO histo-blood group system is associated with AR. This study contributes to the better understanding of the pathophysiology and clinical variability of this disease and may help to improve strategies towards its prevention and diagnosis. Additionally, ABO histo-blood group phenotyping, an inexpensive and easy to perform assay could be used to identify individuals at risk of developing allergic rhinitis.

http://ift.tt/2xjfO5r

Effectiveness of tip rotation in fibreoptic bronchoscopy under different experimental conditions: an in vitro crossover study

Abstract

Background

Proper manipulation of fibreoptic bronchoscopes is essential for successful tracheal intubation or diagnostic bronchoscopy. Failure of proper navigation and rotation of the fibrescope may lead to difficulties in advancing the fibrescope and might also be responsible for (unnecessary) difficulties and delays in fibreoptic tracheal intubation, with subsequent hypoxaemia. The present study, therefore, aimed to assess the effectiveness of tip rotation in flexible bronchoscopes in different experimental conditions.

Methods

Five differently sized pairs of fibrescopes (outer diameters of 2.2, 2.4, 3.5, 4.2, and 5.2 mm) were inserted into paediatric airway manikins via an appropriately sized laryngeal mask and were turned clockwise or anticlockwise at the fibrescope body or cord to 45, 90, and 180°, with the cord held either straight or bent. The primary outcome measure was the ratio of rotation measured at the tip over the rotation performed with the fibrescope body or cord.

Results

Overall, the 'body' turn was significantly less effective when a bent cord was present (mean difference ranging from 29.8% (95% confidence interval 8.8–50.9) to 117.4% (93.6–141.2). This difference was diminished when the 'cord' turn was performed. Smaller fibrescopes, with outer diameters of 2.2 and 2.4 mm, were inferior with respect to the transmission of 'body' rotation to the tip.

Conclusions

'Cord' turning of the fibrescope appears to be more effective in rotating the tip than a turn of the fibrescope 'body' only. Straightening the fibrescope cord and combined 'body' and 'cord' turning are recommended.

http://ift.tt/2fSsAWc

Evidence-based medicine: the clue is in the name

Keane and Berg¹ have taken issue with the scientific basis of medicine. Their premise is built on the following three challenges: that 'science' (in particular, the randomized controlled trial) is fundamentally unsuited to complex health care; that the evolutionary processes described in economics are a better fit to health care; and that attempts to grade recommendations are unnecessary and unhelpful. Their editorial raises genuine concerns and merits careful reading. But this perhaps presents a Utopian fallacy; evidence-based medicine isn't perfect so it must be replaced. The term 'evidence-based medicine' is frequently misused, misapplied, and misunderstood. Evidence-based medicine (if it is to live up to its name) should be open to scrutiny and challenge. It is certainly not a religious creed that cannot be questioned. Unthinking misapplication of 'evidence' leads both directly and indirectly to poor patient outcomes. Evidence-based medicine has many definitions, but Masic and colleagues² described it well: 'Evidence based medicine is the conscientious, explicit, judicious and reasonable use of modern, best evidence in making decisions about the care of individual patients. Evidence based medicine integrates clinical experience and patient values with the best available research information.'

http://ift.tt/2y0CTNX

An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers

Abstract

Background

There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg.

Methods

Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal P_CO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake.

Results

All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference −5.0 L min⁻¹, 95% confidence interval: −7.1 to −2.9 L min⁻¹, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05).

Conclusions

In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

http://ift.tt/2fRf590

Guidelines on informed consent in anaesthesia: unrealistic, unethical, untenable….

'Informed consent' has become the primary paradigm for protecting the legal rights of patients and guiding the ethical practice of medicine.¹ The Association of Anaesthetists of Great Britain and Ireland (AAGBI) 'informed consent' guidelines have recently been updated in response to 'the changing ethical and legal background against which anaesthetists, intensivists and pain specialists, currently work'.² This guidance aims to advise its members (and others) how to provide information about anaesthesia that respects patient autonomy and stays within the law.³ This raises the question, are we really achieving the key principles of primum non nocere,⁴ respect for patient autonomy,⁵ and the need to provide adequate information?⁶ Current guidance has been almost solely based on medicolegal determinations around inadequate informed consent, focusing on the failure to disclose a 'material risk'.⁷⁸ This has led health authorities and many clinicians to interpret the guidelines as a directive, informing patients of an ever-increasing list of potential anaesthesia-related adverse events. Misguided attempts to include every possible 'material risk' are leaving patients bombarded with excessive amounts of largely irrelevant and incomprehensible information.⁹¹⁰ This practice is also leading to unnecessary alarm and confusion, not to mention exposure of patients to the adverse effects of nocebo communications (negative suggestion).¹¹

http://ift.tt/2y13ri2

Big data, small airways, big problems

Some of the earliest airway management interventions in humans occurred in neonates in the 18^th century. Small tubes were passed into the oropharynx of newborn children to support ventilation. Later in that century, the Royal Humane Society was developed in the United Kingdom to address adult drowning, and the first approaches to tracheal intubation were described. Airway management expanded from life-saving interventions such as these to the operating theatre to support surgical procedures with required ventilation. In the operating theatre, the focus of new approaches to airway management has been on adults. Unfortunately, this has left the paediatric provider with adult tools and techniques that have simply been downsized for paediatric airway management. Advancing our knowledge regarding the optimal airway management techniques in children is challenging because of the rare occurrence of difficult events and challenges surrounding enrolling children in clinical trials.

http://ift.tt/2y0u5Yo

Does pharmacokinetic/pharmacodynamic model-guided anaesthesia improve outcome after hip fracture surgery?

Hip fracture affects ∼628 000 patients annually and accounts for ∼200 000 deaths in Europe.¹ The EuroHOPE database, which includes seven European countries, revealed that the 30 day mortality rate after hip fracture surgery ranges from 4 to 12% and reaches up to 35% after 1 yr.² Postoperative complications, such as serious cardiac and pulmonary events, appear most frequently.¹³ Postoperative delirium occurs often and is associated with increased mortality.⁴ Improving outcomes for vulnerable elderly hip-fractured patients is a key goal for perioperative care.¹

http://ift.tt/2fRepjY

Is science the answer?

Nearly ten years ago, Tobin described the irony that evidence-based medicine (EBM) lacks a sound scientific basis.¹ A sentinel paper concluded that most results of medical research were false,² and now the same author, a well-lauded EBM proponent, argues that even if true, most clinical research is not useful³ and now concedes that EBM has been 'hijacked' by 'vested interests' including industry and researchers.⁴ The community expends vast resources on research, yet it has been estimated that there is an 85% 'waste in the production and reporting of research evidence'.⁵

http://ift.tt/2y0QODL

Surgical pleth index: prediction of postoperative pain in children?

Abstract

Background

. Surgical Pleth Index (SPI) is a non-invasive, dimensionless score (0–100) aimed to allow an estimate of intraoperative nociception. Thus, it may be a useful tool to guide intraoperative analgesia. However, no optimum SPI target range for the use in children has yet been defined. It was the aim of this study to define a clinically appropriate SPI target to predict moderate-severe postoperative pain in children.

Methods

. After ethics approval 105 children (2–16 yr) undergoing elective sevoflurane/opioid-based anaesthesia were included. SPI was recorded directly before the end of surgery and compared with acute postoperative pain (age appropriately assessed on different pain scales in the age groups two to three yr, four to eight yr and nine to16 yr) in the postoperative acute care unit (PACU).

Results

Data of 93 children were analysed. A significant negative correlation was found between age and SPI (r=−0.43; P=0.03). The SPI cut-off value with the highest sensitivity (76%) and specificity (62%) in all children combined was 40. The negative predictive value for SPI ≤ 40 to predict the absence of moderate-severe pain in PACU was 87.5%. The commonly used SPI cut-off (50) published in all related studies had neither any clinically relevant sensitivity nor specificity to predict the presence or absence of acute pain in PACU.

Conclusions

. The results suggest that a lower (≤ 40) than previously published (50) target for SPI may be more appropriate in studies investigating SPI guided anaesthesia in children, if the avoidance of moderate-severe postoperative pain is the main goal.

Clinical trial registration

ACTRN12616001139460.

http://ift.tt/2y0i59k

Effectiveness of tip rotation in fibreoptic bronchoscopy under different experimental conditions: an in vitro crossover study

Abstract

Background

Proper manipulation of fibreoptic bronchoscopes is essential for successful tracheal intubation or diagnostic bronchoscopy. Failure of proper navigation and rotation of the fibrescope may lead to difficulties in advancing the fibrescope and might also be responsible for (unnecessary) difficulties and delays in fibreoptic tracheal intubation, with subsequent hypoxaemia. The present study, therefore, aimed to assess the effectiveness of tip rotation in flexible bronchoscopes in different experimental conditions.

Methods

Five differently sized pairs of fibrescopes (outer diameters of 2.2, 2.4, 3.5, 4.2, and 5.2 mm) were inserted into paediatric airway manikins via an appropriately sized laryngeal mask and were turned clockwise or anticlockwise at the fibrescope body or cord to 45, 90, and 180°, with the cord held either straight or bent. The primary outcome measure was the ratio of rotation measured at the tip over the rotation performed with the fibrescope body or cord.

Results

Overall, the 'body' turn was significantly less effective when a bent cord was present (mean difference ranging from 29.8% (95% confidence interval 8.8–50.9) to 117.4% (93.6–141.2). This difference was diminished when the 'cord' turn was performed. Smaller fibrescopes, with outer diameters of 2.2 and 2.4 mm, were inferior with respect to the transmission of 'body' rotation to the tip.

Conclusions

'Cord' turning of the fibrescope appears to be more effective in rotating the tip than a turn of the fibrescope 'body' only. Straightening the fibrescope cord and combined 'body' and 'cord' turning are recommended.

http://ift.tt/2fSsAWc

Evidence-based medicine: the clue is in the name

Keane and Berg¹ have taken issue with the scientific basis of medicine. Their premise is built on the following three challenges: that 'science' (in particular, the randomized controlled trial) is fundamentally unsuited to complex health care; that the evolutionary processes described in economics are a better fit to health care; and that attempts to grade recommendations are unnecessary and unhelpful. Their editorial raises genuine concerns and merits careful reading. But this perhaps presents a Utopian fallacy; evidence-based medicine isn't perfect so it must be replaced. The term 'evidence-based medicine' is frequently misused, misapplied, and misunderstood. Evidence-based medicine (if it is to live up to its name) should be open to scrutiny and challenge. It is certainly not a religious creed that cannot be questioned. Unthinking misapplication of 'evidence' leads both directly and indirectly to poor patient outcomes. Evidence-based medicine has many definitions, but Masic and colleagues² described it well: 'Evidence based medicine is the conscientious, explicit, judicious and reasonable use of modern, best evidence in making decisions about the care of individual patients. Evidence based medicine integrates clinical experience and patient values with the best available research information.'

http://ift.tt/2y0CTNX

An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers

Abstract

Background

There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg.

Methods

Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal P_CO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake.

Results

All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference −5.0 L min⁻¹, 95% confidence interval: −7.1 to −2.9 L min⁻¹, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05).

Conclusions

In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

http://ift.tt/2fRf590

Guidelines on informed consent in anaesthesia: unrealistic, unethical, untenable….

'Informed consent' has become the primary paradigm for protecting the legal rights of patients and guiding the ethical practice of medicine.¹ The Association of Anaesthetists of Great Britain and Ireland (AAGBI) 'informed consent' guidelines have recently been updated in response to 'the changing ethical and legal background against which anaesthetists, intensivists and pain specialists, currently work'.² This guidance aims to advise its members (and others) how to provide information about anaesthesia that respects patient autonomy and stays within the law.³ This raises the question, are we really achieving the key principles of primum non nocere,⁴ respect for patient autonomy,⁵ and the need to provide adequate information?⁶ Current guidance has been almost solely based on medicolegal determinations around inadequate informed consent, focusing on the failure to disclose a 'material risk'.⁷⁸ This has led health authorities and many clinicians to interpret the guidelines as a directive, informing patients of an ever-increasing list of potential anaesthesia-related adverse events. Misguided attempts to include every possible 'material risk' are leaving patients bombarded with excessive amounts of largely irrelevant and incomprehensible information.⁹¹⁰ This practice is also leading to unnecessary alarm and confusion, not to mention exposure of patients to the adverse effects of nocebo communications (negative suggestion).¹¹

http://ift.tt/2y13ri2

Big data, small airways, big problems

Some of the earliest airway management interventions in humans occurred in neonates in the 18^th century. Small tubes were passed into the oropharynx of newborn children to support ventilation. Later in that century, the Royal Humane Society was developed in the United Kingdom to address adult drowning, and the first approaches to tracheal intubation were described. Airway management expanded from life-saving interventions such as these to the operating theatre to support surgical procedures with required ventilation. In the operating theatre, the focus of new approaches to airway management has been on adults. Unfortunately, this has left the paediatric provider with adult tools and techniques that have simply been downsized for paediatric airway management. Advancing our knowledge regarding the optimal airway management techniques in children is challenging because of the rare occurrence of difficult events and challenges surrounding enrolling children in clinical trials.

http://ift.tt/2y0u5Yo

Does pharmacokinetic/pharmacodynamic model-guided anaesthesia improve outcome after hip fracture surgery?

Hip fracture affects ∼628 000 patients annually and accounts for ∼200 000 deaths in Europe.¹ The EuroHOPE database, which includes seven European countries, revealed that the 30 day mortality rate after hip fracture surgery ranges from 4 to 12% and reaches up to 35% after 1 yr.² Postoperative complications, such as serious cardiac and pulmonary events, appear most frequently.¹³ Postoperative delirium occurs often and is associated with increased mortality.⁴ Improving outcomes for vulnerable elderly hip-fractured patients is a key goal for perioperative care.¹

http://ift.tt/2fRepjY

Is science the answer?

Nearly ten years ago, Tobin described the irony that evidence-based medicine (EBM) lacks a sound scientific basis.¹ A sentinel paper concluded that most results of medical research were false,² and now the same author, a well-lauded EBM proponent, argues that even if true, most clinical research is not useful³ and now concedes that EBM has been 'hijacked' by 'vested interests' including industry and researchers.⁴ The community expends vast resources on research, yet it has been estimated that there is an 85% 'waste in the production and reporting of research evidence'.⁵

http://ift.tt/2y0QODL

Surgical pleth index: prediction of postoperative pain in children?

Abstract

Background

. Surgical Pleth Index (SPI) is a non-invasive, dimensionless score (0–100) aimed to allow an estimate of intraoperative nociception. Thus, it may be a useful tool to guide intraoperative analgesia. However, no optimum SPI target range for the use in children has yet been defined. It was the aim of this study to define a clinically appropriate SPI target to predict moderate-severe postoperative pain in children.

Methods

. After ethics approval 105 children (2–16 yr) undergoing elective sevoflurane/opioid-based anaesthesia were included. SPI was recorded directly before the end of surgery and compared with acute postoperative pain (age appropriately assessed on different pain scales in the age groups two to three yr, four to eight yr and nine to16 yr) in the postoperative acute care unit (PACU).

Results

Data of 93 children were analysed. A significant negative correlation was found between age and SPI (r=−0.43; P=0.03). The SPI cut-off value with the highest sensitivity (76%) and specificity (62%) in all children combined was 40. The negative predictive value for SPI ≤ 40 to predict the absence of moderate-severe pain in PACU was 87.5%. The commonly used SPI cut-off (50) published in all related studies had neither any clinically relevant sensitivity nor specificity to predict the presence or absence of acute pain in PACU.

Conclusions

. The results suggest that a lower (≤ 40) than previously published (50) target for SPI may be more appropriate in studies investigating SPI guided anaesthesia in children, if the avoidance of moderate-severe postoperative pain is the main goal.

Clinical trial registration

ACTRN12616001139460.

http://ift.tt/2y0i59k

A high-resolution air pollutants emission inventory in 2013 for the Beijing-Tianjin-Hebei region, China

Publication date: December 2017
Source:Atmospheric Environment, Volume 170
Author(s): Ji Qi, Bo Zheng, Meng Li, Fang Yu, Chuchu Chen, Fei Liu, Xiafei Zhou, Jing Yuan, Qiang Zhang, Kebin He
We developed a high-resolution Beijing-Tianjin-Hebei (BTH) regional air pollutants emission inventory for the year 2013. The inventory was established using a bottom-up approach based on facility-level activity data obtained from multiple data sources. The estimates from the BTH 2013 emission inventory show that the total emissions of SO2, NOX, PM2.5, PM10, CO, NMVOC, NH3, BC, and OC were 2,305, 2,686, 1,090, 1,494, 20,567, 2,207, 623, 160, and 254 Gg, respectively. The industry sector is the largest emissions source for SO2, NOX, PM2.5, PM10, CO, and NMVOC in the BTH region, contributing 72.6%, 43.7%, 59.6%, 64.7%, 60.3%, and 70.4% of the total emissions, respectively. Power plants contributed 11.8% and 23.3% of the total SO2 and NOX emissions, respectively. The transportation sector contributed 28.9% of the total NOX emissions. Emissions from the residential sector accounted for 31.3%, 21.5%, 46.6% and 71.7% of the total PM2.5, NMVOC, BC and OC emissions, respectively. In addition, more than 90% of the total NH3 emissions originate from the agriculture sector, with 44.2% from fertilizer use and 47.7% from livestock. The spatial distribution results illustrate that air pollutant emissions are mainly distributed over the eastern and southern BTH regions. Beijing, Tianjin, Shijiazhuang, Tangshan and Handan are the major contributors of air pollutants. The major NMVOC species in the BTH region are ethylene, acetylene, ethane and toluene. Ethylene is the biggest contributor in Tianjin and Hebei. The largest contributor in Beijing is toluene. There is relatively low uncertainty in SO2 and NOX emission estimates, medium uncertainty in PM2.5, PM10 and CO emission estimates, and high uncertainties in VOC, NH3, BC and OC emission estimates. The proposed policy recommendations, based on the BTH 2013 emission inventory, would be helpful to develop strategies for air pollution control.



http://ift.tt/2yIQxmy

Development of an environmental chamber for evaluating the performance of low-cost air quality sensors under controlled conditions

Publication date: Available online 4 October 2017
Source:Atmospheric Environment
Author(s): Vasileios Papapostolou, Hang Zhang, Brandon J. Feenstra, Andrea Polidori
A state-of-the-art integrated chamber system has been developed for evaluating the performance of low-cost air quality sensors. The system contains two professional grade chamber enclosures. A 1.3 m³ stainless-steel outer chamber and a 0.11 m³ Teflon-coated stainless-steel inner chamber are used to create controlled aerosol and gaseous atmospheres, respectively. Both chambers are temperature and relative humidity controlled with capability to generate a wide range of environmental conditions. The system is equipped with an integrated zero-air system, an ozone and two aerosol generation systems, a dynamic dilution calibrator, certified gas cylinders, an array of Federal Reference Method (FRM), Federal Equivalent Method (FEM), and Best Available Technology (BAT) reference instruments and an automated control and sequencing software. Our experiments have demonstrated that the chamber system is capable of generating stable and reproducible aerosol and gas concentrations at low, medium, and high levels. This paper discusses the development of the chamber system along with the methods used to quantitatively evaluate sensor performance. Considering that a significant number of academic and research institutions, government agencies, public and private institutions, and individuals are becoming interested in developing and using low-cost air quality sensors, it is important to standardize the procedures used to evaluate their performance. The information discussed herein provides a roadmap for entities who are interested in characterizing air quality sensors in a rigorous, systematic and reproducible manner.

Graphical abstract

http://ift.tt/2yZuLvE

Development of a practical animal model of photodynamic therapy using a high concentration of extracellular talaporfin sodium in interstitial fluid: influence of albumin animal species on myocardial cell photocytotoxicity in vitro

Abstract

Photodynamic reaction-induced photocytotoxicity using talaporfin sodium is inhibited by serum proteins binding to talaporfin sodium. The serum albumin binding site for talaporfin sodium differs among animal species. To identify a practical animal therapeutic model, we studied the ability of human, canine, bovine, and porcine albumin to influence talaporfin sodium-induced photocytotoxicity in rat myocardial cells in vitro. Human, canine, bovine, and porcine serum albumins were used. The ratio of talaporfin sodium binding, which is strongly associated with photocytotoxicity, was measured by ultrafiltration with an albumin concentration of 0.5–20 mg/ml and 20 μg/ml talaporfin sodium to mimic interstitial fluid. Rat myocardial cell lethality was measured by the WST assay 2 h after samples were exposed to a radiant exposure of 20 J/cm² by a red diode laser (Optical Fuel™, Sony, Tokyo, Japan) with a wavelength of 663 nm. The binding ratio dependence on albumin concentration differed among the animal species. Bovine albumin exhibited the largest difference from human albumin, with a maximum difference of 31% at 2 mg/ml albumin. The cell lethality characteristic was similar between human and canine albumin. The cell lethality dependence on albumin was not in the same order as the binding ratio. Cell lethality was lowest for human albumin with higher albumin concentrations between 5 and 20 mg/ml. There were no significant differences in cell lethality between bovine and porcine albumin and between human and canine albumin. We suggest that the canine model may be a useful animal therapeutic model for evaluating photodynamic therapy using a high concentration of the photosensitizer in the extracellular space.

http://ift.tt/2y0eAjc

Enrollment of Neonates in More Than One Clinical Trial

Publication date: Available online 4 October 2017
Source:Clinical Therapeutics
Author(s): Jonathan M. Davis, Gerri R. Baer, Ronald Portman, Robert Nelson, Linda Storari, Jacob V. Aranda, Ralph Bax, Anne Zajicek, Agnes Klein, Mark Turner, Simin Baygani, Merran Thomson, Karel Allegaert
Because the highest rates of morbidity and mortality in neonates are seen in those born at <32 weeks' gestation, this group has the most urgent need for novel therapies to improve survival and outcome. Legislative efforts in the United States and Europe have attempted to address this issue by requiring the study of drugs, biological and nutritional products, devices, and other therapies in this population through a combination of high-quality regulatory and clinical trials, quality improvement initiatives, and observational studies. Because there are relatively small numbers of very preterm neonates born each year in any 1 country or continent, and because a significant number of clinical trials are recruiting at any 1 time, a neonate may meet enrollment criteria for >1 clinical trial. Neonatal units that have the infrastructure and resources to engage in research frequently face the question of whether it is permissible to enroll a neonate in >1 trial. This article examines the pertinent scientific, ethical, regulatory, and industry issues that should be taken into account when considering enrolling neonates in multiple clinical studies.



http://ift.tt/2xW47E4

Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects

Publication date: Available online 4 October 2017
Source:Clinical Therapeutics
Author(s): Helen Tomkinson, Eileen McBride, Paul Martin, Eleanor Lisbon, Angela W. Dymond, Mireille Cantarini, Karen So, David Holt
PurposeSelumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective mitogen-activated protein kinase 1/2 inhibitor with a short half-life, has shown activity across various tumor types. Before initiation of Phase III trials, the site, scale, and color (hypromellose shell from white [Phase II] to blue [Phase III]) of the selumetinib 25mg capsule manufacture was changed. We present 2 crossover trials evaluating Phase III capsules in healthy subjects.MethodsThe relative bioavailability trial was a Phase I, open-label, randomized, 3-treatment, 4-period, 6-sequence crossover trial in healthy male subjects (aged 18–55 years). Subjects received selumetinib 75mg (3 × 25 mg) Phase II or Phase III capsules, or a 35mg oral solution, during 4 dosing periods in 1 of 6 randomized treatment sequences. The food effect trial was a Phase I, open-label, randomized, 2-period crossover trial in healthy male subjects (aged 18–45 years). Subjects were randomized to 1 of 2 sequences to receive selumetinib 75mg (3 × 25 mg) Phase III capsules. In sequence 1, subjects received selumetinib after 10 hours of fasting. Following a washout period, selumetinib was administered after a high-fat meal. In sequence 2, subjects received selumetinib in the fed state, before the fasted state. Pharmacokinetic parameters were determined from serial blood sampling.FindingsTwenty-seven subjects were randomized to the relative bioavailability trial; 26 completed all dosing periods. Mean selumetinib AUC was unchanged (geometric least squares mean ratio [GLSMR], 90.01% [90% CI, 81.74–99.11]). Cmax was 18% lower with the Phase III capsules (GLSMR, 81.97% [90% CI, 69.01–97.36]). A post hoc exploratory statistical analysis excluding outlying observations with later Tmax showed that Phase II and III capsules produced similar exposure in terms of Cmax and AUC. High intrasubject variability for Cmax attributed to the pharmacokinetic sampling schedule was judged to have impacted on the estimated GLSMR. In the food effect trial, 34 subjects completed both study periods. A high-fat meal reduced selumetinib Cmax compared with the fasted state (GLSMR, 49.76% [90% CI, 43.82–56.51]); AUC was minimally changed (GLSMR, 84.08% [90% CI, 80.72–87.59]). Median Tmax was prolonged by 1.49 hours. No deaths or serious adverse events were reported.ImplicationsSelumetinib 75mg (3 × 25 mg) Phase III capsules are being used in ongoing pivotal Phase III trials and should be administered in the fasted state. Based on findings from the relative bioavailability trial, pharmacokinetic sampling frequency was increased for healthy subject trials, including the food effect trial. ClinicalTrials.gov identifiers: NCT01635023 (relative bioavailability) and NCT01974349 (food effect).



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Economic growth and CO 2 emissions: an investigation with smooth transition autoregressive distributed lag models for the 1800–2014 period in the USA

Abstract

The study aims to combine the autoregressive distributed lag (ARDL) cointegration framework with smooth transition autoregressive (STAR)-type nonlinear econometric models for causal inference. Further, the proposed STAR distributed lag (STARDL) models offer new insights in terms of modeling nonlinearity in the long- and short-run relations between analyzed variables. The STARDL method allows modeling and testing nonlinearity in the short-run and long-run parameters or both in the short- and long-run relations. To this aim, the relation between CO₂ emissions and economic growth rates in the USA is investigated for the 1800–2014 period, which is one of the largest data sets available. The proposed hybrid models are the logistic, exponential, and second-order logistic smooth transition autoregressive distributed lag (LSTARDL, ESTARDL, and LSTAR2DL) models combine the STAR framework with nonlinear ARDL-type cointegration to augment the linear ARDL approach with smooth transitional nonlinearity. The proposed models provide a new approach to the relevant econometrics and environmental economics literature. Our results indicated the presence of asymmetric long-run and short-run relations between the analyzed variables that are from the GDP towards CO₂ emissions. By the use of newly proposed STARDL models, the results are in favor of important differences in terms of the response of CO₂ emissions in regimes 1 and 2 for the estimated LSTAR2DL and LSTARDL models.

http://ift.tt/2fSgyMt

Fasting the Microbiota to Improve Metabolism?

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Joel T. Haas, Bart Staels
While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues (2017) highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging.

Teaser

While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging.


http://ift.tt/2fKf5nu

Dietary Carbohydrates Impair Healthspan and Promote Mortality

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Meenakshi Ravichandran, Gerald Grandl, Michael Ristow
The prospective cohort study, named PURE, found that in >135,000 participants from 18 countries, nutritive carbohydrates increase human mortality, whereas dietary fat reduces it, requesting a fundamental change of current nutritional guidelines. Experimental evidence from animal models provides synergizing mechanistic concepts as well as pharmacological options to mimic low-carb or ketogenic diets.

Teaser

The prospective cohort study, named PURE, found that in >135,000 participants from 18 countries, nutritive carbohydrates increase human mortality, whereas dietary fat reduces it, requesting a fundamental change of current nutritional guidelines. Experimental evidence from animal models provides synergizing mechanistic concepts as well as pharmacological options to mimic low-carb or ketogenic diets.


http://ift.tt/2y0QtkI

The Burgeoning World of Immunometabolites: Th17 Cells Take Center Stage

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Glenn R. Bantug, Christoph Hess
Dysregulation of the Th17/Treg balance is a key driver of autoimmunity. A new study by Xu et al. (2017) has revealed that small-molecule inhibition of 2-hydroxyglutarate synthesis skews Th17 differentiation to the Treg lineage, which is protective against autoimmune inflammation.

Teaser

Dysregulation of the Th17/Treg balance is a key driver of autoimmunity. A new study by Xu et al. has revealed that small-molecule inhibition of 2-hydroxyglutarate synthesis skews Th17 differentiation to the Treg lineage, which is protective against autoimmune inflammation.


http://ift.tt/2fM9uNE

TREM2: Keeping Microglia Fit during Good Times and Bad

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Soyon Hong, Beth Stevens
Microglia are the macrophages of the brain and play an important role in Alzheimer's disease (AD). In Cell, Ulland et al. (2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques.

Teaser

Microglia are the macrophages of the brain and play an important role in Alzheimer's disease (AD). In Cell, Ulland et al. (2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques.


http://ift.tt/2y0xRRN

Slowing Down Aging

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Katharina Meyer, Bruce A. Yankner
The hypothalamus plays a key role in coordinating the physiological changes that underlie mammalian aging. In a recent issue of Nature, Cai and colleagues (2017) shed new light on the mechanism of this effect by providing evidence that hypothalamic stem cells may regulate aging through the release of microRNAs in exosomes.

Teaser

The hypothalamus plays a key role in coordinating the physiological changes that underlie mammalian aging. In a recent issue of Nature, Cai and colleagues (2017) shed new light on the mechanism of this effect by providing evidence that hypothalamic stem cells may regulate aging through the release of microRNAs in exosomes.


http://ift.tt/2fLV1Bo

Metabolic Disease Therapies

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4

In anticipation of our upcoming Cell Symposium on Metabolic Disease Therapies in San Diego, CA, on October 15^th–17^th (http://ift.tt/2fKf4Qs), the speakers and organizers share their perspectives on why now, more than ever, cutting-edge research is needed to support effective therapies to combat metabolic disease.

Teaser

In anticipation of our upcoming Cell Symposium on Metabolic Disease Therapies in San Diego, CA, on October 15^th–17^th (http://ift.tt/2fKf4Qs), the speakers and organizers share their perspectives on why now, more than ever, cutting-edge research is needed to support effective therapies to combat metabolic disease.


http://ift.tt/2y0No40

Antigen-Specific Peptide Immunotherapy for Type 1 Diabetes: Proof of Safety, Hope for Efficacy

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Ken Coppieters, Matthias von Herrath
Antigen-specific immunotherapy has long been hailed as the ideal disease-modifying approach for type 1 diabetes, both for disease prevention and reversal. A small phase 1 trial now demonstrates safety of a peptide-based treatment in recently diagnosed adults.

Teaser

Antigen-specific immunotherapy has long been hailed as the ideal disease-modifying approach for type 1 diabetes, both for disease prevention and reversal. A small phase 1 trial now demonstrates safety of a peptide-based treatment in recently diagnosed adults.


http://ift.tt/2y0qEB7

Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Ruud S. Kootte, Evgeni Levin, Jarkko Salojärvi, Loek P. Smits, Annick V. Hartstra, Shanti D. Udayappan, Gerben Hermes, Kristien E. Bouter, Annefleur M. Koopen, Jens J. Holst, Filip K. Knop, Ellen E. Blaak, Jing Zhao, Hauke Smidt, Amy C. Harms, Thomas Hankemeijer, Jacques J.G.H.M. Bergman, Hans A. Romijn, Frank G. Schaap, Steven W.M. Olde Damink, Mariette T. Ackermans, Geesje M. Dallinga-Thie, Erwin Zoetendal, Willem M. de Vos, Mireille J. Serlie, Erik S.G. Stroes, Albert K. Groen, Max Nieuwdorp
The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.

Graphical abstract

Teaser

Kootte et al. show that fecal microbiota transplantation from lean donors to obese patients with metabolic syndrome improves insulin sensitivity, a transient effect associated with changes in microbiota composition and fasting plasma metabolites. Baseline fecal microbiota composition in recipients predicts the response to lean donor fecal microbiota transplantation.


http://ift.tt/2fMPVVk

MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Kyung-min Lee, Jennifer M. Giltnane, Justin M. Balko, Luis J. Schwarz, Angel L. Guerrero-Zotano, Katherine E. Hutchinson, Mellissa J. Nixon, Mónica V. Estrada, Violeta Sánchez, Melinda E. Sanders, Taekyu Lee, Henry Gómez, Ana Lluch, J. Alejandro Pérez-Fidalgo, Melissa Magdalene Wolf, Gabriela Andrejeva, Jeffrey C. Rathmell, Stephen W. Fesik, Carlos L. Arteaga
Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1. Increased levels of ROS, a by-product of activated mtOXPHOS, led to the accumulation of HIF-1α. Pharmacological inhibition of HIF-1α attenuated CSC enrichment and tumor initiation in vivo. These data suggest that (1) MYC and MCL1 confer resistance to chemotherapy by expanding CSCs via mtOXPHOS and (2) targeting mitochondrial respiration and HIF-1α may reverse chemotherapy resistance in TNBC.

Graphical abstract

Teaser

MYC and MCL1 are co-amplified in drug-resistant breast cancer. Lee et al. reveal that MYC and MCL1 cooperate to maintain cancer stem cells (CSCs) resistant to chemotherapy by increasing mitochondrial OXPHOS, ROS production, and HIF-1α expression. Inhibition of HIF-1α blocks CSC expansion and restores chemotherapy sensitivity.


http://ift.tt/2fLsdJb

Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity

Publication date: 3 October 2017
Source:Cell Metabolism, Volume 26, Issue 4
Author(s): Lawrence Kazak, Edward T. Chouchani, Gina Z. Lu, Mark P. Jedrychowski, Curtis J. Bare, Amir I. Mina, Manju Kumari, Song Zhang, Ivan Vuckovic, Dina Laznik-Bogoslavski, Petras Dzeja, Alexander S. Banks, Evan D. Rosen, Bruce M. Spiegelman




http://ift.tt/2fL7h57

Facilitating electroconvulsive therapy seizure induction: Lower pulse frequency or longer stimulus duration?

Publication date: Available online 4 October 2017
Source:Brain Stimulation
Author(s): Chittaranjan Andrade




http://ift.tt/2y2whPy

Frequent immunoglobulin G4 expression in a common variant of primary cutaneous marginal zone B-cell lymphoma

Abstract

Immunoglobulin (Ig)G4 expression was recently observed in a proportion of primary cutaneous marginal zone B-cell lymphoma (PCMZL) with plasmacytic differentiation. IgG4-related disease is characterised by polyclonal lymphoplasmacytic infiltration with IgG4 expression, storiform fibrosis and obliterative phlebitis in histopathology. Here we report three cases of common variants of PCMZL with predominant and varied IgG4 expression, suggesting there is an underlying clonal progression between these two entities.

http://ift.tt/2xgyLuN

Growth promoting potential of fresh and stored Moringa oleifera leaf extracts in improving seedling vigor, growth and productivity of wheat crop

Abstract

Wheat is staple food of region, as it contributes 60% of daily caloric intake, but its delayed sowing reduces yield due to short life span. Moringa leaf extract (MLE) is considered to improve growth and development of field crops. Study comprised of two experiments. First experiment, freshly extracted MLE and in combination with growth-promoting substances were stored at two temperature regimes. Chemical analysis, after 1, 2, and 3 months' storage period, showed that phenolics and ascorbic acid concentrations decreased with increasing storage period. Fresh extracts improved speed and spread of emergence and seedling vigor. Effectiveness of MLE in terms of phenolics and ascorbate concentrations was highest up to 1 month which decreased with prolonged storage. Growth enhancing potential of MLE also reduced with increasing storage duration. Under field conditions, the bio-efficacy of these fresh and stored MLE was compared when applied as foliar spray at tillering and booting stages of wheat. Foliar applied fresh MLE was the most effective in improving growth parameters. Fresh MLE enhanced biochemical and yield attributes in late sown wheat. This growth-promoting potential of MLE decreased with storage time. Application of fresh MLE helped to achieve higher economic yield.

http://ift.tt/2y26sz8

Seasonal variation of heavy metals in water and sediments in the Halda River, Chittagong, Bangladesh

Abstract

The present study was carried out to assess the contamination levels of heavy metals (Pb, Cd, Cr, Cu, Hg, Al, Ni, Co, Zn, Mn) in surface water and sediment of the Halda River. The observed order of heavy metal concentration in water for Al > Ni > Zn > Mn > Cu > Cd > Pb > Cr > Co > Hg (mg/l) and for sediments Al > Mn > Zn > Ni > Cr > Pb > Cu > Co > Cd > Hg (mg/kg), respectively. The concentrations of Pb, Cd, Cr, Cu, Hg, Al, Ni, Co, Zn, and Mn in water, whereas in sediment Pb, Cu, Al, Ni, Co, Zn, and Mn were found above the permissible limit (WHO 2004; USEPA 2006; EPA 1986, 2002 and ECR 1997). Significant variations in the concentrations of Al and Ni were found in water (p < 0.05) while Cr, Cu, Pb, Co, Mn, and Ni showed substantial changes in sediment (p < 0.05). Principal component analysis (PCA) and correlation matrix revealed anthropogenic intrusions of Pb, Cd, Cr, Cu, Hg, Al, Ni, Co, Zn, and Mn in water and sediment. In case of water, very strong linear relationship was found in Hg vs Pb (0.941), Mn vs Zn (0.939), and Ni vs Cu (0.922) at the significance level 0.01. In sediment, very strong linear relationships were found in Mn vs Cr (0.999), Co vs Ni (0.999), Ni vs Cu (0.994), Zn vs Pb (0.993), Co vs Cu (0.992), Cu vs Cr (0.990), Mn vs Cu (0.989), Mn vs Ni (0.975), Mn vs Co (0.975), Ni vs Cr (0.974), Co vs Cr (0.972), Mn vs Pb (0.951), Cr vs Pb (0.948), Zn vs Cr (0.944), and Mn vs Zn (0.941) at the significance level 0.01 which direct that their common origin entirely from industrial effluents, municipal wastes, and agricultural activities. The study shows that seasonal water flows/water discharge (pre-monsoon, monsoon, and post-monsoon) have an impact on the mobility of metals. Elevated levels of metals were detected during monsoon in sediments (Pb, Cr, Cu, Al, Ni, Co, Zn, Mn) and post-monsoon in water (Cd, Hg, Ni, Co, Mn). The detection of high-risk metals in the Halda River may demonstrate that metals can cause significant effects on fry and fingerlings of the Gangetic carp fishery and prawn fishery (via sub-lethal and lethal effects and bioaccumulation or secondary poisoning of metals to fish and prawn).

http://ift.tt/2gdlZTg

Frequent immunoglobulin G4 expression in a common variant of primary cutaneous marginal zone B-cell lymphoma

Abstract

Immunoglobulin (Ig)G4 expression was recently observed in a proportion of primary cutaneous marginal zone B-cell lymphoma (PCMZL) with plasmacytic differentiation. IgG4-related disease is characterised by polyclonal lymphoplasmacytic infiltration with IgG4 expression, storiform fibrosis and obliterative phlebitis in histopathology. Here we report three cases of common variants of PCMZL with predominant and varied IgG4 expression, suggesting there is an underlying clonal progression between these two entities.

http://ift.tt/2xgyLuN

Improving cancer patient emergency room utilization: A New Jersey state assessment

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Anthony J. Scholer, Omar M. Mahmoud, Debopyria Ghosh, Jacob Schwartzman, Mohammed Farooq, Javier Cabrera, Robert Wieder, Nabil R. Adam, Ravi J. Chokshi
IntroductionDue to its increasing incidence and its major contribution to healthcare costs, cancer is a major public health problem in the United States. The impact across different services is not well documented and utilization of emergency departments (ED) by cancer patients is not well characterized. The aim of our study was to identify factors that can be addressed to improve the appropriate delivery of quality cancer care thereby reducing ED utilization, decreasing hospitalizations and reducing the related healthcare costs.MethodsThe New Jersey State Inpatient and Emergency Department Databases were used to identify the primary outcome variables; patient disposition and readmission rates. The independent variables were demographics, payer and clinical characteristics. Multivariable unconditional logistic regression models using clinical and demographic data were used to predict hospital admission or emergency department return.ResultsA total of 37,080 emergency department visits were cancer related with the most common diagnosis attributed to lung cancer (30.0%) and the most common presentation was pain. The disposition of patients who visit the ED due to cancer related issues is significantly affected by the factors of race (African American OR=0.6, p value=0.02 and Hispanic OR=0.5, p value=0.02, respectively), age aged 65 to 75years (SNF/ICF OR 2.35, p value=0.00 and Home Healthcare Service OR 5.15, p value=0.01, respectively), number of diagnoses (OR 1.26, p value=0.00), insurance payer (SNF/ICF OR 2.2, p value=0.02 and Home Healthcare Services OR 2.85, p value=0.07, respectively) and type of cancer (breast OR 0.54, p value=0.01, prostate OR 0.56, p value=0.01, uterine OR 0.37, p value=0.02, and other OR 0.62, p value=0.05, respectively). In addition, comorbidities increased the likelihood of death, being transferred to SNF/ICF, or utilization of home healthcare services (OR 1.6, p value=0.00, OR 1.18, p value=0.00, and OR 1.16, p value=0.04, respectively). Readmission is significantly affected by race (American Americans OR 0.41, standard error 0.08, p value=0.001 and Hispanics OR 0.29, standard error 0.11, p value=0.01, respectively), income (Quartile 2 OR 0.98, standard error 0.14, p value 0.01, Quartile 3 OR 1.07, standard error 0.13, p value 0.01, and Quartile 4 OR 0.88, standard error 0.12, p value 0.01, respectively), and type of cancer (prostate OR 0.25, standard error 0.09, p value=0.001).ConclusionWeb based symptom questionnaires, patient navigators, end of life nursing and clinical cancer pathways can identify, guide and prompt early initiation of treat before progression of symptoms in cancer patients most likely to visit the ED. Thus, improving cancer patient satisfaction, outcomes and reduce health care costs.



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Meta-analysis of the clinicopathological characteristics and peri-operative outcomes of colorectal cancer in obese patients

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Ailin C. Rogers, Guy S. Handelman, J. Gemma Solon, Deborah A. McNamara, Joseph Deasy, John P. Burke
BackgroundThe effect of obesity on the clinicopathological characteristics of colorectal cancer (CRC) has not been clearly characterized. This meta-analysis assesses the pathological and perioperative outcomes of obese patients undergoing surgical resection for CRC.MethodsMeta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies reporting outcomes for obese and non-obese patients undergoing primary CRC resection, based on body-mass index measurement. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI).ResultsA total of 2183 citations were reviewed; 29 studies comprising 56,293 patients were ultimately included in the analysis, with an obesity rate of 19.3%. Obese patients with colorectal cancer were more often female (OR 1.2, 95% CI 1.1–1.2, p<0.001) but there was no difference in the proportion of rectal cancers, T4 tumours, tumour differentiation or margin positivity. Obese patients were significantly more likely to have lymph node metastases (OR 1.2, 95% CI 1.1–1.2, p<0.001), have a lower nodal yield, were associated with a longer duration of surgery, more blood loss and conversions to open surgery (OR 2.6, 95% CI 1.6–4.0, p<0.001) but with no difference in length of stay or post-operative mortality.ConclusionThis meta-analysis demonstrates that obese patients undergoing resection for CRC are more likely to have node positive disease, longer surgery and higher failure rates of minimally invasive approaches. The challenges of colorectal cancer resection in obese patients are emphasized.



http://ift.tt/2y0L50C

Health and ecological risk assessment of heavy metals pollution in an antimony mining region: a case study from South China

Abstract

In recent years, international research on the toxicity of the heavy metal, antimony, has gradually changed focus from early medical and pharmacological toxicology to environmental toxicology and ecotoxicology. However, little research has been conducted for sources identification and risk management of heavy metals pollution by long-term antimony mining activities. In this study, a large number of investigations were conducted on the temporal and spatial distribution of antimony and related heavy metal contaminants (lead, zinc, and arsenic), as well as on the exposure risks for the population for the Yuxi river basin in the Hunan province, China. The scope of the investigations included mine water, waste rock, tailings, agricultural soil, surface water, river sediments, and groundwater sources of drinking water. Health and ecological risks from exposure to heavy metal pollution were evaluated. The main pollution sources of heavy metals in the Yuxi River basin were analyzed. Remediation programs and risk management strategies for heavy metal pollution were consequently proposed. This article provides a scientific basis for the risk assessment and management of heavy metal pollution caused by antimony basin ore mining.

http://ift.tt/2gcCNcQ

Genomic and epigenetic characterization for the comparison of synchronous bilateral tongue squamous cell carcinomas - a case report

Publication date: Available online 4 October 2017
Source:Current Problems in Cancer
Author(s): Ilda P. Ribeiro, Leonor Barroso, Francisco Marques, André Santos, Francisco Caramelo, Maria J. Julião, Joana B. Melo, Isabel M. Carreira
IntroductionThe tongue is the most common and aggressive site for tumors in the oral cavity. These tumors are usually located in the lateral border of the tongue and are often related to the use of tobacco and alcohol. Clinical management of these tumors is predominantly based on anatomic location and TNM classification. The identification of molecular signatures with ability to explain the different outcomes observed in these patients is of paramount importance to guide and help their management.Case PresentationWe herein describe an 88-year-old woman diagnosed with synchronous bilateral tongue carcinoma. This woman did not present the traditional risk factors related to oral cancer - alcohol, tobacco or presence of human papiloma virus (HPV). Both tumors were classified by a pathologist as pT2. This patient was submitted to surgery, six months later was diagnosed with cervical metastasis and in the following two months died. Copy number alterations and methylation status of these two simultaneous tumors were analyzed using array Comparative Genomic Hybridization, Multiplex Ligation-dependent Probe Amplification (MLPA) and Methylation Specific MLPA.Discussion and ConclusionIn both tumors we identified several molecular traits usually found among oral cavity tumors and some of those have been associated with clinical outcome, reinforcing their importance to accurately establish biomarkers with clinical applicability. Specific genomic and epigenetic signatures for each of these two tumors were also observed allowing their molecular discrimination. The tumor of the right side of the tongue exhibited more copy number gains than the tumor of the left side. In the left side tumor less and smaller copy number alterations and more methylated genes were observed, which could be indicative of an early phase of tumor development. This case shows the molecular heterogeneity of oral cavity tumors even in the same patient and anatomic site, which could be the key to explain the different outcomes of oral tumor patients.



http://ift.tt/2xUyHh4

Correction to: The changing landscape of dermatology practice: melanoma and pump-probe laser microscopy

Abstract

The published online version contains mistake. Warren S. Warren was not included in the author group section. Corrected author group section is shown above.

http://ift.tt/2y2FWWA

Skin fluorescence following photodynamic therapy with NPe6 photosensitizer

Publication date: Available online 4 October 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Keishi Ohtani, Jitsuo Usuda, Emiyu Ogawa, Sachio Maehara, Kentaro Imai, Yujin Kudo, Shotaro Ono, Shunsuke Shigefuku, Daisuke Eriguchi, Tatsuya Inoue, Junichi Maeda, Koichi Yoshida, Masaru Hagiwara, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Tsunenori Arai, Norihiko Ikeda
BackgroundThe second-generation photosensitizer NPe6 has strong anti-tumor effects with a much shorter photosensitive period than the first-generation photosensitizer Photofrin. Although photosensitive period has been reduced, skin photosensitivity is still a major side effect of photodynamic therapy (PDT). Therefore, we conducted a prospective study to investigate whether the NPe6 fluorescence intensity in skin after PDT could be measured effectively in human patients to improve the management of a patient's photosensitive period.MethodsThe NPe6 fluorescence measurements using a constructed fluorescence sensing system at the inside of the arm were acquired prior to and 5 and 10minutes after NPe6 administration as well as at the time of PDT (4–5hours after administration), at discharge (2 or 3days after PDT), and at 1 or 2 weeks after PDT. Participants were interviewed as to whether they had any complications at 2 weeks after PDT.ResultsNine male patients and one female patient entered this study. Nine patients were inpatients and one patient was an outpatient. All of the measurements of NPe6 fluorescence in the skin could be obtained without any complications. The spectral peak was detected at the time of discharge (2–3days after administration) in most cases and it decreased at 1 or 2 weeks after PDT.ConclusionsThe fluorescence of NPe6 in the skin could be detected feasibly using the fluorescence sensing system in human patients. Measuring the relative concentration of NPe6 in the skin indirectly by measuring fluorescence intensity might be useful to predict the period of skin photosensitivity after PDT.



http://ift.tt/2xUGsDR

Clinical Case Seminar: Post-menopausal ovarian androgen excess: challenges in diagnostic work-up and management of ovarian thecosis

Abstract

A 72 year old female was referred to the Department of Endocrinology with a 20-year history of hirsutes, mostly affecting her face and torso, the initial onset of which dated shortly after menopause age 52 years. There was no history of subfertility, menstrual irregularity, or hyperandrogenism during reproductive life to suggest prior polycystic ovary syndrome (PCOS), with three live births, two miscarriages and one still-birth.

This article is protected by copyright. All rights reserved.

http://ift.tt/2xVIXG7

Prognostic scores for sorafenib-treated hepatocellular carcinoma patients: A new application for the hepatoma arterial embolisation prognostic score

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): J. Edeline, J.-F. Blanc, B. Campillo-Gimenez, Y.-T. Ma, J. King, O. Faluyi, J. Mathurin, S. Ghazi, D.H. Palmer, T. Meyer
BackgroundNo prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC).MethodsWe retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems.ResultsThe training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 μmol/l and albumin <36 g/l. The SAP score was built giving one point to each abnormal variable, and three classes were constructed. The SAP score was significantly associated with OS in the training set, with median OS of 14.9 months for SAP A, 7.2 months for SAP B and 2.5 months for SAP C (P < 0.001). In the validation set, the SAP score was significantly associated with OS, and showed greater discriminative abilities than Barcelona Clinic Liver Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score.ConclusionIn European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making.



http://ift.tt/2hOkWg7

Patient-reported outcomes in KEYNOTE-006, a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Teresa M. Petrella, Caroline Robert, Erika Richtig, Wilson H. Miller, Giuseppe V. Masucci, Euan Walpole, Celeste Lebbe, Neil Steven, Mark R. Middleton, Darcy Hille, Wei Zhou, Nageatte Ibrahim, Jonathan Cebon
ObjectiveReport results of patient-reported health-related quality of life (HRQoL) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma.Patients and methodsPatients received pembrolizumab 10 mg/kg every 2 (Q2W) or every 3 weeks (Q3W) for up to 2 years, or four cycles of ipilimumab 3 mg/kg Q3W. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was administered at baseline and throughout the study. Patient-reported outcome (PRO) analyses were pre-specified exploratory endpoints; the primary PRO assessment was the score change from baseline to week 12 in EORTC QLQ-C30 global health status (GHS)/HRQoL score between the arms using constrained longitudinal data analysis.ResultsThe PRO analysis population included 776 patients: pembrolizumab Q2W (n = 270); pembrolizumab Q3W (n = 266); ipilimumab (n = 240). Baseline GHS was similar across arms. QLQ-C30 compliance rates at week 12 were 87% (n = 214), 97% (n = 226), and 96% (n = 178), for the pembrolizumab Q2W, pembrolizumab Q3W, and ipilimumab arms, respectively. From baseline to week 12, GHS/HRQoL scores were better maintained with pembrolizumab than with ipilimumab (decrease of −1.9 and −2.5 for pembrolizumab versus −10.0 for ipilimumab; p < 0.001 for each pembrolizumab arm versus ipilimumab). Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 (31% for pembrolizumab Q2W; 29% for Q3W and 44% for ipilimumab), with similar trends observed for individual functioning and symptoms scales.ConclusionsHRQoL was better maintained with pembrolizumab than with ipilimumab in patients with ipilimumab-naive advanced melanoma.ClinicalTrials.gov identifierNCT01866319.



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Insight in taste alterations during treatment with protein kinase inhibitors

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): A. van der Werf, M. Rovithi, J.A.E. Langius, M.A.E. de van der Schueren, H.M.W. Verheul
The role of Protein Kinase Inhibitors (PKI) in the treatment of various types of cancer is increasingly prominent. Their clinical application is accompanied by the development of side effects, among which patient-reported taste alterations. These alterations are missed frequently, but impair nutritional intake, are associated with weight loss and often result in significant morbidity, especially in the context of chronic administration. Accurate reporting of taste alterations is hampered by lack of modules for symptom objectification and inadequate understanding on the underlying mechanisms. In this review we initially describe the physiology of taste and smell and the mechanism of action of PKIs. We proceed to summarize taste related side effects as reported in major clinical trials and describe possible causal factors. Lastly, an in-depth analysis is given on potential molecular pathways responsible for the PKI-induced taste alterations. Objectification of patient-reported symptoms and universal reporting, along with a better understanding of the underlying mechanisms, will lead to early recognition and optimized treatment, ultimately improving patient adherence and quality of life.



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Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids

Pediatric Allergy, Immunology, and Pulmonology Sep 2017, Vol. 30, No. 3: 135-140.


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Outcomes for Umbilical Cord Blood Transplantation in Severe Combined Immunodeficiency Disorders: Ten-Year Experience

Pediatric Allergy, Immunology, and Pulmonology Sep 2017, Vol. 30, No. 3: 171-180.


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Inhaling Essential Oils: Purported Benefits and Harms

Pediatric Allergy, Immunology, and Pulmonology Sep 2017, Vol. 30, No. 3: 186-188.


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Towards assessing corticospinal excitability bilaterally: Validation of a double-coil TMS method

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Julien Grandjean, Gerard Derosiere, Pierre Vassiliadis, Louise Quemener, Ysaline de Wilde, Julie Duque
BackgroundFor several decades, Transcranial magnetic stimulation (TMS) has been used to monitor corticospinal excitability (CSE) changes in various contexts. Habitually, single-coil TMS is applied over one primary motor cortex (M1), eliciting motor-evoked potentials (MEPs) in a contralateral limb muscle, usually a hand effector. However, in many situations, it would be useful to obtain MEPs in both hands simultaneously, to track CSE bilaterally. Such an approach requires stimulating both M1 concurrently while avoiding interference between the two descending stimuli.New methodWe examined MEPs obtained at rest using a double-coil TMS approach where the two M1 are stimulated with a 1ms inter-pulse interval (double-coil1ms). MEPs were acquired using double-coil1ms (MEPdouble) or single-coil (MEPsingle) TMS, at five different intensities of stimulation (100, 115, 130, 145 or 160% of the resting motor threshold, rMT). Given the 1ms inter-pulse interval in double-coil1ms trials, MEPdouble were either evoked by a 1st (MEPdouble-1) or a 2nd (MEPdouble-2) TMS pulse.ResultsAll MEPTYPE (MEPTYPE=MEPsingle, MEPdouble-1 and MEPdouble-2) were equivalent, regardless of the hand within which they were elicited, the intensity of stimulation or the pulse order.Comparison with existing methodThis method allows one to observe state-related CSE changes for the two hands simultaneously on a trial-by-trial basis.ConclusionThese results infer the absence of any neural interactions between the two cortico-spinal volleys with double-coil1ms TMS. Hence, this technique can be reliably used to assess CSE bilaterally, opening new research perspectives for scientists interested in physiological markers of activity in the motor output system.



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The Global Bioequivalence Harmonization Initiative: Summary report for EUFEPS international conference

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Mei-Ling Chen, Henning Blume, Gerald Beuerle, Barbara Davit, Mehul Mehta, Henrike Potthast, Barbara Schug, Yu Chung Tsang, Ralph-Steven Wedemeyer, Werner Weitschies, Jan Welink
Bioequivalence (BE) is considered one of the key questions in new and generic drug product development and registration worldwide. However, the regulations and jurisdiction vary from country to country and continent to continent. Harmonization of regulatory requirements and criteria for BE determination may avoid unnecessary repetition of BE studies and minimize drug exposure to humans. Harmonization around the globe may be achieved by a better understanding of scientific principles and expectations from different regulatory authorities. To facilitate global harmonization, the Network on Bioavailability and Biopharmaceutics (BABP) under the European Federation for Pharmaceutical Sciences (EUFEPS) launched a Global Bioequivalence Harmonization Initiative (GBHI) several years ago. This international conference was the first in a series of workshops organized by EUFEPS/BABP under GBHI. The workshop provided a forum for pharmaceutical scientists from academia, industry and regulatory agencies to have open discussions on selected BE issues in the hope of identifying common ground and arriving at a harmonized view on these topics.

Graphical abstract

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Investigation of novel supersaturating drug delivery systems of chlorthalidone: The use of polymer-surfactant complex as an effective carrier in solid dispersions

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Maria Terezinha França, Rafael Pereira Nicolay, Manoela Klüppel Riekes, Juliana Munari Oliveira Pinto, Hellen Karine Stulzer
Supersaturating drug delivery systems (SDDS), as solid dispersions (SDs), stand out among strategies to enhance bioavailability of poorly soluble drugs. After oral administration, their dissolution in gastrointestinal fluids often leads to supersaturation, which drives to a rapid and sustained absorption. Polymers and surfactants play important roles in SDs through inhibiting precipitation caused by transitions from amorphous into crystalline form, in supersaturated solutions, and also through improving SDs physical stability. Novel chlorthalidone SDs, a BCS IV drug, were developed using polymeric and non-polymeric carriers, specially a polymer-surfactant complex. SDs drug releases were evaluated using sink and non-sink conditions in water and biorelevant medium. Their physical stability was also monitored under different storage conditions. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL), sodium lauryl sulfate (SLS) and a combination of both showed promising results in apparent solubility studies, and therefore they were selected to compose the spray dried SDs. Dissolution studies demonstrated the SOL-SLS complex potential for providing chlorthalidone fast release (>80% in 15min), producing and maintaining in vitro supersaturation. This formulation comprising high drug loading (75%) reached a high supersaturation degree under non-sink condition (up to 6-fold the equilibrium solubility) once maintained for 6h in biorelevant medium. In addition, this SD presented better physical stability when compared to the chlorthalidone neat amorphous. The SOL-SLS complex impacts positively on chlorthalidone release and physical stability, highlighting its potential as carrier in SDDS of a poorly soluble drug.

Graphical abstract

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Hand-foot skin reaction with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: A systematic review and meta-analysis

Publication date: Available online 3 October 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Jing Li, Jian Gu
A meta-analysis was conducted to systematically review the risk of hand-foot skin reaction (HFSR) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with cancer. The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with VEGFR-TKIs were retrieved and the systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published till May 2017. Twenty-one RCTs and 9552 patients were included. The current analysis suggested that the use of VEGFR-TKIs increased the risk of all-grade HFSR (7.04;95%CI, 5.33-9.30;p<0.00001) and high-grade (≥grade 3) HFSR (21.62;95%CI, 15.19-30.78;p<0.00001). On subgroup analyses, the risk ratio (RR) of all-grade HFSR varies significantly according to cancer type, whereas the RR of high-grade HFSR did not. The risk of all-grade and high-grade HFSR did not affect by drug types, treatment line, median age and treatment duration.



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Interaction between municipal solid waste leachate and Bauru aquifer system: a study case in Brazil

Abstract

Leachate contamination is a chronic and urgent problem present in municipal solid waste (MSW) landfill. Geochemical mathematical models in this work was suitable to study the dynamics of the leachate from an MSW landfill located in the Midwest of Sao Paulo, Brazil, a region with high precipitation and temperature and rich in chalcophile compounds and lithophile compounds, despite contamination with nitrogenous compounds. After 13 years of local aquifer monitoring, some groundwater samplings in Feb. 2004, Aug. 2007, Nov. 2009, and Feb. 2014 were chosen to be simulated. The hydrolysis is the main process at the landfill, together with absorption, adsorption, complexation, dilution, cation exchange, and oxidation, besides nitrification, reoxidation, and reduction.

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Photodegradative fate and potential phototoxic products of bromocarbazoles and chlorocarbazoles in water

Abstract

Bromocarbazoles and chlorocarbazoles are emerging environmental contaminants that have been reported to be persistent and possessing dioxin-like toxicity; however, their photodegradative fate in water is unknown. The photodegradation of 3-bromocarbazole, 3-chlorocarbazole, and 3,6-dichlorocarbazole was determined in ultrapure water. They proceeded by direct photolysis and followed first-order kinetics. The rate constants (k) were 0.4838, 0.3454, and 0.4422 h⁻¹ corresponding to half-lives (t _1/2) 1.81, 2.01, and 1.62, while the quantum yields (Ф) were 0.232, 0.180, and 0.295 respectively. The maximum wavelengths of absorption (λ _max) were in the near ultraviolet region (295, 296, 299, and 301 nm) implying these compounds are likely to degrade slowly under sunlight in natural aquatic environment. The molar extinction coefficients (ε) determined in acetonitrile were 18,573, 17,028, 13,385, and 14,010 L mol⁻¹ cm⁻¹, respectively, the latter being 3,6-dibromocarbazole. A bathochromic shift was observed with halogen addition on their respective mono-substituted congeners. Bromocarbazoles were observed to degrade faster in water than chlorocarbazoles. In addition, photodegradation was estimated to proceed faster in summer than in winter, in natural water system at 50° N latitude. In the absence of light, hydrolytic degradation occurred but proceeded very slowly. Hexahydroxybenzene and trihydroxycarbazole were positively identified as the likely photoproducts with the former being a known toxic compound. Dehalogenation, oxidative cleavage, hydroxylation, and hydrolysis are suggested as the major photodegradation mechanisms in water, yielding phototoxic products that may be of enhanced toxicity than the parent compounds.

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Fluctuations in episodic and chronic migraine status over the course of 1 year: implications for diagnosis, treatment and clinical trial design

Relatively little is known about the stability of a diagnosis of episodic migraine (EM) or chronic migraine (CM) over time. This study examines natural fluctuations in self-reported headache frequency as well ...

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Neuroprotective effects of curcumin against acetamiprid-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: biochemical, histological, and behavioral changes

Abstract

Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. This study aimed to investigate the effect of curcumin on neurobehavioral and neuropathological alterations induced by acetamiprid on male rats. Three groups of ten male Wistar rats each were used for the study: the first was a control group (CTR) that did not consume acetamiprid (ACE); the second was an experimental group (ACE) that consumed 40 mg/kg body weight/day of acetamiprid; and the third group (CUR) received curcumin (100 mg/kg) and acetamiprid (40 mg/kg) in combination. Neurobehavioral evaluations including inclined plane performance and forepaw grip time were studied. Treatment with CUR significantly prevented ACE-treated rats from impairments in the performance of neurobehavioral tests, indicating the presence of deficits on sensorimotor and neuromuscular responses. In addition, Curcumin administration protects rats against acetamiprid-induced cerebellum toxicity such as increase in AChE and BChE activities, decrease on cells viability, oxidative stress, and an increase of intracellular calcium. Taken together, these results demonstrate for the first time that ACE treatment substantially impairs the survival of primary neuronal cells through the induction of necrosis concomitantly with the generation of an oxidative stress. Additionally, curcumin reduced histopathological changes caused by ACE.

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Advances in the Management of HER2-Positive Early Breast Cancer

Publication date: Available online 4 October 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): José Baselga, Robert E. Coleman, Javier Cortés, Wolfgang Janni




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Denosumab-related osteonecrosis of the jaw: a retrospective study

Abstract

Background

Osteonecrosis of the jaw is a very delicate side effect of Denosumab. The aim of this retrospective study is to assess the occurrence rate of Denosumab-related osteonecrosis of the jaw (DRONJ) at the Cancer Institute of Lorraine (ICL) and to highlight necrosis risk factors.

Methods

To that purpose we analyzed the medical records of 249 consecutive patients treated with Denosumab at the ICL during the past 5 years. Patients who received oro-facial radiotherapy or a previous treatment with a bisphosphonate were excluded. The p value was set at 0.005.

Results

141 patients treated at the ICL between January 2010 and December 2015 were included. All patients were treated with XGEVA^®. Of the 141 patients included in the study, 10 developed DRONJ. The incidence of DRONJ increases with the duration of follow-up: 3% at 1 year, 7% at 2 years and 8% from 30 months on. No risk factor for necrosis could be identified except the realization of prior dental extraction (p=0.025).

Conclusion

Our results raise important questions about the dental management of these patients, in particular concerning the healing period between dental extractions and the initiation of Denosumab.

This article is protected by copyright. All rights reserved.

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Experimental verification of dose enhancement effects in a lung phantom from inline magnetic fields

Publication date: Available online 3 October 2017
Source:Radiotherapy and Oncology
Author(s): Bradley M. Oborn, Maegan A. Gargett, Trent J. Causer, Sarah J. Alnaghy, Nicholas Hardcastle, Peter E. Metcalfe, Paul J. Keall
Background and purposeTo present experimental evidence of lung dose enhancement effects caused by strong inline magnetic fields.Materials and methodsA permanent magnet device was utilised to generate 0.95T–1.2T magnetic fields that encompassed two small lung-equivalent phantoms of density 0.3g/cm³. Small 6MV and 10MV photon beams were incident parallel with the magnetic field direction and Gafchromic EBT3 film was placed inside the lung phantoms, perpendicular to the beam (experiment 1) and parallel to the beam (experiment 2). Monte Carlo simulations of experiment 1 were also performed.ResultsExperiment 1: The 1.2T inline magnetic field induced a 12% (6MV) and 14% (10MV) increase in the dose at the phantom centre. The Monte Carlo modelling matched well (±2%) to the experimentally observed results. Experiment 2: A 0.95T field peaked at the phantom centroid (but not at the phantom entry/exit regions) details a clear dose increase due to the magnetic field of up to 25%.ConclusionsThis experimental work has demonstrated how strong inline magnetic fields act to enhance the dose to lower density mediums such as lung tissue. Clinically, such scenarios will arise in inline MRI-linac systems for treatment of small lung tumours.



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Effects of biodegradable hydrogel spacer injection on contralateral submandibular gland sparing in radiotherapy for head and neck cancers

Publication date: Available online 3 October 2017
Source:Radiotherapy and Oncology
Author(s): Avani D. Rao, Stephanie Coquia, Robert De Jong, Christine Gourin, Brandi Page, Diane Latronico, Samson Dah, Lin Su, Stephen Clarke, Jeffrey Schultz, Lauren M. Rosati, Carole Fakhry, John Wong, Theodore L. DeWeese, Harry Quon, Kai Ding, Ana Kiess
Xerostomia is the most common late toxicity after head and neck radiation. We demonstrate injection of a hydrogel spacer anteriorly displacing the submandibular gland. This procedure enables reduced dose to the displaced submandibular gland in cadaveric models of oropharynx cancer treated with IMRT, with potential implications in reducing xerostomia risk.



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Expression of FK506-binding protein 51 (FKBP51) in Mycosis Fungoides

Summary

Background

Mycosis fungoides (MF) is the major subtype of cutaneous T-cell lymphomas (CTCL). It usually has a prolonged indolent clinical course with a minority of cases acquiring a more aggressive biological profile and resistance to conventional therapies, partially attributed to the persistent activation of Nuclear Factor-kappa B (NF-κB) pathway. In the last decade, several papers suggested an important role for the FK506-binding protein 51 (FKBP51), an immunophilin initially cloned in lymphocytes, in the control of NF-κB pathway in different types of human malignancies.

Objectives

We aimed to investigate the possible value of FKBP51 expression as a new reliable marker of outcome in MF patients.

Methods

We assessed by immunohistochemistry (IHC) FKBP51 expression in 44 patients with MF, representative of different stages of the disease. Immunohistochemical results were subsequently confirmed at mRNA level with quantitative PCR (qPCR) in a subset of enrolled patients. In addition, IHC and qPCR served to study the expression of some NF-κB target genes, including the tumour necrosis factor receptor-associated factor 2 (TRAF2).

Results

Our results show that FKBP51 was expressed in all evaluated cases, with the highest level of expression characterizing MFs with the worst prognosis. Moreover, a significant correlation subsisted between FKBP51 and TRAF2 IHC expression scores.

Conclusions

we hypothesize a role for FKBP51 as a prognostic marker for MF and suggest an involvement of this immunophilin in deregulated NF-κB pathway of this CTCL.

This article is protected by copyright. All rights reserved.

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Reduction in harm from tracheostomy related incidents after implementation of the paediatric National Tracheostomy Safety Project resources: a retrospective analysis from a tertiary paediatric centre

Abstract

In the UK, patient safety issues related to adult tracheostomies are well recognised. A number of reports from the National Patient Safety Agency and National Confidential Enquiry into Patient Outcome and Death highlighted recurrent themes with deficiencies in staff education, resources, equipment provision and emergency guidance.^1,2. Similar patient safety concerns exist in the paediatric population. Studies report overall mortality rates in paediatric patients with tracheostomies varying from 2.2%³ to 58.8%,⁴ whilst tracheostomy-specific mortality is lower at 0.9%⁵ to 5.9%.⁴ Within our institution, concerns were noted regarding the risk of serious avoidable tracheostomy morbidity after merging three paediatric hospitals onto a single site in 2009.

This article is protected by copyright. All rights reserved.

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Dust mite induces multiple polar T-cell axes in human skin

Abstract

Background

House dust mite/HDM atopy patch test/APT elicits positive reactions in a high fraction of atopic dermatitis/AD and healthy individuals. Experimental systems for new-onset/chronic AD are needed to support rapid therapeutic development, particularly since animal models representing human AD are lacking. While HDM APT has been considered to simulate AD, its suitability to model AD's emerging Th2/Th22 phenotype with Th1 and Th17 components is unknown.

Objective

To assess whether HDM APT reproduces AD.

Methods

Positive HDM APTs (n=15) from patients with and without AD were evaluated, using genomic and immunohistochemistry studies, against intrapersonal control skin.

Results

APT lesions showed higher T-cell and dendritic cell infiltrates vs. controls. 743 up- and 326 downregulated genes were differentially expressed in HDM APT (fold-change>2 and false-discovery rate<0.05), with increased expression of Th2, Th9, Th17/Th22 polar cytokines (i.e. IL-5, IL-13, IL-9, IL-17, IL-22).

Conclusion

While HDM caused significant Th2 skewing, it also illustrated differences in Th2 induction and barrier defects, thus HDM APT does not fully simulate AD. Given its widespread availability and sensitization rates, HDM may potentially be a useful tool that represents select aspects of AD, psoriasis, or contact dermatitis.

This article is protected by copyright. All rights reserved.

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Inflammatory proteins in nasal lavage of workers exposed to occupational agents

Abstract

Background

Low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have been recognized as causes of occupational rhinitis (OR). Immunological mechanisms underlying OR differ according to the type of exposure. While HMW agents act mainly through IgE-mediated mechanisms, LMW agents appear to act through both immunologic and non-immunologic mechanisms.

Objective

The objective of this study was to identify potential differences in the upper airways inflammatory response after exposure to LMW and HMW agents by specific inhalation challenge test (SIC).

Methods

Nasal lavage (NL) samples from 20 subjects who were exposed to HMW (n=10, Group I) and LMW (n=10, Group II) at their workplaces were collected after SIC with control and specific occupational agents. These samples were analyzed for 47 inflammatory markers using multiplex bead technology.

Results

After exposure to specific agent, Group I exhibited higher concentrations of the following proteins compared to Group II: fibrinogen (median (interquartile range) Group I: 0.09 (0.00) μg/ml, Group II: 0.04 (0.05) μg/ml, p=0.05); haptoglobin (Group I: 0.86 (0.01) μg/ml, Group II: 0.14 (0.20) μg /ml, p=0.02); vascular cell adhesion molecule-1 (VCAM-1) (Group I: 0.34 (0.67) ng/ml, Group II: 0.11(0.11) ng/ml, p=0.01); vascular endothelial growth factor (VEGF) (Group I: 157.0 (154.0) pg/ml, Group II: 98.0 (20.25) pg/ml, p=0.01) and vitamin D (VDBP) (Group I: 0.06 (0.13) μg /ml, Group II: 0.03 (0.03) μg /ml, p=0.04). No statistically significant differences in proteins profiles were observed between the groups after exposure to control agent. Also, subjects exposed to HMW agents showed a significant increase in NL levels of C-reactive protein compared to control day exposure.

Conclusions and clinical relevance

Exposure to HMW and LMW agents by SIC induced a differential nasal airway response including acute-phase reactants proteins (fibrinogen, haptoblobin and CRP), cell adhesion molecules (VCAM-1), endothelial growth factors (VEGF) and VDBP.

This article is protected by copyright. All rights reserved.

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Response to ‘Serological diagnostics in the detection of IgG autoantibodies against human collagen VII in epidermolysis bullosa acquisita – a multicenter analysis’

Abstract

In a recent retrospective serological study in 95 sera from epidermolysis bullosa acquisita (EBA) patients Schmidt et al. conclude that Col7A-NC1/NC2 ELISA (MBL, Japan) is superior to NC1 ELISA, Western blot and indirect immunofluorescence (IIF) on salt-split skin (SSS) with the highest sensitivity of 97.9%.¹ This sensitivity is an overestimation from a biased sample, since the sera had been preselected from patients with IgG reactivity fitting EBA by at least one of the immune serological assays indirect immunofluorescence, ELISA, and Western blot. The deficiency in study design with an incorrect reference standard creates a bias in estimated test accuracy.

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HLA class II alleles of susceptibility and protection in Brazilian and Dutch pemphigus foliaceus

Abstract

Pemphigus foliaceus (PF) is a worldwide chronic autoimmune bullous disease targeting desmoglein 1 (Dsg 1) on epithelial cell surface of skin and mucous membranes, causing lesions in skin but sparing mucosa, since the latter contain compensating desmoglein 3¹. Several environmental triggers for the autoimmune reaction have been imputed, such as drugs, ultraviolet radiation and mercurium. Human leucocyte antigens class II (HLA-DR4) alleles were linked to the disease in Ashkenazi Jews and other populations². For endemic pemphigus foliaceus in Brazil, named fogo selvagem (FS), HLA-DRB1*04 was shown to have a relative risk >14 for the disease³.

This article is protected by copyright. All rights reserved.

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