The roles of NADPH oxidase in modulating neutrophil effector responses

Abstract

Neutrophils are phagocytic innate immune cells essential for killing bacteria via activation of a wide variety of effector responses and generation of large amounts of reactive oxygen species (ROS). Majority of the ROS in neutrophils is generated by activation of the superoxide‐generating enzyme NADPH oxidase. Independent of their anti‐microbial function, NADPH oxidase‐derived ROS have emerged as key regulators of host immune responses and neutrophilic inflammation. Data from patients with inherited defects in the NADPH oxidase subunit alleles that ablate its enzyme function as well as mouse models demonstrate profound dysregulation of host inflammatory responses, neutrophil hyper‐activation and tissue damage in response to microbial ligands or tissue trauma. A large body of literature now demonstrates how oxidants function as essential signaling molecules that are essential for the regulation of neutrophil responses during priming, degranulation, neutrophil extracellular trap formation, and apoptosis, independent of their role in microbial killing. In this review we summarize how NADPH oxidase‐derived oxidants modulate neutrophil function in a cell intrinsic manner and regulate host inflammatory responses. In addition, we summarize studies that have elucidated possible roles of oxidants in neutrophilic responses within the oral mucosa and periodontal disease.

This article is protected by copyright. All rights reserved.

http://bit.ly/2M5gXGY

Is Targeting the Folate Receptor in Ovarian Cancer Coming of Age?

http://bit.ly/2D3CNrA

Current Treatment Options in Gastroenteropancreatic Neuroendocrine Carcinoma

AbstractPoorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) are a rare neoplasm with a bleak prognosis. Currently there are little prospective data available for optimal treatment. This review discusses the current available regimens and the future direction for the treatment of GEPNECs. Treatment plans for GEPNECs are often adapted from those devised for small cell lung cancer; however, differences in these malignancies exist, and GEPNECs require their own treatment paradigms. As such, current first‐line treatment for GEPNECs is platinum‐based chemotherapy with etoposide. Studies show that response rate and overall survival remain comparable between cisplatin and carboplatin versus etoposide and irinotecan; however, prognosis remains poor, and more efficacious therapy is needed to treat this malignancy. Additional first‐line and second‐line treatment options beyond platinum‐based chemotherapy have also been investigated and may offer further treatment options, but again with suboptimal outcomes. Recent U.S. Food and Drug Administration approval of peptide receptor radionuclide therapy in low‐ and intermediate‐grade neuroendocrine tumors may open the door for further research in its usefulness in GEPNECs. Additionally, the availability of checkpoint inhibitors lends promise to the treatment of GEPNECs. This review highlights the lack of large, prospective studies that focus on the treatment of GEPNECs. There is a need for randomized control trials to elucidate optimal treatment regimens specific to this malignancy.Implications for Practice.There are limited data available for the treatment of poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) because of the rarity of this malignancy. Much of the treatment regimens used in practice today come from research in small cell lung cancer. Given the poor prognosis of GEPNECs, it is necessary to have treatment paradigms specific to this malignancy. The aim of this literature review is to summarize the available first‐ and second‐line GEPNEC therapy, outline future treatments, and highlight the vast gap in the literature.

http://bit.ly/2TJ48ow

Diagnostic performance of 68 Ga-PSMA PET/CT in the detection of prostate cancer prior to initial biopsy: comparison with cancer-predicting nomograms

Abstract

Purpose

To assess the diagnostic performance of ⁶⁸Ga-PSMA PET/CT for detecting suspected prostate cancer (PCa) and to compare it with that of two cancer-predicting nomograms.

Methods

We performed a retrospective analysis of 146 consecutive patients with suspected PCa based on symptoms or elevated total prostate-specific antigen (tPSA) levels who underwent ⁶⁸Ga-PSMA PET/CT and histopathologic examinations from April 2017 to April 2018 in a large tertiary care hospital in China. The ⁶⁸Ga-PSMA PET/CT results (PCa or benignancy) were evaluated by two experienced nuclear medicine specialists. The risk of positive PCa was evaluated using ERSPC and PCPT nomograms. The diagnostic performances of ⁶⁸Ga-PSMA PET/CT and that of the two nomograms were compared via receiver operating characteristic (ROC) curve analysis, decision curve analysis, and logistic regression.

Results

A total of 58 patients with tPSA of 0.4–50 ng/ml were included in the final analysis; PCa diagnosis was confirmed in 37 patients and excluded in 21 patients. ROC analysis showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ⁶⁸Ga-PSMA PET/CT were 91.67, 81.82, 89.19, and 85.71%, respectively, in per-patient analyses. ⁶⁸Ga-PSMA PET/CT exhibited a higher AUC (0.867) than those of ERSPC-RC3 (0.855) and PCPT-RC (0.770). The net benefit of ⁶⁸Ga-PSMA PET/CT was greatest for patients within threshold probabilities of 15–90%. Among the 58 patients, 11 (19%) biopsies suggested by ERSPC-RC3 were unnecessary and could have been avoided if judged by the ⁶⁸Ga-PSMA PET/CT results. Multivariate analysis revealed that the maximum standardised uptake value (SUV_max) and prostate volume were significant predictive factors for positive PCa results.

Conclusion

In suspected PCa patients with tPSA of 0.4–50 ng/ml, ⁶⁸Ga-PSMA PET/CT outperformed the nomograms in predicting cancer and reducing unnecessary biopsies. In addition, the risk of PCa was positively correlated with a higher SUV_max and lower prostate volume, which could help clinicians in making preliminary estimates of individual cancer risk, monitoring ⁶⁸Ga-PSMA PET/CT false-positive results and making biopsy decisions in daily medical practice.

http://bit.ly/2D4zYGJ

An application of advanced hair-save processes in leather industry as the reason of formation of keratinous waste: few peculiarities of its utilisation

Abstract

The application of more environmentally friendly hide and skin unhairing technologies in leather processing results in a significant increase in keratin waste. There are currently two most promising hair-saving unhairing methods: enzymatic and hair immunisation. The complete use of hair-saving unhairing methods in the leather industry will lead to the formation of approximately 143 thousand tons of hair/wool waste annually, which will require disposal. The disposal of keratin wastes from the leather industry has not been adequately studied, bearing in mind the possible amount of such wastes that will be produced in the future. Unfortunately, existing studies pay little attention to the method of unhairing, even though the unhairing method has a vast influence on the properties of keratin in the obtained hair/wool wastes. Accordingly, the present research is an attempt to establish how the differently obtained keratin wastes behave following disposal. The obtained results have shown that waste wool is characterised by different behaviour during burial in soil, and the behaviour depends on the method of unhairing. This proposition is valid for waste wool bioresistance as well. It was concluded that the deterioration of any sort of keratinous waste from the leather industry should be investigated thoroughly before disposal by burial in landfills.

http://bit.ly/2skmy36

Effect of electrolytes on the simultaneous electrochemical oxidation of sulfamethoxazole, propranolol and carbamazepine: behaviors, by-products and acute toxicity

Abstract

In this work, the effect of supporting electrolytes on the simultaneous electrochemical oxidation of the pharmaceuticals sulfamethoxazole (SMX), propranolol (PRO), and carbamazepine (CBZ) in aqueous solutions has been studied. Based on the identified by-products, the degradation mechanisms were proposed and the acute toxicity was evaluated for each electrolyte. Assays were carried out in batch mode in a 2 L undivided reactor using a niobium coated with boron-doped diamond (Nb/BDD) mesh anode and Ti cathode at 2.5 A in presence of different supporting electrolytes (Na₂SO₄, NaCl, or NaBr) at the same concentration of 7 mM. The degradation rates were higher in the assays with NaCl and NaBr. Reaction by-products were identified by gas chromatography–mass spectrometry. Indirect oxidation by electrogenerated reactive halogen species (RHS) was the main mechanism when halide ions were used as electrolytes. Ten by-products were detected using Na₂SO₄ as electrolyte, while 19 (12 non-halogenated and 7 halogenated) and 20 (10 non-halogenated and 10 halogenated) using NaCl and NaBr respectively. The proposed degradation pathways involve transformation (hydroxylation, deamination, desulfonation, and halogenation) and bond rupture to produce less molecular weight compounds and their further transformation until total degradation. Chlorinated and brominated by-products confirm halogenation reactions. The electrogenerated RHS presented a significant inhibition effect on Vibrio fischeri; nevertheless, acute toxicity was not presented using Na₂SO₄ as electrolyte and a pharmaceutical concentration of 5 μg/L. In this view, the role of the supporting electrolyte in electrochemical oxidation process is crucial since it strongly influence degradation rate, by-products, and acute toxicity.

http://bit.ly/2M7IOWR

Laboratory bioassays on the response of honey bee ( Apis mellifera L.) glutathione S -transferase and acetylcholinesterase to the oral exposure to copper, cadmium, and lead

Abstract

In the present study, the influence of cadmium, copper, and lead on two enzymes often used as biomarkers in toxicological analysis was investigated. Bees were fed with 1 M sucrose solution containing 10-fold serial dilutions of CuCl₂ (1000 mg L⁻¹, 100 mg L⁻¹, and 10 mg L⁻¹), CdCl₂ (0.1 mg L⁻¹, 0.01 mg L⁻¹, and 0.001 mg L⁻¹), or PbCl₂ (10 mg L⁻¹, 1 mg L⁻¹, and 0.1 mg L⁻¹) during 48 h. Our results showed that the total glutathione S-transferase activity was not changed under the influence of cadmium and lead, and it was decreased with the highest concentration of copper. The level of gene expression of the three analyzed classes of glutathione S-transferase was significantly increased with increasing concentrations of copper and cadmium. Lead did not cause significant changes in glutathione S-transferase activity and gene expression, while it showed biphasic effect on acetylcholinesterase activity: lower concentration of lead, 0.1 mg L⁻¹ inhibited and higher dose, 10 mg L⁻¹ induced acetylcholinesterase activity in honey bees. Furthermore, our results showed a significant decrease of the acetylcholinesterase activity in honey bees treated with 0.001 and 0.01 mg L⁻¹ CdCl₂. Our results indicate the influence of cadmium, copper, and lead on GST and AChE in the honey bees. These results form the basis for future research on the impact of metallic trace element pollution on honey bees.

http://bit.ly/2skmuQU

Free Tissue Transfer with the Free Rectus Abdominis Flap in High-Risk Patients above 65 Years – A Retrospective Cohort Study

Though technically feasible, free tissue transfer carries the risk of perioperative morbidity and mortality in elderly patients. In order to minimize operative treatment time and complication rates, we choose the rectus abdominis muscle (RAM) flap.

http://bit.ly/2FrjmdG

Allogenic Endothelial Progenitor Cell Transplantation Increases Flap Survival through an Upregulation of eNOs and VEGF on Venous Flap Survival in Rabbits

Endothelial progenitor cells (EPCs) are one type of bone marrow hematopoietic stromal cells which play a vital role in neovascularization and tissue repair. In this study, we investigated whether EPCs promote flap survival in a rabbit venous model.

http://bit.ly/2FlMBQ6

Perceived outcomes of Good Agricultural Practices (GAPs) technologies adoption in citrus farms of Iran (reflection of environment-friendly technologies)

Abstract

The main purpose of this study was to analyze the perceived outcomes of Good Agricultural Practices (GAPs) technologies adoption in order to sustain citrus farms in Mazandaran province, Iran. Study population consisted of all citrus growers in the villages of 12 counties of Mazandaran province, which a sample of 290 orchardmen were selected through a proportional random sampling technique. A questionnaire was designed to collect data which was both valid and reliable according to expert opinion and Cronbach's alpha coefficient respectively. The results of the factor analysis showed that "market access and safe product exports," "consumer' health and environment-friendly behavior," "safe production and public demand," and "information sharing and strengthening local associations" were the four perceived outcomes of GAPs technologies adoption in citrus farms of Iran. These factors explained 65.02% of the total variance. These four perceived outputs of GAPs support economic, environmental, and social sustainability dimensions respectively.

http://bit.ly/2D6acll

A full-scale study of external circulation sludge bed (ECSB) system for anaerobic wastewater treatment in a whiskey distillery

Abstract

Waste liquid streams from distillery were a hurdle in conventional wastewater treatment due to extreme high chemical oxygen demand (COD) and fluctuating feed conditions. A recently commissioned full-scale external circulation sludge bed (ECSB) was applied at a malt whiskey distillery in northeast Taiwan. Start-up of the new ECSB system, which has a total volume of 490 m³ with diameter of 6.55 m (ø) and height of 15.9 m (H), was performed by gradual increasing influent flow rates from zero to the design value of 300 m³ day⁻¹ in the first 90 days. In the subsequent 204 days, both influent flow rates (0–389 m³ day⁻¹) and COD concentrations (2.8–18.1 kg L⁻¹) were highly fluctuated due to diverse batches from the distillery. However, effective bioremediation (COD removal 95.1 ± 2.4%) and biogas production (1195 ± 724 L day⁻¹) were achieved in this system. Intensively, the Imhoff tests were carried out and shown the settled solids concentration by 0.5 ± 0.4 mL L⁻¹, while size distributions of granular sludge were analyzed and observed by SEM-EDS. In addition, developments of the anaerobic systems (including lab, pilot, and full scale from the simplest reactor to the latest ECSB) applied in whiskey wastewater treatment were reviewed with their operational parameters for comparing performances of various anaerobic systems. In general, real-time monitoring and feasible operation strategies were critical to successfully run the system by producing clean energy simultaneously. It provides more economically attractive and sustainable-to-adopt ECSB not only an end-of-pipe process but also a bioresource technology.

http://bit.ly/2TKcig3

A multi‐center, randomized, split face and/or neckcomparisonof 308‐nm excimer laser and0·1%tacrolimus ointmentfor stable vitiligo, plus intramuscular slow releasing betamethasone for active vitiligo

Abstract

Managing patients with vitiligo is no longer whether to treat or not to treat, but to decide what modalities are more appropriate. Both topical calcineurin inhibitors and 308‐nm excimer laser (EL) were generally accepted to treat vitiligo, and the combination of the two achieved better efficacy.However, there has been no strict comparison of the two methods in treating facial/neck vitiligo. Here we conducted a multi‐center,randomized, left‐right comparative trial in face and/or neck vitiligo,between 2012 and 2014.It was approved by medical ethics committees and official registered (ChiCTR‐TRC‐12002593). Informed consents were signed.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RHdu6z

Case Series of Cutaneous Mucormycosis in Setting of Herpesviridae Infection

Abstract

Mucormycosis is an aggressive infection caused by an angioinvasive fungus that results in significant human disease. It most commonly manifests as rhinocerebral, pulmonary, and cutaneous infections. Among healthcare‐associated mucormycosis, cutaneous manifestations are the most common, accounting for >50% of infections. Although mucormycosis can remain limited to the skin, it has the potential to disseminate hematogenously if left unrecognized or untreated, particularly in patients with multiple risk factors.

This article is protected by copyright. All rights reserved.

http://bit.ly/2H5JfSI

Dark skin phototype is associated with more severe ocular complications of Stevens‐Johnson syndrome and toxic epidermal necrolysis

Abstract

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute severe skin reactions with extensive apoptosis of the epidermis and mucous membranes. Ocular involvement occurs in up to 75% of patients at the acute phase, described as mild, moderate and severe involvement and may result in long‐term severe sequelae with dryness, photophobia, cicatrising conjunctivitis complicated with corneal vascularisation and scarring, which may result in severe visual loss. The acute management of SJS/TEN ocular complications has not been codified.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RGXSjC

Effect of dupilumab on atopic manifestations in patients treated for atopic dermatitis in real life practice

Abstract

Dupilumab has demonstrated efficacy in atopic dermatitis (AD)^1–3, asthma⁴, perennial allergic rhinitis⁵ and chronic sinusitis⁶. The objectives of this prospective observational, single‐centre study were to assess 1) dupilumab efficacy in real‐life practice and 2) the evolution of atopic co‐morbidities and specific immunoglobulin E (IgE) levels during dupilumab treatment.

This article is protected by copyright. All rights reserved.

http://bit.ly/2H5knKP

The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice

Abstract

Purpose

To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs).

Methods

Seventy-four patients were recruited from four NEN centers in this observational multicenter study.

Results

Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4–395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589–14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14–463) months.

Conclusions

Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.

http://bit.ly/2Ha1lmK

Prospective comparison of (4 S )-4-(3- 18 F-fluoropropyl)- l -glutamate versus 18 F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study

Abstract

Purpose

(4S)-4-(3-¹⁸F-Fluoropropyl)-l-glutamate (FSPG) positron emission tomography (PET) reflects system x_C⁻ transporter (xCT) expression. FSPG PET has been used to detect brain, lung, breast and liver cancer with only modest success. There is no report on the use of FSPG PET in pancreatic ductal adenocarcinoma (PDAC), presumably because of normal xCT expression in the pancreas. Nonetheless, the tissue-specific expression of xCT in the pancreas suggests that FSPG PET may be ideal for identifying metastasized PDAC.

Methods

The performance of FSPG in detecting PDAC metastases was compared with that of ¹⁸F-fluorodeoxyglucose (FDG) in small-animal PET studies in seven PDAC tumour-bearing mice and in prospective PET/computed tomography (CT) studies in 23 patients with tissue-confirmed PDAC of stage III or stage IV. All PET/CT results were correlated with the results of histopathology or contrast-enhanced CT (ceCT) performed 3 and 6 months later.

Results

In the rodent model, FSPG PET consistently found more PDAC metastases earlier than FDG PET. FSPG PET showed a trend for a higher sensitivity, specificity and diagnostic accuracy than FDG PET in detecting PDAC metastases in a patient-based analysis: 95.0%, 100.0% and 95.7%, and 90.0%, 66.7% and 90.0%, respectively. In a lesion-based analysis, FSPG PET identified significantly more PDAC metastases, especially in the liver, than FDG PET (109 vs. 95; P = 0.0001, 95% CI 4.9–14.6). The tumour-to-background ratios for FSPG and FDG uptake on positive scans were similar (FSPG 4.2 ± 4.3, FDG 3.6 ± 3.0; P = 0.44, 95% CI −1.11 to 0.48), despite a lower tumour maximum standardized uptake value in FSPG-avid lesions (FSPG 4.2 + 2.3, FDG 7.7 + 5.7; P = 0.002, 95% CI 0.70–4.10). Because of the lower physiological activity of FSPG in the liver, FSPG PET images of the liver are more easy to interpret than FDG PET images, and therefore the use of FSPG improves the detection of liver metastasis.

Conclusion

FSPG PET is superior to FDG PET in detecting metastasized PDAC, especially in the liver.

http://bit.ly/2VLiqXq

Spatial and temporal distribution characteristics of different forms of inorganic nitrogen in three types of rivers around Lake Taihu, China

Abstract

In order to control nitrogen (N) pollution of Lake Taihu, China, we studied the spatial and temporal distribution characteristics of inorganic N in inflowing rivers polluted by industry, agriculture, and domestic sewage during low, moderate, and high flow periods. The results showed that dissolved total nitrogen (DTN) was the main fraction of total nitrogen (TN) input from these rivers. Inflowing rivers had distinct impacts on TN, DTN, ammonium N (NH₄⁺), and nitrate N (NO₃⁻) concentrations of Lake Taihu during the low flow period. Particulate nitrogen (PN) had an impact on Lake Taihu during the three flow periods and all the three types of rivers would increase PN concentration in the lake. Rivers polluted by agriculture had the greatest impact on Lake Taihu's TN, DTN, NO₃⁻, and dissolved inorganic N (DIN) concentrations, while rivers polluted by industry had the greatest impact on NH₄⁺ concentration. Therefore, agriculture and industry should be key targets for nutrient reductions. The in-lake N concentrations were higher than those of inflowing rivers during moderate and high flow periods.

http://bit.ly/2TGonTC

A critical review on the effects of zinc at toxic levels of cadmium in plants

Abstract

Increasing cadmium (Cd) pollution in agricultural soils has raised serious concerns worldwide. Several exogenous substances can be used to mitigate the toxic effects of Cd in plants. Zinc (Zn) is one of the essential plant micronutrients and is involved in several physiological functions in plants. Zn may alleviate Cd toxicity in plants owing to the chemical similarity of Zn with Cd. Published reports demonstrated that Zn can alleviate toxic effects of Cd in plants by increasing plant growth, regulating Cd uptake, increasing photosynthesis, and reducing oxidative stress. Literature demonstrated that the role of Zn on Cd accumulation by plants is very controversial and depends upon several factors including concentrations of Cd and Zn in the medium, exposure duration, plant species and genotypes, and growth conditions. This review highlights the role of Zn in reducing Cd toxicity in plants and provides new insight that proper level of Zn in plants may enhance plant resistance to excess Cd.

http://bit.ly/2D1bzla

The association of other autoimmune diseases in patients with Graves' disease (with or without ophthalmopathy): Review of the literature and report of a large series

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Silvia Martina Ferrari, Poupak Fallahi, Ilaria Ruffilli, Giusy Elia, Francesca Ragusa, Salvatore Benvenga, Alessandro Antonelli

Abstract

Graves' disease (GD) and autoimmune thyroiditis (AT) are the two main clinical presentations of AITD, and their clinical hallmarks are thyrotoxicosis and hypothyroidism, respectively. GD, and AT, can be associated with other organ specific, or systemic autoimmune diseases in the same patient. However discordant results have been reported in the literature about the possible associations. Here, we review the association of GD and other autoimmune syndromes. Furthermore, we report the results of our prospective study that investigated the prevalence of other autoimmune disorders in 3209 GD patients (984 with Graves' ophthalmopathy), with respect to 1069 healthy controls, or 1069 patients with AT, or 1069 with multinodular goiter (matched by age, gender, coming from the same area, with a similar iodine intake).

On the whole, 16.7% of GD patients had another associated autoimmune disease; and the most frequently observed were: vitiligo (2.6%), chronic autoimmune gastritis (2.4%), rheumatoid arthritis (1.9%), polymyalgia rheumatica (1.3%), multiple sclerosis (0.3%), celiac disease (1.1%), diabetes (type 1) (0.9%), systemic lupus erythematosus and sarcoidosis (<0.1%), Sjogren disease (0.8%). Moreover, 1.5% patients with GD had three associated autoimmune disorders. Interestingly, patients with Graves' ophthalmopathy (GO) had another autoimmmune disorder more frequently (18.9%), with respect to GD patients without GO (15.6%). However the pattern of the associated autoimmune disorders in GD was not significantly different from that observed in AT patients.

In conclusion, we suggest GD patients who are still sick, or who develop new unspecific symptoms (even if during an appropriate treatment of hyperthyroidism) should be appropriately screened for the presence of other autoimmune disorders.

http://bit.ly/2AHu90p