Medicine

Generic drugs – The Indian scenario SS Joshi, YC Shetty, S Karande Journal of Postgraduate Medicine 2019 65(2):67-69

Interpreting the meta-analysis of efficacy of vitamin D supplementation in major depression L Jeyaseelan Journal of Postgraduate Medicine 2019 65(2):70-71

Transoral thyroidectomy- Breaking new grounds PS Pai Journal of Postgraduate Medicine 2019 65(2):72-73

Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials F Vellekkatt, V Menon Journal of Postgraduate Medicine 2019 65(2):74-80 Background: There is a need to develop and periodically evaluate new treatment strategies in major depression due to the high burden of nonresponse and inadequate response to antidepressants. Aim: We aimed to assess the effect of vitamin D supplementation on depression symptom scores among individuals with clinically diagnosed major depression. Materials and Methods: Electronic search of databases was carried out for published randomized controlled trials in English language, peer-reviewed journals from inception till August 2017. Outcome measure used for effect size calculation was depression symptom scores. Effect sizes for the trials were computed using standardized mean difference (Cohen's d), and I2 test was used to assess sample heterogeneity. Pooled mean effect sizes were derived using both fixed and random-effects model. Critical appraisal of studies was done using the Cochrane risk of bias assessment tool. Results: A total of four trials involving 948 participants were included in the study. In three trials, the intervention group received oral vitamin D supplementation whereas in one parenteral vitamin D was given. Pooled mean effect size for vitamin D supplementation on depressive symptom ratings in major depression was 0.58 (95% confidence interval, 0.45–0.72). The I2 value for heterogeneity was 0 suggesting low heterogeneity among studies. Egger plot intercept indicated minimal publication bias. Conclusion: Vitamin D supplementation favorably impacted depression ratings in major depression with a moderate effect size. These findings must be considered tentative owing to the limited number of trials available and inherent methodological bias noted in few of them.

Transoral endoscopic thyroidectomy using vestibular approach: A single center experience SA Rege, M Janesh, S Surpam, V Shivane, A Arora, A Singh Journal of Postgraduate Medicine 2019 65(2):81-86 Background: Thyroid Natural Orifice Transluminal Endoscopic Surgery (NOTES) or transoral endoscopic thyroidectomy using vestibular approach is a recent advance embraced by the surgical community because of its potential for a scar-free thyroidectomy. In this article, we present our initial experience with this technique. Materials and Methods: We used a three-port technique through the oral vestibule, one 10 mm port for the laparoscope and two additional 5 mm ports for the endoscopic instruments required. The carbon dioxide insufflation pressure was set at 12 mm of Hg. Anterior cervical subplatysmal space was created from the oral vestibule down to the sternal notch, and the thyroidectomy was done using conventional laparoscopic instruments and a harmonic scalpel. Results: From May 2016 to December 2017, we have performed ten such procedures in the Department of General Surgery in our hospital, which is a tertiary referral center. Six patients had solitary thyroid nodules, for which a hemi-thyroidectomy was done. Four patients had multi-nodular goiter and total thyroidectomy or near-total thyroidectomy was done. The preoperative fine-needle aspiration cytology (FNAC) was suggestive of Bethesda class 2 lesions in all the patients with multinodular goiter and in five of the six patients with solitary nodular goiter. Only one patient with solitary nodular goiter had a Bethesda class 3 lesion on FNAC. The final histopathological report of the specimen was benign, either colloid goiter, or degenerative nodule in all cases of multinodular goiter and in four cases of solitary thyroid nodule. In one Bethesda class 2 solitary nodule, the histopathological report was suggestive of follicular carcinoma; in the Bethesda class 3 solitary nodule, the histopathological report was suggestive of follicular variant of papillary carcinoma. No complication such as temporary or permanent vocal cord paralysis, hypoparathyroidism, subcutaneous emphysema, pneumomediastinum, tracheal injury, esophageal injury, mental nerve palsy, or surgical site infection was found postoperatively. However, two patients developed small hematomas in the midline. Conclusion: Transoral endoscopic thyroidectomy is a safe, feasible, and minimally invasive technique with excellent cosmetic results.

Prevalence and correlates of cyberchondria among professionals working in the information technology sector in Chennai, India: A cross-sectional study S Makarla, V Gopichandran, D Tondare Journal of Postgraduate Medicine 2019 65(2):87-92 Background: Cyberchondria is the excessive searching of online health information that leads to anxiety and distress. There is scarce information about its prevalence in low and middle-income country settings. Objectives: The objective of the study was to assess the prevalence and factors influencing cyberchondria among employees working in the information technology sector in India. Methods: An emailed questionnaire-based cross-sectional survey was conducted among 205 employees working in various information technology firms in and around Chennai. The data were analyzed using nonhierarchical k-means cluster analysis to group participants with and without cyberchondria on its four subdomains. The association of cyberchondria with general mental health as measured by the General Health Questionnaire 12 was studied using independent sample t-test. Logistic regression analysis was performed to study the association between general mental health and cyberchondria after adjusting for sociodemographic covariates. Results: The prevalence of cyberchondria was 55.6%. The dominant pattern was excessiveness of online searching, requirement of reassurance followed by distress due to health anxiety, and compulsivity. Cyberchondria was negatively associated with general mental health (adj. OR 0.923; 95% CI 0.882–0.967) after adjusting for age, sex, education, and years of service. Conclusions: Cyberchondria is an emerging public mental health problem in India. Since it is associated with poor mental health, measures need to be adopted to evaluate, prevent, and treat it at the population level.

Comparison of primary arthrodesis versus open reduction with internal fixation for Lisfranc injuries: Systematic review and meta-analysis PF Han, ZL Zhang, CL Chen, YC Han, XC Wei, PC Li Journal of Postgraduate Medicine 2019 65(2):93-100 Objective: Multiple studies have compared primary arthrodesis versus open reduction with internal fixation (ORIF) for surgical treatment of fractures of the Lisfranc joint, but their results have been inconsistent. Therefore, the present systematic review and meta-analysis was performed to compare the clinical efficacy of arthrodesis versus ORIF for the treatment of Lisfranc injuries. Methods: Through searching the Embase, PubMed, PMC, CINAHL, PQDT, and Cochrane Library databases (from July 1998 to July 2018), we identified five case-controlled trials and two randomized controlled trials that compared the clinical efficacy of primary arthrodesis and ORIF for treating Lisfranc injuries. The extracted data were analyzed using Review manager 5.3 software. Results: Through comparisons of data for primary arthrodesis and ORIF groups, we found no significant differences in the anatomic reduction rate, revision surgery rate, and total rate of complications between the different treatment approaches. However, arthrodesis was associated with a significantly better American Orthopedic Foot and Ankle Society (AOFAS) score, return to duty rate, and visual analog scale score with a lower incidence of hardware removal compared with ORIF. Conclusions: For the treatment for Lisfranc injuries, primary arthrodesis was superior to ORIF based on a higher AOFAS score, better return to duty rate, lower postoperative pain, and lower requirement for internal fixation removal. Further evidence from future randomized controlled trials with higher quality and larger sample sizes is needed to confirm these findings.

Predictors of response to pulmonary rehabilitation in stable chronic obstructive pulmonary disease patients: A prospective cohort study S Ragaselvi, AK Janmeja, D Aggarwal, A Sidana, P Sood Journal of Postgraduate Medicine 2019 65(2):101-106 Context: Pulmonary rehabilitation (PR) has become a standard of care in the management of chronic obstructive pulmonary disease (COPD). However, a significant proportion of the patients do not show benefit after the PR program. Aims: The study was planned to find different patient- and/or disease-related factors that may predict response to PR in stable COPD. Subjects and Methods: A total of 102 stable COPD patients were prospectively enrolled. Baseline evaluation and investigations, including spirometry, arterial blood gas analysis, and bone mineral density assessment, were done. Thereafter, all patients underwent an 8-week comprehensive outpatient PR program that consisted of exercise training, education, nutritional, and psychological counseling. The response to PR was dichotomously (yes/no) defined by the combined improvement in exercise tolerance (6-min walk distance [6MWD] +54 m) and quality of life (St. George's Respiratory Questionnaire [SGRQ] score - 4 points) measured before and after the program. Thereafter, different predefined factors were analyzed for their possible association with the PR response. Results: A total of 80 patients (78.4%) completed the PR program and were subjected for analysis. Out of them, 42 (52.5%) showed improvement in both 6MWD and SGRQ score (46 in 6MWD and 54 in SGRQ score). After application of multivariate logistic regression analysis, forced expiratory volume in 1 s <50% predicted (odds ratio [OR]: 2.9; 95% confidence interval [CI]: 1.1–8.3; P = 0.04) and osteoporosis (OR: 0.26; 95% CI: 0.13–0.53; P < 0.001) were found as independent factors predicting PR efficacy. Conclusions: Poor baseline lung function predicts a short-term improvement in exercise capacity and quality of life in COPD patients, whereas osteoporosis is a negative predictor of PR response. Active search for these factors may help in better patient selection, thus leading to improved outcome after PR.

Central institutional ethics committee needed to facilitate timely review of multicenter clinical trials BS Desai, AS Dixit, VS Gota Journal of Postgraduate Medicine 2019 65(2):107-109 A multicenter trial in India undergoes review by Institutional Ethics Committees (IECs) of all participating institutions. The failure to obtain approval even from a single institution's IEC creates a situation of inequitable access to clinical trials. The dichotomy in decisions of different IECs is attributed to lack of standardization and accountability in their functioning. The registration of IECs with Central Drugs Standard Control Organization notwithstanding, the current model of IEC review has failed to ensure uniformity in IEC decisions in multicenter trials. Alternative models that allow central review of multicenter clinical trials should be explored.

Isolated open comminuted fracture of the first rib MH Basha, KP Singaravelu, G Mohana Journal of Postgraduate Medicine 2019 65(2):110-111 In the emergency department, open isolated rib fractures are rarely seen. There is scarce literature related to open isolated first rib comminuted fracture. We report a 33-year-old male who presented with an isolated open first rib comminuted fracture following a road traffic accident. He did not have any neurovascular or major organ injuries and was managed successfully with conservative treatment.

Gastric Cancer

Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer In the original publication of this article, Table 4 was published incorrectly. The correct Table 4 is given below.

Correction to: The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection The article "The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection", written by Motoi Azumi, Manabu Takeuchi, Youhei Koseki, Masaru Kumagai, Yoko Kobayashi, Masafumi Takatsuna, Aiko Yoshioka, Seiichi Yoshikawa, Tsutomu Miura, and Shuji Terai, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 28 September 2018 without open access.

Correction to: Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis In the original publication of this article, most of the reference citations in Tables 1 and 2 were published incorrectly. The corrected tables are given in this correction.

Synergistic triad epistasis of epigenetic H3K27me modifier genes, EZH2, KDM6A , and KDM6B , in gastric cancer susceptibility Abstract Background For an epigenetic regulation of human genome, three enzymes write or erase methylation of lysine-27 residue on histone H3 (H3K27me). This methylation is catalyzed by EZH2 (KMT6A) methyltransferase and reversed by KDM6A (UTX) or KDM6B (JMJD3) demethylase. Genetic cancer risk association has been reported on EZH2, but not on KDM6A or KDM6B yet. Methods A total of 23 tag single-nucleotide polymorphisms (SNPs) of the three genes were genotyped in 2349 Korean participants, and their gastric cancer risk associations and epistases were statistically examined by comparing the SNP genotypes of 1100 gastric cancer patients and 1249 healthy controls. Results All three genes are individually associated with gastric cancer susceptibility, as evident with the genotypes of KDM6A SNP rs5952279 (P = 0.00010) and rs144974719 (P = 0.00024), KDM6B rs78633955 (P = 0.0019) and rs11657063 (P = 0.0036), and EZH2 rs67648693 (P = 0.0028) and rs1061037 (P = 0.023). Furthermore, when odds ratio of interaction (ORint) is calculated for all intergenic SNP pairs, synergistic epistasis is evident among the three genes. Specifically, the interaction is synergistic between EZH2 rs58579167 and KDM6A rs5952279 (ORint = 3.2, P = 0.00066), between KDM6A rs2230018 and KDM6B rs78633955 (ORint = 1.9, P = 0.044), and between KDM6B rs78633955 and EZH2 rs73158295 (ORint = 1.7, P = 0.00030). These inter-SNP interactions together constitute a synergistic triad epistasis of ring-type topology. Conclusions All three H3K27me modifier genes are individually associated with gastric cancer susceptibility with synergistic triad interaction. Not only two enzymes with the same function (KDM6A and KDM6B), but also those with opposite functions (EZH2 versus KDM6A or KDM6B) synergistically affect H3K27me consequences such as gastric cancer susceptibility.

Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer Abstract Background We recently reported the clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using surgical specimens; patients with homogeneously HER2 positive gastric cancer benefitted more from trastuzumab. However, the majority of patients are diagnosed by endoscopic biopsy, and surgical specimens are not available in these patients. The aim of this study is to verify clinical significance of HER2 heterogeneity on trastuzumab efficacy using biopsy specimens. Methods Eighty-seven patients, who received trastuzumab-based chemotherapy and whose endoscopic biopsy specimens were available for HER2 assessment, were consecutively enrolled. When all tumor cells in all biopsy specimens overexpressed HER2 protein, it was defined as homogeneously HER2 (homo-HER2) positive group, and the others were defined as heterogeneously HER2 (hetero-HER2) positive group. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were evaluated. Results Thirty-four patients (39%) were diagnosed as the homo-HER2 group and 53 patients (61%) were the hetero-HER2 group. After the median follow-up period of 17.8 months, the median PFS and OS were 7.6 and 17.8 months, respectively. Significant survival differences were shown between the two groups; the homo-HER2 group showed significantly longer PFS (10.8 vs. 6.1 months, HR 0.469 95% CI 0.29–0.77, p = 0.003) and OS (29.3 vs. 14.4 months, HR 0.352 95% CI 0.20–0.61, p < 0.001). ORR was 68.6% in this cohort. Higher response rate (85.2% vs 58.1%, p = 0.020) and deeper response (− 49.0% vs − 40.0%, p = 0.018) were also found in the homo-HER2 group. Conclusions Similar to surgical specimens, we verified clinical significance of HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens.

Enhanced recovery versus conventional care in gastric cancer surgery: a meta-analysis of randomized and non-randomized controlled trials Abstract Introduction Enhanced recovery after surgery (ERAS) protocols have been successfully integrated into peri-operative management of different cancer surgeries such as colorectal cancer. Their value for gastric cancer surgery, however, remains uncertain. Methods A search for randomized and observational studies comparing ERAS versus conventional care in gastric cancer surgery was performed according to PRISMA guidelines. Random-effects meta-analyses with inverse variance weighting were conducted, and quality of included studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa scale (PROSPERO: CRD42017080888). Results Twenty-three studies involving 2686 patients were included. ERAS was associated with reduced length of hospital stay (WMD—2.47 days, 95% CI − 3.06 to − 1.89, P < 0.00001), time to flatus (WMD—0.70 days, 95% CI − 1.02 to − 0.37, P < 0.0001), and hospitalization costs (WMD—USD$ 4400, 95% CI − USD$ 5580 to − USD$ 3210, P < 0.00001), with consistent results across open and laparoscopic surgery. Postoperative morbidity and 30-day mortality were similar, although a higher rate of readmission was observed in the ERAS group (RR = 1.95, 95% CI 1.03–3.67, P = 0.04). Patients in the ERAS arm had significantly attenuated C-reactive protein levels on days 3/4 and 7, interleukin-6 levels on days 1, and 3/4, and tumor necrosis factor-α levels on days 3/4 postoperatively. Conclusion Compared to conventional care, ERAS reduces hospital stay, costs, surgical stress response and time to return of gut function, without increasing post-operative morbidity in gastric cancer surgery. However, precaution is necessary to reduce the increased risk of hospital readmission when adopting ERAS.

Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma Abstract Background We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients. Methods Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. Results We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively). Conclusions Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.

Equivalent feasibility and safety of perioperative care by ERAS in open and laparoscopy-assisted distal gastrectomy for gastric cancer: a single-institution ancillary study using the patient cohort enrolled in the JCOG0912 phase III trial Abstract Background Laparoscopy-assisted distal gastrectomy (LADG) has an advantage of earlier recovery after surgery due to having lower invasiveness and wound pain than open distal gastrectomy (ODG). However, whether the same enhanced recovery after surgery (ERAS) program for LADG is equally feasible and safe for ODG remains unclear. Methods We retrospectively extracted the clinical data of the patients enrolled in JCOG0912 from the medical record system of our hospital and compared the treatment process and short-term surgical outcomes between LADG and ODG. Our ERAS program consisted of 13 elements (4 preoperative, 4 intraoperative, and 5 postoperative elements). The morbidity was defined as complications of grade 2 or more. Results One hundred and sixty-three patients were entered from our hospital and randomized to undergo ODG (82 patients) or LADG (81 patients). The patient's backgrounds, surgical outcomes, and pathological outcomes were similar between the ODG and LADG groups. The rate of completing the clinical pathway was 95.1% in both groups, and the rates of completing each ERAS element were similar. However, the additional use of acetaminophen was significantly more frequent in the ODG group than in the LADG group (18.3% vs. 6.2%, p = 0.03). The median hospital stay after surgery was 9 days in both groups. Morbidity, defined as Clavien–Dindo classification > grade 2, was observed in 6.1% of the ODG group and 11.1% of the LADG group. No mortality occurred in either group. Conclusion This study showed that the regimen of perioperative care performed by the ERAS program for LADG was equally feasible and safe for ODG with additional pain control. Less pain observed in LADG was not so apparent advantage for completion and safety of ERAS care.

CRP/prealbumin, a novel inflammatory index for predicting recurrence after radical resection in gastric cancer patients: post hoc analysis of a randomized phase III trial Abstract Background Serum prealbumin (PALB) can predict the prognosis of patients with gastric cancer (GC). However, the prognostic value of combination of C-reactive protein and PALB (CRP/PALB) remains unclear. Methods A total of 419 gastric cancer patients included in a clinical trial (NCT02327481) were analyzed. The present study is a substudy of the trial. Receiver operating characteristic (ROC) curves were generated, and by calculating the areas under the curve (AUC) and the C-index, the discriminative ability of each inflammatory index was compared, including CRP/PALB, C-reactive protein/albumin, Glasgow prognostic score (GPS), modified GPS, systemic immune-inflammation index, neutrophil–lymphocyte ratio, and platelet–lymphocyte ratio. Results Ultimately, 401 patients were included in this study. The optimal cutoff value of CRP/PALB was 17.7. According to this cutoff point, the entire sample was divided into a CRP/PALB < 17.7 (LCP) group and a CRP/PALB ≥ 17.7 (HCP) group, comprising 245 and 156 patients, respectively. There were 54 and 22 patients experienced recurrence in the HCP and LCP group, respectively, p < 0.001. Compared with traditional inflammatory indices, CRP/PALB had the highest AUC (0.707) and C-index (0.716), all p < 0.05. The post-recurrence survival (PRS) of patients in the HCP group was significantly shorter than that in the LCP group (p = 0.010), especially for pathological stage III patients (p = 0.015) or patients with distant (p = 0.018) or local (p = 0.023) recurrences. Conclusions The predictive value of preoperative CRP/PALB for the recurrence of GC is significantly better than traditional inflammatory indices. HCP significantly reduces the PRS, especially for pathological stage III patients or patients with distant or local recurrences.

The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection Abstract Background Delayed bleeding is an important complication after gastric endoscopic submucosal dissection (ESD). The search, coagulation, and clipping (SCC) method can be used to prevent delayed bleeding after ESD. However, its safety and efficacy are unclear. We compared the SCC method with post-ESD coagulation (PEC) to clarify the safety and efficacy of the SCC method for preventing delayed bleeding after gastric ESD. Methods This retrospective study included 438 patients (478 lesions) who underwent gastric ESD. Multivariate logistic regression analysis was performed to identify the significant independent factors associated with delayed bleeding and we performed propensity-score matching (PSM) to reduce the effect of procedure-selection bias of SCC method. Results Of the 438 patients, 216 underwent PEC and 222 underwent SCC. Delayed bleeding was significantly less common in the SCC than in the PEC (2.6% vs. 7.2%; P = 0.013). Among patients treated with antithrombotic therapy, the delayed bleeding rate was lower in the SCC group than in the PEC group; however, the difference was not significant (P = 0.15). The SCC method was found to be a significant independent factor for the prevention of delayed bleeding. PSM was performed in 156 patients in the PEC group and SCC group. There was a significant difference in the incidence of bleeding in the PEC and SCC groups (P = 0.013). No patient had perforation/bleeding associated with the SCC method. Conclusions Our findings suggest that the SCC method is a simple, safe, and effective approach for preventing delayed bleeding after gastric ESD.

Allergy and Asthma

The Role of KIT Mutations in Anaphylaxis Abstract Purpose of Review Gain of function KIT mutations are detected in clonal mast cell diseases, namely mastocytosis and monoclonal mast cell activation syndrome. Timely diagnosis and treatment of these disorders are crucial because of their association with severe and life-threatening anaphylaxis. KIT mutations also have implications for targeted therapies of mast cell disorders. This review article strives to serve as an overview of the role of clonal mast cell disorders in anaphylaxis while elucidating current and future therapies. Recent Findings Clonal mast cell disease has been increasingly diagnosed in patients with severe hymenoptera allergy and those with recurrent unexplained anaphylaxis. The current state of knowledge of the epidemiology, pathophysiology, diagnosis, and treatment of mastocytosis with a particular focus on anaphylaxis and its triggers which are described in this context. Novel and forthcoming treatments are discussed including the relevance of KIT mutation status. Summary This review provides an overview of the role of KIT mutations in mastocytosis and anaphylaxis, and highlights emerging therapies for mastocytosis, targeting these mutations.

GRADE-ing the Benefit/Risk Equation in Food Immunotherapy Abstract Purpose of Review We reviewed the existing evidence base to desensitisation for food allergy, applying the Grading of Recommendations, Assessment, Development and Evaluation approach to discuss whether desensitisation is likely to become part of routine treatment for patients with food allergy. Recent Findings Desensitisation for food allergy to peanut, egg and cow's milk is efficacious, but whether such interventions are cost-effective is less clear, due to the issues over a sustained desensitisation effect and the increase in allergic reactions occurring in patients on treatment. Few studies have assessed the change in health-related quality of life associated with treatment, and most have not considered discordance between parent-reported changes in health-related quality of life (HRQL) outcomes compared to those of the patients themselves; none to date have controlled for the improvement in HRQL occurring after initial challenge which will confound outcomes. Summary The lack of longer-term safety and cost-effectiveness data, as well as an absence of current consensus in the reporting of patient-relevant outcomes, must be addressed in order to be able to recommend the introduction of desensitisation as a routine treatment in healthcare systems.

Th9 Cells in Allergic Disease Abstract Purposes of Review Th9 cells are recognized as a novel subset of effector T helper cells that preferentially produce IL-9. Here, we provide a current update on the reports related to the function of Th9 cells in allergic inflammatory diseases. Recent Findings The effector Th9 cells differentiating from naïve T helper cells have recently been identified. Because of accumulating findings of Th9 cells in many inflammatory diseases, including allergic diseases, diverse functions of Th9 cells in regulating immune responses have been suggested. Related reports indicate multiple sources of IL-9 besides Th9 cells and their association with the pathogenesis of allergic rhinitis, asthma, atopic dermatitis, contact dermatitis, and food allergy. More recently, elements of the epigenetic landscape involving in the regulation of IL-9 by Th9 cells have been identified to be the potential target for allergic inflammation. Summary This review provides the most recent information about Th9 cells and their contribution in airway allergic disease, skin, and food allergy.

Evaluating Penicillin Allergies Without Skin Testing Abstract Purpose of Review An unconfirmed penicillin allergy is known to confer significant risk to patients. Only a small minority of patients labeled with penicillin allergy will be confirmed to be hypersensitive with the current reference standard test, an oral amoxicillin therapeutic dose challenge. Skin testing has been recommended prior to oral challenges to reduce the risk of severe acute challenge reactions. The rate of severe acute anaphylactic reactions with oral amoxicillin is currently extremely low. Unfortunately, penicillin skin testing, as commonly performed, has a high rate of false positive results. Recent Findings Encouraging skin testing in all individuals with an unconfirmed penicillin allergy, prior to a confirmatory oral challenge, would be technically difficult, make testing all individuals with an unconfirmed penicillin allergy very unlikely, and ultimately increase the risk to patients because of suboptimal antibiotic use. Most patients, who are appropriate candidates for a direct oral amoxicillin challenge, to confirm current penicillin tolerance, can be safely identified by their clinical histories. Higher risk individuals, those with a history of anaphylaxis or other acute onset potentially IgE-mediated reaction such as hives within 6 h of the first dose of the last course of a penicillin, may benefit from properly performed puncture and intradermal skin testing, using commercially available penicilloyl-polylysine, prior to an oral challenge, if skin test negative. Summary Direct oral amoxicillin challenges in low-risk individuals are well accepted by patients and a safe and effective part of penicillin allergy delabeling.

Contributions of Innate Lymphoid Cells in Chronic Rhinosinusitis Abstract Purpose of Review To review innate lymphoid cells (ILCs) and their role in chronic rhinosinusitis (CRS). Recent Findings The immune system consists of the innate and adaptive response. Until the recognition of ILCs, chronic inflammatory diseases were characterized by cytokines linked only to T helper cells. However, these immune responses are now described more broadly to include contributions from both the innate and adaptive immunity. In CRS, focus had been on ILC2s in CRS with nasal polyps. These studies also highlight the importance of epithelial cell–derived cytokines in coordinating these responses. In addition to indirect crosstalk via cytokines, ILCs and T helper cells can utilize the OX40/OX40 ligand and major histocompatibility complex class II pathways to directly interact and coordinate responses. Summary In addition to T helper cells, ILCs contribute to the inflammatory response associated with CRS. The understanding of these cells along with pathways that activate and perpetuate these cells leads to new potential therapeutic targets for CRS treatment.

Exosomes in Allergic Airway Diseases Abstract Purpose of Review This review will cover what is known regarding exosomes and allergy, and furthermore discuss novel mechanism of exosome-mediated immune modulation and metabolic regulation via the transfer of mitochondria. Recent Findings Exosomes are nano-sized extracellular vesicles (EVs) derived from the endosome that play a direct role in governing physiological and pathological conditions by transferring bioactive cargo such as proteins, enzymes, nucleic acids (miRNA, mRNA, DNA), and metabolites. Recent evidence suggest that exosomes may signal in autocrine but, most importantly, in paracrine and endocrine manner, being taken up by neighboring cells or carried to distant sites. Exosomes also mediate immunogenic responses, such as antigen presentation and inflammation. In asthma and allergy, exosomes facilitate cross-talk between immune and epithelial cells, and drive site-specific inflammation through the generation of pro-inflammatory mediators like leukotrienes. Recent studies suggest that myeloid cell-generated exosomes transfer mitochondria to lymphocytes. Summary Exosomes are nano-sized mediators of the immune system which can modulate responses through antigen presentation, and the transfer of pro- and anti-inflammatory mediators. In addition to conventional mechanisms of immune modulation, exosomes may act as a novel courier of functional mitochondria that is capable of modulating the recipient cells bioenergetics, resulting in altered cellular responses. The transfer of mitochondria and modulation of bioenergetics may result in immune activation or dampening depending on the context.

Microbial Adjuncts for Food Allergen Immunotherapy Abstract Purpose of Review Food allergen immunotherapy may benefit from adjunct therapies to enhance safety and efficacy. We review preclinical studies investigating the effects of probiotics and other microbial-based interventions on oral tolerance, describe the human clinical trial evidence thus far for microbial adjuncts, and discuss steps for translating research findings in this area to clinical therapy. Recent Findings Murine studies support that microbial-based interventions confer protection against sensitization and may augment treatment efficacy for food allergy. Microbial adjunct therapies can promote regulatory T cells and modulate Th1 vs. Th2 responses. There is a wide array of novel modalities utilizing microbial components. Ongoing efforts are focused on translating preclinical data into potential treatments. Summary Probiotics, prebiotics, and microbial components have all been examined as microbial adjunct therapies in murine models of food allergy. The effects of probiotics appear to be strain-specific. Prebiotics and bacterial components are innovative modalities to modulate oral tolerance. Better characterization of dysbiosis in human cohorts with food allergy, deeper mechanistic understanding of microbial adjunct therapies, safety evaluation, and careful clinical trial design will be crucial for the development of microbial adjuncts for food allergen immunotherapy. Microbial adjunct therapies have the potential to enhance the efficacy, safety, and durability of food allergen immunotherapy.

Osteitis in Chronic Rhinosinusitis Abstract Purpose of Review Osteitis is recognized as a common factor in recalcitrant chronic rhinosinusitis (CRS). There is evidence for the association of osteitis with revision surgeries and CRS severity, in terms of higher Lund-Mackay scores. This is a narrative review on the osteitis in CRS patients. Recent Findings Evidence to date is inconclusive with regard to the etiology and pathogenesis of this bony thickening. Histopathology of osteitis in primary CRS is likely a process of neo-osteogenesis and bone remodeling. For better understanding, various associating factors have been studied including an inflammatory pattern of rhinosinusitis. Recent studies have associated osteitis with nasal polyps and tissue eosinophilia with the increase in periostin expression and P-glycoprotein mucosal expression. There is no association of osteitis to symptoms or quality of life. Osteitis is an outcome of neo-osteogenesis rather than inflammatory processes in CRS patients without a prior history of surgery. While CT has become a staple in osteitis assessment, the standards for grading osteitic severity remain in an experimental stage. There is no association between the presence or severity of osteitis at the time of surgery and clinical outcomes at 1 year after surgery. Summary This review provides a comprehensive overview of the pathogenesis, epidemiology, and correlation with clinical and biological factors of osteitis in CRS patients.

Chlorhexidine Allergy: On the Rise and Often Overlooked Abstract Purpose of Review In recent years, the risk of allergy to chlorhexidine is increasingly recognised. In this review, we discuss why the allergy is so easily overlooked and point out several preventative initiatives that can minimise the risk of both chlorhexidine sensitisation and allergy development and accidental re-exposure in patients with chlorhexidine allergy. Testing for chlorhexidine allergy is also discussed. Recent Findings Numerous reports have been published from many different specialties. Symptoms range from mild skin symptoms to life-threatening anaphylaxis. Testing for chlorhexidine allergy is based on skin testing and in vitro testing. Recently, it was found that both skin prick testing and specific IgE have high sensitivities and specificities. Summary This review gives an overview of chlorhexidine allergy with a special focus on preventative initiatives and testing.

The Role of Staphylococcus aureus in Patients with Chronic Sinusitis and Nasal Polyposis Abstract Purpose of Review Staphylococcus aureus (S. aureus) is correlated with the development of persistent severe inflammatory disease of the upper airway including chronic rhinosinusitis with nasal polyps (CRSwNP). The presence of S. aureusis associated with atopic disease including allergic rhinitis and atopic dermatitis and is associated with poor outcomes. Recent Findings Several different strains of S. aureus generate different toxins and gene products that can account for organism pathogenicity. S. aureus bacteria and its antigens shape the bacterial and fungal microbiome and the mucosal niche which generates host responses that can account for inflammation. The multiple disease phenotypes and molecular endotypes seen in CRSwNP can be characterized by T-helper cell environment within the inflammatory milieu, the presence of epithelial barrier dysfunction, aberrant eicosanoid metabolism, poor wound healing, and dysfunctional host-bacteria interactions which lead to recalcitrant disease and worse surgical outcomes. Summary Understanding the pathomechanisms that S. aureus utilizes to promote nasal polyp formation, prolonged tissue inflammation, and bacterial dysbiosis are essential in our efforts to identify new therapeutic approaches to resolve this chronic inflammatory process.

Neurosurgical Anesthesiology

Intraoperative-evoked Potential Monitoring: From Homemade to Automated Systems No abstract available

Securing Endotracheal Tube in a Bearded Patient Undergoing Surgery for Cerebellopontine Angle Tumor in Lateral Position—A Different Approach No abstract available

Hypotension and Hypocapnia During General Anesthesia in Piglets: Study of S100b as an Acute Biomarker for Cerebral Tissue Injury Background: Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA. Methods: Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery. Results: Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001). Conclusion: S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported. The study is part of Mrs. Clausen's PhD project, which was awarded the ESA MAQUET GRANT at the annual meeting of the European Society of Anesthesia 2015. Mrs Clausen's project is further supported by funds provided by the Department of Anesthesiology and Intensive Care Medicine, University Hospital Odense. The authors have no conflicts of interest to disclose. Address correspondence to: Nicola G. Clausen, MD, PhD, E-mail: nicola@nicola.dk. Received September 9, 2018 Accepted March 14, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Effects of Vasopressors on Cerebral Circulation and Oxygenation: A Narrative Review of Pharmacodynamics in Health and Traumatic Brain Injury The clinical use of vasoactive drugs aims to improve hemodynamic variables and thereby maintain or restore adequate perfusion and oxygenation in accordance with metabolic demands. A main focus in the management of patients with brain pathology during surgery and neurointensive care is restoring and/or maintaining adequate cerebral perfusion pressure in order to ensure cerebral blood flow in accordance with metabolic demands. One commonly used clinical strategy is the administration of vasoactive drugs aiming to increase mean arterial blood pressure and thereby cerebral perfusion pressure. Here, we first describe the anatomic and physiological basis for the cerebrovascular effects of vasopressor agents. Next, we review the pharmacodynamics of commonly used vasopressors under normal circumstances and in the presence of head injury. We further discuss the role of blood-brain barrier disruption and microvascular dysfunction with regard to the effects of the reviewed vasopressor agents. M.R. was funded by the Health Research Fund of Central Denmark Region, Viborg, Denmark. The remaining authors have no conflicts of interest to disclose. Address correspondence to: Mads Rasmussen, MD, PhD, Department of Anesthesia and Intensive Care, Section of Neuroanesthesia, Aarhus University Hospital, 8000 Aarhus C, Denmark (e-mail: mads.rasmussen@vest.rm.dk). Received December 7, 2018 Accepted February 27, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Journal Club No abstract available

Journal Club No abstract available

Cervical Spine Movement During Awake Orotracheal Intubation With Fiberoptic Scope and McGrath Videolaryngoscope in Patients Undergoing Surgery for Cervical Spine Instability: A Randomized Control Trial Background: Cervical spine movement during intubation with direct laryngoscopy can predispose to new-onset neurological deficits in patients with cervical spine instability. While fiberoptic-guided intubation (FGI) is mostly preferred in such patients, this is not always possible. Videolaryngoscopy results in less cervical spine movement than direct laryngoscopy and may be an alternative to FGI in patients with cervical spine instability. The objective of this study was to compare cervical spine movement during awake FGI with those during awake McGrath videolaryngoscope-guided intubation (VGI) in patients undergoing surgery for cervical spine instability. Methods: Forty-six adult patients with upper cervical spine instability scheduled for stabilization surgery were randomized to awake FGI or awake VGI. Cervical spine movement during intubation was assessed by changes in lateral fluoroscopic-measured angles (α and β at C1/C2 and C3 levels, respectively) at 3 time points: T1, preintubation; T2, during intubation; T3, postintubation. Motor power was assessed before and after intubation. Results: Patient demographics and airway characteristics were similar between the 2 groups. Cervical spine motion (in degrees) during intubation was significantly greater with VGI than FGI at C1/C2 (T3-T1, −8.02±8.11 vs. −1.47±3.31; P<0.001) but not at C3 (T3-T1, −2.17±5.16 vs. −1.85±3.29; P=0.960). No patient developed new-onset motor deficits following intubation in either group. Conclusions: Compared with FGI, VGI results in a greater degree of cervical spine movement at C1/C2 but not at C3. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Kamath Sriganesh, DM. E-mail: drsri23@gmail.com. Received November 25, 2018 Accepted February 21, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Hyperlactatemia After Intracranial Tumor Surgery Does Not Affect 6-Month Survival: A Retrospective Case Series Background: Patients undergoing neurosurgery frequently exhibit hyperlactatemia. The aim of this study was to identify factors associated with hyperlactatemia and assess how hyperlactatemia impacts survival and hospital length of stay after intracranial tumor surgery. Materials and Methods: This retrospective cohort study included 496 adult patients that underwent surgery between January 1, 2014 and December 31, 2015. We evaluated patient characteristics, surgery characteristics, pH, lactate, and blood glucose from blood samples collected on admission to the high-dependency unit and the morning after surgery, and 6-month outcome data. Results: Hyperlactatemia (>2.0 mmol/L) occurred in >50% of patients, but only 7.7% had acidosis. Postoperative hyperlactatemia was not correlated with 6-month survival (P=0.987), but was correlated with (median [interquartile range]) longer hospital stays (6 [4 to 8.5] d vs. 5 [4 to 8] d; P=0.006), longer surgery duration (4:53 [4:01 to 6:18] h:min vs. 4:28 [3:33 to 5:53] h:min; P=0.001), higher dexamethasone dose (16 [16 to 35] mg vs. 16 [16 to 20] mg; P<0.001), and higher blood glucose concentration (8.4 [7.5 to 9.6] mmol/L vs. 8.0 [7.1 to 8.9] mmol/L; P<0.001). Patients that received total intravenous anesthesia developed hyperlactatemia less frequently than those that received balanced anesthesia with inhalational agents (48.4% vs. 61.5%, P=0.008). Hyperlactatemia was not associated with increased postoperative neurological deficits or the need for rehabilitation therapy. Conclusions: Hyperlactatemia was common after intracranial tumor surgery. It did not influence 6-month outcomes but was associated with longer hospital length of stay. Several potential causative factors for hyperlactatemia were identified. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ The authors have no funding or conflicts of interest to disclose. Address correspondence to: Peter P. de Smalen, MD, Department of Anesthesiology, Erasmus University Medical Center, Kamer Na-1718, Postbus 2040, 3000 CA Rotterdam, The Netherlands (e-mail: p.desmalen@erasmusmc.nl). Received April 2, 2018 Accepted February 22, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Transient Neurological Events After Surgery for Pediatric Moyamoya Disease: A Retrospective Study of Postoperative Sedation Practices Background: Moyamoya disease is a cerebrovascular disease characterized by bilateral stenosis of the intracranial internal carotid arteries and an abnormal collateral vascular network at the base of the brain. Transient neurological events (TNEs), which are episodes of neurological dysfunction lasting <24 hours, are associated with stroke in pediatric patients with Moyamoya disease. Perioperative agitation often occurs in pediatric patients. We hypothesized that anesthetic technique and postoperative sedation would modify the association between TNE and superficial temporal artery-middle cerebral artery (STA-MCA) bypass in pediatric patients with Moyamoya disease. Methods: We retrospectively reviewed the medical records of patients with Moyamoya disease aged 15 years and below who underwent STA-MCA bypass under general anesthesia at a single cerebrovascular center in Japan between January 1999 and March 2016. The primary outcome was TNE. Mixed-effects logistic regression was used to evaluate whether postoperative sedation and anesthetic agents were associated with TNE. Results: Among 277 hemispheres in 154 pediatric patients who underwent STA-MCA bypass, 107 patients (39%) experienced TNE within 1 week after surgery. Crying (adjusted odds ratio, 3.11; 95% confidence interval, 1.01-9.59; P=0.048) was an independent risk factor for TNE. Postoperative sedation was associated with a lower incidence of TNE (adjusted odds ratio, 0.514; 95% confidence interval, 0.264-0.997; P=0.049), but premedication and anesthetic agents were not associated with TNE. Conclusion: In pediatric patients with Moyamoya disease, crying was associated with increased TNE and postoperative sedation is associated with decreased TNE. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Kenji Yoshitani, MD, Department of Anesthesiology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan (e-mail: ykenji@ncvc.go.jp). Received November 17, 2018 Accepted February 11, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Near-Infrared Spectroscopy–derived Cerebral Autoregulation Indices Independently Predict Clinical Outcome in Acutely Ill Comatose Patients Objective: Outcome prediction in comatose patients with acute brain injury remains challenging. Regional cerebral oxygenation (rSO2) derived from near-infrared spectroscopy (NIRS) is a surrogate for cerebral blood flow and can be used to calculate cerebral autoregulation (CA) continuously at the bedside from the derived cerebral oximetry index (COx). We hypothesized that COx derived thresholds for CA are associated with outcomes in patients with acute coma from neurological injury. Methods: A prospective cohort study was conducted in 88 acutely comatose adults with heterogenous brain injury diagnoses who were continuously monitored with COx for up to 3 consecutive days. Multivariable logistic regression was performed to investigate association between averaged COx and short (in-hospital and 3 mo) and long-term (6 mo) outcomes. Results: Six month mortality rate was 62%. Median COx in nonsurvivors at hospital discharge was 0.082 [interquartile range, IQR: 0.045 to 0.160] compared with 0.042 [IQR: −0.005 to 0.110] in survivors (P=0.012). At 6 months, median COx was 0.075 [IQR: 0.27 to 0.158] in nonsurvivors compared with 0.029 [IQR: −0.015 to 0.077] in survivors (P=0.02). In the multivariable logistic regression model adjusted for confounders, average COx ≥0.05 was associated with both in-hospital mortality (adjusted odds ratio [OR]=2.9, 95% confidence interval [CI]=1.15-7.33, P=0.02), mortality at 6 months (adjusted OR=4.4, 95% CI=1.41-13.7, P=0.01), and severe disability (modified Rankin Score ≥4) at 6 months (adjusted OR=4.4, 95% CI=1.07-17.8, P=0.04). Area under the receiver operating characteristic curve for predicting mortality and severe disability at 6 months were 0.783 and 0.825, respectively. Conclusions: Averaged COx ≥0.05 is independently associated with short and long-term mortality and long-term severe disability in acutely comatose adults with neurological injury. We propose that COx ≥0.05 represents an accurate threshold to predict long-term functional outcome in acutely comatose adults. C.H. and W.C.Z. are senior authors. C.H. is the PI on an NIH-sponsored clinical study (R01 HL 92259). C.H. receives research funding from Medtronic/Covidien, Dublin, IR, and he serves as a consultant to Medtronic/Covidien and Ornim Medical Inc., Foxborough, MA. L.R.-L. is the PI on an American Academy of Neurology/American Brain Foundation and grant from Medtronic/Covidien, Dublin, IR. The remaining authors have no conflicts of interest to disclose. Address correspondence to: Lucia Rivera-Lara, MD, MPH, Department of Neurology, Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD 21287 (e-mail: lriver14@jhmi.edu). Received July 27, 2018 Accepted January 17, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Environmental Science and Pollution Research

Your mycotoxins in water paper

Subject: Reply to letter to the Editor (ESPR-D-18-05279) about our manuscript

Biochemical impacts in adult and juvenile farmed European seabass and gilthead seabream from semi-intensive aquaculture of southern European estuarine systems Abstract The nutritional value and developmental variations of cultured fish were assessed for European seabass and gilthead seabream specimens reared in semi-intensive aquaculture systems in two Portuguese estuaries. Quantification of total protein and of carbohydrate and fatty acid profiles was carried out to determine differences between the composition of the same species in two development stages reared in four distinct farms. A significant influence of the rearing site on the nutritional composition of the same species was found for adult European seabass regarding saturated, monounsaturated and highly unsaturated fatty acids contents, both between estuaries and within each estuary. In gilthead seabream, saturated, monounsaturated, polyunsaturated and highly unsaturated fatty acids content were also influenced by the rearing site. Carbohydrate analysis showed a significant influence of the rearing site on free sugar and polysaccharide content in fish of both species, and there was no influence on the species' protein content. Differences in fatty acid and carbohydrate content among juvenile and adult stages were found for all the groups studied. The present study supported the existing evidence that semi-intensive rearing systems are subjected to the variability of extrinsic factors in the rearing sites, influencing the nutritional value of the same species, namely regarding lipid and carbohydrate profiles, depending on the production site. From a consumer's perspective, such differences may come as a disadvantage of the rearing method, as it is expected for a product to provide equal nutritional properties and benefits regardless its origin, especially within the same country.

Lower cadmium accumulation and higher antioxidative capacity in edible parts of Brassica campestris L . seedlings applied with glutathione under cadmium toxicity Abstract Glutathione (GSH) is involved in not only plant developmental processes but also plant responses to abiotic stresses. A hydroponic experiment was performed to explore the protective roles of exogenous GSH in mitigating cadmium (Cd) stress in Brassica campestris L. seedlings by analyzing the morphological and physiological parameters. Results showed that Cd caused severe growth inhibition and Cd accumulation. However, application of GSH significantly mitigated toxic symptoms induced by Cd, including the improvement of the photosynthesis-, plant growth-, and root morphology-related parameters in seedlings under Cd stress. These responses were associated with a striking increase in activities of representative antioxidative enzymes and contents of corresponding non-enzymatic antioxidants. In vivo imaging of O2.- and H2O2, and the detection of lipid peroxidation further demonstrated that increased ability by GSH for Brassica campestris L. seedlings to endure Cd stress was consistent with a striking elevation of ratios of reduced to oxidized glutathione (GSH/GSSG) and ascorbic acid to dehydroascorbic acid (AsA/DHA). Additionally, GSH application increased Cd retained in roots, thus significantly decreased its translocation from root to shoot, ultimately decreased Cd accumulation in shoots. Taken together, our results proved evidence for GSH in ameliorating Cd toxicity via reducing Cd accumulation in shoots and increasing oxidation resistance. Accordingly, application of GSH could be a high-efficiency and promising strategy to decrease Cd concentration in edible parts of Brassica campestris L. in agricultural production.

Highly efficient removal of Cr(VI) and Cu(II) by biochar derived from Artemisia argyi stem Abstract In this work, a novel biochar was prepared from the Artemisia argyi stem at 300 °C (AS300), 450 °C (AS450), and 600 °C (AS600). The structural properties of these biochars were characterized with various tools. The sorption kinetic processes of Cr(VI) and Cu(II) onto these biochars were better described by the pseudo-second order. The sorption isotherm processes of Cr(VI) onto these biochars were better described by the Freundlich model while the adsorption processes of Cu(II) were consistent with the Langmuir model. Batch sorption experiments showed that AS600 had the maximum adsorption capacity to Cr(VI) and Cu(II) with 161.92 and 155.96 mg/g, respectively. AS600 was selected for the follow-up batch and dynamic adsorption experiments. Results showed that AS600 had larger adsorption capacity for Cr(VI) at lower pH while the larger adsorption capacity for Cu(II) was found at higher pH. The effect of ionic strength on the adsorption of Cu(II) by AS600 was greater than that on the adsorption of Cr(VI). Dynamic adsorption experiments showed that Cu(II) had a higher affinity for the adsorption sites on the AS600 compared with Cr(VI). The adsorption mechanisms mainly involved electrostatic attraction, ion exchange, pore filling, and chemical bonding effect. Graphical abstract

Modulation of photosynthetic parameters, sugar metabolism, polyamine and ion contents by silicon amendments in wheat ( Triticum aestivum L.) seedlings exposed to arsenic Abstract The objective of the present investigation was to consider the effectiveness of exogenous silicate supplementation in reviving the arsenate imposed alterations on pigment content, Hill activity, photosynthetic parameters, sugar metabolism, polyamine, and ion contents in wheat (Triticum aestivum L. cv. PBW-343) seedlings. Experiments were conducted under different levels of arsenate (0, 25 μM, 50 μM, and 100 μM) in combination with silicate (0, 5 mM) in a hydroponic environment with modified Hoagland's solution for 21 days to determine the ameliorative role of silicon (Si). Arsenate exposure led to a decline in chlorophyll content by 28% and Hill activity by 30% on an average along with photosynthetic parameters. Activity of starch phosphorylase increased causing a subsequent decrease in starch contents by 26%. Degradation of starch enhanced sugar contents by 61% in the test cultivar. Dose-dependant increments in the activities of carbohydrate metabolizing enzymes viz., sucrose synthase, sucrose phosphate synthase, and acid invertase were also noted. Putrescine content was significantly enhanced along with a consequent decline in spermidine and spermine contents. The macro- and micronutrient contents declined proportionally with arsenate imposition. Conversely, silicate amendments irrespective of all arsenate concentrations brought about considerable alterations in all parameters tested with respect to arsenate treatment alone. Marked improvement in pigment content and Hill activity also improved the gas exchange parameters. Soluble sugar contents decreased and starch contents were enhanced. Increase in polyamine contents improved the ionic balance in the test cultivar as well. This study highlights the potentiality of silicon in ameliorating the ecotoxicological risks associated with arsenic pollution and the probable ability of silicon to offer an approach in mitigating arsenate-induced stress leading to restoration of growth and metabolism in wheat seedlings.

Study on the purification effect of aeration-enhanced horizontal subsurface-flow constructed wetland on polluted urban river water Abstract The issue of urban river pollution has attracted great attention due to high concentrations of ammonia nitrogen (NH4+-N) and low concentrations of dissolved oxygen (DO) in polluted water bodies. In order to investigate the effects of aeration-enhanced horizontal subsurface-flow constructed wetlands on polluted river water, unaerated aeration (NA), continuous aeration (CA), and intermittent aeration (IA) constructed wetlands were established. The purification effects of the wetland on various pollutants and the form of effluent nitrogen, influences of temperature on the removal rates of pollutants, the change of redox potential—oxidation reduction potential (ORP)—and the difference of dissolved oxygen (DO) between influent and effluent were investigated. The results indicated that aeration enhancement can improve the purification efficiencies of chemical oxygen demand (COD) and NH4+-N in constructed wetlands. The purification efficiencies of TN in IA and CA constructed wetlands were 91.9% and 53.7%, respectively, indicating that IA is the optimized aeration method for removal of various pollutants in wetlands. Changes of DO and ORP in effluent under IA and CA suggested improvement of aeration on the water environment. Meanwhile, DO was more sensitive to temperature compared with ORP. Additionally, a study of the nitrogen content in effluent suggested that the aeration method had a significant influence on the nitrogen content in effluent. The removal rates of both NH4+-N and TN degraded as the temperature dropped. The results also demonstrated that the removal rate of NH4+-N under aeration condition was more sensitive to temperature than that under NA condition and the effect of temperature on the removal rate of NH4+-N was greater than that of TN.

Nutritional and toxicity constraints of phytoplankton from a Brazilian reservoir to the fitness of cladoceran species Abstract Camorim is a small, eutrophic reservoir in Rio de Janeiro, Brazil, with a phytoplankton community dominated most of the year by the filamentous diatom Aulacoseira spp. and the toxic cyanobacterium Cylindrospermopsis raciborskii. As filamentous species can be a poor food for grazers, we hypothesize that phytoplankton from this reservoir would constrain cladoceran fitness due to nutritional limitation and/or toxicity when animals fed mixtures of cultured green algae and natural seston. Clones of different cladoceran species were exposed either to seston from Camorim reservoir sampled in different seasons or to a C. raciborskii strain (CYLCAM-2) isolated from the reservoir. In short-term assays, cladocerans were exposed to either 100% seston or mixtures of 50% seston added to green algae (200 μg C L−1), and their survivorship and somatic growth were measured for 4 days. In life table assays, neonates were exposed to the same seston treatments over 14 days and age at first reproduction, survivorship, fecundity, total offspring, and the intrinsic rate of natural increase (r) were assessed. In general, seston negatively affected cladoceran survivorship and fitness (r), but this response was seasonally and species specific. Stronger effects of CYLCAM-2 than those caused by seston on survivorship, somatic growth, and r were found for all cladoceran species, especially when the proportion of CYLCAM-2 was higher than 50% in relation to green algae in a fixed total food concentration. Our results suggest that both nutritional (C/P and morphology) and toxicity factors can act to impair cladoceran fitness and help explain the absence of cladocerans in Camorim reservoir.

Environmental improvement in the printing industry: the case study of self-adhesive labels Abstract Labels are used for marketing, technical information, local of production and environmental declarations of products. The aim of the study was to evaluate the life cycle of two sets of front and back adhesive labels made with different liners: polyethylene terephthalate (PET) and glassine paper. The study is a pioneering initiative in the labelling industry using life cycle assessment, especially in Brazil. The attributional life cycle assessment method was based on the ISO 14044 standard and covered the entire life cycle, cradle to grave. Primary data for key suppliers, printing facility and label use composed the foreground data, while the ecoinvent database composed the background data. The material efficiency was assessed through mass balance. The impact assessment methods were cumulative energy demand for non-renewable energy and ILCD 2011 midpoint for the environmental categories. The glassine liner is heavier than the PET which resulted in larger environmental indicator values for production, transportation and waste treatment. On the other hand, energy demand of label set with glassine liner was lower than the PET. Furthermore, the hotspot analysis of each impact category was presented per process and substance. The label set made with glassine liner tended to present larger environmental indicator values in most categories, 13 of the 16 assessed, compared to the label set made with PET liner, despite the uncertainties. Contribution analysis identified that the pre-manufacturing step presented larger environmental indicator values than manufacturing, use and post-use steps along the label set life cycle. Therefore, environmental improvement opportunities were evaluated through scenarios of end of life, recycled inputs, domestic suppliers, waste prevention and product redesign. Moreover, the life cycle assessment was useful for diagnosing the energy and environmental profiles of self-adhesive labels and planning cleaner production measures that avoid environmental tradeoffs.

Adsorption of pharmaceuticals from biologically treated municipal wastewater using paper mill sludge-based activated carbon Abstract A waste-based alternative activated carbon (AAC) was produced from paper mill sludge under optimized conditions. Aiming its application in tertiary wastewater treatment, AAC was used for the removal of carbamazepine, sulfamethoxazole, and paroxetine from biologically treated municipal wastewater. Kinetic and equilibrium adsorption experiments were run under batch operation conditions. For comparison purposes, they were also performed in ultrapure water and using a high-performance commercial AC (CAC). Adsorption kinetics was fast for the three pharmaceuticals and similar onto AAC and CAC in either wastewater or ultrapure water. However, matrix effects were observed in the equilibrium results, being more remarkable for AAC. These effects were evidenced by Langmuir maximum adsorption capacities (qm, mg g−1): for AAC, the lowest and highest qm were 194 ± 10 (SMX) and 287 ± 9 (PAR), in ultrapure water, and 47 ± 1 (SMX) and 407 ± 14 (PAR), in wastewater, while for CAC, the lowest and highest qm were 118 ± 7 (SMX) and 190 ± 16 (PAR) in ultrapure water and 123 ± 5 (SMX) and 160 ± 7 (CBZ) in wastewater. It was found that the matrix pH played a key role in these differences by controlling the surface electrostatic interactions between pharmaceutical and AC. Overall, it was evidenced the need of adsorption results in real matrices and demonstrated that AAC is a promising option to be implemented in tertiary wastewater treatments for pharmaceuticals' removal. Graphical abstract Production of an alternative activated carbon (AC) comparing favourably with a commercial AC in the removal of neutral and positive pharmaceuticals from wastewater