Environmental Sciences

News: Dr. Xing-Fang Li is awarded Canada Research Chair in Analytical Chemistry and Environmental Toxicology Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s):

Mercury bioaccumulation in fish in an artificial lake used to carry out cage culture Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Yongmin Wang, Qing Xie, Qinqin Xu, Jinping Xue, Cheng Zhang, Dingyong Wang Abstract As a global toxic pollutant, mercury (Hg) bioaccumulation within food chain could be influenced by human disturbance. Ten typical fish species were collected from Changshou Lake, an artificial lake used to carry out cage fish culture, to investigate the C/N isotopic compositions and Hg bioaccumulation in fish. The results showed that the total Hg (THg) and methylmercury (MeHg) levels in fish muscles ((56.03 ± 43.96) and (32.35 ± 29.57) ng/g, wet weight), comparable with those in most studies in China, were significantly lower than the international marketing limit (0.5 mg/kg). Past human input for cage culture in this lake led to abnormal 15N enrichment in food chain, as the quantitative trophic levels based on δ15N were different with that classified by feeding behaviors. This phenomenon subsequently demonstrated that it should be considered thoughtfully with respect to the application of the traditional method for understanding Hg bioaccumulation power by the slope of log10[Hg] with δ15N regression in specific water body (i.e., Changshou Lake). In addition, no significant linear correlation between Hg and body weight or length of some fish species was observed, suggesting that the fish growth in the eutrophic environment was disproportionate with Hg bioaccumulation, and fish length or weight was not the main factor affecting Hg transfer with food web. The occurrence of human disturbance in aquatic system presents a challenge to a better understanding of the Hg bioaccumulation and biomagnification within the food chain. Graphical abstract

The effect of interaction between Bacillus subtilis DBM and soil minerals on Cu(II) and Pb(II) adsorption Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Jun Bai, Yuanqing Chao, Yanmei Chen, Shizhong Wang, Rongliang Qiu Abstract The effects of interaction between Bacillus subtilis DBM and soil minerals on Cu(II) and Pb(II) adsorption were investigated. After combination with DBM, the Cu(II) and Pb(II) adsorption capacities of kaolinite and goethite improved compared with the application of the minerals independently. The modeling results of potentiometric titration data proved that the site concentrations of kaolinite and goethite increased by 80% and 30%, respectively after combination with DBM. However, the involvement of functional groups in the DBM/mineral combinations resulted in lower concentrations of observed sites than the theoretical values and led to the enhancement of desorption rates by NH4NO3 and EDTA-Na2. The DBM-mineral complexes might also help to prevent heavy metals from entering DBM cells to improve the survivability of DBM in heavy metal-contaminated environments. During the combination process, the extracellular proteins of DBM provided more binding sites for the minerals to absorb Cu(II) and Pb(II). In particular, an especially stable complexation site was formed between goethite and phosphodiester bonds from EPS to enhance the Pb(II) adsorption capacity. So, we can conclude that the DBM–mineral complexes could improve the Cu(II) and Pb(II) adsorption capacities of minerals and protect DBM in heavy metal-contaminated environments. Graphical abstract

Enhanced removal of organic matter and typical disinfection byproduct precursors in combined iron–carbon micro electrolysis-UBAF process for drinking water pre-treatment Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Yinghan Chen, Tao Lin, Wei Chen Abstract The organic matter and two types of disinfection byproduct (DBP) precursors in micro-polluted source water were removed using an iron–carbon micro-electrolysis (ICME) combined with up-flow biological aerated filter (UBAF) process. Two pilot-scale experiments (ICME-UBAF and UBAF alone) were used to investigate the effect of the ICME system on the removal of organic matter and DBP precursors. The results showed that ICME pretreatment removed 15.6% of dissolved organic matter (DOM) and significantly improved the removal rate in the subsequent UBAF process. The ICME system removed 31% of trichloromethane (TCM) precursors and 20% of dichloroacetonitrile (DCAN) precursors. The results of measurements of the molecular weight distribution and hydrophilic fractions of DOM and DBP precursors showed that ICME pretreatment played a key role in breaking large-molecular-weight organic matter into low-molecular-weight components, and the hydrophobic fraction into hydrophilic compounds, which was favorable for subsequent biodegradation by UBAF. Three-dimensional fluorescence spectroscopy (3D-EEM) further indicated that the ICME system improved the removal of TCM and DCAN precursors. The biomass analysis indicated the presence of a larger and more diverse microbial community in the ICME-UBAF system than for the UBAF alone. The high-throughput sequencing results revealed that domination of the genera Sphingomonas, Brevundimonas and Sphingorhabdus contributed to the better removal of organic matter and two types of DBP precursors. Also, Nitrosomonas and Pseudomonas were beneficial for ammonia removal. Graphical abstract

Investigation of adsorption/desorption behavior of Cr(VI) at the presence of inorganic and organic substance in membrane capacitive deionization (MCDI) Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Lin Chen, Chengyi Wang, Shanshan Liu, Liang Zhu Abstract The adsorption and desorption behavior of Cr(VI) in membrane capacitive deionization (MCDI) was investigated systematically in the presence of bovine serum albumin (BSA) and KCl with different concentrations, respectively. Results revealed that Cr(VI) absorption was enhanced and the adsorption amount for Cr(VI) increased from 155.7 to 190.8 mg/g when KCl concentration increased from 100 to 200 mg/L in the adsorption process, which was attributed to the stronger driving force. However, the adsorption amount sharply decreased to 90.2 mg/g when KCl concentration reached up to 1000 mg/L suggesting the negative effect for Cr(VI) removal that high KCl concentration had. As for the effect of BSA on ion adsorption, the amount for Cr (VI) significantly declined to 78.3 mg/g and pH was found to be an important factor contributing to this significant reduction. Then, the desorption performance was also conducted and it was obtained that the presence of KCl had negligible effect on Cr(VI) desorption, while promoted by the addition of BSA. The incomplete desorption was obtained and the residual chromium ions onto the electrode after desorption was detected via energy-dispersive X-ray spectroscopy (EDS). Based on above analysis, the enhanced removal mechanism for Cr(VI) in MCDI was found to be consisted of ion adsorption onto electrode surface, the redox reaction of Cr(VI) into Cr(III) and precipitation, which was demonstrated by X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM). Graphical abstract

A monitoring-modeling approach to SO42 − and NO3− secondary conversion ratio estimation during haze periods in Beijing, China Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Xiaoqi Wang, Wei Wei, Shuiyuan Cheng, Chong Zhang, Wenjiao Duan Abstract SO42 − and NO3− are important chemical components of fine particulate matter (PM2.5), especially during haze periods. This study selected two haze episodes in Beijing, China with similar meteorological conditions. A monitoring-modeling approach was developed to estimate the secondary conversion ratios of sulfur and nitrogen based on monitored and simulated concentrations. Measurements showed that in Episode 1 (24th–25th October, 2014), the concentrations (proportions) of SO42 − and NO3− reached 35.1 μg/m3 (14.9%) and 55.0 μg/m3 (22.9%), while they reached 14.4 μg/m3 (9.3%) and 59.1 μg/m3 (38.1%) in Episode 2 (26th–27th October, 2017). A modeling system was applied to apportion Beijing's SO42 − and NO3− in primary and secondary SO42 −/NO3− emitted from local and regional sources. Thus, secondary conversion contributions considering the local and regional level were defined. The former primarily focused on Beijing atmospheric oxidation ability and the latter mainly considered the existence form of Beijing SO42 −/NO3− under the regional transport impacts. Finally, secondary oxidation ratios were estimated through combining secondary conversion contribution coefficients for simulated and monitored concentrations. At regional level, sulfur oxidation ratios in polluted (clean) days during two sampling periods were 0.57–0.72 (0.07–0.52) and 0.74–0.80 (0.08–0.61), nitrogen oxidation ratios were 0.20–0.29 (0.05–0.15) and 0.34–0.38 (0.02–0.29), indicating that atmospheric oxidation was enhanced when considering regional transport through 2014–2017. At the local level, sulfur oxidation ratios were 0.66–0.71 (0.04–0.48) in haze (clean) days, while nitrogen oxidation ratios were 0.16–0.29 (0.02–0.16). The atmospheric oxidation ability markedly increased in PM2.5 pollution days, but changed only slightly between the two periods. Graphical abstract

Removal of cyanide adsorbed on pyrite by H2O2 oxidation under alkaline conditions Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Yubo Tu, Peiwei Han, Lianqi Wei, Xiaomeng Zhang, Bo Yu, Peng Qian, Shufeng Ye Abstract Large amounts of cyanide tailings are produced during the cyanidation process in gold extraction, which are hazardous solid wastes due to the toxic cyanide. Pyrite is one of the main minerals in cyanide tailings. The removal of cyanide adsorbed on pyrite by H2O2 oxidation under alkaline conditions was investigated in this study. It was found that the removal efficiency was positively correlated with pH from 5 to 12, but remained almost constant when pH was higher than 12. The highest cyanide removal efficiency of 91.10% was achieved by adding no less than 0.6 wt.% of H2O2. Cyanide removal was positively correlated with the CN− adsorption amount between 1.06 and 8.5 mg/g, and temperature between 25 and 85°C. The removal of cyanide adsorbed on pyrite by H2O2 oxidation under alkaline conditions was due to the oxidation of pyrite. Hexacyanoferrate, thiocyanate and sulfate were generated with mole ratios of about 2.03:1.12:3.17 during the cyanide removal. Graphical abstract

Changes in distribution and microstructure of bauxite residue aggregates following amendments addition Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Shengguo Xue, Yuzhen Ye, Feng Zhu, Qiongli Wang, Jun Jiang, William Hartley Abstract Bauxite residue is a highly alkaline byproduct which is routinely discarded at residue disposal areas. Improving soil formation process to revegetate the special degraded lands is a promising strategy for sustainable management of the refining industry. A laboratory incubation experiment was used to evaluate the effects of gypsum and vermicompost on stable aggregate formation of bauxite residue. Aggregate size distribution was quantified by fractal theory, whilst residue microstructure was determined by scanning electron microscopy and synchrotron-based X-ray micro-computed tomography. Amendments addition increased the content of macro-aggregates (> 250 μm) and enhanced aggregate stability of bauxite residue. Following gypsum and vermicompost addition, fractal dimension decreased from 2.84 to 2.77, which indicated a more homogeneous distribution of aggregate particles. Images from scanning electron microscopy and three-dimensional microstructure demonstrated that amendments stimulate the formation of improved structure in residue aggregates. Pore parameters including porosity, pore throat surface area, path length, and path tortuosity increased under amendment additions. Changes in aggregate size distribution and microstructure of bauxite residue indicated that additions of gypsum and vermicompost were beneficial to physical condition of bauxite residue which may enhance the ease of vegetation. Graphical abstract

Removal characteristics of microplastics by Fe-based coagulants during drinking water treatment Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Baiwen Ma, Wenjing Xue, Yanyan Ding, Chengzhi Hu, Huijuan Liu, Jiuhui Qu Abstract Microplastics have caused great concern worldwide recently due to their ubiquitous presence within the marine environment. Up to now, most attention has been paid to their sources, distributions, measurement methods, and especially their eco-toxicological effects. With microplastics being increasingly detected in freshwater, it is urgently necessary to evaluate their behaviors during coagulation and ultrafiltration (UF) processes. Herein, the removal behavior of polyethylene (PE), which is easily suspended in water and is the main component of microplastics, was investigated with commonly used Fe-based salts. Results showed that although higher removal efficiency was induced for smaller PE particles, low PE removal efficiency (below 15%) was observed using the traditional coagulation process, and was little influenced by water characteristics. In comparison to solution pH, PAM addition played a more important role in increasing the removal efficiency, especially anionic PAM at high dosage (with efficiency up to 90.9%). The main reason was ascribed to the dense floc formation and high adsorption ability because of the positively charged Fe-based flocs under neutral conditions. For ultrafiltration, although PE particles could be completely rejected, slight membrane fouling was caused owing to their large particle size. The membrane flux decreased after coagulation; however, the membrane fouling was less severe than that induced by flocs alone due to the heterogeneous nature of the cake layer caused by PE, even at high dosages of Fe-based salts. Based on the behavior exhibited during coagulation and ultrafiltration, we believe these findings will have potential application in drinking water treatment. Graphical abstract

Iron toxicity resistance strategies in tropical grasses: The role of apoplastic radicular barriers Publication date: April 2019 Source: Journal of Environmental Sciences, Volume 78 Author(s): Advanio Inácio Siqueira-Silva, Camilla Oliveira Rios, Eduardo Gusmão Pereira Abstract The revegetation of mined areas poses a great challenge to the iron ore mining industry. The initial recovery process in degraded areas might rely on the use of Fe-resistant grasses. Tropical grasses, such as Paspalum densum and Echinochloa crus-galli, show different resistance strategies to iron toxicity; however, these mechanisms are poorly understood. The Fe-resistance mechanisms and direct iron toxicity as a function of root apex removal were investigated. To achieve this purpose, both grass species were grown for up to 480 hr in a nutrient solution containing 0.019 or 7 mmol/L Fe-EDTA after the root apices had been removed or maintained. Cultivation in the presence of excess iron-induced leaf bronzing and the formation of iron plaque on the root surfaces of both grass species, but was more significant on those plants whose root apex had been removed. Iron accumulation was higher in the roots, but reached phytotoxic levels in the aerial parts as well. It did not hinder the biosynthesis of chloroplastidic pigments. No significant changes in gas exchange and chlorophyll afluorescence occurred in either grass when their roots were kept intact; the contrary was true for plants with excised root apices. In both studied grasses, the root apoplastic barriers had an important function in the restriction of iron translocation from the root to the aerial plant parts, especially in E. crus-galli. Root apex removal negatively influenced the iron toxicity resistance mechanisms (tolerance in P. densum and avoidance in E. crus-galli). Graphical abstract

Surgery

ORIGINAL ARTICLES
	Surgical treatment of noncaustic benign esophageal stenosis	p. 1
	Ming-Ho Wu, Han-Yun Wu DOI:10.4103/fjs.fjs_19_18   Background: Noncaustic benign esophageal stenosis is an uncommon esophageal disorder. We report herein our surgical results for this type of esophageal stenosis. Materials and Methods: A retrospective review of 30 patients presenting with noncaustic benign esophageal stenosis between June 2009 and February 2018 was conducted. Patient demographics, preoperative diagnoses, treatment strategies, surgical procedures, and the postoperative course of treatment were investigated. Results: No hospital death occurred. Four (13.3%) patients had operative complications, namely, one incident of a duodenal bleeding ulcer, one incident of respiratory failure, and two incidents of wound infections. One patient with primary achalasia required a second myotomy 5 months after initial surgery. All other patients resumed a regular diet after surgery. Conclusion: Delayed diagnosis and treatment of noncaustic benign esophageal stenosis are common. The surgical approach depends on the location and nature of the esophageal disease. Quality of life of patients can be enhanced through careful surgery.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Minimally invasive removal of mediastinal ectopic parathyroid glands: A single-center experience	p. 6
	Pin-Li Chou, Yin-Kai Chao, Yun-Hen Liu DOI:10.4103/fjs.fjs_33_18   Background: The last few years have seen the emergence of minimally invasive mediastinal parathyroidectomy. Here, we report our single-center experience with this procedure. Materials and Methods: Between December 2002 and September 2017, we performed minimally invasive mediastinal parathyroidectomy in 12 patients with primary (n = 4) or secondary (n = 8) hyperparathyroidism (median age: 54.5 years; interquartile range: 50.5 − 62.75 years). The following variables were retrospectively collected from clinical records: demographic characteristics, results of imaging studies, surgical approach, complications, and final pathological diagnosis.Results: Technetium-99 m sestamibi examinations were performed for preoperative localization of the ectopic parathyroid glands in 11 patients (91.67%). All cases successfully underwent minimally invasive mediastinal parathyroidectomy, without the necessity to convert to open surgery. The most commonly used minimally invasive approach was video-assisted thoracoscopic surgery (n = 10; 83.33%) followed by mediastinoscopy (n = 2; 16.67%). The anatomical locations of the ectopic glands were as follows: intrathymic in six patients (50%), within the aortopulmonary window in 1 patient (8%), and in other intrathoracic sites in five patients (42%). Parathyroid adenomas and parathyroid hyperplasias were diagnosed in 5 (42%) and seven patients (58%), respectively. There were no perioperative deaths, and the median length of hospital stay was 5.5 days.Conclusion: Minimally invasive removal of mediastinal ectopic parathyroid glands is safe and feasible if their anatomical position is accurately determined. Surgical approaches depend on gland location and the surgeon's preference.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Management of tailgut cysts in a single institute in Taiwan	p. 11
	Yu-Zu Lin, Wen-Yih Liang, Hung-Hsin Lin, Chun-Chi Lin, Jeng-Kai Jiang, Sheng-Chieh Huang DOI:10.4103/fjs.fjs_61_18   Background: Tailgut cysts are rare congenital lesions that are generally located in the retrorectal regions. We performed a cases series in Taiwan to compare with others. Materials and Methods: The demographics, clinical presentation, surgical management, pathological features, and long-term outcome of 14 patients of tailgut cysts diagnosed at Taipei Veterans General Hospital from 1989 to 2018 were reviewed. Results: In this series, 11 patients (78.6%) were female with the mean age of 46.7 (18–75) years. The majority of cases (83.3%) were symptomatic with variable manifestations. All patients received radiological examination and/or endoscopy. One case underwent biopsy before the therapy. Surgical methods included Kraske, transanal, abdominal, and combined approaches. Tailgut cysts were benign in ten patients (71.4%) and malignancy included mixed adenoneuroendocrine carcinoma, carcinoid tumor, and borderline mucinous tumor. No long-term adverse effect was reported. There was no recurrence of benign tailgut cysts during the median follow-up of 3 years.Conclusion: Tailgut cysts are uncommon and diagnosed predominantly in the middle-aged female. They can present with variable clinical manifestations, and diagnosis relies on image study. A routine preoperative biopsy is not indicated as it can be uninformative or false negative. Complete surgical excision is recommended even in asymptomatic cases for definite diagnosis and the possibility of malignant transformation. A variety of surgical approaches can achieve complete surgical removal and avoid recurrence if being planned ahead by image carefully.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Prophylatic efficacy of dexamethasone, ketamine and dexmedetomidine against intra- and postoperative nausea and vomiting under spinal anesthesia	p. 17
	Hesameddin Modir, Esmail Moshiri, Alireza Kamali, Maryam Shokrpour, Nilufar Shams DOI:10.4103/fjs.fjs_37_18   Background: This study aims to compare the prophylactic effects of dexamethasone, ketamine, and dexmedetomidine versus normal saline on intra- and postoperative nausea and vomiting (PONV) associated with cesarean section (CS) under spinal anesthesia. Materials and Methods: A double-blind prospective clinical trial was performed on 140 patients scheduled for elective CS and was assigned randomly to four groups. The first group received 20 cc normal saline; the second group received dexamethasone at a dose of 0.1 mg/kg; the third group received ketamine at a dose of 0.5 mg/kg; and the fourth group received IV dexmedetomidine (1 μg/kg). Nausea and vomiting score was measured by visual analog scale and sedation levels by Ramsay sedation scale (RSS). Results: There was a significant difference among the four groups in PONV scores immediately after and 1, 2, 3, and 4 h following administration of the drug (P = 0.001). Nausea and vomiting score was the lowest in the dexmedetomidine group. Significant differences were observed in Ramsey score at the 10th–110th min following administration, and the dexmedetomidine group had a higher RSS than the other groups. The incidence of metoclopramide intervention in three experimental groups is comparable. Heart rate (HR) and mean blood pressure show decreasing trend following spinal anesthesia in dexmedetomidine group. Conclusion: The tested groups (dexamethasone, dexmedetomidine, and ketamine) all present a lower incidence of nausea and vomiting than the placebo group. In addition, dexmedetomidine provides the best efficacies in the reduction of nausea and vomiting but is more liable in lowering blood pressure and HRs. We recommend that dexmedetomidine is the drug of choice in decreasing nausea and vomiting for patients undergoing CS with spinal anesthesia.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
CASE REPORTS
	Neglected giant dermatofibrosarcoma protuberans	p. 24
	Gautam Prakash, Manojit Midya, Pankaj Sharma, Rakesh K Jain DOI:10.4103/fjs.fjs_57_18   Dermatofibrosarcoma protuberans (DFSP) is a rare, slow growing, intermediate to low grade malignant soft tissue neoplasm originating from the dermal layer of the skin. Scalp DFSP is even a rarer entity occurring at less than 1% of all DFSP. We recently encountered a massive DFSP on the scalp which presented to us in the emergency settings with acute bleeding. This was successfully managed by wide local excision of the tumour. This case is remarkable due to the large size of tumour on the rather rare site on the scalp presenting unusually as acute bleeding and its successful management with wide local excision as a life saving procedure.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Metastatic lung neuroendocrine carcinoma presenting as a breast lump	p. 28
	Tai-Chien Huang, Wan-Yi Kang, Shu-Yi Tsao, Yu-Lin Chang DOI:10.4103/fjs.fjs_55_18   This case is a 78-year-old woman with hypertension, diabetes mellitus, cardiovascular disease, valvular heart failure and hepatitis C. She presented to outpatient department for her right breast lump. The pathology of the core biopsy under breast sonography showed carcinoma with neuroendocrine features. Its immunohistochemical study showed negative for estrogen receptor (ER), progesterone Receptor (PR), HER2/neu and GATA-3, and positive for chromogranin A, synaptophysin, and TTF-1. A staging workup was then performed. The computed tomography (CT) of chest and abdomen revealed another mass in the left lung. CT-guided biopsy was done for the lung mass. According to the results of immunostains, a primary lung large cell neuroendocrine carcinoma (LCNEC) with breast metastasis was diagnosed. The patient received chemotherapy with etoposide and carboplatin for 6 cycles. The CT performed 3 and 5 months later showed that the response of the tumors was stable.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Primary small gut lymphoma presenting as an incarcerated inguinal hernia in an adult	p. 33
	Prosanta Kumar Bhattacharjee, Amitabha Sarkar, Somnath Biswas, Tanvi Goel DOI:10.4103/fjs.fjs_70_18   A 73-year-male presented with features of subacute small gut obstruction of 10 days duration. He also complained of a painless, slowly enlarging swelling in the right groin, which was first noticed 10 years ago. There was a history of weight loss, anorexia, and asthenia but no history of fever, respiratory, or urinary symptoms. He was a smoker and was on medication for hypertension and type 2 diabetes mellitus. The general health of the patient was poor. He appeared pale and dehydrated. No lymphadenopathy was evident on the general survey. The abdomen was distended, tense with hyperactive bowel sounds. Examination of the groin and genitalia revealed right inguinal hernia and an irreducible, firm, solid, nontender, 6 cm × 5 cm scrotal mass separate from the right testis. Digital rectal examination revealed no abnormality. Contrast-enhanced computed tomography of the abdomen showed dilated gut loops, right inguinal hernia, and a gut related endophytic soft-tissue mass in the scrotum. Exploration after resuscitation revealed a firm, endoluminal soft-tissue mass arising from the apex of the herniated loop of the small gut which was obliterating its lumen. The tumor-bearing segment of the gut was resected through a groin incision. We then performed a laparotomy to bring out the ends of the bowel loops as double barrel ileostomy. The hernial defect was then repaired. Postoperative recovery was uneventful. Histopathology of the excised specimen suggested the possibility of Non-Hodgkin's lymphoma of small gut. Immunohistochemistry confirmed it to be low-grade follicular B-cell NHL.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
SHORT COMMUNICATIONS
	Low-tidal-volume ventilation for recipients of lung transplant: Ready for clinical use?	p. 37
	Manijeh Yousefi Moghadam DOI:10.4103/fjs.fjs_35_18
	[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta

Immunogenetics

Biology, evolution, and history of antigen processing and presentation: Immunogenetics special issue 2019

Class I transactivator, NLRC5: a central player in the MHC class I pathway and cancer immune surveillance Abstract Major histocompatibility complex (MHC) class I and class II molecules play critical roles in the activation of the adaptive immune system by presenting antigens to CD8+ and CD4+ T cells, respectively. Although it has been well known that CIITA (MHC class II transactivator), an NLR (nucleotide-binding domain, leucine-rich-repeat containing) protein, as a master regulator of MHC class II gene expression, the mechanism of MHC class I gene transactivation was unclear. Recently, another NLR protein, NLRC5 (NLR family, CARD domain-containing 5), was identified as an MHC class I transactivator (CITA). NLRC5 is a critical regulator for the transcriptional activation of MHC class I genes and other genes involved in the MHC class I antigen presentation pathway. CITA/NLRC5 plays a crucial role in human cancer immunity through the recruitment and activation of tumor killing CD8+ T cells. Here, we discuss the molecular function and mechanism of CITA/NLRC5 in the MHC class I pathway and its role in cancer.

Genetics of antigen processing and presentation Abstract Immune response to disease requires coordinated expression of an army of molecules. The highly polymorphic MHC class I and class II molecules are key to control of specificity of antigen presentation. Processing of the antigen, to peptides or other moieties, requires other sets of molecules. For classical class I, this includes TAP peptide transporters, proteasome components and Tapasin, genes which are encoded within the MHC. Similarly, HLA-DO and -DM, which influence presentation by HLA class II molecules, are encoded in the MHC region. Analysis of MHC mutants, including point mutations and large deletions, has been central to understanding the roles of these genes. Mouse genetics has also played a major role. Many other genes have been identified including those controlling expression of HLA class I and class II at the transcriptional level. Another genetic approach that has provided insight has been the analysis of microorganisms, including viruses and bacteria that escape immune recognition by blocking these antigen processing and presentation pathways. Here, we provide a brief history of the genetic approaches, both traditional and modern, that have been used in the quest to understand antigen processing and presentation.

MHC class II fine tuning by ubiquitination: lesson from MARCHs Abstract Ubiquitination, a posttranscriptional modification, has been known to contribute to many aspects of cellular event (e.g., protein quality control, signal transduction). In 2007 and 2016, we reported physiological E3 ubiquitin ligases for MHC class II; these are membrane-associated ring-CH-type finger (MARCH)-1 and MARCH-8. Importantly, MARCH-1 and -8 are structurally close to each other, but have different expression profiles. MARCH-1 and -8 are expressed at secondary lymphoid organs and thymic epithelial cells, respectively. These findings suggest contribution of MARCHs to immunological disorders in human; however, its contribution remains to be elucidated. In this review, recent progress on MARCHs will be summarized from molecular and/or immunological point of view and future direction would be discussed.

Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire Abstract The lifespan of T cells is determined by continuous interactions of their T cell receptors (TCR) with self-peptide-MHC (self-pMHC) complexes presented by different subsets of antigen-presenting cells (APC). In the thymus, developing thymocytes are positively selected through recognition of self-pMHC presented by cortical thymic epithelial cells (cTEC). They are subsequently negatively selected by medullary thymic epithelial cells (mTEC) or thymic dendritic cells (DC) presenting self-pMHC complexes. In the periphery, the homeostasis of mature T cells is likewise controlled by the interaction of their TCR with self-pMHC complexes presented by lymph node stromal cells while they may be tolerized by DC presenting tissue-derived self-antigens. To perform these tasks, the different subsets of APC are equipped with distinct combination of antigen processing enzymes and consequently present specific repertoire of self-peptides. Here, we discuss one such antigen processing enzyme, the thymus-specific serine protease (TSSP), which is predominantly expressed by thymic stromal cells. In thymic DC and TEC, TSSP edits the repertoire of peptide presented by class II molecules and thus shapes the CD4 T cell repertoire.

What to do with HLA-DO/H-2O two decades later? Abstract The main objective of antigen processing is to orchestrate the selection of immunodominant epitopes for recognition by CD4 T cells. To achieve this, MHC class II molecules have evolved with a flexible peptide-binding groove in need of a bound peptide. Newly synthesized MHC-II molecules bind a class II invariant chain (Ii) upon synthesis and are shuttled to a specialized compartment, where they encounter exogenous antigens. Ii serves multiple functions, one of which is to maintain the shape of the MHC-II groove so that it can readily bind exogenous antigens upon dissociation of the Ii peptide in MHC- II compartment. MIIC contains processing enzymes, one or both accessory molecules, HLA-DM/H2-M (DM) and HLA-DO/H2-O (DO), and optimal denaturing conditions. In a process known as "editing," DM facilitates the dissociation of the invariant chain peptide, CLIP, for exchange with exogenous antigens. Despite the availability of mechanistic insights into DM functions, understanding how DO contributes to epitope selection has proven to be more challenging. The current dogma assumes that DO inhibits DM, whereas an opposing model suggests that DO fine-tunes the epitope selection process. Understanding which of these, or potentially other models of DO function is important, as DO variants have been linked to autoimmunity, cancer, and the generation of broadly neutralizing antibodies to viruses. This review therefore attempts to evaluate experimental evidence in support of these hypotheses, with an emphasis on the less discussed model, and to explore intriguing questions about the importance of DO in biology.

Origin and evolution of the specialized forms of proteasomes involved in antigen presentation Abstract Proteasomes are a multi-subunit protease complex that produces peptides bound by major histocompatibility complex (MHC) class I molecules. Phylogenetic studies indicate that two specialized forms of proteasomes, immunoproteasomes and thymoproteasomes, and the proteasome activator PA28αβ emerged in a common ancestor of jawed vertebrates which acquired adaptive immunity based on the MHC, T cell receptors, and B cell receptors ~ 500 million years ago. Comparative genomics studies now provide strong evidence that the genes coding for the immunoproteasome subunits emerged by genome-wide duplication. On the other hand, the gene encoding the thymoproteasome subunit β5t emerged by tandem duplication from the gene coding for the β5 subunit. Strikingly, birds lack immunoproteasomes, thymoproteasomes, and the proteasome activator PA28αβ, raising an interesting question of whether they have evolved any compensatory mechanisms.

Ancient features of the MHC class II presentation pathway, and a model for the possible origin of MHC molecules Abstract Major histocompatibility complex (MHC) molecules are only found in jawed vertebrates and not in more primitive species. MHC class II type structures likely represent the ancestral structure of MHC molecules. Efficient MHC class II transport to endosomal compartments depends on association with a specialized chaperone, the MHC class II invariant chain (aliases Ii or CD74). The present study identifies conserved motifs in the CLIP region of CD74 molecules, used for binding in the MHC class II binding groove, throughout jawed vertebrates. Peculiarly, in CD74a molecules of Ostariophysi, a fish clade including for example Mexican tetra and zebrafish, the CLIP region has duplicated. In mammals, in endosomal compartments, the peptide-free form of classical MHC class II is stabilized by binding to nonclassical MHC class II "DM," a process that participates in "peptide editing" (selection for high affinity peptides). Hitherto, DM-lineage genes had only been reported from the level of amphibians, but the present study reveals the existence of DMA and DMB genes in lungfish. This is the first study which details how classical and DM lineage molecules have distinguishing glycine-rich motifs in their transmembrane regions. In addition, based on extant MHC class II structures and functions, the present study proposes a model for early MHC evolution, in which, in an ancestral jawed vertebrate, the ancestral MHC molecule derived from a heavy-chain-only antibody type molecule that cycled between the cell surface and endosomal compartments.

Class II MHC antigen processing in immune tolerance and inflammation Abstract Presentation of peptide antigens by MHC-II proteins is prerequisite to effective CD4 T cell tolerance to self and to recognition of foreign antigens. Antigen uptake and processing pathways as well as expression of the peptide exchange factors HLA-DM and HLA-DO differ among the various professional and non-professional antigen-presenting cells and are modulated by cell developmental state and activation. Recent studies have highlighted the importance of these cell-specific factors in controlling the source and breadth of peptides presented by MHC-II under different conditions. During inflammation, increased presentation of selected self-peptides has implications for maintenance of peripheral tolerance and autoimmunity.

A personal retrospective on the mechanisms of antigen processing Abstract My intention here is to describe the history of the molecular aspects of the antigen processing field from a personal perspective, beginning with the early identification of the species that we now know as MHC class I and MHC class II molecules, to the recognition that their stable surface expression and detection by T cells depends on peptide association, and to the unraveling of the biochemical and cell biological mechanisms that regulate peptide binding. One goal is to highlight the role that serendipity or, more colloquially, pure blind luck can play in advancing the research enterprise when it is combined with an appropriately receptive mind. This is not intended to be an overarching review, and because of my own work I focus primarily on studies of the human MHC. This means that I neglect the work of many other individuals who made advances in other species, particularly those who produced the many knockout mouse strains used to demonstrate the importance of the antigen processing machinery for initiating immune responses. I apologize in advance to colleagues around the globe whose contributions I deal with inadequately for these reasons, and to those whose foundational work is now firmly established in text books and therefore not cited. So many individuals have worked to advance the field that giving all of them the credit they deserve is almost impossible. I have attempted, while focusing on work from my own laboratory, to point out contemporaneous or sometimes earlier advances made by others. Much of the success of my own laboratory came because we simultaneously worked on both the MHC class I and class II systems and used the findings in one area to inform the other, but mainly it depended on the extraordinary group of students and fellows who have worked on these projects over the years. To those who worked in other areas who are not mentioned here, rest assured that I appreciate your efforts just as much.

Pediatric Drugs : Pancreatic Enzyme Supplementation in Patients with Atopic Dermatitis and Food Allergies,Serious Adverse Events Associated with Off-Label Use of Azithromycin or Fentanyl,Neuropathic Pain in Pediatric Oncology,Pharmacotherapeutic Management of Wilms Tumor,,Treatment of Down Syndrome Arthropathy,Treatment of Childhood Absence Epilepsy,Cortisol Replacement Therapy,Changes in Hemoglobin Concentrations Post-immunoglobulin Therapy in Patients with Kawasaki Disease

Neuropathic Pain in Pediatric Oncology: A Clinical Decision Algorithm Abstract Neuropathic pain in pediatric oncology can be caused by distinct lesions or disease processes affecting the somatosensory system, including chemotherapy-related neuronal injury, solid tumor-related involvement of neural structures, post-surgical neuropathic pain—including phantom limb pain and pain after limb-sparing surgery—and the complex circumstances of neuropathic pain at the end of life. Treatment algorithms reflect the general treatment principles applied for adult neuropathic pain, but the dose regimens applied in children are modest and rarely escalated to the maximum doses to optimize analgesic efficacy. Pharmacological management of neuropathic pain should be based on a stepwise intervention strategy, as combinations of medications are the most effective approach. Gabapentinoids and tricyclic antidepressants are recommended as first-line therapy. Methadone, ketamine, and lidocaine may be useful adjuvants in selected patients. Prospective studies extended over a substantial length of time are recommended because of the nature of neuropathic pain as persistent, chronic pain and based on the need for sufficient time to escalate medication dose regimens to full analgesic efficacy.

Pharmacotherapeutic Management of Wilms Tumor: An Update Abstract Although differences exist in treatment and risk-stratification strategies for children with Wilms tumor (WT) between the European [International Society of Paediatric Oncology (SIOP)] and American [Children's Oncology Group (COG)] study groups, outcomes are very similar, with an overall survival of > 85%. Future strategies aim to de-intensify treatment and reduce toxicity for children with a low risk of relapse and intensify treatment for children with high-risk disease. For metastatic WT, response of lung nodules to chemotherapy is used as a marker to modify treatment intensity. For recurrent WT, a unified approach based on the use of agents that were not used for primary therapy is being introduced. Irinotecan is being explored as a new strategy in both metastatic and relapsed WT. Introduction of biology-driven approaches to risk stratification and new drug treatments has been slower in WT than in some other childhood cancers. While several new biological pathways have been identified recently in WT, their individual rarity has hampered their translation into clinical utility. Identification of robust prognostic factors requires extensive international collaborative studies because of the low proportion who relapse or die. Molecular profiling studies are in progress that should ultimately improve both risk classification and signposting to more targeted therapies for the small group for whom current therapies fail. Accrual of patients with WT to early-phase trials has been low, and the efficacy of these new agents has so far been very disappointing. Better in vitro model systems to test mechanistic dependence are needed so available new agents can be more rationally prioritized for recruitment of children with WT to early-phase trials.

Pancreatic Enzyme Supplementation in Patients with Atopic Dermatitis and Food Allergies: An Open-Label Pilot Study Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects both patients and their families. Current therapies often alleviate symptoms but do not prevent or eradicate the disease. Objectives Our objective was to determine whether pancreatic enzyme supplementation is an effective and safe treatment in refractory pediatric AD associated with food allergies. Methods We conducted an open-label pilot study using a case–control design. Patients with severe AD and known food allergies refractory to conventional therapies and exclusion diets were recruited and treated for 6 weeks with oral supplementation of pancreatic enzymes. The primary endpoint was the severity of AD, using the Scoring Atopic Dermatitis (SCORAD) index. Secondary measures included markers of intestinal permeability (urinary sucrose and lactulose/mannitol excretion). Results A total of 11 patients met all eligibility criteria and completed the trial. Significant improvement in AD was observed after 6 weeks of pancreatic enzyme supplementation (SCORAD index 52.3 ± 5.5 vs. 34.6 ± 7.6; p = 0.0008). Beneficial effect was observed in 9 of 11 patients, without adverse events. Fractional urinary sucrose excretion improved to a level comparable to that of age-matched controls (p < 0.05). However, urinary lactulose:mannitol ratios remained abnormally high compared with those of controls (p = 0.01). Conclusions Pancreatic enzyme supplementation was associated with improved AD and gastroduodenal permeability. Additional randomized placebo-controlled studies are required before this treatment can be recommended in this clinical setting.

Serious Adverse Events Associated with Off-Label Use of Azithromycin or Fentanyl in Children in Intensive Care Units: A Retrospective Chart Review Abstract Objectives Half of prescription drugs commonly given to children lack product labeling on pediatric safety, efficacy, and dosing. Two drugs most widely used off-label in pediatrics are azithromycin and fentanyl. We sought to determine the risk of serious adverse events (SAEs) when oral azithromycin or intravenous/intramuscular fentanyl are used off-label compared to on-label in pediatric intensive care units (ICUs). Study Design Six pediatric hospitals participated in a retrospective chart review of patients administered oral azithromycin (n = 241) or intravenous/intramuscular fentanyl (n = 367) between January 5, 2013 and December 26, 2014. Outcomes were SAEs by drug and labeling status: off-label compared to on-label by Food and Drug Administration (FDA)-approved age and/or indication. Statistical analysis was performed using logistic regression to estimate odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs). Results Twenty-one (9%) children receiving azithromycin experienced SAEs. Off-label use of azithromycin was not associated with a higher risk of SAE (OR 0.87, 95% CI 0.27–2.71, p = 0.81). Ninety-five (26%) children receiving fentanyl experienced SAEs. Fentanyl off-label use by both age and indication was not associated with a higher risk of overall SAEs compared to on-label use (OR 1.99, 95% CI 0.94–4.19, p = 0.07). However, the risk of the SAE respiratory depression was significantly greater when fentanyl was used off-label by both age and indication (OR 5.05, 95% CI 1.08–23.56, p = 0.044). Results based on HRs were similar. Conclusions Azithromycin off-label use in pediatric ICUs does not appear to be associated with an increased risk of SAEs. Off-label use of fentanyl appears to be more frequently associated with respiratory depression when used off-label by both age and indication in pediatric ICUs. Prospective studies should be undertaken to assess the safety and efficacy of fentanyl in the pediatric population so that data can be added to the FDA labeling.

Clinical Features and Treatment of Down Syndrome Arthropathy: Experience from Two US Tertiary Hospitals Abstract Background Arthropathy of Down syndrome (DA) is largely under-recognized, with an average 2-year delay in diagnosis. Most patients present with polyarthritis, and treatment has historically been challenging. Objectives Our objective was to investigate the clinical features and treatment of DA in the largest cohort reported to date. Methods In a retrospective chart review at two tertiary care hospitals, International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes for Down syndrome (DS) and juvenile idiopathic arthritis (JIA), between 1 January 1995 and 31 December 2015, were identified and charts reviewed. Results In total, 43 patients were identified, with an average (± standard deviation [SD]) follow-up period of 6 ± 4.4 years. The average age of symptom onset was 7.4 ± 3.9 years, with a mean delay of 19 ± 17 months from symptom onset to diagnosis. At diagnosis, 77% of patients had morning stiffness and 72% had abnormal laboratory values; there was an average of 15 ± 13 active joints (range 1–56). Treatment approaches varied, and there was a significant decrease in joints with active arthritis (p < 0.001), with 25% and 39% having at least one change in disease-modifying antirheumatic drug (DMARD) and biologic therapy, respectively. DMARD therapy was discontinued in 60% because of side effects, and 39% had inadequate response to first-line biologic therapy. Conclusions DA remains under-recognized, with delays in diagnosis and extensive musculoskeletal symptoms at presentation. While DA can improve with current therapy for JIA (corticosteroids, DMARDs, biologics), barriers include medication toxicity, intolerance, and ineffectiveness. Earlier diagnosis through improved screening and more targeted treatment may allow for earlier disease control and better outcomes.

Topical Pharyngeal Lidocaine Reduces Respiratory Adverse Events During Upper Gastrointestinal Endoscopies Under Ketamine Sedation in Children Abstract Background Upper gastrointestinal endoscopies (UGEs) performed under ketamine sedation may increase the risk of respiratory adverse events (RAEs) due to pharyngeal stimulation. Topical lidocaine prevents general anesthesia-induced laryngospasm. Objective Our objective was to determine whether topical lidocaine may reduce the incidence of RAEs induced by pharyngeal stimulation in UGEs performed on children sedated with ketamine. Methods We conducted a single-center prospective study. We included every patient admitted for an elective diagnostic UGE under ketamine sedation who received lidocaine prior to the technique. Patients requiring any other medication were excluded. Our main outcome measure was the number of desaturation episodes. We then compared these results with those obtained in an historic group who did not receive topical lidocaine, in which we registered a total of 54 desaturation episodes. Results In total, 88 children (52.3% boys) were included. The median age was 7 years [interquartile range (IQR) 3–11]. The mean duration of the procedure was 6.5 ± 2.4 min, and the median initial ketamine dose was 1.76 mg/kg (IQR 1.56–2.03). The total number of desaturation episodes was 3 (3.4%), and two of these occurred prior to the introduction of the endoscope. This result represents a lower incidence than in previously reported series, and a significant decrease (p < 0.0001) with respect to the 54 RAEs registered in the historic group of 87 children. Conclusions Topical lidocaine premedication significantly reduced the incidence of RAEs in children during UGEs under ketamine sedation. Our findings should be confirmed by a double-blind randomized controlled trial.

A Practical Guide to Treatment of Childhood Absence Epilepsy Abstract Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome with distinct seizure semiology, electroencephalography (EEG) features, and treatment. A diagnosis of CAE can be obtained during an office visit with a careful history, physical exam including prolonged hyperventilation, and a routine EEG. The treatment of choice for CAE with absence seizures only is ethosuximide. Valproic acid and lamotrigine are also effective treatments for many patients, but when compared to ethosuximide, valproic acid has more adverse effects and lamotrigine is less effective. Attention to predictors of response to treatment, including clinical, electrographic, and genetic factors, is increasing. Refractory CAE occurs in fewer than half of patients, and treatment strategies are available, though efficacy data are lacking. Careful assessment and treatment of psychosocial comorbidities is essential in caring for patients with CAE.

Acknowledgement to Referees

The Challenges of Cortisol Replacement Therapy in Childhood: Observations from a Case Series of Children Treated with Modified-Release Hydrocortisone Abstract Background Hydrocortisone is the preferred treatment for adrenal insufficiency in childhood. A small minority of children experience low cortisol concentrations and symptoms of cortisol insufficiency, poorly responsive to modifications in dosing. We speculated that treatment with modified-release hydrocortisone Plenadren® may be beneficial in these selected patients. Objective The aim of this article was to report cortisol profiles during treatment with standard formulation hydrocortisone and Plenadren, and growth and weight gain during treatment with Plenadren in selected children with adrenal insufficiency. Patients and Methods Data are reported as median (range). Eight patients (5 male) age 11.0 years (8.8–13.3), with adrenal insufficiency for 4.3 years (2.2–10.0) were treated with Plenadren in doses derived from cortisol concentrations measured during treatment with standard formulation hydrocortisone. Results Plasma cortisol was 262 nmol/L (114–654) 2 h after the morning dose (hydrocortisone dose 6.1 mg/m2 [4.3–7.1]) of standard formulation hydrocortisone. After 4 h, cortisol concentration was 81 nmol/L (56–104) and was < 100 nmol/L in six patients. Two hours after Plenadren administration (hydrocortisone dose 12.1 mg/m2 [8.3–17.6]), plasma cortisol concentration was 349 nmol/L (150–466), and after 4 h it was 239 nmol/L (99–375) and < 100 nmol/L in one patient. Six hours after the Plenadren dose, cortisol concentration was < 100 nmol/L in four patients and after 8 h cortisol concentration was < 100 nmol/L in seven patients (sample not obtained in one patient). Six patients elected to continue treatment with Plenadren. After 4.2 years (2.7–6.0), change in height standard deviation score (SDS) was 0.1 SD (− 0.2 to 0.2) and body mass index SDS was 0.3 SD (0–1.1). Conclusion Smoother cortisol profiles and more sustained cortisol exposure were achieved during treatment with Plenadren, which was the preferred treatment in most patients. Robust clinical trials are required to determine the place of this medication in paediatric practice.

Changes in Hemoglobin Concentrations Post-immunoglobulin Therapy in Patients with Kawasaki Disease: A Population-Based Study Using a Claims Database in Japan Abstract Background We sought to quantify the degree of anemia after high-dose intravenous immunoglobulin (IVIG) therapy in patients with Kawasaki disease (KD) by assessing hemoglobin (Hb) dynamics and determining the risk of transfusion. Methods We analyzed data from a database containing inpatient data collected from 230 hospitals in Japan. In addition to administrative records, this database included laboratory results for some patients. We searched for individuals aged ≤ 18 years with a diagnosis of KD (International Statistical Classification of Diseases and Related Health Problems, 10th revision, code M30.3) who had received high-dose (≥ 1 g/kg) IVIG therapy. The primary outcome measure was post-IVIG therapy Hb dynamics in patients for whom laboratory findings were available. Secondary outcomes included the proportion of patients whose Hb value decreased below a specified threshold (e.g., 1 g/dL) and the number who received red blood cell transfusions, identified by a Japanese administrative code, in the whole cohort. Results Laboratory data were available for 979 of 8262 patients with KD receiving high-dose IVIG. Hb dynamics assessed on spline curves showed that mild anemia commonly occurred 1–2 days after IVIG infusion and returned to the baseline thereafter. Declines of Hb > 1 g/dL and > 2 g/dL were found in 21.8% and 4.3% of patients, respectively. Two of the 8262 individuals with KD had received transfusions after IVIG therapy (incidence rate 0.024%; 95% confidence interval 0.003–0.087), but the indication for transfusion could not be determined from our records. Conclusions Although mild anemia commonly occurred post-IVIG therapy in Japanese individuals with KD, severe anemia necessitating transfusion was rare in these patients.