Low-dissolved-oxygen nitrification in tropical sewage: an investigation on potential, performance and functional microbial community.

Intensive aeration for nitrification is a major energy consumer in sewage treatment plants (STPs). Low-dissolved-oxygen (low-DO) nitrification has the potential to lower the aeration demand. However, the applicability of low-DO nitrification in the tropical climate is not well-understood. In this study, the potential of low-DO nitrification in tropical setting was first examined using batch kinetic experiments. Subsequently, the performance of low-DO nitrification was investigated in a laboratory-scale sequential batch reactor (SBR) for 42 days using real tropical sewage. The batch kinetic experiments showed that the seed sludge has a relatively high oxygen affinity. Thus, the rate of nitrification was not significantly reduced at low DO concentrations (0.5 mg/L). During the operation of the low-DO nitrification SBR, 90% of NH4-N was removed. The active low-DO nitrification was mainly attributed to the limited biodegradable organics in the sewage. Fluorescence in-situ hybridisation and 16S rRNA amplicon sequencing revealed the nitrifiers were related to Nitrospira genus and Nitrosomonadaceae family. Phylogenetic analysis suggests 47% of the operational taxonomic units in Nitrospira genus are closely related to a comammox bacteria. This study has demonstrated active low-DO nitrification in tropical setting, which is a more sustainable process that could significantly reduce the energy footprint of STPs.

Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

BACKGROUND: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. METHODS: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin. Model health states included stable disease, disease progression, and death. Efficacy inputs were based on the RADIANT-4 trial and utilities were mapped from quality-of-life data retrieved from RADIANT-4. Resource utilization inputs were derived from a Canadian physician survey, while cost inputs were obtained from official reimbursement lists from Ontario and other published sources. Costs and efficacy outcomes were discounted 5% annually over a 10-year time horizon, and sensitivity analyses were conducted to test the robustness of the base case results. RESULTS: Everolimus had an incremental gain of 0.616 QALYs (0.823 LYs) and CA$89,795 resulting in an incremental cost-effectiveness ratio of CA$145,670 per QALY gained (CA$109,166 per LY gained). The probability of cost-effectiveness was 52.1% at a willingness to pay (WTP) threshold of CA$150,000 per QALY. CONCLUSIONS: Results of the probabilistic sensitivity analysis indicate that everolimus has a 52.1% probability of being cost-effective at a WTP threshold of CA$150,000 per QALY gained in Canada.

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe-/- × Tfr2mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P<0.04, n ≥5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (P<0.05), although gross myelin structure and integrity appear unaffected (P>0.05). Overlap (P<0.0001) of differentially expressed genes in Hfe-/- × Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (P<0.0001) of genes differentially expressed in Hfe-/- × Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe-/- × Tfr2mut mice were hyperactive (P<0.0112) without apparent cognitive impairment by IntelliCage testing (P>0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

Long-term performance evaluation of EBPR process in tropical climate: start-up, process stability, and the effect of operational pH and influent C:P ratio.

To date, little information is known about the operation of the enhanced biological phosphorus removal (EBPR) process in tropical climates. Along with the global concerns on nutrient pollution and the increasing array of local regulatory requirements, the applicability and compliance accountability of the EBPR process for sewage treatment in tropical climates is being evaluated. A sequencing batch reactor (SBR) inoculated with seed sludge from a conventional activated sludge (CAS) process was successfully acclimatized to EBPR conditions at 28 °C after 13 days' operation. Enrichment of Candidatus Accumulibacter phosphatis in the SBR was confirmed through fluorescence in situ hybridization (FISH). The effects of operational pH and influent C:P ratio on EBPR were then investigated. At pH 7 or pH 8, phosphorus removal rates of the EBPR processes were relatively higher when operated at C:P ratio of 3 than C:P ratio of 10, with 0.019-0.020 and 0.011-0.012 g-P/g-MLVSS•day respectively. One-year operation of the 28 °C EBPR process at C:P ratio of 3 and pH 8 demonstrated stable phosphorus removal rate of 0.020 ± 0.003 g-P/g-MLVSS•day, corresponding to effluent with phosphorus concentration <0.5 mg/L. This study provides the first evidence on good EBPR activity at relatively high temperature, indicating its applicability in a tropical climate.

Comparing the use of glycerol preserved and cryopreserved allogenic skin for the treatment of severe burns: differences in clinical outcomes and in vitro tissue viability.

Cryopreserved (CryoPA) and Glycerol-preserved (GPA) skin allografts are commonly used in the treatment of severe burn injuries. However, comparable data on their differences in clinical outcome is scarce. This retrospective review aims to study the effect of allograft viability on clinical outcomes. The records of 48 severe burn patients who either received CryoPA or GPA were reviewed. Key burn mortality determinants were used to match the 2 groups. Clinical outcomes such as mortality rate (MR) and the length of hospital stay (LOS) were obtained. A separate in vitro comparison included histological assessments and the use of tetrazolium reductase activity to compare tissue viability. Both groups showed a comparable profile in burn mortality determinants. Patients who received CryoPA had a lower MR of 25% compared to 34.8% (P=0.250) in the GPA group and a lower LOS of 39.2-45.9 days (P=0.730), respectively. The histological structural integrity was found to be well preserved with both methods although CryoPA was confirmed to be the more viable product (P<0.05). The lower MR associated with CryoPA cannot be totally ignored. However, the mechanism through which viable skin allografts improves MR of severe burns patients remains to be elucidated.

Human keratinocytes contain mRNA indistinguishable from monocyte interleukin 1 alpha and beta mRNA. Keratinocyte epidermal cell-derived thymocyte-activating factor is identical to interleukin 1.

Keratinocytes produce an IL-1 like factor termed epidermal cell-derived thymocyte-activating factor (ETAF). In this study, we show that ETAF and IL-1 are identical by the following criteria: Both normal and malignant human keratinocytes contain mRNAs identical to monocytic IL-1 alpha and IL-1 beta mRNA, as determined by an S1 nuclease protection assay; and IL-1 activity in medium conditioned by these cells can be neutralized by antibodies specific for human IL-1. The IL-1 alpha and IL-1 beta mRNAs can be identified in cultured human keratinocytes in the absence of identifiable stimulation; this basal level of mRNA can be further induced to accumulate with certain defined stimuli. Cultured normal human keratinocytes (HFKs) contain 2-4 times more IL-1 alpha than IL-1 beta mRNA; in contrast, human peripheral blood monocytes contain 10-20 times more IL-1 beta than IL-1 alpha mRNA. The IL-1 activity released by these HFK can be neutralized by an antibody that neutralizes both alpha and beta IL-1, but not by an antibody that neutralizes only IL-1 beta. While human monocytes produce a large excess of IL-1 beta after appropriate stimulation, these data suggest that IL-1 alpha is a major (and may be the predominant) form of IL-1 produced by human keratinocytes.

Transnasal frontal intersinus septum takedown for frontal sinus pyocele.

INTRODUCTION: The open frontal intersinus septum takedown (FISST) technique was first described in 1976. We describe our experience with an endoscopic transnasal approach to manage a frontal sinus pyocele arising from an obstructed frontal sinus outflow tract due to anterolateral thigh flap reconstruction of a maxillectomy defect. CASE REPORT: A 40-year-old lady experienced upper eyelid swelling and purulent nasal discharge 3 weeks after undergoing a left extended medial maxillectomy with free anterolateral thigh flap reconstruction. A computed tomography (CT) scan revealed total opacification of the left frontal sinus. There was no improvement with intravenous antibiotics and she underwent a surgery, whenshe was found intraoperatively to have a frontal sinus pyocele, which was then drained. She then underwent an endoscopic transnasal FISST to ventilate the left frontal sinus via the contralateral frontal recess with good results. A CT scan performed 3 months postoperatively showed a widely patent interfrontal sinus septal window and right frontal outflow tract with no disease recurrence. DISCUSSION: The FISST is a useful technique to manage unilateral frontal sinus disease by taking advantage of the contralateral outflow tract when the ipsilateral frontal recess is obstructed.

Incidence and characteristics of viral community-acquired pneumonia in adults.

BACKGROUND: In adults, viral causes of community-acquired pneumonia (CAP) are poorly characterised. The aims of this study were to characterise the viral aetiology of CAP in adults by using an extensive array of viral diagnostic tests and to compare the characteristics of viral pneumonia with those of pneumococcal pneumonia. METHODS: Adults admitted to Christchurch Hospital over a 1-year period with CAP were included in the study. Microbiological testing methods included blood and sputum cultures, urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila, antibody detection in paired sera and detection of respiratory viruses in nasopharyngeal swabs by immunofluorescence, culture and PCR. RESULTS: Of 304 patients with CAP, a viral diagnosis was made in 88 (29%), with rhinoviruses and influenza A being the most common. Two or more pathogens were detected in 49 (16%) patients, 45 of whom had mixed viral and bacterial infections. There were no reliable clinical predictors of viral pneumonia, although several variables were independently associated with some aetiologies. The presence of myalgia was associated with pneumonia caused by any respiratory virus (OR 3.62, 95% CI 1.29 to 10.12) and influenza pneumonia (OR 190.72, 95% CI 3.68 to 9891.91). Mixed rhinovirus/pneumococcal infection was associated with severe disease. CONCLUSIONS: Virus-associated CAP is common in adults. Polymicrobial infections involving bacterial and viral pathogens are frequent and may be associated with severe pneumonia.

In vitro evaluation of fibrin mat and Tegaderm wound dressing for the delivery of keratinocytes--implications of their use to treat burns.

The effectiveness of fibrin mat and Tegaderm delivery systems to maintain clonogenic keratinocytes in culture were evaluated using in vitro methods. A fibrin mat was found to provide a culture environment that is conducive for the proliferation of keratinocytes and supporting their ability to form colonies of good growth potential in vitro. This confirms that the fibrin mat is a good delivery system for cultured epithelial autograft (CEA). In our unit, fibrin-CEA is limited only for the treatment of severe burns due to the high cost of fibrin glue. However, this substrate is able to maintain the regenerative properties of the CEA which is crucial for the treatment of extensive and full thickness burns. Tegaderm, a cost-effective polyurethane wound dressing is able to support keratinocyte cell growth but at a slower rate and with fewer colonies formed compared to the fibrin system. This suggests that Tegaderm can be an alternative approach of delivering autologous cells, limited to treat chronic wounds and less extensive burns. The use of simple and relatively inexpensive bench techniques can potentially serve as a quality control to check for keratinocytes cultured and delivered to every patient in the clinical setting.

Erratum: Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

[This corrects the article on p. 32 in vol. 25, PMID: 29507481.].

The role of chronic viral hepatitis on tuberculosis treatment interruption.

BACKGROUND: Tuberculosis (TB) drug-induced liver injury (TB-DILI) usually occurs within 8 weeks of anti-tuberculosis drug initiation. In Singapore, we suspected that the onset of TB drug-induced transaminitis may be confounded with hepatitis C virus (HCV) and hepatitis B (HBV) virus co-infection. OBJECTIVE: To determine the impact of HCV/HBV co-infection on the course of treatment in patients with TB treatment interrupted due to transaminitis. DESIGN: TB patients with treatment interruption during 2013-2014 were identified through the Singapore national TB registry. Case notes of those with transaminitis were perused. RESULTS: Of 3860 TB patients notified, 140 had suspected TB-DILI. Of these, respectively 20/140 (14.3%) and 16/140 (11.4%) were HCV- or HBV-positive. The median time to treatment interruption/transaminitis was 5 weeks vs. 9.9 weeks and 9.6 weeks for transaminitis patients without chronic liver disease and with HCV/HBV co-infection (P < 0.01). Multivariate logistic regression analysis revealed that having HCV/HBV co-infection was associated with treatment interruption occurring beyond 8 weeks (adjusted OR [aOR] 4.06, 95%CI 1.28-12.85); HCV transaminitis patients were more likely to take 10 months to complete anti-tuberculosis treatment (aOR 5.11, 95%CI 1.21-21.67) than those without chronic liver disease. CONCLUSION: TB treatment interruption due to transaminitis in HCV/HBV co-infected patients occurred later than in those without liver disease. Most had completed 2 months of pyrazinamide-containing intensive phase treatment before the onset of transaminitis.

Predictors of hematological abnormalities in multiple sclerosis patients treated with fingolimod and dimethyl fumarate and impact of treatment switch on lymphocyte and leukocyte count.

BACKGROUND: There is limited data regarding the predictors of hematological abnormalities in multiple sclerosis (MS) patients treated with dimethyl fumarate (DMF) or fingolimod (FNG), and the impact of treatment switch on lymphocyte and leukocyte count METHODS: We identified 405 patients on DMF and 300 patients on FNG (treatment duration: at least 12 month) within a large prospective study of MS patients conducted at the Partners MS Center, Brigham and Women's Hospital (CLIMB study) between Jan 2011 to Feb 2016. Patients had complete blood counts with differentials at baseline and every 6 months while on treatment. Most participants had a clinical visit with complete neurologic examinations every 6 months and brain MRI scan every 12 months. T cell subset profile was available for subgroup of patients (n = 116). RESULTS: In the FNG group, the risk of developing lymphopenia grade 4 (< 200) was higher in female patients (p = 0.0117) and those who were previously treated with natalizumab (p = 0.0116), while the risk of lymphopenia grade 3b+4 (< 350) was higher in female patients (p = 0.0009). DMF treated patients with lower baseline lymphocyte count had a higher chance of developing lymphopenia grade 2 (< 800) (p < 0.0001) or 2+3 (< 500) (p < 0.0001). We examined the effect of treatment switch between DMF and FNG. No significant recovery in lymphocyte and leukocyte count was observed after treatment switches. Reduced dosing of FNG in patients with lymphopenia led to increase in lymphocyte count but also increased disease activity in 25% of patients. CONCLUSION: Female sex and prior exposure to natalizumab increased the probability of lymphopenia on FNG, while low absolute lymphocyte count was associated with increased risk of lymphopenia on DMF. Parallel switch did not lead to recovery from hematological abnormalities. Long-term studies with larger number of patients are required to confirm our findings and to establish guidelines for prediction and management of hematological abnormalities.

Interleukin 1 gene expression in cultured human keratinocytes is augmented by ultraviolet irradiation.

Interleukin 1 (IL-1) is a family of polypeptides initially found to be produced by activated monocytes and macrophages that mediate a wide variety of cellular responses to injury and infection. Epidermal epithelial cells (keratinocytes) produce "epidermal cell-derived thymocyte activating factor" or ETAF, which has been recently shown to be identical to IL-1. Human epidermis is normally exposed to significant amounts of solar ultraviolet radiation. Certain ultraviolet wavelengths (UVB, 290-320 nm) are thought to be responsible for most of the immediate and long-term pathological consequences of excessive exposure to sunlight. In this study, we asked whether exposure to UVB irradiation induced IL-1 gene expression in cultured human keratinocytes. Cultured human keratinocytes contain detectable amounts of IL-1 alpha and beta mRNA and protein in the absence of apparent stimulation; these levels could be significantly enhanced 6 h after exposure to 10 ng/ml of 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Exposure to UVB irradiation with an emission spectrum comparable to that of sunlight (as opposed to that of an unfiltered artificial UV light source) significantly increased the steady state levels IL-1 alpha and beta mRNA in identical populations of human keratinocytes. This was reflected in the production of increased IL-1 activity by these cultures in vitro. In the same cell population, exposures to UVB irradiation did not alter the level of actin mRNA; therefore, the effect of UV irradiation on IL-1 represents a specific enhancement of IL-1 gene expression. Local increases of IL-1 may mediate the inflammation and vasodilation characteristic of acute UVB-injured skin, and systemic release of this epidermal IL-1 may account for fever, leukocytosis, and the acute phase response seen after excessive sun exposure.

Interleukin 1 gene expression in adult T cell leukemia.

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations.

Use of skin allograft and its donation rate in Singapore: an 11-year retrospective review for burns treatment.

An 11-year retrospective review (1993 to 2003) of 102 severe burn patients (>40% total body surface area and undergone wound excision surgery) was performed to determine the efficacy of early wound debridement and coverage of large burns with skin allografts, a treatment introduced here in 1998 with the establishment of a skin banking facility. While there was no significant reduction in mortality, length of hospital stay decreased by 15.7 days (P < .05) during the post-skin-banking period. Skin allograft donation rates from multiorgan donors were consistently fewer compared with corneal donation, mainly due to strong cultural beliefs and public misconceptions regarding skin harvesting. The overall tissue donation rate in Singapore may improve if efforts focus on deceased cases sent to the state coroner where retrieval and counseling can be centralized.

The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry.

PURPOSE: Well-functioning vascular access is essential for the provision of adequate CRRT. However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. METHODS: Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. RESULTS: Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). CONCLUSIONS: Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

The association between distance to public amenities and cardiovascular risk factors among lower income Singaporeans.

Existing evidence on the association between built environment and cardiovascular disease (CVD) risk factors focused on the general population, which may not generalize to higher risk subgroups such as those with lower socio-economic status (SES). We examined the associations between distance to 5 public amenities from residential housing (public polyclinic, subsidized private clinic, healthier eatery, public park and train station) and 12 CVD risk factors (physical inactivity, medical histories and unhealthy dietary habits) among a study sample of low income Singaporeans aged ≥ 40 years (N = 1972). Using data from the Singapore Heart Foundation Health Mapping Exercise 2013-2015, we performed a series of logistic mixed effect regressions, accounting for clustering of respondents in residential blocks and multiple comparisons. Each regression analysis used the minimum distance (in km) between residential housing and each public amenity as an independent continuous variable and a single risk factor as the dependent variable, controlling for demographic characteristics. Increased distance (geographical inaccessibility) to a train station was significantly associated with lower odds of participation in sports whereas greater distance to a subsidized private clinic was associated with lower odds of having high cholesterol diagnosed. Increasing distance to park was positively associated with higher odds of less vegetable and fruits consumption, deep fried food and fast food consumption in the preceding week/month, high BMI at screening and history of diabetes, albeit not achieving statistical significance. Our findings highlighted potential effects of health-promoting amenities on CVD risk factors in urban low-income setting, suggesting gaps for further investigations.