A regional examination of the footprint of agriculture and urban cover on stream water quality.

Freshwater systems in cold regions, including the Laurentian Great Lakes, are threatened by both eutrophication and salinization, due to excess nitrogen (N), phosphorus (P) and chloride (Cl-) delivered in agricultural and urban runoff. However, identifying the relative contribution of urban vs. agricultural development to water quality impairment is challenging in watersheds with mixed land cover, which typify most developed regions. In this study, a self-organizing map (SOM) analysis was used to evaluate the contributions of various forms of land cover to water quality impairment in southern Ontario, a population-dense, yet highly agricultural region in the Laurentian Great Lakes basin where urban expansion and agricultural intensification have been associated with continued water quality impairment. Watersheds were classified into eight spatial clusters, representing four categories of agriculture, one urban, one natural, and two mixed land use clusters. All four agricultural clusters had high nitrate-N concentrations, but levels were especially high in watersheds with extensive corn and soybean cultivation, where exceedances of the 3 mg L-1 water quality objective dramatically increased above a threshold of |∼30 % watershed row crop cover. Maximum P concentrations also occurred in the most heavily tile-drained cash crop watersheds, but associations between P and land use were not as clear as for N. The most urbanized watersheds had the highest Cl- concentrations and expansions in urban area were mostly at the expense of surrounding agricultural land cover, which may drive intensification of remaining agricultural lands. Expansions in tile-drained corn and soybean area, often at the expense of mixed, lower intensity agriculture are not unique to this area and suggest that river nitrate-N levels will continue to increase in the future. The SOM approach provides a powerful means of simplifying heterogeneous land cover characteristics that can be associated with water quality patterns and identify problem areas to target management.

Urban green waste bulking agent is the major source of antimicrobial resistance genes persisted in home compost, not animal manure.

Urban green waste and food waste are often used as bulking agents to prepare home compost in combination with animal manure in urban horticulture and community gardening. Although it is known that antimicrobial resistance genes (ARGs) persist in home compost, their origins have not been determined. In addition, the factors contributing to ARGs persistence remain unclear. In this study, we aim to (i) characterize the changes in the microbiome and antimicrobial resistome during the composting process of home compost using metagenomics shotgun sequencing, (ii) identify the source of the ARGs persisted in home compost using SourceTracker, and (iii) elucidate the collective effect of compost microbiome and environmental factors, including the physicochemical properties and antibiotics concentration of home compost, in contributing to ARG persistence using Procrustes analysis, co-occurrence network analysis, variation partitioning analysis, and structural equation modeling. SourceTracker analysis indicated that urban green waste bulking agent was the major source of the persisting ARGs in home compost instead of animal manure. Procrustes analysis and co-occurrence network analysis revealed a strong association between microbiome and antimicrobial resistome. Variation partitioning analysis and structural equation modeling suggested that physicochemical properties shaped the antimicrobial resistome directly and indirectly by influencing the microbiome. Our results indicated that the persistence of ARGs in home compost might be due to the succession of microbial species from the urban green waste bulking agent, and the physicochemical properties might have defined the compost environment to shape the microbiome in the compost, thus, in turn, the persisting antimicrobial resistome.

Saikosaponin-d, a novel SERCA inhibitor, induces autophagic cell death in apoptosis-defective cells.

Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, leading to autophagy induction through the activation of the Ca(2+)/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells.

A profile of gout patients in Sarawak.

We performed a prospective study of all patients diagnosed with gout and who received treatment in Sarawak General Hospital from 1 July 2010 to 31 December 2010. There was a total of 138 patients in our study of which 92 (66.7%) were from the indigenous populations. They have a mean age of 56.5 ± 12.5 years with a mean duration of illness of 11.6 ± 8.7 years. The mean lag time between symptom onset to the diagnosis of gout was 2.8 ± 4.8 years and a mean lag time to appropriate treatment of gout of 8.8 ± 8.4 years. Sixty-six (47.8%) patients have family history of gout. The common complications of gout in our patients were tophi (47.1%), joint deformities (39.1%), kidney stones (16.7%), and uric acid nephropathy (0.7%). Hospitalization occurred in 93 (67.4%) patients. Gout is a serious medical problem in our centre. Gout affects middle-aged men, especially the indigenous populations. Almost half of our patients have a family history of gout and have tophi formations. Our gout patients have a significant delay in diagnosis and appropriate treatment, thus contributing to more complications and hospitalizations in our centre. There is an urgent need to educate both patients and healthcare workers on gout and its treatment to reduce the burden of chronic gout in Sarawak.

Global guidelines for treatment of tuberculosis among persons living with HIV: unresolved issues.

The Revised National Tuberculosis Control Programme (RNTCP) in India uses a fully intermittent thrice-weekly rifampicin-containing regimen for all tuberculosis (TB) patients, including those who are human immunodeficiency virus (HIV) infected, whereas the World Health Organization (WHO) recommends daily anti-tuberculosis treatment at least during the intensive phase. The WHO recommendation was based on the results of a meta-analysis demonstrating increased risk of recurrence and failure among HIV-infected TB patients receiving intermittent TB treatment compared to a daily regimen. Review of the primary evidence indicates limited, low-quality information on intermittency, mostly from observational studies in the pre-antiretroviral treatment (ART) era. Molecular epidemiology in India indicates that most of the recurrences and many of the failures result from exogenous re-infection, suggesting poor infection control and high transmission rather than poor regimen efficacy. Subsequently published studies have shown acceptable treatment outcomes among HIV-infected TB patients receiving intermittent anti-tuberculosis regimens with concomitant ART. Treatment outcomes among HIV-infected TB patients treated under programmatic conditions show low failure rates but high case fatality; death has been associated with lack of ART. The highest priority is therefore to reduce mortality by linking all HIV-infected TB patients to ART. While urgently seeking to reduce death rates among HIV-infected TB patients, given the poor evidence for change and operational advantages of an intermittent regimen, the RNTCP intends to collect the necessary evidence to inform national policy decisions through randomised clinical trials.

Comprehensive characterization of indoor airborne bacterial profile.

This is the first detailed characterization of the airborne bacterial profiles in indoor environments. Two restaurants were selected for this study. Fifteen genera of bacteria were isolated from each restaurant and identified by three different bacterial identification systems including MIDI, Biolog and Riboprinter. The dominant bacteria of both restaurants were Gram-positive bacteria in which Micrococcus and Bacillus species were the most abundant. Most bacteria identified were representative species of skin and respiratory tract of human, and soil. Although the bacterial levels in these two restaurants were below the limit of the Hong Kong Indoor Air Quality Objective (HKIAQO) Level 1 standard (i.e., < 500 cfu/m3), the majority of these bacteria were opportunistic pathogens. These results suggested that the identity of airborne bacteria should also be included in the IAQ to ensure there is a safety guideline for the public.

Microbial synthesis and characterization of physiochemical properties of polyhydroxyalkanoates (PHAs) produced by bacteria isolated from activated sludge obtained from the municipal wastewater works in Hong Kong.

The first objective of this study was the measurement of physical properties of P(3HB-co-3HV) copolymers with different (hydroxybutyrate) HB to (hydroxyvalerate) HV ratios produced by Bacillus cereus (TRY2) isolated from activated sludge. The 3HV PHBV copolymers were 0.05, 22.6, 39.2, 54.1, and 69.1 mol%, respectively. The second objective was to study possible waste water treatment and production of PHAs at the same time by B. cereus (TRY2) and Pseudomonas spp. (TOB17) (both were isolated from activated sludge), recombinant Bacillus DH5alpha, and a combination of the above three bacteria. The results were satisfactory; the maximum COD and TOC of the sewage sludge reduced were 53.5% and 67.5%, respectively.

A comparison of the prevalence of domestic violence between patients seeking termination of pregnancy and other general gynecology patients.

OBJECTIVES: (1) To determine and compare the prevalence of domestic violence among abortion-seeking patients with other general gynecology patients; (2) to see if a follow-up interview 6 weeks after abortion can improve the abuse disclosure rate; (3) to see if the abused victims accept direct referral to their gynecologists/social workers for help. METHODS: This is a prospective questionnaire survey in a university teaching hospital on patients seeking abortion and an approximately equal number of other general gynecology patients. Participants were interviewed by a designated project nurse in a private setting, using a structured questionnaire (Modified Abuse Assessment Screen Questionnaire) to assess the past and recent history of abuse. The interview was repeated 6 weeks after the abortion for the abortion-seeking group. RESULTS: Five hundred and one participants were interviewed, including 245 seeking abortion (TOP group) and 256 other general gynecology patients (non-TOP group). The lifetime prevalence of abuse in the TOP group (27.3%) was significantly higher than the non-TOP group (8.2%) (P<0.001). Repeating the interview 6 weeks after the abortion did not increase the disclosure rate. Most abused victims were unwilling to disclose their information of abuse to their gynecologists or social workers at the time of interview. CONCLUSIONS: Domestic violence is a significant problem among the gynecology patients, particularly those seeking abortion. A single interview prior to abortion is adequately effective for screening. However, the most effective and acceptable way of helping these victims needs to be explored further.

Intubation through intubating laryngeal mask with and without a lightwand: a randomized comparison.

The combined use of a lightwand and the intubating laryngeal mask airway (ILMA) was compared with the use of the ILMA alone to determine whether the combination was a more efficient method of endotracheal intubation. One hundred healthy patients were randomly assigned to two groups. After induction of anaesthesia, Group A patients were intubated blindly through the ILMA while in Group B, intubation was guided by a lightwand. A sequence of standard manoeuvres was followed it attempts at intubation failed. The number of manoeuvres used, the time taken for successful intubation and complications associated with intubation were recorded. Intubations were successful in all patients, but the mean endotracheal intubation time was longer in Group A than in Group B (38.3 +/- 10.4 s versus 26.4 +/- 9.1 s, P < 0.001). The number of patients who needed one or more manoeuvres was significantly higher in Group A than in Group B (76% versus 42%, P = 0.001). We conclude that the lightwand is a useful adjunct in endotracheal intubation through an ILMA.

Gestational diabetes mellitus in the last trimester - a feature of maternal iron excess?

AIM: To determine whether non-anaemic women with gestational diabetes mellitus (GDM) diagnosed in third trimester pregnancy have evidence of increased iron stores compared with matched non-diabetic controls. METHODS: In a prospective study, women who had antenatal booking before 20 weeks' gestation and without anaemia or diabetes mellitus were recruited at the time of the oral glucose tolerance test (OGTT) at 28-31 weeks' gestation for the study of serum ferritin, iron and transferrin concentrations. The results were blinded to the managing obstetricians. After delivery, the records were reviewed. The cases diagnosed as GDM were compared with a control group (two controls for each index case matched for parity) selected at random from the at-risk but nondiabetic cases. RESULTS: GDM was diagnosed in 97 of the 401 women recruited. Compared with the 194 controls, there was no difference in the weight, body mass index, booking and third trimester haemoglobin, or third trimester red cell indices, but concentrations of serum ferritin, iron, transferrin saturation, and the post-natal haemoglobin were significantly higher. On multiple regression analysis, maternal BMI and the log-transformed ferritin concentration remained significant determinants of the OGTT 2-h glucose value. CONCLUSION: The results suggest an association between increased iron stores and glucose intolerance at the third trimester in non-anaemic women. The role of iron excess in the pathogenesis of GDM needs to be examined.

Drug treatment effects on disease progression.

Degenerative diseases are characterized by a worsening of disease status over time. The rate of deterioration is determined by the natural rate of progression of the disease and by the effect of drug treatments. A goal of drug treatment is to slow disease progression. Drug treatments can be categorized as symptomatic or protective. Symptomatic treatments do not affect the rate of disease progression whereas protective treatments have the ability to slow disease progression down. Many current methods for describing disease progression have two common drawbacks: a linear relationship between time and disease status is assumed, and within- and between-subject variability is ignored. Disease progress models combined with pharmacokinetic pharmacodynamic models and hierarchical random effects statistical models provide insights into understanding the time course and management of degenerative disease.

Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children.

AIMS: Paracetamol has a central action for both antipyresis and analgesia. Maximum temperature decrease and peak analgesia are reported at 1-2 h after peak plasma paracetamol concentration. We wished to determine the relationship between plasma and cerebrospinal fluid (CSF) pharmacokinetics in children. METHODS: Concentration-time profiles in plasma and CSF after nasogastric paracetamol 40 mg kg(-1) were measured in nine children who had indwelling ventricular drains. Estimation of population pharmacokinetic parameters was made using both a standard two-stage population approach (MKMODEL) and a nonlinear mixed effect model (NONMEM). Results were standardized to a 70 kg person using an allometric power model. RESULTS: Both approaches gave similar estimates. NONMEM parameter estimates were clearance 10.21 h(-1) (CV 47%), volume of distribution 67.11 (CV 58%) and absorption rate constant 0.77 h(-1) (CV 49%). Cerebrospinal fluid concentrations lagged behind those of plasma. The equilibration half time was 0.72 h (CV 117%). The CSF/plasma partition coefficient was 1.18 (CV 8%). CONCLUSIONS: Higher concentrations in the CSF probably reflect the lower free water volume of plasma. The CSF equilibration half time suggests that CSF kinetics approximate more closely to the effect compartment than plasma, but further time is required for paracetamol to exert its effects. Effect site concentrations equilibrate slowly with plasma. Paracetamol should be given 1-2 h before anticipated pain or fever in children.

Assay of Salmonella in enrichment cultures of foods, feeds and environmental samples by the polymyxin-cloth enzyme immunoassay.

A variety of foods, animal feeds and environmental samples were analyzed for the presence of Salmonella using the polymyxin-cloth enzyme immunoassay (p-CEIA) system. Salmonella lipopolysaccharide (LPS) antigens were captured from test samples on polymyxin-coated polyester cloth, followed by immunoenzymatic detection of bound antigens using a monoclonal antibody recognizing an LPS common core oligosaccharide. Dairy and egg products, animal feeds and environmental samples from food processing plants were pre-enriched for 24 h, followed by selective enrichment for a further 24 h in either tetrathionate brilliant green (TBG), selenite cystine (SC) or brain-heart infusion broth containing 0.5% yeast extract, 0.5% cholate and 0.3% selenite (BYCS). The samples were assayed by the p-CEIA after each stage of enrichment. After selective enrichment, the p-CEIA gave results which were in complete agreement with the standard culture technique in the analysis of all foods examined. On the other hand, a combination of selective enrichment and the p-CEIA out-performed the Modified Semi-Solid Rappaport Vassiliadis (MSRV) method in screening pre-enrichment cultures of feeds and environmental samples. Use of the new selective medium BYCS prior to performing the p-CEIA gave the highest recovery of Salmonella from feeds and environmental samples.

Value of standardized gestational age charts for fetuses of first-generation Oriental immigrants to Canada.

OBJECTIVE: to ascertain if standard gestational age charts can be used to accurately predict the gestational age of fetuses of first-generation Oriental immigrants to Canada. PATIENTS AND METHODS: Over a 3-year period, all patients presenting for obstetric ultrasound examinations were invited to participate in the study. The authors recorded biparietal diameter, head circumference, femur length and abdominal circumference for 139 fetuses in the second and third trimesters. A study performed in the first trimester was used as the baseline for gestational age. The data for 126 of the fetuses were complete, and these data were used for the analysis. RESULTS: For 77 of the fetuses, both parents were Oriental, and for 49, one or both parents were not Oriental; the latter constituted the control group. A total of 1008 individual measurements were obtained, and of these, all but 14 fell within two standard deviations of the norm, according to standard gestational age charts. Of the abnormal measurements, seven were obtained from five fetuses with Oriental parents, and seven were obtained from six fetuses in the control group. The difference between the two groups in the proportion of measurements falling either above or below two standard deviations from the norm was not statistically significant (Fisher's exact test, p = 0.41694). CONCLUSION: The authors conclude that standard gestational age charts can be used to determine gestational age in first-generation Oriental immigrants to Canada.

Use of limiting-dilution type long-term marrow cultures in frequency analysis of marrow-repopulating and spleen colony-forming hematopoietic stem cells in the mouse.

We have developed an in vitro clonal assay of murine hematopoietic precursor cells that form spleen colonies (CFU-S day 12) or produce in vitro clonable progenitors in the marrow (MRA cells) of lethally irradiated mice. The assay is essentially a long-term bone marrow culture in microtiter wells containing marrow-derived stromal "feeders" depleted for hematopoietic activity by irradiation. To test the validity of the assay as a quantitative in vitro stem cell assay, a series of unsorted and physically sorted bone marrow cells were simultaneously assayed in vivo and overlaid on the feeders in a range of concentrations, while frequencies of cells forming hematopoietic clones (cobblestone area forming cells, CAFC) were calculated by means of Poisson statistics. Linear regression analysis of the data showed high correlations between the frequency of CFU-S day 12 and CAFC day 10, and between MRA cells and CAFC day 28. A majority of MRA activity and CAFC day 28 was separable from CFU-S day 12 and CAFC day 10. This correlation study validates the CAFC system as a clonal assay facilitation both the quantitative assessment of a series of subsets in the hematopoietic stem cell hierarchy and the study of single long-term repopulating cells in vitro.

Physical aspects of wet granulations II: factors involved in prolonged and excessive mixing.

Evidence is presented that excessive blending in a wet granulation process shifts the packing arrangement of the wet granule, causing it to become dense and nonporous. With prolonged kneading, a large amount of the water-soluble excipients dissolves in the granulating fluid, and these two factors make the drying slower. This result, coupled with the previous finding that a certain time is required to attain an equilibrium size granule, explains why there exists an optimum kneading time for a wet granulation from a mechanical performance point of view.

Interference with antibody-feedback by irradiation, thymus cells, the allogeneic effect, and serum factors.

Low doses of irradiation, increased number of T cells, increased T cell activity as in the allogeneic effect, or early activation of an in vitro cell-mediated immune response all confer resistance to antibody feedback. In some of these systems, the resistance is directed against immunosuppression by intact IgG antibody whereas suppression by F(ab')2 antibody is either not changed or increased. These forms of interference with immunosuppression by antibody, are explained in terms of an Fc-dependent model for antibody-feedback regulation.