Sensitivity of larval and juvenile freshwater mussels (unionidae) to ammonia, chloride, copper, potassium, and selected binary chemical mixtures.

In aquatic environments, organisms such as freshwater mussels are likely exposed to complex contaminant mixtures related to industrial, agricultural, and urban activities. With growing interest in understanding the risk that chemical mixtures pose to mussels, this investigation focused on the effects of various waterborne contaminants (ammonia, chloride, copper, and potassium) and selected binary mixtures of these chemicals following a fixed-ratio design to Villosa iris glochidia and juvenile Lampsilis fasciola. In individual exposures, 48-h EC50 values were determined for V. iris glochidia exposed to ammonia chloride (7.4 [95% confidence interval (CI) 6.6-8.2] mg N/L), ammonia sulfate (8.4 [7.6-9.1] mg N/L), copper sulfate (14.2 [12.9-15.4] µg Cu2+/L), potassium chloride (12.8 [11.9-13.7] mg K+/L), potassium sulfate (10.1 [8.9-11.2] mg K+/L), and sodium chloride (480.5 [435.5-525.5] mg Cl-/L). The 7-d LC50 values for juvenile L. fasciola were determined for potassium sulfate (45.0 [18.8-71.2] mg K+/L), and sodium chloride (1738.2 [1418.6-2057.8] mg Cl-/L). In Ontario these waterborne contaminants have been reported to co-occur, with concentrations exceeding the EC10 for both life stages at some locations. Data from binary mixture exposures for V. iris glochidia (chloride-ammonia, chloride-copper, and copper-ammonia) and juvenile L. fasciola (chloride-potassium) were analyzed using a regression-based, dose-response mixture analysis modeling framework. Results from the mixture analysis were used to determine if an additive model for mixture toxicity [concentration addition (CA) or independent action (IA)] best described the toxicity of each mixture and if deviation towards dose-ratio (DR) or dose-level (DL) synergism/antagonism (S/A) occurred. For all glochidia binary mixture exposures, CA was the best fit model with DL deviation reported for the chloride-copper mixture and DR deviation reported for the copper-ammonia mixture. Using the model deviation ratio (MDR), the observed toxicity in all three glochidia mixture exposures were adequately described by both CA (mean = 0.71) and IA (mean = 0.97) whereas the juvenile mixture exposure was only adequately described by CA (mean = 0.64; IA mean = 0.05).

Attenuation of maternal weight gain impacts infant birthweight: systematic review and meta-analysis.

Despite many interventions aiming to reduce excessive gestational weight gain (GWG), it is currently unclear the impact on infant anthropometric outcomes. The aim of this review was to evaluate offspring anthropometric outcomes in studies designed to reduce GWG. A systematic search of seven international databases, one clinical trial registry and three Chinese databases was conducted without date limits. Studies were categorised by intervention type: diet, physical activity (PA), lifestyle (diet + PA), other, gestational diabetes mellitus (GDM) (diet, PA, lifestyle, metformin and other). Meta-analyses were reported as weighted mean difference (WMD) for birthweight and birth length, and risk ratio (RR) for small for gestational age (SGA), large for gestational age (LGA), macrosomia and low birth weight (LBW). Collectively, interventions reduced birthweight, risk of macrosomia and LGA by 71 g (WMD: -70.67, 95% CI -101.90 to -39.43, P<0.001), 16% (RR: 0.84, 95% CI 0.73-0.98, P=0.026) and 19% (RR: 0.81, 95% CI 0.69-0.96, P=0.015), respectively. Diet interventions decreased birthweight and LGA by 99 g (WMD -98.80, 95% CI -178.85 to -18.76, P=0.016) and 65% (RR: 0.35, 95% CI 0.17-0.72, P=0.004). PA interventions reduced the risk of macrosomia by 51% (RR: 0.49, 95% CI 0.26-0.92, P=0.036). In women with GDM, diet and lifestyle interventions reduced birthweight by 211 and 296 g, respectively (WMD: -210.93, 95% CI -374.77 to -46.71, P=0.012 and WMD:-295.93, 95% CI -501.76 to -90.10, P=0.005, respectively). Interventions designed to reduce excessive GWG lead to a small reduction in infant birthweight and risk of macrosomia and LGA, without influencing the risk of adverse outcomes including LBW and SGA.

Investigating the relationship between sleep and macronutrient intake in women of childbearing age.

BACKGROUND/OBJECTIVE: Reduced sleep is a strong and independent risk factor for weight gain and obesity. Maternal obesity preconception and throughout gestation can increase the risk of adverse pregnancy outcomes and impact on offspring health in later life. This study investigated the relationship between sleeping behaviour and macronutrient intake in childbearing aged women. SUBJECTS/METHODS: We used cross-sectional data from the Australian Longitudinal Study on Women's Health 1973-78 cohort, aged 31-36 years in 2009 (n=8200). Subjective sleeping behaviour was reported and macronutrient intake was measured using a validated food frequency questionnaire. Latent class analysis (LCA) was used to derive sleeping patterns. Multivariate regression analysis was used to investigate the relationships between sleep and macronutrient intake. RESULTS: LCA identified three sleep patterns: (LC1) average sleep (~8 h) with no adverse sleep-related symptoms (n=3570); (LC2) average sleep (~8 h) with sleeping difficulties and severe tiredness (n=2109); and (LC3) short sleep (~6 h) with sleeping difficulties and severe tiredness (n=915). In fully adjusted models, LC2 was inversely associated with percentage energy as protein (b=-0.24; P=0.01) and the protein-to-carbohydrate ratio (b=-0.01; P<0.05). LC3 was positively associated with percentage of energy as fat (b=0.29; P=0.01), saturated fat (b=0.24; P=<0.001) and monounsaturated fat (b=0.09; P=0.04). CONCLUSIONS: Sleeping behaviour patterns were associated with macronutrient intake in childbearing aged women. Improved sleep patterns, together with diet and physical activity strategies, may make it easier for women to achieve a balanced diet and optimise their weight status in preparation for pregnancy.

Whole organism responses and intersex severity in rainbow darter (Etheostoma caeruleum) following exposures to municipal wastewater in the Grand River basin, ON, Canada. Part A.

Municipal wastewater effluents (MWWEs) contain anthropogenic substances that can exhibit endocrine-disrupting activity. These complex mixtures have been observed to exert adverse effects on fish. Rainbow darter (Etheostoma caeruleum, RBD) is a small benthic fish that is widespread throughout the Grand River, Ontario, Canada, and has been previously shown to be adversely affected by MWWE exposure in this watershed. The objectives of this study were to quantify biological responses in this sentinel species and intersex severity in male fish, in relation to the area of urbanization. It focused on RBD populations adjacent to wastewater outfalls in the Grand River watershed. In May 2011, nine sites across the urban gradient were selected to evaluate the impact of MWWEs. Endpoints for energy storage (i.e. condition factor, k; liversomatic index, LSI) as well as reproductive endpoints (i.e. gonadosomatic index, GSI; gonad development, hormone production), and intersex were assessed in the fish. Rainbow darter showed a high incidence of intersex downstream of the wastewater outfalls, especially below the largest treatment plant outfall at Kitchener (∼85%). We applied an intersex index (score from 0 to 7) that considers the number of eggs within the testis and the stage of maturation of the egg. RBD exposed downstream of the largest wastewater outfall at Kitchener had a score of 3.81±0.37 compared to upstream to the urban areas where there were no intersex males found other than a single individual with a score 1 (average intersex score of site 0.06±0.06). In addition, several fish associated with the Kitchener outfall had macroscopic vitellogenic eggs in the testes (intersex scores 5 and 6). The sub-population of fish located at the wastewater outfall also showed a tendency towards skewed sex ratios (greater proportion of females to male fish) compared to the population at the reference sites. Male fish inhabiting the urbanized area of the Grand River also showed reduced levels of testosterone (T) and 11-ketotestosterone (11KT). Intersex males had the lower levels of 11KT relative to the upstream reference fish but could not be distinguished from normal males collected at the exposed sites. Despite the high levels of intersex at these sites, no relationships were evident among intersex severity and other measured endpoints such as GSI, LSI or in vitro steroid production. The effects observed appear to be associated with urbanization and exposure to treated MWWEs in the watershed. Although intersex incidence and severity was a very good indicator of wastewater exposure, intersex could not be directly linked to other effects in this wild population. The effects of MWWEs on transcriptional changes in adult RBD exposed to the effluents are reported in the corresponding report (Part B).

Towards more effective use of decision support in clinical practice: what the guidelines for guidelines don't tell you.

The Brisbane Cardiac Consortium Clinical Support Systems Program used multiple strategies in optimising quality of care of patients with either of two cardiac conditions. One of these strategies was the development and active implementation of decision support systems centred on evidence-based, locally agreed clinical practice guidelines. Our experience in undertaking this task highlighted numerous operational challenges for which solutions were difficult to extract from existing published literature. In the present article we provide a methodology grounded in both theory and real-world experience that may assist others in developing and implementing systems of guideline-based decision support.

Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats.

The present study has used capsaicin-induced neuropeptide depletion to examine the role of neurogenic inflammation in the development of edema and functional deficits following traumatic brain injury (TBI). Adult, male rats were treated with capsaicin (neuropeptide-depleted) or equal volume vehicle (controls) 14 days prior to induction of moderate/severe diffuse TBI. Injury in vehicle treated control animals resulted in acute (4-5 h) edema formation, which was confirmed as being vasogenic in origin by diffusion weighted magnetic resonance imaging and the presence of increased permeability of the blood-brain barrier (BBB) to Evans blue dye. There was also a significant decline in brain magnesium concentration, as assessed by phosphorus magnetic resonance spectroscopy, and the development of profound motor and cognitive deficits. In contrast, capsaicin pre-treatment resulted in a significant reduction in post-traumatic edema formation (p < 0.001), BBB permeability (p < 0.001), free magnesium decline (p < 0.01) and both motor and cognitive deficits (p < 0.001). We conclude that neurogenic inflammation may play an integral role in the development of edema and functional deficits following TBI, and that neuropeptides may be a novel target for development of interventional pharmacological strategies.

Quality of care of patients hospitalized with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) is an increasingly prevalent poor-prognosis condition for which effective interventions are available. It is -therefore important to determine the extent to which patients with CHF receive appropriate care in Australian hospitals and identify ways for improving suboptimal care, if it exists. AIM: To evaluate the quality of in-hospital acute care of patients with CHF using explicit quality indicators based on published guidelines. METHODS: A retrospective case note review was -performed, involving 216 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between October 2000 and April 2001. Outcome measures were process-of-care quality -indicators calculated as proportions of all, or strongly -eligible (ideal), patients who received -specific interventions. RESULTS: Assessment of underlying causes and acute precipitating factors was undertaken in 86% and 76% of patients, respectively, and objective evaluation of left ventricular function was performed in 62% of patients. Prophylaxis for deep venous thrombosis (DVT) was used in only 29% of ideal patients. Proportions of ideal patients receiving pharmacological treatments at discharge were: (i) angiotensin--converting enzyme inhibitors (ACEi) (82%), (ii) target doses of ACEi (61%), (iii) alternative vasodilators in patients ineligible for ACEi (20%), (iv) beta-blockers (40%) and (v) warfarin (46%). CONCLUSIONS: Opportunities exist for improving quality of in-hospital care of patients with CHF, -particularly for optimal prescribing of: (i) DVT prophylaxis, (ii) ACEi, (iii) second-line vasodilators, (iv) beta-blockers and (v) warfarin. More research is needed to identify methods for improving quality of in-hospital care.

Neuropeptide release influences brain edema formation after diffuse traumatic brain injury.

The mechanisms associated with edema formation after traumatic brain injury (TBI) have not been fully elucidated. In peripheral tissue injury, the neurogenic component of inflammation plays a significant role in increased vascular permeability and edema formation. However, few studies have examined the role of neuropeptide induced neurogenic inflammation following TBI. Adult male Sprague-Dawley rats were either left untreated, or pre-treated with capsaicin (125 mg/kg s.c.) or equal volume vehicle, and injured 14 days later using the 2-meter impact-acceleration model. Subgroups of animals were assessed for blood brain barrier (BBB) permeability (Evans Blue), brain edema (wet weight/dry weight) and functional outcome (Barnes maze and Rotarod) for up to 2 weeks post-trauma. Increased BBB permeability was present in untreated animals between 3 and 6 h after injury but not at later time-points. Edema was maximal at 5 h after trauma, declined and then significantly increased over the 5 days post-trauma. In contrast, capsaicin pre-treated, neuropeptide-depleted animals exhibited no significant increase in BBB permeability or edema compared to vehicle treated animals after injury. Notably, motor and cognitive impairments were significantly reduced in the capsaicin-pretreated animals. We conclude that neurogenic inflammation contributes to the development of edema and posttraumatic deficits after diffuse TBI.

Quality of care of patients hospitalized with acute coronary syndromes.

BACKGROUND: Measurement and improvement of quality of care is a priority issue in health care. Patients hospitalized with acute coronary syndromes (ACS) constitute a high-risk population whose care, if shown to be suboptimal on the basis of available research evidence, may benefit from quality improvement interventions. AIM: To evaluate the quality of in-hospital care for patients with ACS, using explicit quality indicators. METHODS: Retrospective case note review was undertaken of 397 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between 1 October 2000 and 17 April 2001. The main outcome measures were 12 process-of-care quality indicators, calculated as either: (i) the proportion of all patients who received specific interventions or (ii) the proportion of ideal patients who received specific interventions (i.e. patients with clear indications and lacking contraindications). RESULTS: Quality indicators with values above 80% included: (i) patient selection for thrombolysis (100%) and discharge prescription of beta-blockers (84%), (ii) antiplatelet agents (94%) and (iii) lipid-lowering agents (82%). Indicators with values between 50% and 80% included: (i) timely performance of electrocardiogram (ECG) on admission (61%), (ii) early coronary angiography (75%), (iii) measurement of serum lipids (71%) and (iv) discharge prescription of angiotensin-converting-enzyme (ACE) inhibitors (73%). Indicators with values <50% included: (i) timely administration of thrombolysis (35%), (ii) non-invasive risk assessment (23%) and (ii) formal in-hospital, and post-hospital cardiac rehabilitation (47% and 7%, respectively). CONCLUSION: There were delays in performing ECG and administering thrombolysis to patients who presented to emergency departments with ACS. Improvement is warranted in use of non-invasive procedures for identifying high-risk patients who may benefit from coronary revascularization as well as use of serum lipid measurements, ACE inhibitors and cardiac rehabilitation.

Patient and partner satisfaction with Viagra (sildenafil citrate) treatment as determined by the Erectile Dysfunction Inventory of Treatment Satisfaction Questionnaire.

OBJECTIVES: To assess the efficacy and safety of Viagra (sildenafil citrate) in male outpatients with erectile dysfunction and patient and partner satisfaction with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). METHODS: A total of 247 patients with erectile dysfunction of broad-spectrum etiology were treated in a randomized, double-blind, parallel-group, multicenter study conducted at outpatient clinics. Patients receiving oral sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo during a 12-week period. The principal efficacy measures were responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) on the International Index of Erectile Function and three global efficacy questions. Patient and partner satisfaction with treatment were assessed, for the first time, using the EDITS questionnaire. RESULTS: Efficacy scores for the International Index of Erectile Function questions and the global efficacy questions were significantly higher for patients receiving sildenafil than for those receiving placebo (P <0.001). Both patients and partners receiving sildenafil also had significantly higher EDITS scores than those receiving placebo (P <0.001). Adverse events were chiefly mild or moderate. Two patients receiving sildenafil and none receiving placebo discontinued treatment because of adverse events. CONCLUSIONS: Sildenafil was an effective, well-tolerated treatment for erectile dysfunction in an outpatient setting. Partner evaluations corroborated patient assessments. The results from the EDITS questionnaire indicated that after 12 weeks of receiving sildenafil both patients and partners reported higher levels of treatment satisfaction relative to placebo.

Comparison of bone marrow extracellular matrices.

We have compared the structure and composition of adult and fetal bovine bone marrow extracellular matrices. In contrast to fetal bone marrow, adult bone marrow has more oval fenestration and accumulation of adipocytes as well as lower protein content. These differences could be due to remodeling of bone marrow tissue as it develops. Zymogram analysis of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) activities showed that fetal, but not adult bone marrow extract contained a 96-kDa MMP and TIMP-1 and -2. These activities may contribute to the structural differences between adult and fetal bone marrow tissues.

Tissue expression and subcellular localization of CLN3, the Batten disease protein.

Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a progressive neurologic disorder which results from mutations in the CLN3 gene, which normally produces a 48-kDa polypeptide of unknown function. To help characterize the CLN3 protein, we have studied its tissue distribution and subcellular localization in human tissues using three epitope-specific polyclonal antibodies to human CLN3 by immunoblot, immunocytochemical, and immunoelectron microscopic analysis. The most abundant CLN3 protein expression was in the gray matter of the brain, where it was localized to astrocytes, capillary endothelium, and neurons. CLN3 was also evident in peripheral nerve, in pancreatic islet cells, and within the seminiferous tubules in the testis. Staining was generally diffuse within the cytoplasm with some nuclear reactivity. Subcellular localization identified the CLN3 protein within the nucleus and along cell membranes. These results were contrasted with the cellular distribution of palmitoyl-protein thioesterase (PPT), the enzyme whose deficiency is responsible for infantile neuronal ceroid lipofuscinosis (CLN1). PPT was most abundant in brain and visceral macrophages where it displayed a coarse granular staining pattern typical of lysosomal distribution. Immunoelectron microscopy confirmed that PPT immunoreactivity was limited to lysosomes.

Adverse prognostic features of collagen injection therapy for urinary incontinence following radical retropubic prostatectomy.

PURPOSE: We identified and characterized predictive factors associated with an unfavorable outcome of collagen injection therapy in post-radical prostatectomy incontinence. MATERIALS AND METHODS: A total of 46 patients, 49 to 85 years old (mean age 67) and incontinent after radical retropubic prostatectomy, underwent a mean of 2.8 transurethral injections of collagen (mean cumulative volume injected 31 ml.). Preoperatively, all patients underwent fluoroscopic multichannel video urodynamics including determination of Valsalva's leak point pressure. Stress urinary incontinence was subjectively graded as 1 (0 to 1 pad per day), 2 (2 to 3 pads per day) and 3 (greater than 3 pads per day). Patient age, duration and severity of pretreatment incontinence, presence of detrusor instability and anastomotic strictures, number of injections, total volume of collagen delivered and the impact of a nerve sparing procedure plus adjuvant radiation therapy were assessed and correlated with treatment outcome. RESULTS: Of the patients 11 (24%) became completely dry (9 after 3 or fewer treatments), 21 (41%) improved (17 after 3 or fewer treatments) and 14 (30%) showed no benefit (after more than 3 treatments). Of the 14 patients in whom treatment failed 6 had undergone adjuvant radiation treatment, pretreatment urinary incontinence was grade 3 in all, and concomitant detrusor instability was present in 11 (79%). All patients had received more than 3 treatments (mean total volume injected 37 ml.). CONCLUSIONS: Notwithstanding the need for multiple treatments, the prospect for cure by collagen injection of the post-radical prostatectomy incontinent patient is significantly affected by the severity of pretreatment incontinence, concomitant detrusor overactivity and exposure to radiation therapy. Age, duration of incontinence, presence of mild to moderate anastomotic strictures and a nerve sparing technique did not seem to influence treatment outcome.

The effect of urethral introducer tip catheters on the incidence of urinary tract infection outcomes in spinal cord injured patients.

PURPOSE: We attempted to determine whether an introducer tip catheter reduces urinary tract infection in spinal cord injured patients on intermittent catheterization. MATERIALS AND METHODS: The introducer tip catheter bypasses the colonized 1.5 cm. of the distal urethra. Enrolled patients were prospectively entered into the study in alternate groups depending on whether they reflex voided: group 1--on intermittent catheterization with the introducer tip catheter but not voiding spontaneously or wearing an external urinary catheter, group 2--same as group 1 but using a nonintroducer tip catheter; group 3--on intermittent catheterization with the introducer tip catheter, voiding by reflex and wearing an external urinary catheter, and group 4--same as group 3 but using a nonintroducer tip catheter. RESULTS: Statistical significance was shown when comparing patients using versus not using the introducer tip catheter regardless of whether an external urinary catheter was worn (p = 0.0121). A greater difference was noted between patients using and not using the introducer tip catheter in the intermittent catheterization only group (p = 0.0093). CONCLUSIONS: The introducer tip catheter decreased urinary tract infections in hospitalized men with spinal cord injury on intermittent catheterization.

Is combined modality therapy necessary for advanced Hodgkin's disease?

PURPOSE: To determine whether single-modality therapy is optimal management for patients with Stage III-IV Hodgkin's disease. METHODS AND MATERIALS: All patients with advanced (Stage III and IV) Hodgkin's disease treated at the University of Florida from 1964 through 1989 (n = 141) were studied retrospectively for factors predictive of good outcome with single-modality therapy. Treatment modalities varied and were distributed as follows: combined-modality therapy (CMT), 55 patients; chemotherapy alone (CX), 50 patients; and radiotherapy alone (RT), 36 patients. RESULTS: Ten-year rates of freedom from relapse and overall survival for all Stage III patients were 66% and 59% compared with 36% and 35% for Stage IV patients. The RT subset was highly selected with the majority of patients having nonbulky Stage IIIA disease. Within the RT group, multivariate analysis identified the degree of splenic involvement and age as the factors most associated with freedom from relapse. In patients treated with CX, multivariate analysis identified bulky tumor (maximum transverse tumor dimension > 6 cm) as the most important prognostic factor for relapse. In patients without bulky disease (< or = 6 cm), the probabilities of freedom from relapse and overall survival at 10 years, respectively, according to treatment group were 53% and 58% for RT patients, 60% and 56% for CX patients, and 83% and 71% for CMT patients. For patients without bulky disease, the probability of freedom from relapse was significantly better for the CMT group than for CX patients (p = 0.03) or RT patients (p = 0.04), but there was no statistical difference in overall survival among the three groups. In patients with bulky disease (> 6 cm), the probabilities of freedom from relapse and overall survival at 10 years were 44% and 45% for RT patients, 9% and 0% for CX patients, and 72% and 58% for CMT patients. Freedom from relapse and overall survival were significantly better (p = 0.0001) for CMT patients compared with CX patients. Fatal hematopoietic disorders developed in 10 patients: 2 of 36 RT patients, 2 of 50 CX patients, and 6 of 55 CMT patients. Nine patients had received chemotherapy, and eight had six or more cycles of alkylator-based chemotherapy. CONCLUSION: This retrospective study suggests that combined-modality therapy is preferable to single-modality therapy in the majority of patients with advanced Hodgkin's disease.

Urethral cultures in female patients with a spinal cord injury.

Quantitative cultures of the urethral meatus were obtained from women with SCI undergoing intermittent catheterization. When compared with the urethral cultures of a group of female subjects, women with SCI had a greater number of isolates of Klebsiella pneumonia and Pseudomonas aeruginosa in the urethral flora. However there was not a significantly greater number of isolates or log numbers of E. coli or Enterococcus sp. in the urethral flora. The E. coli and Enterococcus sp. isolated from the urine were not isolated from the urethra of female patients with SCI in one third of the patients. This poor correlation between the simultaneous urethral and urine cultures of female subjects with SCI may reflect colonization of the urine with organisms that were unable to adhere to the mucosa and colonize the urethra. To what extent these organisms colonize or are temporary residents may be important in the pathogenicity of the infection.