The global expansion of toxic Microcystis blooms, and production of cyanotoxins including microcystins, are an increasing risk to freshwater fish. Differentiating intracellular and extracellular ...microcystin toxicity pathways (i.e., within and outside of cyanobacterial cells) in fish is necessary to assess the severity of risks to populations that encounter harmful algal blooms in pre-to-postsenescent stages. To address this, adult and juvenile Rainbow Trout (Oncorhynchus mykiss) were, respectively, exposed for 96 h to intracellular and extracellular microcystins (0, 20, and 100 μg L–1) produced by Microcystis aeruginosa. Fish were dissected at 24 h intervals for histopathology, targeted microcystin quantification, and nontargeted proteomics. Rainbow Trout accumulated intracellular and extracellular microcystins in all tissues within 24 h, with greater accumulation in the extracellular state. Proteomics revealed intracellular and extracellular microcystins caused sublethal toxicity by significantly dysregulating proteins linked to the cytoskeletal structure, stress responses, and DNA repair in all tissues. Pyruvate metabolism in livers, anion binding in kidneys, and myopathy in muscles were also significantly impacted. Histopathology corroborated these findings with evidence of necrosis, apoptosis, and hemorrhage at similar severity in both microcystin treatments. We demonstrate that sublethal concentrations of intracellular and extracellular microcystins cause adverse effects in Rainbow Trout after short-term exposure.
Background We prospectively evaluated the safety and efficacy of adding preoperative chemoprophylaxis to our institution's operative venous thromboembolism (VTE) prophylaxis policy as part of a ...physician-led quality improvement initiative. Study Design Patients undergoing major cancer surgery between August 2013 and January 2014 were screened according to service-specific eligibility criteria and targeted to receive preoperative VTE chemoprophylaxis. Bleeding, transfusion, and VTE rates were compared with rates of historical controls who had not received preoperative chemoprophylaxis. Results The 2,058 eligible patients who underwent operation between August 2013 and January 2014 (post-intervention) were compared with a cohort of 4,960 patients operated on between January 2012 and June 2013, who did not receive preoperative VTE chemoprophylaxis (pre-intervention). In total, 71% of patients in the post-intervention group were screened for eligibility; 82% received preoperative anticoagulation. When compared with the pre-intervention group, the post-intervention group had significantly lower transfusion rates (pre- vs post-intervention, 17% vs 14%; difference 3.5%, 95% CI 1.7% to 5%, p = 0.0003) without significant difference in major bleeding (difference 0.3%, 95% CI −0.1% to 0.7%, p = 0.2). Rates of deep venous thrombosis (1.3% vs 0.2%; difference 1.1%, 95% CI 0.7% to 1.4%, p < 0.0001) and pulmonary embolus (1.0% vs 0.4%; difference 0.6%, 95% CI 0.2% to 1%, p = 0.017) were significantly lower in the post-intervention group. Conclusions In patients undergoing major cancer surgery, institution of a single dose of preoperative chemoprophylaxis, as part of a physician-led quality improvement initiative, did not increase bleeding or blood transfusions and was associated with a significant decrease in VTE rates.
Peptides folded through interwoven disulfides display extreme biochemical properties and unique medicinal potential. However, their exploitation has been hampered by the limited amounts isolatable ...from natural sources and the expense of chemical synthesis. We developed reliable biological methods for high-throughput expression, screening and large-scale production of these peptides: 46 were successfully produced in multimilligram quantities, and >600 more were deemed expressible through stringent screening criteria. Many showed extreme resistance to temperature, proteolysis and/or reduction, and all displayed inhibitory activity against at least 1 of 20 ion channels tested, thus confirming their biological functionality. Crystal structures of 12 confirmed proper cystine topology and the utility of crystallography to study these molecules but also highlighted the need for rational classification. Previous categorization attempts have focused on limited subsets featuring distinct motifs. Here we present a global definition, classification and analysis of >700 structures of cystine-dense peptides, providing a unifying framework for these molecules.
Entrustable Professional Activities (EPAs) have emerged to bridge the gap between the learning of individual competencies and competence in real world practice. EPAs capture the critical core work of ...a discipline integrating competencies from multiple domains. This report describes the development of a set of EPAs for specialty training in Public Health and Preventive Medicine (PHPM) in Canada.
The PHPM EPAs were developed using multiple existing sources. A combination of workshops and a national online survey was used to consult with PHPM program directors, the national specialty committee, and competency-based education experts.
A national survey of PHPM program directors had a 71% response rate with 80% or more of respondents agreeing with all of the 20 EPA titles and all but one of their descriptions. Competency developmental stage-specific milestones were identified for each EPA.
The identification of the EPAs and their milestones will increase emphasis on the demonstrated performance of the specialty's core work. Simulations applicable to several EPAs have been developed. The EPAs have also been incorporated into a PHPM National Review Course and will be used to develop a national PHPM curriculum, as well as a national written practice examination.
Objective: The optimal diet for weight loss in type 2 diabetes remains controversial. This study examined a low-carbohydrate, high-fat diet with detailed physiological assessments of insulin ...sensitivity, glycemic control, and risk factors for cardiovascular disease.
Methods: Fourteen obese patients (body mass index BMI 40.6 ± 4.9 kg/m
2
) with type 2 diabetes were recruited for an "Atkins"-type low-carbohydrate diet. Measurements were made at 0, 12, and 24 weeks of weight, insulin sensitivity, HbA1c, lipids, and blood pressure.
Results: Twelve completers lost a mean of 9.7 ± 1.8 kg over 24 weeks attributable to a major reduction in carbohydrates and resultant reduction in total energy intake. Glycemic control significantly improved (HbA1c −1.1 ± 0.25%) with reductions in hypoglycemic medication. Fasting glucose, homeostasis model assessment (HOMA), and area under the curve (AUC) glucose (intravenous glucose tolerance test IVGTT) were significantly reduced by week 12 ( p < 0.05). There were nonsignificant improvements in insulin sensitivity (S
I
) at week 12 ( p = 0.19) and week 24 ( p = 0.31). Systolic blood pressure was reduced (mean −10.0 mmHg between weeks 0 and 24, p = 0.13). Mean high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol all increased. The ratio of total: HDL cholesterol and triglycerides was reduced.
Conclusion: A low-carbohydrate diet was well tolerated and achieved weight loss over 24 weeks in subjects with diabetes. Glycemic control improved with a reduction in requirements for hypoglycemic agents.
An intrapartum fetal death within 20 minutes of a reassuring acoustically stimulated fetal heart rate acceleration is reported. The cause of death in this instance was congenital pneumonia, ...gram-negative sepsis, and meconium aspiration. Umbilical cord pH values obtained at delivery did not demonstrate asphyxia (ie, low pO2, high pCO2, and low pH), but suggested a metabolic acidosis typical of sepsis.
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