Concentration of Selected Priority Organic Contaminants in Fish Maintained on Formulated Diets in Lake Ontario Waters

Fish were grown in Lake Ontario water under conditions simulating commercial aquaculture and then analyzed for 10 priority organic contaminants. Black bullheads (Ameiurus meias) were grown in cages placed in a bay of Lake Ontario. Rainbow trout (Oncorhynchus mykiss) were grown in terrestrial raceways served with Lake Ontario water. Yearlings were reared on a commercial ration in these systems, which partially isolated them from the contaminant-laden food web and bottom sediments, to an average weight of 93 g for black bullheads (range, 31-220 g) and 213 g (29-558 g) for rainbow trout. Concentrations of contaminants in skinless fillets of both rainbow trout cultivated 6 months and black bullheads cultured 3.5 months in Lake Ontario waters were nondetectable or less than one-sixth the action levels defined by the U.S. Food and Drug Administration. Contaminant levels in rainbow trout were consistently less than concentrations observed in black bullheads. Of the 10 priority contaminants surveyed, 7 were nondetectable in rainbow trout and 3 were nondetectable in black bullheads. Concentrations of contaminants in both species were generally much lower than levels observed in wild fish from Lake Ontario. This investigation demonstrated that bioaccumulation of lipophilic contaminants by fish cultured under simulated commercial conditions in Lake Ontario was not significant. These findings have implications for commercial aquaculture, regulatory decisions, and fish consumers in the Great Lakes basin and elsewhere

Uptake and Retention of Mirex By Fish Maintained on Formulated and Natural Diets in Lake Ontario Waters

Fish with no detectable levels of the contaminant mirex were grown in Lake Ontario waters under conditions simulating commercial aquaculture. Benthic black bullheads (Ameiurus me/as) were grown in cages placed in a bay of the lake. Pelagic rainbow trout (Oncorhynchus mykiss) were grown in terrestrial raceways served with Lake Ontario waters. Contaminant-free fingerlings were reared to a large size on a commercial ration in these systems, which partially isolated them from the contaminant-laden food web and bottom sediments. Black bullheads fed a mirex-spiked, commercially prepared food had mirex concentrations that exceeded the U.S. Food and Drug Administration (FDA) action level of 0.1 p,g/g, significantly higher than concen, trations in fish receiving the same commercial food without mirex. Ninety percent offish receiving the unspiked ration had nondetectable levels of mirex (values below 0.002 p,g/g). The 10% containing mirex had concentrations 94% below FDA action level. In the rainbow trout study, 97% of the fish had no detectable levels ofmirex. This investigation demonstrated that bioaccumulation of the lipophilic contaminant mirex by fish cultured under simulated commercial conditions in Lake Ontario waters was not significant. These findings have implications for commercial aquaculture, regulatory decisions, and health-conscious fish consumers in the Great Lakes Basin

Phytoplankton, Zooplankton, Macrobenthos and lchthyoplankton Abundance, Biomass and Species Composition in Onondaga Lake, 1994

Once a pristine recreational center and a productive fishery that supplied New York City markets with fresh fish, Onondaga Lake is now considered one of the most badly degraded bodies of water in the entire world (Sage 1993). The Onondaga Lake Management Conference was established to develop a comprehensive restoration, conservation, and management plan for Onondaga Lake that recommends priority corrective actions and a compliance schedule for cleanup of the lake. Biological assessment of the lake has been infrequent and concentrated on a few biological groups. This study either updates or establishes baseline characteristics for the following biological components of the Onondaga Lake ecosystem: phytoplankton, zooplankton, ichthyoplankton and macrobenthos

Macrofilaricidal Activity after Doxycycline Only Treatment of Onchocerca volvulus in an Area of Loa loa Co-Endemicity: A Randomized Controlled Trial

The control of onchocerciasis in Africa relies on the sustained delivery of ivermectin. In certain areas, annual treatments delivered with high population coverage for at least 15–17 years can break transmission. In other endemic settings this strategy alone is thought to be insufficient to eradicate the disease. One of the major limitations occurs in areas that are co-endemic with another filarial infection caused by Loa loa, due to the risk of a rare severe adverse event associated with the rapid killing of L. loa microfilariae in heavily parasitized individuals. There are also concerns over recent evidence of reduced efficacy of ivermectin and the possible development of resistance. An alternative approach is to target the Wolbachia bacterial endosymbionts of Onchocerca volvulus with the antibiotic, doxycycline. In an area of Cameroon co-endemic for onchocerciasis and loiasis we conducted a trial comparing doxycycline with or without ivermectin treatment to ivermectin treatment alone. A six-week course of doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. The trial indicates that anti-wolbachial therapy is a feasible alternative to ivermectin in communities co-endemic for onchocerciasis and loiasis

Multilab Direct Replication of Flavell, Beach, and Chinsky (1966): Spontaneous Verbal Rehearsal in a Memory Task as a Function of Age

Work by Flavell, Beach, and Chinsky indicated a change in the spontaneous production of overt verbalization behaviors when comparing young children (age 5) with older children (age 10). Despite the critical role that this evidence of a change in verbalization behaviors plays in modern theories of cognitive development and working memory, there has been only one other published near replication of this work. In this Registered Replication Report, we relied on researchers from 17 labs who contributed their results to a larger and more comprehensive sample of children. We assessed memory performance and the presence or absence of verbalization behaviors of young children at different ages and determined that the original pattern of findings was largely upheld: Older children were more likely to verbalize, and their memory spans improved. We confirmed that 5- and 6-year-old children who verbalized recalled more than children who did not verbalize. However, unlike Flavell et al., substantial proportions of our 5- and 6-year-old samples overtly verbalized at least sometimes during the picture memory task. In addition, continuous increase in overt verbalization from 7 to 10 years old was not consistently evident in our samples. These robust findings should be weighed when considering theories of cognitive development, particularly theories concerning when verbal rehearsal emerges and relations between speech and memory

Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.</p> <p>Methods</p> <p>Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).</p> <p>Results</p> <p>Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.</p> <p>Conclusions</p> <p>Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.</p

Deletion of Cryptococcus neoformans AIF Ortholog Promotes Chromosome Aneuploidy and Fluconazole-Resistance in a Metacaspase-Independent Manner

Apoptosis is a form of programmed cell death critical for development and homeostasis in multicellular organisms. Apoptosis-like cell death (ALCD) has been described in several fungi, including the opportunistic human pathogen Cryptococcus neoformans. In addition, capsular polysaccharides of C. neoformans are known to induce apoptosis in host immune cells, thereby contributing to its virulence. Our goals were to characterize the apoptotic signaling cascade in C. neoformans as well as its unique features compared to the host machinery to exploit the endogenous fungal apoptotic pathways as a novel antifungal strategy in the future. The dissection of apoptotic pathways revealed that apoptosis-inducing factor (Aif1) and metacaspases (Mca1 and Mca2) are independently required for ALCD in C. neoformans. We show that the apoptotic pathways are required for cell fusion and sporulation during mating, indicating that apoptosis may occur during sexual development. Previous studies showed that antifungal drugs induce ALCD in fungi and that C. neoformans adapts to high concentrations of the antifungal fluconazole (FLC) by acquisition of aneuploidy, especially duplication of chromosome 1 (Chr1). Disruption of aif1, but not the metacaspases, stimulates the emergence of aneuploid subpopulations with Chr1 disomy that are resistant to fluconazole (FLCR) in vitro and in vivo. FLCR isolates in the aif1 background are stable in the absence of the drug, while those in the wild-type background readily revert to FLC sensitivity. We propose that apoptosis orchestrated by Aif1 might eliminate aneuploid cells from the population and defects in this pathway contribute to the selection of aneuploid FLCR subpopulations during treatment. Aneuploid clinical isolates with disomies for chromosomes other than Chr1 exhibit reduced AIF1 expression, suggesting that inactivation of Aif1 might be a novel aneuploidy-tolerating mechanism in fungi that facilitates the selection of antifungal drug resistance

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council