Development and characterization of 36 novel microsatellite markers for lake chub (Couesius plumbeus) using illumina paired-end sequencing

Lake chub is a common freshwater cyprinid found throughout Canada and parts of the northern United States. Here we describe 36 novel microsatellite loci, 25 of which are polymorphic, exhibiting between 2 and 17 alleles each, while the remaining 11 loci are monomorphic. Observed and expected heterozygosities for the polymorphic markers ranged from 0.125 to 0.875 and 0.146 to 0.878, respectively. There was no evidence of linkage disequilibrium between any locus pairs, nor was there any evidence of null alleles. There were however, six markers deviating from Hardy–Weinberg Equilibrium, a result we attribute to relatively small sample size.     

Effects of Ethanol on Monoamine and Amino Acid Release from Cerebral Cortical Slices of the Alcohol-Preferring P Line of Rats

The effects of 250 mg/100 ml ethanol on the efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and the 35 mM K+-stimulated, Ca2+-dependent release of norepinephrine (NE), dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate, and aspartate from cerebral cortical slices of the alcohol-preferring P line of rats and stock Wistar rats were studied. The K+-stimulated, Ca2+-dependent release of GABA for the P rats was 35% lower, while the release of glutamate was almost twice that of the stock animals. The release of the other compounds was similar for the two groups. Addition of 250 mg/100 ml ethanol to the superfusion media did not alter the release of NE, DA, and 5-HT nor the efflux of DOPAC from cortical slices of either group of rats. However, the K+-stimulated, Ca2+-dependent release of GABA, glutamate, and aspartate was significantly enhanced by ethanol for both the P and stock group of rats. These in vitro data do not support a direct action of ethanol on DA, NE, and 5-HT release or on DOPAC efflux, but suggest a direct action on the transmitter release process for GABA, glutamate, and aspartate in the cerebral cortex.     

Designing a Primary Care–Based Deprescribing Intervention for Patients with Dementia and Multiple Chronic Conditions: a Qualitative Study

BackgroundPatients with dementia and multiple chronic conditions (MCC) frequently experience polypharmacy, increasing their risk of adverse drug events.ObjectivesTo elucidate patient, family, and physician perspectives on medication discontinuation and recommended language for deprescribing discussions in order to inform an intervention to increase awareness of deprescribing among individuals with dementia and MCC, family caregivers and primary care physicians. We also explored participant views on culturally competent approaches to deprescribing.DesignQualitative approach based on semi-structured interviews with patients, caregivers, and physicians.ParticipantsPatients aged ≥ 65 years with claims-based diagnosis of dementia, ≥ 1 additional chronic condition, and ≥ 5 chronic medications were recruited from an integrated delivery system in Colorado and an academic medical center in Maryland. We included caregivers when present or if patients were unable to participate due to severe cognitive impairment. Physicians were recruited within the same systems and through snowball sampling, targeting areas with large African American and Hispanic populations.ApproachWe used constant comparison to identify and compare themes between patients, caregivers, and physicians.Key ResultsWe conducted interviews with 17 patients, 16 caregivers, and 16 physicians. All groups said it was important to earn trust before deprescribing, frame deprescribing as routine and positive, align deprescribing with goals of dementia care, and respect caregivers’ expertise. As in other areas of medicine, racial, ethnic, and language concordance was important to patients and caregivers from minority cultural backgrounds. Participants favored direct-to-patient educational materials, support from pharmacists and other team members, and close follow-up during deprescribing. Patients and caregivers favored language that explained deprescribing in terms of altered physiology with aging. Physicians desired communication tips addressing specific clinical situations.ConclusionsCulturally sensitive communication within a trusted patient-physician relationship supplemented by pharmacists, and language tailored to specific clinical situations may support deprescribing in primary care for patients with dementia and MCC.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06063-y) contains supplementary material, which is available to authorized users.KEY WORDS: deprescribing, patient-physician communication, dementia     

Theatre of paediatric surgery

In the 50 years since the first edition of this journal, operative paediatric surgery has undergone radical change. Many of the most common instruments are unchanged, both as a testament to their utility and in recognition of past surgeons remembered eponymously. Surrounding that basic core of instruments, theatre has changed radically as new tools and techniques have arisen. Surgeons have come down from their pedestals, recognising surgery as a team sport rather than a solo performance. More than half of the current paediatric surgical trainees are women, a higher proportion than in any other craft group of the Royal Australasian College of Surgeons. The appearance, and rapid development, of laparoscopy is to many observers the most notable change in surgery over the last 50 years. Placed in its context though, it is simply the most prominent example of a frameshift in surgical thinking. The patient as a whole is now the focus, rather than just the disease. Recent developments are as much about minimising harm to normal tissues as they are about extirpating pathology. As a surgical maxim, ‘Primum non nocere’ is even more in evidence in 2015 than it was in 1965.     

Voluntary ethanol drinking during the first three postnatal weeks in lines of rats selectively bred for divergent ethanol preference

BACKGROUND: Using a procedure first developed by Hall (1979), we examined ethanol self-administration in preweanling pups from Wistar rats and in lines of rats selectively bred for divergent ethanol preference (alcohol-preferring P, alcohol-nonpreferring NP, high-alcohol-drinking HAD-1 and -2, and low-alcohol-drinking LAD-2) to determine if factors contributing to high and low alcohol intakes are present early in development. METHODS: From postnatal days 5 to 20, nondeprived male and female rat pups received 30 min daily access to either water or a 15% (v/v) ethanol solution. In each daily session, pups were placed in a heated chamber containing Kimwipes soaked with a water or ethanol solution. Pups were weighed before and after each session, and intake levels were calculated as a percentage of body weight change. RESULTS: Similar to previous reports, Wistar pups exhibited over a 2-fold higher level of ethanol ingestion than water on postnatal days 9 through 14, with ethanol intakes approaching 3 g/kg body weight. When the drinking patterns of the selected lines were examined, only the HAD replicate lines showed a comparable preference for ethanol versus water during the preweanling period. The ethanol consumption of P, NP, and LAD lines was not consistently distinguishable from water intake levels. To reveal whether early ethanol exposure would influence later ethanol drinking behavior, a subset of HAD and LAD rat pups received free-choice ethanol access upon weaning. Although the divergent ethanol preference between high- and low-alcohol-drinking lines was evident within the first 4 days of access (>4 g/kg/day for HAD; <2 g/kg/day for LAD), preweanling ethanol exposure did not alter the acquisition or maintenance of ethanol drinking in either line. CONCLUSIONS: Overall, these results suggest that (a) the enhanced ethanol ingestion observed during the middle portion of the preweanling period is a robust phenomenon and generalizes across nonselected strains of rats, (b) selective breeding for divergent alcohol preference has arrested this age-specific effect in all but the HAD lines of rats, and (c) early ethanol exposure does not alter genetic dispositions for later high or low alcohol preference.     

Influence of the HLA-DQB1*0201 allele on the immune response in a Schistosoma mansoni infection

We previously reported the association of the major histocompatibility complex class II HLA-DQB1*0201 allele with hepatosplenic schistosomiasis. The aim of this study was to evaluate the cytokine responses of peripheral blood mononuclear cells (PBMCs) and the serum levels of immunoglobulin isotypes. The study population was selected from a schistosomiasis endemic area. No significant differences in cytokine profiles were detected in PBMCs stimulated with Schistosoma mansoni soluble egg antigen (SEA), regardless of the subjects DQB1*0201 genotype or infection status. However, previously infected DQB1*0201 positive individuals had significantly lower levels of IgG4 compared to DQB1*0201 negative individuals (P<0.05).     

Quantitative autoradiography of mu-opioid receptors in the CNS of high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats

Background: The binding of [³H]DAMGO to mu‐opioid sites was measured in the CNS of selectively bred high–alcohol‐drinking (HAD) and low–alcohol‐drinking (LAD) rats to test the hypothesis that high alcohol preference is associated with higher densities of mu‐opioid receptors. Methods: Adult, alcohol‐naïve male HAD and LAD rats from replicate line 1 were decapitated and their brains frozen in isopentane. Brain sections were incubated with 5 nM [³H]DAMGO, and nonspecific binding was determined in the presence of unlabeled DAMGO. Films were exposed for 60 days, then analyzed using quantitative autoradiography. Results: The densities of [³H]DAMGO binding sites were measured within subregions of neocortex, limbic system, basal ganglia, diencephalon, and brainstem. LAD rats had significantly higher [³H]DAMGO binding (10–30%) than HAD rats within the anterior dorsal hippocampus (CA2), posterior hippocampus (dorsal CA1, and ventral CA1, CA3, and dentate gyrus), thalamus (medial dorsal, lateral, medial dorsal, central, ventral lateral, ventral medial, and ventral medial geniculate nuclei), habenula, and amygdala. No significant interline differences were found in the prefrontal, cingulate, frontal, parietal, temporal, occipital or entorhinal cortices, olfactory tubercle, nucleus accumbens, lateral septum, ventral tegmental area, hypothalamus, caudate‐putamen, substantia nigra, claustrum, central gray, or superior colliculus. Conclusions: The present findings with the HAD and LAD lines do not support the hypothesis that high alcohol preference is associated with higher densities of CNS mu‐opioid receptors. Instead, the present results, in combination with previously published findings, suggest that the mu‐opioid system may play a complex role in regulating high–alcohol‐drinking behavior.