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"Chase, Tara"
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Doctor Proctor's fart powder : who cut the cheese?
New adventures await Doctor Proctor, Lisa, and Nilly as they try to protect Oslo, Norway, from invading aliens, enormous snakes in the sewers, seven-legged Peruvian sucking spiders, and sinister waffle irons.
Book
FINANCIAL SERVICES
Talk that Canadian Imperial Bank of Commerce might require an equity infusion has reopened one of Bay Street's longest-running debates, with some investors arguing it bolsters the case for bank mergers.
Newspaper Article
Bubble in the bathtub
A mysterious postcard leads Lisa and Nilly from Oslo to Paris in search of Doctor Proctor but, once there, all they find of their missing friend is a time-traveling bathtub powered by a special soap and several sinister individuals determined to do all they can to locate the eccentric inventor.
Book
Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses
Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity
1
,
2
and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus–NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus–NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour.
Dopamine-independent induction of long-term potentiation at hippocampal synapses onto the nucleus accumbens modulates reward-related behaviour.
Journal Article
Genetic diversity and population structure of Piper nigrum (black pepper) accessions based on next-generation SNP markers
Despite the economic importance of
Piper nigrum
(black pepper), a highly valued crop worldwide, development and utilization of genomic resources have remained limited, with diversity assessments often relying on only a few samples or DNA markers. Here we employed restriction-site associated DNA sequencing to analyze 175
P
.
nigrum
accessions from eight main black pepper growing regions in Sri Lanka. The sequencing effort resulted in 1,976 million raw reads, averaging 11.3 million reads per accession, revealing 150,356 high-quality single nucleotide polymorphisms (SNPs) distributed across 26 chromosomes. Population structure analysis revealed two subpopulations (
K
= 2): a dominant group consisting of 152 accessions sourced from both home gardens and large-scale cultivations, and a smaller group comprising 23 accessions exclusively from native collections in home gardens. This clustering was further supported by principal component analysis, with the first two principal components explaining 35.2 and 12.1% of the total variation. Genetic diversity analysis indicated substantial gene flow (
Nm
= 342.21) and a low fixation index (
F
ST
= 0.00073) between the two subpopulations, with no clear genetic differentiation among accessions from different agro-climatic regions. These findings demonstrate that most current black pepper genotypes grown in Sri Lanka share a common genetic background, emphasizing the necessity to broaden the genetic base to enhance resilience to biotic and abiotic stresses. This study represents the first attempt at analyzing black pepper genetic diversity using high-resolution SNP markers, laying the foundation for future genome-wide association studies for SNP-based gene discovery and breeding.
Journal Article
Prevalence of potentially harmful multidrug interactions on medication lists of elderly ambulatory patients
Background
It has been hypothesized that polypharmacy may increase the frequency of multidrug interactions (MDIs) where one drug interacts with two or more other drugs, amplifying the risk of associated adverse drug events (ADEs). The main objective of this study was to determine the prevalence of MDIs in medication lists of elderly ambulatory patients and to identify the medications most commonly involved in MDIs that amplify the risk of ADEs.
Methods
Medication lists stored in the electronic health record (EHR) of 6,545 outpatients ≥60 years old were extracted from the enterprise data warehouse. Network analysis identified patients with three or more interacting medications from their medication lists. Potentially harmful interactions were identified from the enterprise drug-drug interaction alerting system. MDIs were considered to amplify the risk if interactions could increase the probability of ADEs.
Results
MDIs were identified in 1.3 % of the medication lists, the majority of which involved three interacting drugs (75.6 %) while the remainder involved four (15.6 %) or five or more (8.9 %) interacting drugs. The average number of medications on the lists was 3.1 ± 2.3 in patients with no drug interactions and 8.6 ± 3.4 in patients with MDIs. The prevalence of MDIs on medication lists was greater than 10 % in patients prescribed bupropion, tramadol, trazodone, cyclobenzaprine, fluoxetine, ondansetron, or quetiapine and greater than 20 % in patients prescribed amiodarone or methotrexate. All MDIs were potentially risk-amplifying due to pharmacodynamic interactions, where three or more medications were associated with the same ADE, or pharmacokinetic, where two or more drugs reduced the metabolism of a third drug. The most common drugs involved in MDIs were psychotropic, comprising 35.1 % of all drugs involved. The most common serious potential ADEs associated with the interactions were serotonin syndrome, seizures, prolonged QT interval and bleeding.
Conclusions
An identifiable number of medications, the majority of which are psychotropic, may be involved in MDIs in elderly ambulatory patients which may amplify the risk of serious ADEs. To mitigate the risk, providers will need to pay special attention to the overlapping drug-drug interactions which result in MDIs.
Journal Article
Genetic diversity and population structure of Piper nigrum
Despite the economic importance of Piper nigrum (black pepper), a highly valued crop worldwide, development and utilization of genomic resources have remained limited, with diversity assessments often relying on only a few samples or DNA markers. Here we employed restriction-site associated DNA sequencing to analyze 175 P. nigrum accessions from eight main black pepper growing regions in Sri Lanka. The sequencing effort resulted in 1,976 million raw reads, averaging 11.3 million reads per accession, revealing 150,356 high-quality single nucleotide polymorphisms (SNPs) distributed across 26 chromosomes. Population structure analysis revealed two subpopulations (K = 2): a dominant group consisting of 152 accessions sourced from both home gardens and large-scale cultivations, and a smaller group comprising 23 accessions exclusively from native collections in home gardens. This clustering was further supported by principal component analysis, with the first two principal components explaining 35.2 and 12.1% of the total variation. Genetic diversity analysis indicated substantial gene flow (Nm = 342.21) and a low fixation index (F.sub.ST = 0.00073) between the two subpopulations, with no clear genetic differentiation among accessions from different agro-climatic regions. These findings demonstrate that most current black pepper genotypes grown in Sri Lanka share a common genetic background, emphasizing the necessity to broaden the genetic base to enhance resilience to biotic and abiotic stresses. This study represents the first attempt at analyzing black pepper genetic diversity using high-resolution SNP markers, laying the foundation for future genome-wide association studies for SNP-based gene discovery and breeding.
Journal Article
Near-Universal Resistance to Macrolides of Treponema pallidum in North America
Of 604
Treponema pallidum
(syphilis) strains sampled from 13 U.S. states, Washington, D.C., and two Canadian provinces from 2017 through 2023, a total of 599 (99.2%) had genotypic resistance to azithromycin.
Journal Article
Comparing infant pain and stress during retinopathy of prematurity screening using ophthalmoscopy and non-contact imaging
The current standard of care for retinopathy of prematurity (ROP) screening eye examinations, binocular indirect ophthalmoscopy (BIO), is associated with discomfort and stress in infants. In this study, we compared pain scores and vital signs during examination with BIO and non-contact laser speckle contrast imaging (LSCI). Preterm neonates underwent retinal exam with BIO and LSCI during ROP screening. Infant stress was scored using the Neonatal Pain, Agitation, and Sedation Scale (N-PASS), and collected with vital signs, before, during, and after eye examination. Seventy-one infants with gestational ages 22–32 weeks and birthweights 400–1900 g underwent 196 BIO examinations and 101 LSCI examinations. N-PASS scores during BIO were significantly higher than LSCI (8.8 vs. 3.7,
p
< 0.0001). Maximum heart rate was significantly higher during BIO compared to LSCI (182 ± 19 beats per minute vs. 175 ± 20 beats per minute,
p
= 0.008). Minimum oxygen saturation was significantly lower during BIO compared to LSCI (83 ± 12% vs. 86 ± 10%,
p
= 0.035). After BIO, vital sign instability remained for 30 s, whereas vital signs returned to baseline after LSCI. We found lower pain scores and more stable vital signs during LSCI compared to BIO.
Journal Article
Retinal blood flow association with age and weight in infants at risk for retinopathy of prematurity
This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA) and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP). 38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27 and 47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/− 4.0 IU. BFV positively correlated with PMA (r = 0.3,
p
= 0.01), CA (r = 0.3,
p
= 0.005), and CW (r = 0.3,
p
= 0.02). BFV did not correlate with GA nor BW (r = − 0.2 and r = − 0.05,
p
> 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (
p
= 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.
Journal Article