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1.
Hum Brain Mapp ; 41(7): 1806-1818, 2020 05.
Article in English | MEDLINE | ID: mdl-31880365

ABSTRACT

The precise understanding of the dopaminergic (DA) system and its pharmacological modifications is crucial for diagnosis and treatment of neuropsychiatric disorders, as well as for understanding basic processes, such as motivation and reward. We probed the functional connectivity (FC) of subcortical nuclei related to the DA system according to seed regions defined according to an atlas of subcortical nuclei. We conducted a large pharmaco-fMRI study using a double-blind, placebo-controlled design, where we examined the effect of l -DOPA, a dopamine precursor, and amisulpride, a D2/D3-receptor antagonist on resting-state FC in 45 healthy young adults using a cross-over design. We examined the FC of subcortical nuclei with connection to the reward system and their reaction to opposing pharmacological probing. Amisulpride increased FC from the putamen to the precuneus and from ventral striatum to precentral gyrus. l -DOPA increased FC from the ventral tegmental area (VTA) to the insula/operculum and between ventral striatum and ventrolateral prefrontal cortex and it disrupted ventral striatal and dorsal caudate FC with the medial prefrontal cortex. In an exploratory analysis, we demonstrated that higher self-rated impulsivity goes together with a significant increase in VTA-mid-cingulate gyrus FC during l -DOPA-challenge. Therefore, our DA challenge modulated distinct large-scale subcortical connectivity networks. A dopamine-boost can increase midbrain DA nuclei connectivity to the cortex. The involvement of the VTA-cingulum connectivity in dependence of impulsivity has implications for diagnosis and therapy in disorders like ADHD.


Subject(s)
Amisulpride/pharmacology , Basal Ganglia/drug effects , Basal Ganglia/diagnostic imaging , Dopamine Agents/pharmacology , Levodopa/pharmacology , Neural Pathways/drug effects , Neural Pathways/diagnostic imaging , Adolescent , Adult , Brain Mapping , Double-Blind Method , Female , Healthy Volunteers , Humans , Impulsive Behavior , Magnetic Resonance Imaging , Male , Middle Aged , Movement/drug effects , Rest , Ventral Tegmental Area/diagnostic imaging , Ventral Tegmental Area/drug effects , Young Adult
2.
Attach Hum Dev ; 21(4): 313-331, 2019 08.
Article in English | MEDLINE | ID: mdl-29768982

ABSTRACT

Reflective functioning (RF) is defined as the ability to infer mental states of others and oneself. While RF has been predominantly studied in attachment research, it might also occur in other autobiographical narratives because of its strong connection to self-organization and self-understanding. Therefore, this study took a first step combining research on RF with developmental narrative research. In a longitudinal lifespan study covering up to three measurements across 8 years and six age groups (N = 172), we aimed to detect RF in entire life narratives to explore its development with age and its contribution to causal-motivational coherence of life narratives. Although scores were initially low, RF could be identified in life narratives, and was found to develop throughout adolescence and to predict life narrative coherence above and beyond age. Results confirm RF as significantly contributing to narrative self-organization, indicating promising new paths in research on autobiographical narratives and self.


Subject(s)
Mentalization , Narration , Self Concept , Humans , Motivation
3.
Microb Drug Resist ; 21(3): 253-60, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25545311

ABSTRACT

The usefulness of carbapenems for gram-negative infections is becoming compromised by organisms harboring carbapenemases, enzymes which can hydrolyze the drug. Currently KPC (class A), NDM (class B), and OXA-48 types (class D) are the most globally widespread carbapenemases. However, among the GES-type class A extended-spectrum ß-lactamases (ESBLs) there are variants that hydrolyze carbapenems, with blaGES-5 being the most common. Two Escherichia coli and two Serratia marcescens harboring blaGES-5 on plasmids were isolated by the Canadian Nosocomial Infection Surveillance Program (CNISP) from four different patients in a single hospital over a 2-year period. Complete sequencing of the blaGES-5 plasmids indicated that all four had nearly identical backbones consisting of genes for replication, partitioning, and stability, but contained variant accessory regions consisting of mobile elements and antimicrobial resistance genes. The plasmids were of a novel replicon type, but belonged to the MOBQ1 group based on relaxase sequences, and appeared to be mobilizable, but not self-transmissible. Considering the time periods of bacterial isolation, it would appear the blaGES-5 plasmid has persisted in an environmental niche for at least 2 years in the hospital. This has implications for infection control and clinical care when it is transferred to clinically relevant gram-negative organisms.


Subject(s)
Drug Resistance, Bacterial/genetics , Escherichia coli/genetics , Gene Expression Regulation, Bacterial , Genome, Bacterial , Plasmids/metabolism , Serratia marcescens/genetics , beta-Lactamases/genetics , Aged , Aged, 80 and over , Amino Acid Sequence , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Canada/epidemiology , Carbapenems/pharmacology , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/microbiology , Endodeoxyribonucleases/genetics , Endodeoxyribonucleases/metabolism , Escherichia coli/classification , Escherichia coli/enzymology , Escherichia coli/isolation & purification , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Female , Hospitals , Humans , Interspersed Repetitive Sequences , Male , Middle Aged , Molecular Sequence Data , Phylogeny , Plasmids/chemistry , Replicon , Sequence Alignment , Sequence Analysis, DNA , Serratia Infections/drug therapy , Serratia Infections/epidemiology , Serratia Infections/microbiology , Serratia marcescens/classification , Serratia marcescens/enzymology , Serratia marcescens/isolation & purification , beta-Lactamases/metabolism
4.
Can J Gastroenterol ; 22(6): 571-3, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18560636

ABSTRACT

Infection with Dicrocoelium dendriticum in humans is rarely reported in the medical literature. This liver fluke, which commonly infects ruminants, has a complex life cycle with two intermediate hosts--the land snail and the ant. True human infection occurs by ingestion of the second intermediate host, but spurious infections have occurred after consumption of undercooked animal liver. The present report describes a patient with active Crohn's disease whose stool contained D dendriticum eggs. A brief discussion of the medical literature is presented.


Subject(s)
Crohn Disease/complications , Dicrocoeliasis/complications , Dicrocoelium/isolation & purification , Feces/parasitology , Animals , Colonoscopy , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Diagnosis, Differential , Dicrocoeliasis/drug therapy , Dicrocoeliasis/parasitology , Follow-Up Studies , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Tomography, X-Ray Computed
5.
Antimicrob Agents Chemother ; 48(9): 3305-11, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15328089

ABSTRACT

Empirical treatment is best guided by current surveillance of local resistance patterns. The goal of this study is to characterize the prevalence of antimicrobial nonsusceptibility within pneumococcal isolates from Canada. The Canadian Bacterial Surveillance Network is comprised of laboratories from across Canada. Laboratories collected a defined number of consecutive clinical and all sterile site isolates of S. pneumoniae in 2002. In vitro susceptibility testing was performed by broth microdilution with NCCLS guidelines. Rates of nonsusceptibility were compared to previously published reports from the same network. A total of 2,539 isolates were tested. Penicillin nonsusceptibility increased to 15% (8.5% intermediate, 6.5% resistant) compared to 12.4% in 2000 (P < or = 0.025, chi(2)). Only 32 (1.3%) isolates had an amoxicillin MIC of > or = 4 microg/ml and only 2 of 32 cerebrospinal fluid isolates had an intermediate susceptibility to ceftriaxone by meningeal interpretive criteria (MIC = 1 microg/ml). A total of 354 (13.9%) isolates were macrolide nonsusceptible (46.3% MLS(B), 56.7% M phenotype), increasing from 11.4% in 2000 (P < or = 0.0075, chi(2)). Only 13 (<1%) isolates had a telithromycin MIC of >1 microg/ml. Ciprofloxacin nonsusceptibility (defined as an MIC of > or = 4 microg/ml) increased to 2.7% compared to 1.4% in 2000 (P < or = 0.0025, chi(2)) and was primarily found in persons > or =18 years old (98.5%). Nonsusceptibility to penicillin, macrolides, and fluoroquinolones is increasing in Canada. Nonsusceptibility to amoxicillin and ceftriaxone remains uncommon. Newer antimicrobials such as telithromycin and respiratory fluoroquinolones have excellent in vitro activity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/drug effects , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Canada/epidemiology , Child , Child, Preschool , Drug Resistance, Bacterial , Humans , Infant , Middle Aged , Pneumococcal Infections/epidemiology , Population Surveillance
6.
Antimicrob Agents Chemother ; 46(5): 1295-301, 2002 May.
Article in English | MEDLINE | ID: mdl-11959559

ABSTRACT

A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected from 63 microbiology laboratories from across Canada during 2000 and characterized at a central laboratory. Of these isolates, 12.4% were not susceptible to penicillin (penicillin MIC, >or=0.12 microg/ml) and 5.8% were resistant (MIC, >or=2 microg/ml). Resistance rates among non-beta-lactam agents were the following: macrolides, 11.1%; clindamycin, 5.7%; chloramphenicol, 2.2%; levofloxacin, 0.9%; gatifloxacin, 0.8%; moxifloxacin, 0.4%; and trimethoprim-sulfamethoxazole, 11.3%. The MICs at which 90% of the isolates were inhibited (MIC90s) of the fluoroquinolones were the following: gemifloxacin, 0.03 microg/ml; BMS-284756, 0.06 microg/ml; moxifloxacin, 0.12 microg/ml; gatifloxacin, 0.25 microg/ml; levofloxacin, 1 microg/ml; and ciprofloxacin, 1 microg/ml. Of 578 isolates from the lower respiratory tract, 21 (3.6%) were inhibited at ciprofloxacin MICs of >or=4 microg/ml. None of the 768 isolates from children were inhibited at ciprofloxacin MICs of >or=4 microg/ml, compared to 3 of 731 (0.6%) from those ages 15 to 64 (all of these >60 years old), and 27 of 707 (3.8%) from those over 65. The MIC90s for ABT-773 and telithromycin were 0.015 microg/ml for macrolide-susceptible isolates and 0.12 and 0.5 microg/ml, respectively, for macrolide-resistant isolates. The MIC of linezolid was

Subject(s)
Anti-Bacterial Agents/pharmacology , Pneumococcal Infections/epidemiology , Population Surveillance , Streptococcus pneumoniae/drug effects , Adolescent , Adult , Aged , Canada/epidemiology , Child , Child, Preschool , Drug Resistance, Bacterial , Humans , Infant , Infant, Newborn , Microbial Sensitivity Tests , Middle Aged , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/isolation & purification
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