Treatment efforts for cocaine addiction are hampered by high relapse rates. To map brain areas underlying relapse, we used electrical brain stimulation and intracranial injection of pharmacological ...compounds after extinction of cocaine self-administration behavior in rats. Electrical stimulation of the hippocampus containing glutamatergic fibers, but not the medial forebrain bundle containing dopaminergic fibers, elicited cocaine-seeking behavior dependent on glutamate in the ventral tegmental area. This suggests a role for glutamatergic neurotransmission in relapse to cocaine abuse. The medial forebrain bundle electrodes supported intense electrical self-stimulation. These findings suggest a dissociation of neural systems subserving positive reinforcement (self-stimulation) and incentive motivation (relapse).
The biology of chronic wounds is complex and many factors act concurrently to impede healing progress. In this study, the dynamics of microflora changes and their antibiotic susceptibility patterns ...were evaluated longitudinally over 30 days using data from 28 patients with a total of 47 chronic lower extremity wounds.
In this study, colonized wound isolates were characterized using cultural, biochemical, and VITEK 2 methods. Antibiotic susceptibility patterns of the wound isolates were analyzed using various phenotypic assays. Furthermore, antimicrobial resistance patterns and the presence of mutations were evaluated by a genotypic assay, whole-genome sequencing (WGS).
and
were found to be the most common strains at early time points, while members of
were prevalent at later stages of infection. Antimicrobial resistance testing and whole-genome sequencing revealed that the molecular and phenotypic characteristics of the identified wound pathogens remained relatively stable throughout the study period. It was also noted that
and
species may serve as reservoirs for quinolone resistance in the Pacific region.
Our observations showed that wounds were colonized with diverse bacteria and interestingly their numbers and/or types were changed over the course of infection. The rapid genetic changes that accompanied the first 4 weeks after presentation did not directly contribute to the development of antibiotic resistance. In addition, standard wound care procedures did not appear to select for resistant bacterial strains. Future efforts should focus on defining those genetic changes associated with the wound colonizing microorganisms that occur beyond 4 weeks.
Key message
Multi-environment models using marker-based kinship information for both additive and dominance effects can accurately predict hybrid performance in different environments.
Sorghum is an ...important hybrid crop that is grown extensively in many subtropical and tropical regions including Northern NSW and Queensland in Australia. The highly varying weather patterns in the Australian summer months mean that sorghum hybrids exhibit a great deal of variation in yield between locations. To ultimately enable prediction of the outcome of crossing parental lines, both additive effects on yield performance and dominance interaction effects need to be characterised. This paper demonstrates that fitting a linear mixed model that includes both types of effects calculated using genetic markers in relationship matrices improves predictions. Genotype by environment interactions was investigated by comparing FA1 (single-factor analytic) and FA2 (two-factor analytic) structures. The G×E causes a change in hybrid rankings between trials with a difference of up to 25% of the hybrids in the top 10% of each trial. The prediction accuracies increased with the addition of the dominance term (over and above that achieved with an additive effect alone) by an average of 15% and a maximum of 60%. The percentage of dominance of the total genetic variance varied between trials with the trials with higher broad-sense heritability having the greater percentage of dominance. The inclusion of dominance in the factor analytic models improves the accuracy of the additive effects. Breeders selecting high yielding parents for crossing need to be aware of effects due to environment and dominance.
Is remotely delivered physiotherapy as good or better than face-to-face physiotherapy for the management of musculoskeletal conditions?
Randomised controlled, non-inferiority trial with concealed ...allocation, blinded assessors and intention-to-treat analysis.
A total of 210 adult participants with a musculoskeletal condition who presented for outpatient physiotherapy at five public hospitals in Sydney.
One group received a remotely delivered physiotherapy program for 6 weeks that consisted of one face-to-face physiotherapy session in conjunction with weekly text messages, phone calls at 2 and 4 weeks, and an individualised home exercise program delivered through an app. The other group received usual face-to-face physiotherapy care in an outpatient setting.
The primary outcome was the Patient Specific Functional Scale at 6 weeks with a pre-specified non-inferiority margin of –15 out of 100 points. Secondary outcomes included: the Patient Specific Functional Scale at 26 weeks; kinesiophobia, pain, function/disability, global impression of change and quality of life at 6 and 26 weeks; and satisfaction with service delivery at 6 weeks.
The mean between-group difference (95% CI) for the Patient Specific Functional Scale at 6 weeks was 2.7 out of 100 points (–3.5 to 8.8), where a positive score favoured remotely delivered physiotherapy. The lower end of the 95% CI was greater than the non-inferiority margin. Whilst non-inferiority margins were not set for the secondary outcomes, the 95% CI of the mean between-group difference ruled out clinically meaningful differences.
Remotely delivered physiotherapy with support via phone, text and an app is as good as face-to-face physiotherapy for the management of musculoskeletal conditions.
ACTRN12619000065190.
The basolateral complex of the amygdala (BLC) is part of a neural circuit that is activated in humans during cocaine craving elicited by exposure to drug-related environmental cues. In animals, the ...BLC is necessary for cocaine-seeking behavior elicited by cocaine-associated cues. It has not been determined whether BLC activation is sufficient to reinstate cocaine seeking.
To determine whether electrical or excitatory amino-acid stimulation of the BLC is sufficient to induce reinstatement of cocaine seeking in rats.
Rats were catheterized and trained to lever-press for intravenous cocaine infusions on a fixed ratio (FR)-1 schedule of reinforcement. Once baseline cocaine-taking criteria were met, lever-pressing behavior was extinguished by substitution of saline for cocaine. After meeting criteria for extinction, animals were subjected to brief electrical (20 Hz, 400 microA or 2 Hz, 400 microA; 200 pulses per stimulation) or N-methyl- d-aspartate (NMDA; 250 ng/0.5 microl) BLC stimulation and lever pressing behavior was monitored. RESULTS. Electrical BLC stimulation with 20-Hz produced reinstatement of lever pressing previously associated with cocaine self-administration, while 2-Hz stimulation did not. Electrical stimulation of cerebellar and medial forebrain bundle loci did not reinstate cocaine seeking. Hence, the reinstatement was frequency dependent and anatomically selective. NMDA microinjections into the BLC also reinstated cocaine-seeking behavior.
BLC stimulation is sufficient to reinstate cocaine-seeking behavior in the rat. These results are congruent with the hypothesis that the basolateral complex of the amygdala is part of a neural system mediating drug-seeking behavior.
ABSTRACT SOX requires the establishment of anonymous whistleblowing channels for public companies, but private companies are free to implement the channel(s) of their choosing. Although anonymous ...channels have long been considered a “best practice,” the evidence on their efficacy is mixed, creating confusion as to how private companies should proceed. Additionally, most studies comparing non-anonymous and anonymous channels have used a within-participants design, where both channels are available, limiting their ability to determine the incremental effectiveness of different whistleblowing systems. We find that offering either an anonymous channel or dual channels improves reporting intentions, relative to a non-anonymous channel, but primarily when tone at the top is weak. When tone at the top is strong, reporting intentions are not statistically different across the three systems. We also find no evidence that dual channels improve whistleblowing intentions relative to an anonymous channel, regardless of the tone at the top.
We have reported early attenuation of hemodynamic effects of transdermal nitroglycerin in patients with heart failure. We now report nitroglycerin plasma levels in those same patients. We ...administered transdermal nitroglycerin, 60 mg/24 h, to eight patients or placebo to seven patients in a double-blind fashion, and monitored pulmonary wedge pressure and nitroglycerin plasma levels for 24 hours. After placebo administration, nitroglycerin plasma levels and pulmonary wedge pressure remained unchanged. During transdermal nitroglycerin administration, the plasma nitroglycerin level rose from 0.04 +/- 0.12 ng/mL at baseline to near peak levels at 2 hours (7.43 +/- 7.21 ng/mL). Between 2 and 24 hours, levels fluctuated at a steady state. Pulmonary wedge pressure fell from 22 +/- 7 mm Hg at control to a nadir of 14 +/- 5 mm Hg at 4 hours (p less than 0.01). Despite persistently high plasma nitroglycerin levels, by 18 hours pulmonary wedge pressure was no longer significantly reduced (20 +/- 9 mm Hg). These results indicate that rapid development of tolerance is the cause of attenuated hemodynamic efficacy of transdermal nitroglycerin.
Variability in the uptake of enflurane has been studied using a computer-controlled “overpressure” induction technique in 23 paediatric patients. The administration of enflurane was ...feedback-controlled and its uptake measured using a closed anaesthesia delivery system with the end-tidal concentration held constant at 2.0%. The standard deviation in uptake was greater than 28% of the average uptake during the first 60 min of enflurane anaesthesia. The uptake at 60min ranged from 5.7 to 16.2ml min−1 m−2. The variability in enflurane uptake between patients was best minimized by normalizing the patient’s uptake according to body surface area. Although the average total volume of enflurane calculated according to a model compared well with the average total volume given in our study, the variation in uptake between patients indicated that a single model cannot be used to deliver anaesthesia to a varied patient population. The system described in this paper demonstrates the feasibility of using feedback control of fresh gas delivery for the automatic control of an “overpressure” induction technique.
This study compared the use of high-frequency jet ventilation (HFJV) and tidal ventilation (TV) in a group of dogs with induced global myocardial ischemia before and after cardiopulmonary bypass. ...Transesophageal echocardiography was used to determine whether HFJV with its lower airway pressures could improve cardiac performance. The surgical procedure was separated into four study periods: closed chest before bypass, open chest before bypass, open chest after bypass, and closed chest after bypass. During each of these study periods, the dogs were randomly ventilated with alternate periods of TV and HFJV to maintain the PaCO2 at 34.3 +/- 3.3 mm Hg (mean +/- SEM). Cardiac output, stroke volume, systemic mean blood pressure, left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular dP/dt, left ventricular stroke work, and expiratory volumetric flows were higher during HFJV, whereas airway pressures and pulmonary vascular resistance were lower. Increases in cardiac output and stroke volume during HFJV were due to a combination of improved left ventricular contractility indicated by increased LV dP/dt and increased left ventricular end-diastolic volume accompanying decreased airway pressures. These data indicate that HFJV with its lower airway pressure is associated with significantly less impairment of cardiovascular function than TV in dogs with induced global myocardial ischemia.
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