Search

Emerging research shows that many individuals commonly consume cannabis while gambling. However, individuals' expectations for how cannabis consumption will impact their gambling behavior remain unknown. Participants who gambled weekly ( N = 472) were recruited from Amazon Mechanical Turk and completed assessments of gambling behaviors, cannabis consumption, and expectations about the influence of cannabis on gambling. Almost all participants (94%) screened positive for problem gambling. Over half of participants (55%) reported lifetime cannabis consumption, and almost all those participants (99%) reported gambling under the influence of cannabis (GUIC) in the past month. Most participants agreed with positive expectations of gambling; they expected that they would feel calmer when under the influence of cannabis (61.4%), that gambling would be more enjoyable (61.0%), and that their gambling skills would increase when GUIC (60.6%). At the same time, most participants also agreed with negative expectations of GUIC. They expected cannabis use would make them more careless (56.4%), more anxious (54.8%), and less able to concentrate (53.7%) while gambling. Negative cannabis expectancies were significantly associated with the severity of cannabis consumption. Both positive and negative cannabis expectancies were significantly associated with gambling problems and time spent gambling under the influence of cannabis. These findings indicate that expectations may influence the decision to consume cannabis and gamble simultaneously. This study contributes to the need for addressing cannabis expectations during treatment of gambling problems., Competing Interests: No authors have competing interests., (© 2024 Authors et al.)

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies., (Copyright © 2020 Stewart, MacLean, Stromberg, Whelan, Bailey, Gensel and Wilson.)

Background: Photoselective vaporization of the prostate (PVP) is a bloodless, relatively painless alternative to transurethral resection of the prostate (TURP) for relief of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH)., Objective: We compare the effectiveness, safety and cost-effectiveness of Greenlight Laser PVP (HPS-120) and TURP., Methods: We conducted a prospective, non-randomized trial in 3 Ontario centres from March 2008 to February 2011. Assessments were completed at baseline, 1 and 6 months following surgery at the physicians' offices and at 12 and 24 months by phone. The primary outcome was the change in International Prostate Symptoms Score (IPSS) score at 6 months versus baseline. Secondary outcomes were changes in flow rate, postvoid residual (PVR), prostate-specific antigen (PSA) and sexual health inventory for men (SHIM) scores. Adverse events, health-related quality of life (HRQoL), resource utilization and productivity losses were collected., Results: Although the IPSS decreased in both arms (n = 140 for PVP and n = 24 for TURP) between baseline and 6 months, the difference in change over time between the groups was not statistically significant (p = 0.718). Other outcomes improved equally from baseline and 6 months (Qmax, SHIM, PSA and HRQoL), with only changes in PVR favouring PVP (p = 0.018). There were no statistical differences in serious adverse events. In total, 130 of 140 PVP patients were outpatients, all TURP subjects were inpatients. PVP was less costly than TURP ($3891 vs. $4863; p < 0.001) with similar quality-adjusted life years (0.448 vs. 0.441; p = 0.658)., Conclusion: Greenlight Laser PVP (HPS-120) is a safe and cost-effective alternative to TURP for outpatient treatment of LUTS and can be completed as an outpatient with minimal blood loss.

Background: As an alternative to transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP) provides a bloodless, relatively painless relief of lower urinary tract symptoms for men with benign prostatic hyperplasia. Following a review of the evidence in 2006, the Ontario Health Technology Advisory Committee recommended that a study be conducted to evaluate PVP in Ontario., Objectives: To compare the clinical effectiveness, safety, cost-effectiveness, and budget impact of PVP compared to conventional TURP for the treatment of benign prostatic hyperplasia in Ontario., Methods: A prospective, nonrandomized trial was conducted in 3 Ontario centres. Consenting subjects were assessed at baseline and 1, 3, and 6 months following surgery. Outcome measures included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), post-void residual (PVR) volume, prostate-specific antigen (PSA), health-related quality of life (HRQOL) using the EuroQol 5 Domain questionnaire, and the Sexual Health Inventory for Men (SHIM) score. Adverse events, resource utilization, and productivity losses were also assessed. Cost-effectiveness and budget impact analyses were completed using data from the study., Results: Between February 2008 and August 2010, 164 subjects were enrolled in the study (n = 140 for PVP and n = 24 for TURP). Treatment outcomes were similar between the 2 groups at 6 months, with the IPSS decreasing similarly over time (P = 0.718). For other treatment outcomes (Qmax, PSA, HRQOL, SHIM) both treatments provided similar benefit over time; only changes in PVR volume favoured PVP (P = 0.018). The majority of PVP patients were managed on an outpatient basis, with only 7.1% requiring admission (all TURP subjects were inpatients). At 6 months, PVP was less costly than TURP ($3,891 versus $4,863; P = 0.001), with similar quality-adjusted life-years (0.448 versus 0.441; P = 0.658). PVP remained the most cost-effective treatment across all decision-making thresholds, with the technology costing less and providing similar clinical outcomes. Extrapolating the results to a provincial level indicated (based on an estimated case volume of 12,335 TURPs) that there is an opportunity to reallocate just over $14 million (Cdn), primarily related to the reduced need for hospital admission., Limitations: This study was nonrandomized, and the results should be interpreted with some caution, despite generally similar baseline characteristics between the 2 groups. Recruiting individuals to the TURP arm was a challenge, resulting in a size imbalance between treatment arms., Conclusions: Based on this analysis, PVP appears to be a cost-effective alternative to TURP, providing similar clinical benefit at a lower cost to the health system.

Background: Canada, akin to other developed nations, faces the growing challenges of end-stage renal disease (ESRD). Even with expanded donor criteria for renal transplantation (the treatment of choice for ESRD), the supply of kidneys is outpaced by the escalating demand. Remuneration for kidney donation is proscribed in Canada. Without an option of living-related transplantation (biological or emotional donors), patients often struggle with long waiting lists for deceased donor transplantation. Accordingly, many patients are now opting for more expedient avenues to obtaining a renal transplant. Through commercial organ retrieval programs, from living and deceased donors, patients are travelling outside Canada to have the procedure performed., Methods: Between September 2001 and July 2007, 10 patients (7 males, 3 females) underwent commercial renal transplantation outside Canada. We describe the clinical outcomes of these patients managed postoperatively at our single Canadian transplant centre., Results: Six living unrelated and 4 deceased donor renal transplantations were performed on these 10 patients (mean age 49.5 years). All procedures were performed in developing countries and the postoperative complications were subsequently treated at our centre. The mean post-transplant serum creatinine was 142 μmol/L. The average follow-up time was 29.8 months (range: 3 to 73 months). One patient required a transplant nephrectomy secondary to fungemia and subsequently died. One patient had a failed transplant and has currently resumed hemodialysis. Acute rejection was seen in 5 patients with 3 of these patients requiring re-initiation of hemodialysis. Only 1 patient had an uncomplicated course after surgery., Discussion: Despite the kidney trade being a milieu of corruption and commercialization, and the high risk of unconventional complications, patients returning to Canada after commercial renal transplantation are the new reality. Patients are often arriving without any documentation; therefore, timely, goal-directed therapy for surgical and infectious complications is frequently delayed because of the time taken to establish an accurate diagnosis. Refuting the existence of commercial renal transplantation may not be a practical solution; more consistent communication and documentation with transplant teams may be more pragmatic. In the current climate, patients considering the option of overseas commercial renal transplantation should be advised of the potential increased risks.

Objective: The open Anderson-Hynes procedure has an overall success rate of 90% for ureteropelvic junction obstruction. Laparoscopic pyeloplasty (LP) was developed to reduce morbidity and hospital stay while preserving the excellent results. We report on the results of our experience with laparoscopic pyeloplasty., Methods: Between January 2001 and May 2006, 77 consecutive patients underwent LP performed by one of 4 surgeons at our institution. Patients were reassessed with ultrasound (U/S) or intravenous pyelogram (IVP) at 6 weeks. Diuretic renal scan and U/S or IVP were performed at 6 months, and subsequent follow-up included a U/S or IVP as well as clinical assessment. Patients were assessed for pain and hydronephrosis on radiologic imaging, clearance on diuretic renal scan (T(1/2)) and differential renal function., Results: We evaluated 73 patients. The mean patient age was 38 years (range 16-71 yr), the mean operating time was 218 minutes (range 110-409 min), and the mean blood loss was 57 mL (range 25-250 mL). Mean hospital stay was 3.0 days (range 2-7 d). The success rate was 90.4%, and failures were mainly due to poor function after surgery (3 patients). Pyelolithotomy was performed concomitantly on 6 patients, which on average extended operative time by 36 minutes., Conclusion: Our success rates are consistent with the LP experience of other centres and are comparable with rates for the open technique. Patients had short hospital stays, and complications were negligible. With experienced surgeons, LP should be the first-line treatment for ureteropelvic junction obstruction.

A PEGylated glucagon-like peptide-1 (GLP-1) agonist and glucagon antagonist hybrid peptide was engineered as a potential treatment for type 2 diabetes. To support preclinical development of this PEGylated dual-acting peptide for diabetes (DAPD), we developed a reproducible method for PEGylation, purification, and analysis. Optimal conditions for site-specific PEGylation with 22 and 43 kDa maleimide-polyethylene glycol (maleimide-PEG) polymers were identified by evaluating pH, reaction time, and reactant molar ratio parameters. A 3-step purification process was developed and successfully implemented to purify PEGylated DAPD and remove excess uncoupled PEG and free peptide. Five lots of 43 kDa PEGylated DAPD with starting peptide amounts of 100 mg were produced with overall yields of 53% to 71%. Analytical characterization by N-terminal sequencing, amino acid analysis, matrix-assisted laser desorption/ionization mass spectrometry, and GLP-1 receptor activation assay confirmed site-specific attachment of PEG at the engineered cysteine residue, expected molecular weight, correct amino acid sequence and composition, and consistent functional activity. Purity and safety analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), analytical ion-exchange chromatography, reversed-phase high-performance liquid chromatography, and limulus amebocyte lysate test showed that the final products contained <1% free peptide, <5% uncoupled PEG, and <0.2 endotoxin units per milligram of peptide. These results demonstrate that the PEGylation and purification process we developed was consistent and effective in producing PEGylated DAPD preclinical materials at the 100 mg (peptide weight basis) or 1.2 g (drug substance weight basis) scale.

The closely related peptides glucagon-like peptide (GLP-1) and glucagon have opposing effects on blood glucose. GLP-1 induces glucose-dependent insulin secretion in the pancreas, whereas glucagon stimulates gluconeogenesis and glycogenolysis in the liver. The identification of a hybrid peptide acting as both a GLP-1 agonist and a glucagon antagonist would provide a novel approach for the treatment of type 2 diabetes. Toward this end a series of hybrid peptides made up of glucagon and either GLP-1 or exendin-4, a GLP-1 agonist, was engineered. Several peptides that bind to both the GLP-1 and glucagon receptors were identified. The presence of glucagon sequence at the N terminus removed the dipeptidylpeptidase IV cleavage site and increased plasma stability compared with GLP-1. Targeted mutations were incorporated into the optimal dual-receptor binding peptide to identify a peptide with the highly novel property of functioning as both a GLP-1 receptor agonist and a glucagon receptor antagonist. To overcome the short half-life of this mutant peptide in vivo, while retaining dual GLP-1 agonist and glucagon antagonist activities, site-specific attachment of long chained polyethylene glycol (PEGylation) was pursued. PEGylation at the C terminus retained the in vitro activities of the peptide while dramatically prolonging the duration of action in vivo. Thus, we have generated a novel dual-acting peptide with potential for development as a therapeutic for type 2 diabetes.

Objective: To assess the effects of different cognitive orientations focused on social comparison or self-comparison, followed by success or failure feedback, on mood, task persistence, and task difficulty choice in children with cancer., Method: Children with cancer (N = 79) and a group of age-matched controls (N = 72 were randomly assigned in a 2 (Achievement Orientation) x 2 (Feedback) between-subjects design., Results: Between-group differences revealed that children with cancer chose more difficult tasks for the future than those in the comparison group, while the comparison subjects chose to persist longer with the problems than did children with cancer, with no significant differences on measures of mood., Conclusions: The beneficial effects of achievement orientation as a clinical manipulation may not be as robust as expected with a medically ill population, due to the apparent stability of achievement orientations.

The flow immunosensor works on a principle somewhat distinct from other immunoassay systems in that it performs a displacement immunoassay. Antibody-coated matrices are saturated with fluorescently labeled benzoylecgonine (BE), which is released and measured in the presence of BE-containing urine and measured downstream from the matrix. The same antibody matrix can be used for many samples. A flow immunosensor instrument, built by US Drug Testing, Inc., has recently received "Premarket Notification' (510(K)) from the Food and Drug Administration (FDA) to screen urine for the presence of the cocaine metabolite BE. The performance of the flow immunosensor for screening BE in urine was validated by comparison with results of a blind study using the Syva EMIT, the Abbott TDx and gas chromatography-mass spectroscopy (GC-MS). Potentially interfering drugs were also spiked into urine and evaluated using the flow immunosensor. While the FDA approval is for determining whether the BE concentration is above or below the 300 micrograms/l cutoff recommended by the National Institute of Drug Abuse, we have also shown that the flow immunosensor can be adapted to produce quantitative determinations of the amount of BE in the urine samples. The reliability of the quantitation was confirmed by testing 100 urine samples containing unknown amounts of BE using the flow immunosensor. GC-MS and the Abbott TDx system. Comparison of quantitative data obtained using the immunosensor and GC-MS showed a 97% correlation, compared with a much lower value for data from the TDx and GC-MS.

Mouse S-antigen clones were isolated from a mouse retinal cDNA library using a bovine S-antigen cDNA probe. The largest clone (MSC-242) comprised 1532 bp and contained the entire coding sequence. The nucleotide sequence homology between the mouse and bovine coding regions was 84%, while non-coding regions appeared to be more divergent. The deduced amino acid sequence indicated that the mouse S-antigen had 403 residues and its molecular ratio was 44,930. An overall amino acid sequence similarity of 84% was observed between the mouse and bovine proteins. This degree of similarity dropped to 60% and 47% at the N and the C termini, respectively. The local homology with alpha-transducin observed in the bovine proteins, including the putative phosphoryl and rhodopsin binding sites, was conserved in the mouse as well. There was no overall sequence similarity with other proteins listed in the National Biomedical Research Foundation (NBRF) protein sequence database. Among the uveitopathogenic sites for experimental autoimmune uveitis (EAU), peptides N and M were identical to their bovine counterparts. Peptides 3 and K, however, were more divergent. The short repeats within these peptides were conserved.

Ten solid neuroblastoma tumors were examined for beta 2-microglobulin (beta 2-m) and HLA-class I expression in an immunocytochemical assay. Blood vessel endothelium and a small population of cells (less than 6% of small round cells) were consistently stained in frozen sections of each tumor. No beta 2-m or HLA-class I reactivity was detected in the remainder (greater than 94%) of the small round cells in each tumor. The localization of most of the positive cells near stromal tissue and blood vessels suggests that most of these cells may be of non-tumor origin. The patients from which the tumors were taken varied in degree of disease involvement, yet no differences with respect to beta 2-m and HLA-class I expression were found among the tumors. A procedure for visualizing beta 2-m and HLA-class I molecules in formaldehyde-fixed, paraffin-embedded tissue is described. This confirmed the results in frozen sections. These findings extend previous reports of weak beta 2-m and HLA-class I levels in cells of neuronal origin. The clinical implications are discussed.

Metronidazole was found to be active against Bacteroides fragilis strains isolated from human lesions. The minimal inhibitory concentrations (MIC) were from 0.16 to 2.5 mug/ml and the minimal bactericidal concentrations (MBC) were from 0.16 to 2.5 mug/ml; usually the MIC and MBC figures were equivalent. These levels are easily attainable in the serum following normal therapeutic doses. The drug is not toxic and side effects are rare and it would therefore seem highly suitable for treating Bacteroides infections and also may be considered prophylactically in certain situations that are described.