Coevolution of cytokine receptor families in the immune and nervous systems.

Close relationships between the nervous system and immune systems at molecular levels have now become evident. Receptors for CDF/LIF and CNTF, i.e., factors which play important roles in the nervous system, share a close structural similarity to those for IL-6, which is a molecule acting in the immune system. Receptors for these three factors belong to a subtype of cytokine receptor family (class IB cytokine receptor). We have constructed a higher subdomain structure of the receptor for CDF/LIF based on its known primary structures. The receptor contains immunoglobulin and fibronectin-like domains, in addition to common domains of the cytokine receptor, similar to those cell surface molecules of the neural immunoglobulin gene super family. These domains appear to have similar structures to the immunoglobulin. These lines of evidence suggest that the class IB cytokine receptor was formed as a result of those fusion of the genes for a more primitive cytokine receptor IA and for the neural immunoglobulin super gene family, and that, likewise, many molecules regulating neural development and those which act in the immune system have a common evolutionary origin.     

Pharmacokinetics of amitriptyline and its demethylated metabolite in serum and specific brain regions of rats after acute and chronic administration of amitriptyline

The concentrations of amitriptyline (AMT) and its demethylated metabolite nortriptyline (NRT) in the serum and in specific brain regions were determined periodically after acute or chronic administration of 20 mg/kg of AMT in rats. Both AMT and NRT declined from the serum in a biexponential manner and were eliminated monoexponentially from the brain regions, with no significant difference in elimination among the eight brain regions examined. In the brain, both AMT and NRT were unevenly distributed after chronic administration, whereas an even distribution was observed after acute administration. The AUCbrain:AUCserum ratio of AMT was higher than that of NRT, indicating greater transport of AMT into the brain regions. The AUCAMT value in the serum increased 1.6 times after chronic administration, whereas no significant changes were observed in the brain regions. The AUCNRT values increased 9.0 times in the serum and 6.8 times in the brain, with the increase in the serum being greater. These results suggest inhibited distribution of the drugs into the tissues, including the brain regions, and enhanced metabolism of AMT.     

Transition from Film to Electronic Media in the First-Year Medical School Gross Anatomy Lab

For the benefit of the first-year gross anatomy students, we digitized and published on a Web site images that had been collected over a 30-year period. We provided a CD-ROM (compact disk, read-only media) containing the image set in higher quality format to students and faculty. We supplemented basic images with hot topics such as CT angiography, virtual colonography, computer-aided diagnosis, and 3D post-processing. Full motion video and moving JPEG (Joint Photo Expert Group) animations were integrated into the atlas. On the post course questionnaire medical students reported that the images on CD-ROM were helpful during the course and for review prior to examinations. Faculty and medical students used the CD-ROM for problem-based learning sections and facilitator training. The images were clear and easily projected during review sessions and were useful for the small group sessions, where they served as examples of normal anatomy.     

Factors associated with intention to receive vaccines for bacterial sexually transmitted infections among young HPV-vaccinated Canadian women

ObjectiveThe aim of this study was to explore the acceptability of bacterial STI vaccines among young HPV-vaccinated Canadian women to inform future vaccine program implementation.MethodsA 20-item cross-sectional questionnaire was administered from June 2019 to June 2020 to HPV-vaccinated participants of the pan-Canadian QUEST cohort. Multivariable logistic regression models assessed interest in chlamydia, syphilis, and gonorrhea vaccines using a priori variables and factors significant in bivariate analysis.ResultsOf the 1092 respondents analyzed, 82% indicated interest in receiving one or more future STI vaccines. Respondents had a median age of 19.6 years (range 16.9–23.4), and 75% of respondents identified as white/European descent. In adjusted analyses, intent to engage in positive health behaviours was associated with vaccine interest for syphilis (OR = 5.76, 95% CI 4.03–8.27), chlamydia (OR = 5.27, 95% CI 3.66–7.63), and gonorrhea (OR = 5.96, 95% CI 4.15–8.60). Willingness to pay for an STI vaccine was also associated with vaccine interest for syphilis (OR = 2.02, 95% CI 1.29–3.19), chlamydia (OR = 2.41, 95% CI 1.50–3.90), and gonorrhea (OR = 2.29, 95% CI 1.44–3.63). Ever having sexual intercourse and identifying as LGBTQ were significantly associated with vaccine interest for all infections, while age and ever being immunosuppressed were not significant in any adjusted models.ConclusionFindings indicate over 80% of participants in a cohort of young HPV-vaccinated Canadian women are interested in receiving future bacterial STI vaccines. Further exploration of STI vaccine acceptability among diverse populations is required to inform future bacterial STI vaccine program implementation.Supplementary InformationThe online version contains supplementary material available at 10.17269/s41997-022-00648-2.     

Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results

Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial. Bivariate and multivariable logistic regression assessed factors that influence willingness to self-collect on 4945 respondents. Overall, 52.1% of respondents indicated willingness to self-collect an HPV sample. In multivariable analysis, the odds of willingness to self-collect were significantly higher in participants who agreed that screening with an HPV test instead of a Pap test was acceptable to them (odds ratio (OR): 1.45 (95% confidence interval (CI): 1.15, 1.82), those who indicated that collecting their own HPV sample was acceptable to them (p < 0.001), and those with higher educational ascertainment (OR: 1.31, 95% CI: 1.12, 1.54). The findings offer insight into the intentions to self-collect in those already engaged in screening, and can inform cervical cancer screening programs interested in offering alternative approaches to HPV-based screening.     

Conservative,open or percutaneous repair for acute rupture of the Achilles tendon

Purpose. To review the complications and recovery of patients with Achilles tendon rupture managed by percutaneous repair, open repair, and non-operative means in a tertiary referral centre between 2001 and 2003.

Methods. The operating theatre register and logbooks of the Consultants were used to identify surgically managed patients, while plaster room records were used for conservatively managed patients. We collated demographic and management details.

Results. The number of plaster changes (p < 0.001), median length of time in cast (p < 0.001), and number of outpatient visits (p < 0.05) was greater in conservatively managed patients. We performed no formal statistical analysis given the small numbers. Conservative management was the least expensive and open surgery the most costly modality of management. Percutaneous surgery was approximately a third of the cost of open surgery when performed under local anaesthetic.

Conclusion. In our setting, percutaneous repair and conservative management are viable alternatives to open surgery, which carries higher complications rates and was the most costly of the three. Individual patients will have different needs due to their age, occupation, or level of sporting activity.     

Synergistic Effect of Hydrotrope and Surfactant on Solubility and Dissolution of Atorvastatin Calcium: Screening Factorial Design Followed by Ratio Optimization

The present study was aimed at investigating the effect of hydrotrope and surfactant on poor solubility of atorvastatin calcium. Excipients screening followed by factorial design was performed to study effect of excipients and manufacturing methods on solubility of drug. Three independent factors (carrier, surfactant and manufacturing method) were evaluated at two levels using solubility as a dependant variable. Solid-state characterisation was performed using Fourier transform infrared spectroscopy and differential scanning calorimetry. Optimised complex were incorporated into orally disintegrating micro tablets and in vitro dissolution test was performed. Nicotinamide, Plasdone and sodium dodecyl sulphate were emerged as promising excipients from excipient screening. General regression analysis revealed only the type of carrier has significantly enhanced (P<0.05) the solubility of drug while other factors were found to be nonsignificant. Ratio optimisation trial revealed that drug to nicotinamide ratio is more critical in enhancing the solubility of drug (40 fold increases in solubility compared to pure drug) in comparison to drug-surfactant ratio; however the presence of surfactant deemed essential. Significantly higher rate and extent of dissolution was observed from solid dispersion complex and tablets compared to dissolution of pure drug (P<0.05). Study revealed hydrotrope and surfactant have synergistic effect on solubility and dissolution of atorvastatin calcium and this can be explored further.