Personal values influencing career path in academic medicine: Perspectives of selected Canadian trainees [version 2; referees: 2 approved, 1 approved with reservations]

To pursue research, education, and health policy in one’s career, broadly defined as academic medicine, is one of the most important decisions of a trainee doctor’s career. Despite this, there is scant literature on which factors influence trainees’ choices towards clinical work or academic research. As the MD/PhD is a relatively young training path compared to the traditional PhD (Doctor of Philosophy) and MD (Doctor of Medicine) programs, it prompts the question: at the crossroads of a career, what sways the individual to select an MD, PhD, or MD/PhD program? This is a valuable question to be answered for trainees who are considering multiple career paths, for educators who want to guide undifferentiated students, and for policy makers who develop and coordinate research programs. “Intellectual stimulation” is the most consistently identified personal value which draws trainees to academic medicine. Mentorship is linked strongly to success in the field. Conversely, long training periods, a lack of autonomy, and financial considerations are deterrents from a career in academic medicine. Insight into the decision-making process is provided by recent Canadian trainees in these respective fields, in a series of short interviews

Characterization of a novel family of fibronectin-binding proteins with M23 peptidase domains from <i>Treponema denticola</i>

Interactions with fibronectin are important in the virulence strategies of a range of disease-related bacteria. The periodontitis-associated oral spirochaete Treponema denticola expresses at least two fibronectin-binding proteins, designated Msp (major surface protein) and OppA (oligopeptide-binding protein homologue). To identify other T. denticola outer membrane fibronectin-binding proteins, the amino acid sequence of the Treponema pallidum fibronectin-binding protein Tp0155 was used to survey the T. denticola genome. Seven T. denticola genes encoding orthologous proteins were identified. All but two were expressed in Escherichia coli and purified recombinant proteins bound fibronectin. Using antibodies to the N-terminal region of Tp0155, it was demonstrated that T. denticola TDE2318, with highest homology to Tp0155, was cell surface localized. Like Tp0155, the seven T. denticola proteins contained an M23 peptidase domain and four (TDE2318, TDE2753, TDE1738, TDE1297) contained one or two LysM domains. M23 peptidases can degrade peptidoglycan whereas LysM domains recognize carbohydrate polymers. In addition, TDE1738 may act as a bacteriocin based on homology with other bacterial lysins and the presence of an adjacent gene encoding a putative immunity factor. Collectively, these results suggest that T. denticola expresses fibronectin-binding proteins associated with the cell surface that may also have cell wall modifying or lytic functions

Cocaine hydrochloride, cocaine methiodide and methylenedioxypyrovalerone (MDPV) cause distinct alterations in the structure and composition of the gut microbiota

Abstract Cocaine is a highly addictive psychostimulant drug of abuse that constitutes an ongoing public health threat. Emerging research is revealing that numerous peripheral effects of this drug may serve as conditioned stimuli for its central reinforcing properties. The gut microbiota is emerging as one of these peripheral sources of input to cocaine reward. The primary objective of the present study was to determine how cocaine HCl and methylenedioxypyrovalerone, both of which powerfully activate central reward pathways, alter the gut microbiota. Cocaine methiodide, a quaternary derivative of cocaine that does not enter the brain, was included to assess peripheral influences on the gut microbiota. Both cocaine congeners caused significant and similar alterations of the gut microbiota after a 10-day course of treatment. Contrary to expectations, the effects of cocaine HCl and MDPV on the gut microbiota were most dissimilar. Functional predictions of metabolic alterations caused by the treatment drugs reaffirmed that the cocaine congeners were similar whereas MDPV was most dissimilar from the other two drugs and controls. It appears that the monoamine transporters in the gut mediate the effects of the treatment drugs. The effects of the cocaine congeners and MDPV on the gut microbiome may form the basis of interoceptive cues that can influence their abuse properties

The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models

Cocaine use disorder remains a major global health concern, with growing evidence that the gut microbiome modulates drug-related behaviors. This study examines the microbiome&rsquo;s role in cocaine-induced psychomotor activation and context-dependent reward responses using germ-free (GF) and antibiotic-treated (ABX) models. In GF mice, the absence of a microbiome blunted cocaine-induced psychomotor activation (p = 0.013), which was restored after conventionalization. GF mice also showed reduced cocaine-conditioned place preference (CPP) (p = 0.002), which normalized after conventionalization. Dopaminergic function, critical for psychomotor responses and reward, was microbiome-dependent, with increased dopamine levels (p = 0.009) and normalized turnover ratios after conventionalization. In the ABX model, microbiome depletion reduced both cocaine-induced locomotion and CPP responses (p &le; 0.009), further supporting the role of gut microbes in modulating psychomotor and reward behaviors. ABX-treated mice also showed significant declines in microbial diversity, shifts in bacterial structure, and dysregulation in metabolic, immune, and neurotransmitter pathways (p &le; 0.0001), including alterations in short-chain fatty acids and gamma-aminobutyric acid metabolism. These findings highlight the gut microbiome&rsquo;s critical role in regulating cocaine&rsquo;s psychomotor and rewarding effects, offering insights into potential therapeutic strategies for cocaine use disorder

Effects of a high fat diet on gut microbiome dysbiosis in a mouse model of Gulf War Illness

AbstractGulf War Illness (GWI) is a chronic health condition that appeared in Veterans after returning home from the Gulf War. The primary symptoms linked to deployment are posttraumatic stress disorder, mood disorders, GI problems and chronic fatigue. At first glance, these symptoms are difficult to ascribe to a single pathological mechanism. However, it is now clear that each symptom can be linked individually to alterations in the gut microbiome. The primary objective of the present study was to determine if gut microbiome dysbiosis was evident in a mouse model of GWl. Because the majority of Gulf War Veterans are overweight, a second objective was to determine if a high fat diet (HF) would alter GWI outcomes. We found that the taxonomic structure of the gut microbiome was significantly altered in the GWI model and after HF exposure. Their combined effects were significantly different from either treatment alone. Most treatment-induced changes occurred at the level of phylum in Firmicutes and Bacteroidetes. If mice fed HF were returned to a normal diet, the gut microbiome recovered toward normal levels in both controls and GWI agent-treated mice. These results add support to the hypotheses that dysbiosis in the gut microbiome plays a role in GWI and that life-style risk factors such as an unhealthy diet can accentuate the effects of GWI by impacting the gut microbiome. The reversibility of the effect of HF on the gut microbiome suggests new avenues for treating GWI through dietary intervention.</jats:p

Supplementary Material for: Sterile corneal infiltrates following cataract surgery: case series.

We report a case series of twenty-six eyes of 26 patients undergoing planned cataract surgery from December 2021 to March 2022, who were diagnosed as having whitish round infiltrates in the surgical corneal incisions. The infiltrates were detected at the first check after 5 to 8 days from cataract surgery and were located either within the main corneal incision and/or in the smaller incisions. Corneal infiltrates (CIs) were single or multiple, without epithelial defects and painless. All infiltrates were initially treated with full topical antibiotic coverage, in order to control eventual and serious post-surgical infection. However, at daily checks, the clinical course of CIs suggested a sterile etiology. For this reason, steroidal topical treatment was maintained for a long time with slow tapering until complete remission of the CIs. All infiltrates resolved completely in around 30-40 days. The surgical instruments and the sterilization process were scrutinized. A white amorphous material was found mainly on non-disposable anterior chamber cannulas and on I/A tips. Disposable cannulas were adopted, and machinery for cleaning and sterilization procedures were reviewed, with specific reference to water softener renewal. Thanks to these precautions, CIs never occurred again. Finally, our hypothesis was an immune corneal reaction to amorphous deposit on cannula tips. This case series describes a previously unknown complication of cataract surgery and our experience might be useful for other surgeons

Long access heroin self-administration significantly alters gut microbiome composition and structure

Introduction It is well known that chronic opioid use disorder is associated with alterations in gastrointestinal (GI) function that include constipation, reduced motility, and increased bacterial translocation due to compromised gut barrier function. These signs of disrupted GI function can be associated with alterations in the gut microbiome. However, it is not known if long-access opioid self-administration has effects on the gut microbiome.Methods We used 16S rRNA gene sequencing to investigate the gut microbiome in three independent cohorts (N=40 for each) of NIH heterogeneous stock rats before onset of long-access heroin self-administration (i.e., naive status), at the end of a 15-day period of self-administration, and after post-extinction reinstatement. Measures of microbial alpha- and beta-diversity were evaluated for all phases. High-dimensional class comparisons were carried out with MaAsLin2. PICRUSt2 was used for predicting functional pathways impacted by heroin based on marker gene sequences.Results Community alpha-diversity was not altered by heroin at any of the three phases by comparison to saline-yoked controls. Analyses of beta-diversity showed that the heroin and saline-yoked groups clustered significantly apart from each other using the Bray-Curtis (community structure) index. Heroin caused significant alterations at the ASV level at the self-administration and extinction phases. At the phylum level, the relative abundance of Firmicutes was increased at the self-administration phase. Deferribacteres was decreased in heroin whereas Patescibacteria was increased in heroin at the extinction phase. Potential biomarkers for heroin emerged from the MaAsLin2 analysis. Bacterial metabolomic pathways relating to degradation of carboxylic acids, nucleotides, nucleosides, carbohydrates, and glycogen were increased by heroin while pathways relating to biosynthesis of vitamins, propionic acid, fatty acids, and lipids were decreased.Discussion These findings support the view that long access heroin self-administration significantly alters the structure of the gut microbiome by comparison to saline-yoked controls. Inferred metabolic pathway alterations suggest the development of a microbial imbalance favoring gut inflammation and energy expenditure. Potential microbial biomarkers and related functional pathways likely invoked by heroin self-administration could be targets for therapeutic intervention