"We regret to inform you that you did not match": Reflections on how to improve the match experience.

There is increasing concern amongst stakeholders over the high numbers of unmatched Canadian Medical Graduates (CMGs), yet little is known from the perspective of those who go unmatched. We present an opinion-based narrative analysis examining the matching process by reflecting on the pre- and post-match period and provide suggestions related to the Canadian context from the unmatched perspective. The challenge in the pre-match period was a lack of transparency around elective availability, resident selection criteria, and what happens after going unmatched. For the post-matched period, we were challenged with decision-making during a time-sensitive period, scheduling post-match electives, handling our finances, and improving our future residency applications without feedback. We have tried to identify the most impactful issues we encountered as applicants and unmatched students, and offered suggestions to improve the applicant experience. In addition to sharing our reflection in going unmatched, we also highlight the positive side of this formative experience.

Les parties prenantes sont de plus en plus préoccupées par le nombre élevé de diplômés canadiens en médecine (DCM) qui ne sont pas jumelés. Or, l'on sait peu de choses sur leur perspective sur le sujet. Nous présentons une analyse narrative fondée sur les opinions qui examine le processus de jumelage en réfléchissant aux périodes précédant et suivant le jumelage. Nous fournissons également des suggestions pouvant s'appliquer aux individus non jumelés dans le contexte canadien. Le défirencontré en ce qui concerne la période précédant le jumelage tenait au manque de transparence en ce qui a trait à la disponibilité de stages à option, les critères de sélection des résidents et ce qui arrive aux étudiants une fois qu'ils ne sont pas jumelés. En ce qui concerne la période suivant le jumelage, nous avons eu de la difficulté à prendre des décisions étant donné la période de temps limitée ; planifier les stages à option après le jumelage ; gérer nos finances et améliorer notre processus d'application à un poste de résidence sans avoir obtenu de rétroaction. Nous avons tenté d'identifierles problèmes ayant eu le plus d'impact sur nous comme candidats et les étudiants non jumelés et nous avons proposé des suggestions afin d'améliorer l'expérience des candidats. En plus de partager nos réflexions sur le fait de ne pas être jumelé, nous mettons également en évidence le côté positif de cette expérience formative.

In vitro leishmanicidal activity of monoterpenes present in two species of Protium (Burseraceae) on Leishmania amazonensis.

ETHNOPHARMACOLOGICAL RELEVANCE: Leishmaniasis is a neglected disease that affects millions of people around the world. Parasite resistance and the toxicity to the current treatments lead to the search for new effective molecules. Plants are widely used in traditional and indigenous medicine to treat different diseases. The oleoresin of the genus Protium, which is rich in volatile compounds active against different microorganisms, is among these plants. AIM: The aim of this study was to evaluate the leishmanicidal potential of Protium altsonii (PaEO) and P. hebetatum (PhEO) (Burseraceae) oleoresins, as well as of three representative monoterpenes in their constitution: α-pinene, p-cymene and 1,8-cineole. MATERIALS AND METHODS: Protium altsonii (PaEO) and P. hebetatum (PhEO) oleoresins and three of their constituents were tested in vitro on promastigotes and amastigotes-infected macrophages in different concentrations. Their toxicity for macrophages was analyzed by XTT assay and phagocytic ability. It was evaluated the ability of the compounds to induce NO production on treated-macrophages using Griess reaction and the effect of them in lipid profile on treated-parasite through Thin Layer Chromatography. RESULTS: Our data showed that both essential oils have toxic effect on promastigotes and amastigotes of L. amazonensis in vitro in a dose-dependent manner. PaEO IC50 were 14.8 µg/mL and 7.8 µg/mL and PhEO IC50s were 0.46 µg/mL and 30.5 µg/m for promastigotes and amastigotes, respectively. Toxicity to macrophages was not observed at 50 µg/mL with both EOs. The compounds 1,8- cineole, α-pinene, and p-cymene inhibited amastigotes survival in a dose-dependent manner with IC50s of 48.4 µg/mL, 37 µg/mL, 46 µg/mL, respectively. Macrophage viability was around 90% even at 200 µg/mL and the phagocytic capacity was not altered in the treated-macrophages to up 50 µg/mL. The compounds were not able to modulate the nitric oxide production either at rest or LPS-activated macrophages. In addition, treated promastigote revealed an important change in their lipid profile after 48 h at 50 µg/mL in the presence of the compounds. CONCLUSIONS: The results indicate that oleoresins of Protium genus are potent against Leishmania and α-pinene, p-cymene and 1,8-cineole have anti-Leishmania properties that could be explored in synergistic assays in order to develop new drug candidates.

The in vitro antileishmanial activity of essential oil from Aloysia gratissima and guaiol, its major sesquiterpene against Leishmania amazonensis.

Leishmaniases is a tropical disease caused by protozoa of the genus Leishmania for which the current treatment is expensive, besides increasing reports of parasite resistance. This study investigated the anti-Leishmania amazonensis activity of the essential oil from Aloysia gratissima (AgEO) and guaiol, the major sesquiterpene constituent in the oil. Our results showed that AgEO killed promastigotes and intracellular amastigotes at an IC50 of 25 and 0·16 µg mL-1, respectively, while guaiol killed amastigotes at an IC50 of 0·01 µg mL-1. Both AgEO and guaiol were safe for macrophages up to 100 µg mL-1, as evaluated by the dehydrogenase activity, membrane integrity and phagocytic capacity. AgEO and guaiol did not induce nitrite oxide (NO) in resting macrophages and inhibited the production of NO in lipopolysaccharide-stimulated macrophages. The ultrastructural analysis suggested that AgEO and guaiol act directly on parasites, affecting promastigotes kinetoplast, mitochondrial matrix and plasma membrane. Together, these results pointed out that AgEO and guaiol could be promising candidates to develop anti-Leishmania drugs.

Neonatal Proinflammatory Stress Induces Accumulation of Corticosterone and Interleukin-6 in the Hippocampus of Juvenile Rats: Potential Mechanism of Synaptic Plasticity Impairments.

Infectious diseases in early postnatal ontogenesis can induce neuroinflammation, disrupt normal central nervous system development, and contribute to pathogenesis of cerebral pathologies in adults. To study long-term consequences of such early stress, we induced neonatal proinflammatory stress (NPS) by injecting bacterial lipopolysaccharide into rat pups on postnatal days 3 and 5 and then assessed the levels of corticosterone, proinflammatory cytokines and their mRNAs, and neurotrophins and their mRNAs in the hippocampus and neocortex of the one-month-old animals. Long-term potentiation (LTP) was studied in hippocampal slices as an index of synaptic plasticity. NPS-induced impairments of LTP were accompanied by the accumulation of corticosterone and IL-6 in the hippocampus. In the neocortex, a decrease in exon IV BDNF mRNA was detected. We suggest that excessive corticosterone delivery to hippocampal receptors and proinflammatory changes persisting during brain maturation are among the principal molecular mechanisms responsible for NPS-induced neuroplasticity impairments.

[The effect of childhood stress on the development of mental disorders in adults].

There is evidence that not only severe stressful events, but also common low-threat events, in particular chronic ones, may cause or provoke some mental disorders. The literature data on the degree of pathogenicity of stress factors are insufficient. Authors attempted to summarize the established facts in the following aspects: current conceptions on the physiology and pathology of stress in the frames of the problem of psychosomatic disorders, deprivation in childhood, neurobiological consequences of childhood stress, psychiatric consequences of stress in childhood. Authors believe that this problem demands further investigation to find possible predictors of mental disorders in patients who had experienced stressful life events in childhood.

Anterior interosseous nerve palsy associated with Galeazzi fracture.

Galeazzi fracture is more common in adults than in children. Associated neurologic deficits are rare and easily missed at the first clinical examination. The authors describe a case of anterior interosseous nerve palsy after closed Galeazzi fracture. Conservative treatment resulted in complete return of normal nerve function, suggesting that this is a neurapraxia type of injury.

Simultaneous Scaphoid and Galeazzi Fractures.

Among wrist injuries, scaphoid fractures are second only in number to fractures of the distal radius, while Galeazzi fractures are relatively infrequent. It is rare for the two fractures to occur concomitantly. We report such a case in a 65-year-old woman.

Effect of Percoll wash on sperm motion parameters and subsequent fertility in intrauterine insemination cycles.

PURPOSE: This study examined sperm motion parameters as measured by computerized automated semen analysis before and after a Percoll wash and determined if differences in any parameter were correlated with fertility subsequent to intrauterine insemination (IUI). RESULTS: Total motile sperm decreased following the washing procedure from 79.0 +/- 9.0 to 37.2 +/- 7.6 million sperm. Motility increased from a mean of 43.4% to 61.7% (P < 0.001). Other motility parameters also changed significantly (P < 0.001) as follows: curvilinear velocity (VCL), 43.4 to 61.7 microns/s; straight-line velocity (VSL), 21.3 to 26.7 microns/s; linearity 53.1 to 45.2%; lateral head displacement (ALH), 2.97 to 3.94 microns. Similar changes occurred following a swim-up preparation, although changes in mean motility, VCL, and ALH were significantly greater when compared to Percoll. The postwash changes were not accounted for merely by time lapse in preparation since reanalyzed untreated controls did not show the same changes in motion parameters. Prewash linearity in those specimens which resulted in pregnancies was greater than in those which did not (P = 0.28). No other significant differences in pre- or post-Percoll washed sperm motion parameters were found between pregnant vs nonfertile cycles. CONCLUSION: Following Percoll wash all CASA-generated motility parameters were significantly altered, but there was little association between these parameters and pregnancy achieved in IUI cycles.

Management of uterine perforation following elective abortion.

Experience is reported with 28 uterine perforations encountered from June 1, 1973, to June 1, 1976, among 20,000 first trimester abortion patients at Reproductive Health Services, St. Louis, Missouri. In order to prevent this complication, one must perform an exacting pelvic examination. The use of a sound is controversial. Dilators should be introduced only a short distance through the internal os, and as much of the products of conception as possible should be aspirated. A sharp curette should be diagnostically. Various questions should be asked before the operator constructs a scheme for managing perforation. The current policy for management used at this clinic is outlined.

PIP: 28 uterine perforations occurred from June 1, 1973, to June 1, 1976, among 20,000 first trimester abortion patients at Reproductive Health Services, St. Louis, Missouri. The management of such perforations should depend on the site of the perforation and the completeness of the abortion. These questions should also be answered: 1) How many weeks pregnant is the patient? 2) Is there extragenital injury? 3) Is there hematoma formation or evidence of continuing intraperitoneal blood loss? The laparascope is valuable in evaluation of the perforation damage and in determining if laparatomy is necessary. If bleeding is extensive, laparotomy is indicated for uterine and vessel repair which may even involve hysterectomy. If the perforation is discovered before removal of all products of conception, the plan depends on the site of the perforation. If vital signs are steady either 1) the patient may be returned to the procedure room and a 2nd evacuation performed, avoiding the area of perforation; or 2) the patient may be admitted to hospital for laparascopic study and evaluation for a 2nd vaginal evacuation. If perforation seems to be lateral, with intraabdominal bleeding, the patient should be hospitalized at once for close observation.

Elective abortion. Complications seen in a free-standing clinic.

Experience is reported with the elective first trimester abortion of 16,410 pregnancies during a 31-month period by Reproductive Health Services of St. Louis, a free-standing clinic. Incidence of complications was 1.54%. The most common of these were incomplete evacuation, excessive postabortal bleeding, and uterine perforation. In patients with unquestioned perforation, the use of laparoscopy has been very valuable in ascertaining the exact nature of the perforation, in avoiding unnecessary laparotomy, and in giving intraabdominal visual guidance to concomitant suction evacuation in cases of an incomplete procedure. Aspects of the other complications are also discussed. In general, the findings support the view that even in the first trimester, the earlier in pregnancy that suction abortion is performed, the less likely it is to result in major complications. It is possible to perform first trimester abortions in a free-standing clinic with a satisfactorily low complication rate.

PIP: In elective first trimester of 16,410 pregnancies between June 1973-January 1976 at Reproductive Health Services of St. Louis, incidence of complications was 1.54%. The most common complication (32% of total complications) was incomplete evacuation of the uterus. Perforations of the uterus occurred in 34 patients (.2%); 1/3 of the perforations occurred in primigravidas. Excessive postabortal bleeding occurred in 41 patients and cervical lacerations in 22. 11 patients developed postabortal syndrome (PAS). In patients with unquestioned perforation, the use of laparoscopy is valuable in ascertaining the exact nature of the perforation, in avoiding unnecessary laparotomy, and in giving intraabdominal visual guidance to concomitant suction evacuation in cases of an incomplete procedure. The earlier that suction abortion is performed, the less likely it is to result in major complications; 56% of the complications occurred after the 10th week of pregnancy which represented 36% of the total procedures.