Effects of the antidepressants desipramine and fluvoxamine on latency to immobility and duration of immobility in the forced swim test in adult male C57BL/6J mice.

The forced swim test in rodents allows rapid detection of substances with antidepressant-like activity, evidenced as a decreased duration of immobility that is produced by the majority of clinically used antidepressants. Antidepressants also increase the latency to immobility, and this additional measure reportedly can increase the sensitivity of the forced swim test in mice. Extending these findings, the present study examined the effects of desipramine and fluvoxamine in a forced swim test in C57BL/6J mice, a strain commonly used as background for genetic modifications, analyzing results with a method (i.e. survival analysis) that can model the skewed distribution of latencies and that can deal with censored data (i.e. when immobility does not occur during the test), in comparison with the more traditional Student's t-test. Desipramine increased the latency to immobility at 32 mg/kg, but not at lower doses. Fluvoxamine also did not affect latency at lower doses, but in contrast to desipramine, fluvoxamine decreased the latency to immobility at the highest dose (i.e. 32 mg/kg). At doses affecting latency to immobility, neither desipramine nor fluvoxamine significantly affected duration of immobility. Together, these results are generally consistent with the suggestion that inclusion of the latency measure can increase the sensitivity of the forced swim test to detect antidepressant-like effects in mice.

DO seniors and IMGs have lower match probabilities than MD seniors after adjusting for specialty choice and USMLE Step 1 score.

CONTEXT: It is unknown if US residency applicants of different educational backgrounds (US allopathic [MD], Doctor of Osteopathic Medicine [DO], and international medical graduates [IMG]) but comparable academic performance have similar match success. OBJECTIVES: Our objective was to compare match probabilities between applicant types after adjusting for specialty choice and United States Medical Licensing Examination (USMLE) Step 1 scores. METHODS: We performed a secondary analysis of published data in National Resident Matching Program (NRMP) reports from 2016, 2018, 2020, and 2022 for US MD seniors, DO seniors, and IMGs (US citizens and non-US citizens). We examined the 10 specialties with the most available spots in 2022. Average marginal effects from a multiple variable logistic regression model were utilized to estimate each non-MD senior applicant type's probability of matching into their preferred specialty compared to MD seniors adjusting for specialty choice, Step 1 score, and match year. RESULTS: Each non-MD applicant type had a lower adjusted percent difference in matching to their preferred specialty than MD seniors, -7.1 % (95 % confidence interval [CI], -11.3 to -2.9) for DO seniors, -45.6 % (-50.6 to -40.5) for US IMGs, and -56.6 % (-61.5 to -51.6) for non-US IMGs. Similarly, each non-MD applicant type had a lower adjusted percent difference in matching than MD seniors across almost all Step 1 score ranges, except for DO seniors with Step 1 scores <200 (-2.0 % [-9.5 to 5.5]). CONCLUSIONS: After adjusting for specialty choice, Step 1 score, and match year, non-US MD applicants had lower probabilities of matching into their preferred specialties than their US MD colleagues.

Distinct pathways of homologous recombination controlled by the SWS1-SWSAP1-SPIDR complex.

Homology-directed repair (HDR), a critical DNA repair pathway in mammalian cells, is complex, leading to multiple outcomes with different impacts on genomic integrity. However, the factors that control these different outcomes are often not well understood. Here we show that SWS1-SWSAP1-SPIDR controls distinct types of HDR. Despite their requirement for stable assembly of RAD51 recombinase at DNA damage sites, these proteins are not essential for intra-chromosomal HDR, providing insight into why patients and mice with mutations are viable. However, SWS1-SWSAP1-SPIDR is critical for inter-homolog HDR, the first mitotic factor identified specifically for this function. Furthermore, SWS1-SWSAP1-SPIDR drives the high level of sister-chromatid exchange, promotes long-range loss of heterozygosity often involved with cancer initiation, and impels the poor growth of BLM helicase-deficient cells. The relevance of these genetic interactions is evident as SWSAP1 loss prolongs Blm-mutant embryo survival, suggesting a possible druggable target for the treatment of Bloom syndrome.