Spectrum of Dermatologic Adverse Events Associated With Amivantamab Use.

This case series describes the different dermatologic adverse events that patients experienced while using amivantamab.

Rad52's DNA annealing activity drives template switching associated with restarted DNA replication.

It is thought that many of the simple and complex genomic rearrangements associated with congenital diseases and cancers stem from mistakes made during the restart of collapsed replication forks by recombination enzymes. It is hypothesised that this recombination-mediated restart process transitions from a relatively accurate initiation phase to a less accurate elongation phase characterised by extensive template switching between homologous, homeologous and microhomologous DNA sequences. Using an experimental system in fission yeast, where fork collapse is triggered by a site-specific replication barrier, we show that ectopic recombination, associated with the initiation of recombination-dependent replication (RDR), is driven mainly by the Rad51 recombinase, whereas template switching, during the elongation phase of RDR, relies more on DNA annealing by Rad52. This finding provides both evidence and a mechanistic basis for the transition hypothesis.

Teaching and Learning Tips 12: Peer observation of teaching.

Challenge: How can clinical teachers continually improve their teaching skills? In addition to student feedback, peer and expert opinion can also provide valuable formative and evaluative feedback to guide self-improvement efforts. Here, we discuss ways to structure peer observation of teaching in dermatological settings and offer tips on how to optimize the learning experience for both the educator and peer observer.

Perceptions of U.S. dermatology residency program directors regarding the adequacy of phototherapy training during residency.

BACKGROUND/PURPOSE: Phototherapy utilization has declined over the last 20 years despite its efficacy and cost-effectiveness. Adequacy of phototherapy training in residency may be a contributing factor. The purpose of this study was to evaluate perceptions of U.S. dermatology residency program directors (PDs) regarding the effectiveness of their programs' phototherapy training and what constitutes adequate phototherapy education. METHODS: A questionnaire was sent to PDs to assess phototherapy training within their program; aspects such as dedicated time, exposure to different modalities, and barriers to resident education were surveyed. We assessed the statistical association between these aspects and the perception by PDs that a program's training was adequate. Statistical testing was reported using Fisher's exact tests. RESULTS: A total of 42 PDs responded. Residency training in oral psoralen and ultraviolet A therapy (PUVA), home phototherapy, and excimer laser, respectively, is not provided in 19.0%, 31.0%, and 47.6% of programs. 38.1% of programs provide ≤5 hours of phototherapy training over 3 years of training. 59.5% of PDs cited lack of curriculum time as the most common barrier to phototherapy education. 19.0% of PDs reported completely adequate phototherapy training, which was significantly associated with inclusion of faculty-led didactics, assigned reading, or hands-on clinical training in the curriculum. CONCLUSIONS: There is a mismatch between the resources devoted to phototherapy education and the need for dedicated training reported by PDs. Limited time is allocated to phototherapy training during dermatology residency, and a large majority of PDs do not feel that the phototherapy training offered is completely adequate.

Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication.

Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination. Collapsed forks can be rescued by homologous recombination, which restarts replication. However, replication restart is relatively slow and, therefore, replication termination may frequently occur by an active fork converging on a collapsed fork. We find that this type of non-canonical fork convergence in fission yeast is prone to trigger deletions between repetitive DNA sequences via a mechanism we call Inter-Fork Strand Annealing (IFSA) that depends on the recombination proteins Rad52, Exo1 and Mus81, and is countered by the FANCM-related DNA helicase Fml1. Based on our findings, we propose that IFSA is a potential threat to genomic stability in eukaryotes.

Gender and Ethnic Diversity in Academic PM&R Faculty: National Trend Analysis of Two Decades.

Over the years, a number of studies have demonstrated an increase in gender and ethnic diversity among US physicians. Despite substantial progress in eliminating gender and racial inequities in the field of medicine, women and ethnic minorities are still underrepresented among medical faculty at academic institutions. This study aims to describe the trends in gender and ethnic diversity among Physical Medicine and Rehabilitation (PM&R) faculty through statistical analysis of data describing gender and ethnicity of full-time academic faculty gathered from the Association of American Medical Colleges Faculty Roster from 1994 to 2014. Proportions representing the percentages of females and ethnic minorities of a given faculty position in medical schools were compared across each of the other faculty ranks. Results showed that the average yearly percent increases in the proportion of female PM&R faculty in associate professor (0.68%) and full professor (0.54%) positions were greater than those in instructor (0.30%) and assistant professor (0.35%) positions. In contrast, the average yearly percent increase in the proportion of non-Caucasian PM&R faculty in full professor positions (0.19%) was less than those in instructor (0.84%), assistant (0.93%), and associate professor (0.89%) positions. Overall, trends among faculty exhibit a steady increase in gender and ethnic diversity, although promotion disparity continues to exist among specific academic positions for some groups. This study provides a current perspective on recent changes in diversity among faculty in PM&R and may prove useful when defining strategies to improve workforce diversity.

The impact of body habitus on outcomes after aneurysmal subarachnoid hemorrhage: a Nationwide Inpatient Sample analysis.

OBJECTIVE Although the prevalence of obesity is increasing rapidly both nationally and internationally, few studies have analyzed outcomes among obese patients undergoing cranial neurosurgery. The goal of this study, which used a nationwide data set, was to evaluate the association of both obesity and morbid obesity with treatment outcomes among patients with aneurysmal subarachnoid hemorrhage (SAH); in addition, the authors sought to analyze how postoperative complications for obese patients with SAH differ by the treatment modality used for aneurysm repair. METHODS Clinical data for adult patients with SAH who underwent microsurgical or endovascular aneurysm repair were extracted from the Nationwide Inpatient Sample (NIS). The body habitus of patients was classified as nonobese (body mass index [BMI] < 30 kg/m2), obese (BMI ≥ 30 kg/m2 and ≤ 40 kg/m2), or morbidly obese (BMI > 40 kg/m2). Multivariable logistic regression analyzed the association of body habitus with in-hospital mortality rate, complications, discharge disposition, and poor outcome as defined by the composite NIS-SAH outcome measure. Covariates included patient demographics, comorbidities (including hypertension and diabetes), health insurance status, the NIS-SAH severity scale, treatment modality used for aneurysm repair, and hospital characteristics. RESULTS In total, data from 18,281 patients were included in this study; the prevalence of morbid obesity increased from 0.8% in 2002 to 3.5% in 2011. Obese and morbidly obese patients were significantly younger and had a greater number of comorbidities than nonobese patients (p < 0.001). Mortality rates for obese (11.5%) and morbidly obese patients (10.5%) did not significantly differ from those for nonobese patients (13.5%); likewise, no differences in neurological complications or poor outcome were observed among these 3 groups. Morbid obesity was associated with significantly increased odds of several medical complications, including venous thromboembolic (OR 1.52, 95% CI 1.01-2.30, p = 0.046) and renal (OR 1.64, 95% CI: 1.11-2.43, p = 0.01) complications and infections (OR 1.34, 95% CI 1.08-1.67, p = 0.009, attributable to greater odds of urinary tract and surgical site infections). Moreover, morbidly obese patients had higher odds of a nonroutine hospital discharge (OR 1.33, 95% CI 1.03-1.71, p = 0.03). Patients with milder obesity had decreased odds of some medical complications, including cardiac, pulmonary, and infectious complications, primarily among patients who had undergone coil embolization. CONCLUSIONS In this study involving a nationwide administrative database, milder obesity was not significantly associated with increased mortality rates, neurological complications, or poor outcomes after SAH. Morbid obesity, however, was associated with increased odds of venous thromboembolic, renal, and infectious complications, as well as of a nonroutine hospital discharge. Notably, milder obesity was associated with decreased odds of some medical complications, primarily in patients treated with coiling.

Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse.

The completion of genome duplication during the cell cycle is threatened by the presence of replication fork barriers (RFBs). Following collision with a RFB, replication proteins can dissociate from the stalled fork (fork collapse) rendering it incapable of further DNA synthesis unless recombination intervenes to restart replication. We use time-lapse microscopy and genetic assays to show that recombination is initiated within ∼ 10 min of replication fork blockage at a site-specific barrier in fission yeast, leading to a restarted fork within ∼ 60 min, which is only prevented/curtailed by the arrival of the opposing replication fork. The restarted fork is susceptible to further collapse causing hyper-recombination downstream of the barrier. Surprisingly, in our system fork restart is unnecessary for maintaining cell viability. Seemingly, the risk of failing to complete replication prior to mitosis is sufficient to warrant the induction of recombination even though it can cause deleterious genetic change.