Wilderness Medicine Physician Education: How an Elective Can Spark a Fire.

Background Wilderness medicine (WM) electives offer an opportunity for medical trainees to learn an additional skillset outside of the traditional medical education curricula. Prior literature has yet to detail how participation in WM electives during medical training informs future training (i.e., master's degree, fellowship) or career involvement in the field. Methodology A 25-question survey was completed by former participants of 25 WM electives based in the United States. Survey questions focused on the demographics, motivations, current involvement, and additional WM training among those who participated in WM electives. The survey was completed by 102 eligible participants. Results Of the 102 participants, 53% had been engaged with WM since completing their elective; 18% of the participants had completed additional formal training in WM (i.e., master's degree, fellowship). Further, 95% of participants felt that the elective enhanced their resilience and critical thinking. Of those currently most involved in WM (n = 26), half (46%) were unsure about integrating WM into their careers prior to their elective. Among the uncertain yet highly engaged cohort, 98% cited the elective as the reason they stayed involved in WM. Conclusions These findings underscore the importance of WM electives in fostering interest among medical trainees in WM, and suggest that participation in WM electives may promote further involvement after medical school and residency.

Incidence of Mild Cognitive Impairment with Ascending Altitude.

Background: This study aimed to longitudinally quantify the prevalence of mild cognitive impairment (MCI) in individual trekkers at three different ascending altitudes (Site 1: ∼3500 m, Site 2: ∼4400 m, and Site 3: ∼5100 m). We correlated these findings with the presence of acute mountain sickness (AMS). Materials and Methods: We performed serial assays using the environmental quick mild cognitive impairment (eQMCI) score on 103 English-speaking 18- to 65-year-old volunteers trekking to Everest Base Camp in Nepal during spring 2016. We defined MCI as a score less than 67 (lower scores indicating more cognitive impairment). Additional data collected included the Lake Louise Score, demographics, and other possible confounders. Results: eQMCI scores significantly decreased with ascent from Site 1 to 2 (a score of 78.95 [SD = 7.96] to 74.67 [SD = 8.8] [Site 1-2 p = 0.04]), but then increased on ascent to Site 3 to 83.68 (SD = 8.67) (Site 1-3 p = <0.0001, Site 2-3 p = <0.0001). However, subjects who fulfilled eQMCI criteria for MCI increased despite the overall improvement in score: 6.8% (N = 7) at Site 1, 18.7% (N = 14) at Site 2, and 3.3% (N = 2) at Site 3. Incidence of AMS at Sites 1, 2, and 3 was 22.3% (N = 23), 21.3% (N = 16), and 48.3% (N = 29), respectively. Of those with MCI, 1.94% met criteria for AMS at Site 1 (p = 0.0017), 2.67% at Site 2 (p = 0.6949), and 3.33% at Site 3 (p = <0.0001). Conclusions: There is a significant incidence of MCI at high altitude, even in those without subjective findings of AMS. Interestingly, subjects with a decline in cognitive function show an increasing trend for developing AMS at higher altitude. Future research on the clinical impact of MCI on a subject's health, judgment, and performance remains to be elucidated.

Characteristics and Motivating Factors of Attendees of a Regional Student-Run Wilderness Medicine Conference.

Despite recent growth, opportunities for preclinical medical students to engage with the field of wilderness medicine remain geographically, financially, and logistically limited. Attendees of the 2018 Mid-Atlantic Student Wilderness Medicine Conference were invited to complete a post hoc web-based survey after the event. Results of the survey were analyzed to determine the demographic characteristics and motivating factors for attendance, as well as perceived conference performance and future behavioral intention of survey respondents. The majority of attendees were preclinical level medical students, 37% of whom were affiliated with their institutions' wilderness medicine interest group and 40% of whom were affiliated with an emergency medicine interest group. Intrinsically motivating factors such as personal interest and opportunities for educational enrichment were significantly more important in determining conference attendance than extrinsically motivating factors such as cost and networking opportunities. Data from this conference support many encouraging trends and suggest that regional conferences may represent a practical way to increase access to wilderness medicine in the preclinical medical student population and thereby influence career decision.

Trends in Skin and Soft Tissue-Related Injuries in NOLS Wilderness Expeditions from 1984 to 2012.

OBJECTIVE: Wilderness expeditions inevitably involve risk to participants. Understanding of expedition-related illnesses and injuries allows institutions and individuals to develop strategies to mitigate risk. We describe findings and trends in soft tissue injuries, the second-most common type of injury, among participants in the National Outdoor Leadership School expeditions from 1984 to 2012. METHODS: Injuries and illnesses sustained by students and staff have been recorded continuously since 1984 in the extensive National Outdoor Leadership School database. We performed a retrospective analysis of incidence of soft tissue injuries in this population. Data before 1996 were standardized in order to make use of the entire dataset. RESULTS: Of 9734 total reported incidents, 2151 (22%) were soft tissue related, 707 (33%) of which required evacuation. The sex distribution of incidents was similar to the sex distribution of participants. The largest incidence of soft tissue injuries occurred independent of activity (711 incidents, 33%). The most commonly associated activities were hiking (528 incidents, 25%), camping (301 incidents, 14%), and cooking (205 incidents, 10%). Over the study period, rates of injury declined overall and in every individual category except cooking. CONCLUSIONS: Over this 28-year period, the incidence of soft tissue injuries associated with the most common activities decreased. Incidence of activity-independent injuries did not change significantly, but reported severity decreased. These data provide unique insights to help improve wilderness risk management for institutions and individuals and suggest areas in which educational efforts may further reduce risk.

Findings of Cognitive Impairment at High Altitude: Relationships to Acetazolamide Use and Acute Mountain Sickness.

Phillips, Lara, Buddha Basnyat, Yuchiao Chang, Erik R. Swenson, and N. Stuart Harris. Findings of cognitive impairment at high altitude: relationships to acetazolamide use and acute mountain sickness. High Alt Med Biol. 18:121-127, 2017. OBJECTIVE: Acute mountain sickness (AMS) is defined by patient-reported symptoms using the Lake Louise Score (LLS), which provides limited insight into any possible underlying central nervous system (CNS) dysfunction. Some evidence suggests AMS might coexist with altered neural functioning. Cognitive impairment (CI) may go undetected unless a sensitive test is applied. Our hypothesis was that a standardized test for mild CI would provide an objective measure of CNS dysfunction, which may correlate with the symptoms of AMS and so provide a potential new tool to better characterize altitude-related CNS dysfunction. We compared a cognitive screening tool with the LLS to see if it correlated with CNS dysfunction. METHODS: Adult native English-speaking subjects visiting Himalayan Rescue Association aid stations in Nepal at 3520 m (11,548 ft) and 4550 m (14,927 ft) were recruited. Subjects were administered the LLS and a slightly modified version of the environmental Quick mild cognitive impairment screen (eQmci). Medication use for altitude illness was recorded. Scores were compared using the Spearman's correlation coefficient. Data also included medication use. RESULTS: Seventy-nine subjects were enrolled. A cut-off of three or greater was used for the LLS to diagnose AMS and 67 or less for the eQmci to diagnose CI. There were 22 (28%) subjects who met criteria for AMS and 17 (22%) subjects who met criteria for CI. There was a weak correlation (r2 = 0.06, p = 0.04) between eQmci score and LLS. In matched subjects with identical LLS, recent acetazolamide use was associated with significantly more CI. CONCLUSION: Field assessment of CI using a rapid standardized tool demonstrated that a substantial number of subjects were found to have mild CI following rapid ascent to 3520-4550 m (11,548-14,927 ft). The weak correlation between the LLS and eQmci suggests that AMS does not result in CI. Use of acetazolamide appears to be associated with CI at all levels of AMS severity.

Addressing Ophthalmology Education for Newly Matriculated Emergency Medicine Residents Using Innovative Models.

INTRODUCTION: A majority of newly matriculated emergency medicine residents begin their residencies without any formal ophthalmology training received in medical school. Research on available eye models for procedural education and an eye emergencies curriculum is limited. METHODS: We developed an eye emergencies curriculum that incorporated a series of lectures and case presentations over the academic year with a biannual "ophthalmology day", which included an intense skills laboratory with novel models. RESULTS: From July 2012 to July 2013, 24 newly matriculated interns and 20 upper-level residents participated in the curriculum. The simulations were successfully implemented during multiple sessions. Reasonable material, faculty, and facility resources allowed for continuation of the curriculum. CONCLUSIONS: The eye emergencies curriculum provides a well-received and practical model for residents to gain ophthalmology experience. Novel eye simulation models may be useful for other programs to implement to enhance postgraduate education.

The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ.

The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with normal kinetics. Like its counterpart in yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety of DNA damaging agents, a diminished ability to maintain replication fork progression after UV irradiation and a significant decrease in abasic site-induced mutagenesis in the immunoglobulin loci. However, these defects appear to be largely independent of Polζ, suggesting that POLD3 makes a significant contribution to TLS independently of Polζ in DT40 cells. Indeed, combining polη, polζ and pold3 mutations results in synthetic lethality. Additionally, we show in vitro that POLD3 promotes extension beyond an abasic by the Polδ holoenzyme suggesting that while POLD3 is not required for normal replication, it may help Polδ to complete abasic site bypass independently of canonical TLS polymerases.

Diagnosing frontal lobe epilepsy in the ED.

Frontal lobe seizures are a common form of epilepsy. It has a variable presentation and can often be missed in the emergency department (ED). Missing this diagnosis can lead to a delay in treatment and poor outcome for cognitive function. We hereby present a case of a 14-year-old girl who presented to our ED after the development of abnormal movements. Knowledge of the anatomy behind the development of partial seizures and the best testing modality can aid in the diagnosis. In this review, we attempt to discuss the pathophysiology of frontal lobe epilepsy and what physical examination findings and testing will best lead to a diagnosis.

Pediatric ptosis as a sign of treatable autonomic dysfunction.

PURPOSE: To report the ophthalmic findings in young patients with dopamine ß-hydroxylase deficiency and to assess them in the context of other reports in an attempt to discern if ophthalmic criteria may assist in early detection of this debilitating, yet treatable, disorder. DESIGN: Prospective, observational case series. METHODS: An ophthalmic examination, including measuring intraocular and systemic blood pressures while supine, sitting, and standing, and eyelid function and pupillary function testing, was completed on 3 young patients with recently documented dopamine ß-hydroxylase deficiency at a single institution. RESULTS: Mean arterial blood pressures were 90.1 ± 18.5 mm Hg supine, 79.1 ± 25.7 mm Hg sitting, and 45.8 ± 11.6 mm Hg standing (P = .021). Mean intraocular pressures in these patients were 15.8 ± 1.0 mm Hg supine, 15.0 ± 3.6 mm Hg sitting, and 7.7 ± 2.3 mm Hg standing (P = .03). Mean palpebral fissure, levator function, and margin reflex distance were 8.2 ± 1.0 mm, 16.0 ± 0 mm, and 2.8 ± 0.6 mm, respectively. Measurable miosis was present in only 1 patient, and pupillary supersensitivity to 2.5% phenylephrine was not observed. CONCLUSIONS: The ophthalmologic findings of the patients in this case series documented mild ptosis and striking orthostatic reductions in intraocular pressure and mean arterial blood pressure, as might be expected with a lack of intrinsic sympathetic function. Orthostatic intraocular pressure and mean arterial blood pressure may be a helpful early screening tool for autonomic dysfunction in children undergoing a ptosis evaluation.

Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's disease.

Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated.

FANCJ coordinates two pathways that maintain epigenetic stability at G-quadruplex DNA.

We have previously reported that DT40 cells deficient in the Y-family polymerase REV1 are defective in replicating G-quadruplex DNA. In vivo this leads to uncoupling of DNA synthesis from redeposition of histones displaced ahead of the replication fork, which in turn leads to loss of transcriptional repression due to failure to recycle pre-existing repressive histone post-translational modifications. Here we report that a similar process can also affect transcriptionally active genes, leading to their deactivation. We use this finding to develop an assay based on loss of expression of a cell surface marker to monitor epigenetic instability at the level of single cells. This assay allows us to demonstrate G4 DNA motif-associated epigenetic instability in mutants of three helicases previously implicated in the unwinding of G-quadruplex structures, FANCJ, WRN and BLM. Transcriptional profiling of DT40 mutants reveals that FANCJ coordinates two independent mechanisms to maintain epigenetic stability near G4 DNA motifs that are dependent on either REV1 or on the WRN and BLM helicases, suggesting a model in which efficient in vivo replication of G-quadruplexes often requires the established 5'-3'-helicase activity of FANCJ acting in concert with either a specialized polymerase or helicase operating in the opposite polarity.

The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA.

DNA damage tolerance pathways facilitate the bypass of DNA lesions encountered during replication. These pathways can be mechanistically divided into recombinational damage avoidance and translesion synthesis, in which the lesion is directly bypassed by specialised DNA polymerases. We have recently shown distinct genetic dependencies for lesion bypass at and behind the replication fork in the avian cell line DT40, bypass at the fork requiring REV1 and bypass at post-replicative gaps requiring PCNA ubiquitination by RAD18. The WRN helicase/exonuclease, which is mutated in the progeroid and cancer predisposition disorder Werner's Syndrome, has previously been implicated in a RAD18-dependent DNA damage tolerance pathway. However, WRN has also been shown to be required to maintain normal replication fork progression on a damaged DNA template, a defect reminiscent of REV1-deficient cells. Here we use the avian cell line DT40 to demonstrate that WRN assists REV1-dependent translesion synthesis at the replication fork and that PCNA ubiquitination-dependent post-replicative lesion bypass provides an important backup mechanism for damage tolerance in the absence of WRN protein.

Timing matters: error-prone gap filling and translesion synthesis in immunoglobulin gene hypermutation.

By temporarily deferring the repair of DNA lesions encountered during replication, the bypass of DNA damage is critical to the ability of cells to withstand genomic insults. Damage bypass can be achieved either by recombinational mechanisms that are generally accurate or by a process called translesion synthesis. Translesion synthesis involves replacing the stalled replicative polymerase with one of a number of specialized DNA polymerases whose active sites are able to tolerate a distorted or damaged DNA template. While this property allows the translesion polymerases to synthesize across damaged bases, it does so with the trade-off of an increased mutation rate. The deployment of these enzymes must therefore be carefully regulated. In addition to their important role in general DNA damage tolerance and mutagenesis, the translesion polymerases play a crucial role in converting the products of activation induced deaminase-catalysed cytidine deamination to mutations during immunoglobulin gene somatic hypermutation. In this paper, we specifically consider the control of translesion synthesis in the context of the timing of lesion bypass relative to replication fork progression and arrest at sites of DNA damage. We then examine how recent observations concerning the control of translesion synthesis might help refine our view of the mechanisms of immunoglobulin gene somatic hypermutation.

Reconstitution and analysis of the multienzyme Escherichia coli RNA degradosome.

The Escherichia coli RNA degradosome is a multienzyme assembly that functions in transcript turnover and maturation of structured RNA precursors. We have developed a procedure to reconstitute the RNA degradosome from recombinant components using modular coexpression vectors. The reconstituted assembly can be purified on a scale that has enabled biochemical and biophysical analyses, and we compare the properties of recombinant and cell-extracted RNA degradosomes. We present evidence that auxiliary protein components can be recruited to the 'superprotomer' core of the assembly through a dynamic equilibrium involving RNA intermediaries. We discuss the implications for the regulation of RNA degradosome function in vivo.