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The position of chief resident involves increased leadership, mentorship, and management responsibilities. There is no standardized procedure in which dermatology chief residents are trained and prepared for their final year of residency. In 2008, an annual Dermatology Chief Academy conference was initiated in which incoming chief residents were given formal leadership training for their new role. At the 2020 conference, residents completed a survey regarding their expectations and experience of this conference. After the conference, residents felt significantly better prepared for their new role as chief residents, handling conflicts, and effective leadership. A formal leadership conference for incoming chief residents is vital for improving the success of a residency program., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

With an increasing number of adolescents participating in international travel, little is known about travel-related behaviors and health risks in this age group. In the years 2015-2016, we conducted an anonymous, posttravel, questionnaire-based survey with the aim to compare self-reported practices and travel-related symptoms between adolescents (< 18 years old, N = 87) and adults (≥ 18 years old, N = 149) who came to our travel clinic before their humanitarian missions. They had the same pretravel health education, and traveled together to perform similar activities. In univariate analysis, compared with adults, we found that adolescents reported less prior international travel (P < 0.001), more often wore long-sleeved clothing for malaria prevention (P < 0.001) but less often for sun protection (P = 0.009), more often used insect repellents (P = 0.011), and less often had diarrhea (P = 0.024). All other practices and health outcomes were similar between the groups. Multivariate analyses using Bayesian network show strong associations between adults and prior travel experience, and not wearing long-sleeve clothing for malaria prevention. We also found strong associations between prior international travel and sustaining an injury, and having jet lag, as well as between taking malaria prophylaxis and not having diarrhea. Overall, most practices and health outcomes were similar between age groups. Adolescent age and lack of prior international travel experience did not have significant impacts on practices and health outcomes. Our findings highlight the need for more effective strategies to improve the behaviors and health outcomes in both adolescents and adults.

We used metagenomic next-generation sequencing to longitudinally assess the gut microbiota and antimicrobial resistomes of international travelers to clarify global exchange of resistant organisms. Travel resulted in an increase in antimicrobial resistance genes and a greater proportion of Escherichia species within gut microbial communities without impacting diversity.

Background: Vibrio cholerae causes over 2 million cases of cholera and 90,000 deaths each year. Serosurveillance can be a useful tool for estimating the intensity of cholera transmission and prioritizing populations for cholera control interventions. Current methods involving venous blood draws and downstream specimen storage and transport methods pose logistical challenges in most settings where cholera strikes. To overcome these challenges, we developed methods for determining cholera-specific immune responses from dried blood spots (DBS)., Methodology/principal Findings: As conventional vibriocidal assay methods were unsuitable for DBS eluates from filter paper, we adopted a drop-plate culture method. We show that DBS collected from volunteers in South Sudan, and stored for prolonged periods in field conditions, retained functional vibriocidal antibodies, the titers of which correlated with paired serum titers determined by conventional spectrophotometric methods (r = 0.94, p = 0.00012). We also showed that eluates from DBS Serum Separator cards could be used with conventional spectrophotometric vibriocidal methods, and that they correlated with paired serum at a wide range of titers (r = 0.96, p<0.0001). Similarly, we used ELISA methods to show that V. cholerae O-specific polysaccharide antibody responses from DBS eluates correlated with results from paired serum for IgG (r = 0.85, p = 0.00006), IgM (r = 0.79, p = 0.00049) and IgA (r = 0.73, p = 0.0019), highlighting its potential for use in determination of isotype-specific responses. Storage of DBS cards at a range of temperatures did not change antibody responses., Conclusion: In conclusion, we have developed and demonstrated a proof-of-concept for assays utilizing DBS for assessing cholera-specific immune responses.

Background: Host factors play an important role in pathogenesis and disease outcome in Clostridium difficile infection (CDI), and characterization of these responses could uncover potential host biomarkers to complement existing microbe-based diagnostics., Methods: We extracted RNA from fecal samples of patients with CDI and profiled human mRNA using amplicon-based next-generation sequencing (NGS). We compared the fecal host mRNA transcript expression profiles of patients with CDI to controls with non-CDI diarrhea., Results: We found that the ratio of human actin gamma 1 (ACTG1) to 16S ribosomal RNA (rRNA) was highly correlated with NGS quality as measured by percentage of reads on target. Patients with CDI could be differentiated from those with non-CDI diarrhea based on their fecal mRNA expression profiles using principal component analysis. Among the most differentially expressed genes were ones related to immune response (IL23A, IL34) and actin-cytoskeleton function (TNNT1, MYL4, SMTN, MYBPC3, all adjusted P -values < 1 × 10 -3 )., Conclusions: In this proof-of-concept study, we used host fecal transcriptomics for non-invasive profiling of the mucosal immune response in CDI. We identified differentially expressed genes with biological plausibility based on animal and cell culture models. This demonstrates the potential of fecal transcriptomics to uncover host-based biomarkers for enteric infections., Competing Interests: CONFLICTS OF INTEREST R.S. is a coinventor on a patent application pending for Taxonomer, which has been licensed by IDbyDNA from the University of Utah. He owns equity in and consults for IDbyDNA. B.K.L. has received research support from OpGen, travel support for a speaking engagement from Luminex, and is a member of the scientific advisory board of Merck. All other authors report no potential conflicts of interest.

Background: Venous ulcers are very common with few curative treatment options., Objective: To report the closure rate and clinical characteristics of active venous ulcers in a vein clinic using endovenous laser ablation (EVLA) with a 1,320-nm laser., Methods and Materials: A prospective database was kept consisting of patients with an active venous ulcer at the time of consultation in a single-practitioner academic vein clinic from March 2007 to May 2014. A database was maintained and charts were reviewed with attention to the length of time the patient reported having the ulcer, procedures performed, and time to ulcer healing., Results: Thirty-one patients were identified at consultation with venous ulceration. One patient's ulcer was healed with conservative medical management before receiving treatment. The remaining 30 patients were treated with a combination of EVLA of the great and/or short saphenous veins, foam sclerotherapy of insufficient varicose and reticular veins, and phlebectomy as appropriate. Two patients were lost to follow up after partial treatment. Ulcer healing occurred in more than 93% (27/29) of patients with a median healing time of 55 days from the time of first treatment. The median follow-up time after treatment was 448 days., Conclusion: Endovenous laser ablation with a 1,320-nm laser in combination with foam sclerotherapy and phlebectomy as appropriate is effective treatment of chronic venous ulcers and should be considered as a treatment option for patients with C6 venous insufficiency. To the authors' knowledge, this is the largest, prospective series of chronic venous ulcers treated with EVLA. Further randomized controlled studies are needed to confirm these findings.

Objective: To determine the safety and tolerability of mexiletine in a phase II double-blind randomized controlled trial of sporadic amyotrophic lateral sclerosis (SALS)., Methods: Sixty participants with SALS from 10 centers were randomized 1:1:1 to placebo, mexiletine 300 mg/d, or mexiletine 900 mg/d and followed for 12 weeks. The primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetic study from plasma and CSF, ALS Functional Rating Scale-Revised (ALSFRS-R) score, slow vital capacity (SVC), and muscle cramp frequency and severity., Results: The only serious adverse event among active arm participants was one episode of imbalance. Thirty-two percent of participants receiving 900 mg of mexiletine discontinued study drug vs 5% on placebo (p = 0.026). Pharmacokinetic study demonstrated a peak plasma concentration 2 hours postdose and strong correlation between plasma and CSF (p < 0.001). Rates of decline of ALSFRS-R and SVC did not differ from placebo. Analysis of all randomized patients demonstrated significant reductions of muscle cramp frequency (300 mg: rate = 31% of placebo, p = 0.047; 900 mg: 16% of placebo, p = 0.002) and cramp intensity (300 mg: mean = 45% of placebo, p = 0.08; 900 mg: 25% of placebo, p = 0.005)., Conclusions: Mexiletine was safe at both doses and well-tolerated at 300 mg/d but adverse effects at 900 mg/d led to a high rate of discontinuation. Mexiletine treatment resulted in large dose-dependent reductions in muscle cramp frequency and severity. No effect on rate of progression was detected, but clinically important differences could not be excluded in this small and short-duration study., Classification of Evidence: This study provides Class I evidence that mexiletine is safe when given daily to patients with amyotrophic lateral sclerosis at 300 and 900 mg and well-tolerated at the lower dose., (© 2016 American Academy of Neurology.)

Background: Antiseptics are chemical agents used to reduce the microbial population on the surface of the skin and are used in nearly every surgical procedure today. Despite this, there are currently no definitive guidelines on surgical preoperative antisepsis that indicate a specific regimen based on demonstration of superior efficacy., Objective: This review serves to examine preoperative antisepsis, including cutaneous bacteriology, preoperative hair removal, preoperative decolonization, surgical attire, and the antiseptic agents themselves., Materials and Methods: A review of the literature on surgical antiseptics was performed., Results: Although numerous studies have demonstrated differences in bacterial colonization rates, few well-controlled investigations have demonstrated superiority of a given regimen. The alcohol-based iodophor and chlorhexidine products seem to exhibit greater efficacy than their aqueous counterparts., Conclusion: More randomized controlled trials will be needed to determine if any specific regimen is most effective. At this point in time, product usage should be based on specific attributes relating to the products, such as iodophors around the eyes and/or ears to avoid irritation and aqueous-based solutions in hair bearing areas because of concern for flammability. Ultimately, it is up to the individual surgeon to tailor the optimal antiseptic regimen for their specific scope of practice.

Few reports of cutaneous Burkitt lymphoma exist in the literature. Here, the authors describe the case of a human immunodeficiency virus-positive individual with the rare diagnosis of cutaneous Burkitt lymphoma. Three weeks before the development of his cutaneous lesions, the patient experienced bilateral lower extremity paralysis, and an epidural mass was found. Bone marrow biopsy findings and serum protein electrophoresis seemed consistent with multiple myeloma. The visible appearance of the skin lesions raised concern for cutaneous involvement by myeloma; however, the skin biopsy showed morphological and immunohistochemical features of Burkitt lymphoma. In this case report, the authors discuss the histopathologic findings of the cutaneous lesions in consideration with the bone marrow biopsy findings.

Background: Given the high cost of plasma derived intravenous alpha 1-antitrypsin (AAT), a more efficient method of delivery to the lungs is desirable. Inhaled AAT has been shown feasible for the treatment of alpha 1-antitrypsin deficiency (AATD) and is currently in clinical trials. To better understand patient preferences about possible inhaled AAT therapy, a survey was conducted to explore patient attitudes., Methods: We conducted an email based survey of patients in the Alpha-1 Foundation Research Registry with AATD on intravenous AAT replacement. Respondents were asked to rate their interest in hypothetical nebulized or dry powder inhaled AAT., Results: Respondents reported high levels of interest in both dried powder inhaler and nebulizer delivered inhaled AAT. The interest in dried powder inhaled was higher than interest in nebulized AAT (71% vs 64%, p = 0.0001). The interest in dried powder inhaled AAT was particularly high in respondents currently on bronchodilator therapy (p = 0.0053). Patients were just as likely to use or not use the product if it required 20% more out of pocket cost., Conclusions: There is a high level of patient interest in the development of a commercially available inhaled AAT replacement product.

The purpose of this study was to compare absorption properties of a variety of wound dressing products that are available on the market. A simple, inexpensive method of evaluation was utilized so that new dressings could easily be tested and added to the data set.

Frequent and excessive tanning persists despite a growing understanding of its associated morbidity and mortality, suggesting that ultraviolet radiation may impart rewarding effects beyond the assumed cosmetic benefits. To empirically measure putative centrally rewarding properties of ultraviolet radiation (UVR), we assessed the effects of a commercially available tanning bed upon regional cerebral blood flow (rCBF), a measure of brain activity, using single-photon emission computed tomography (SPECT). Seven frequent salon bed tanners were placed under a UVA/UVB tanning light during two sessions; one session with UVR and the other with filtered UVR (sham UVR). Session order was randomized and subjects were blinded to study order. During the UVR session, relative to sham UVR session, subjects demonstrated a relative increase in rCBF of the dorsal striatum, anterior insula and medial orbitofrontal cortex, brain regions associated with the experience of reward. These changes were accompanied by a decrease in the subjective desire to tan. These findings suggest that UVR may have centrally rewarding properties that encourage excessive tanning., (© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.)

Defining long-term outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) has been complicated by varying definitions of treatment response and differing scales measuring impairment or disability. An expert panel was convened to devise a CIDP Disease Activity Status (CDAS) and to classify long-term outcome by applying it to 106 patients with a consensus diagnosis of CIDP. Sixty of these cases were graded blindly by three independent reviewers to assess inter-rater reliability. The mean duration of follow-up was 6.4 years (range, 3 months-23 years). Eleven percent of patients were classified as cured (stable examination and off treatment for ≥5 years), 20% were in remission (stable and off treatment for <5 years), 44% had stable active disease but required ongoing therapy for at least 1 year, 7% were improving after recent initiation of therapy, and 18% had unstable active disease (treatment naïve or treatment refractory). Excellent inter-rater reliability was observed (kappa scores: 0.93-0.97; p < 0.0001). The CDAS is considered a simple and reproducible tool to classify patients with CIDP according to disease activity and treatment status that can be applied easily in practice and potentially to select patients for clinical trials., (© 2010 Peripheral Nerve Society.)

Prior to European contact in 1778, Hawaiians developed intensive irrigated pondfield agricultural systems in windward Kohala, Hawai'i. We evaluated three potential sources of nutrients to windward systems that could have sustained intensive agriculture: (1) in situ weathering of primary and secondary minerals in upland soils; (2) rejuvenation of the supply of rock-derived nutrients on eroded slopes and in alluvium; and (3) transport of rock-derived nutrients to crops via irrigation water. Our results show that most windward soils are infertile and suggest that weathering of minerals within upland soils was insufficient to sustain intensive agriculture without substantial cultural inputs. Erosion enhances weathering and so increases nutrient supply, with soils of the largest alluvial valleys (>200 m deep) retaining 37% of calcium from parent material (compared to 2% in upland sites). However, soils of smaller valleys that also supported pre-contact agricultural systems are substantially less enriched. Isotopic 87Sr/86Sr analyses of stream water demonstrate that at low to moderate stream flow over 90% of dissolved strontium derives from weathering of basalt rather than deposition of atmospheric sources; most other dissolved cations also derive from basalt weathering. We calculate that irrigation water could have supplied approximately 200 kg ha(-1) yr(-1) of calcium to pondfield systems, nearly 100 times more than was supplied by weathering in soils on stable geomorphic surfaces. In effect, irrigation waters brought nutrients from rocks to the windward crops.

Combining agents with different mechanisms of action may be necessary for meaningful results in treating ALS. The combinations of minocycline-creatine and celecoxib-creatine have additive effects in the murine model. New trial designs are needed to efficiently screen the growing number of potential neuroprotective agents. Our objective was to assess two drug combinations in ALS using a novel phase II trial design. We conducted a randomized, double-blind selection trial in sequential pools of 60 patients. Participants received minocycline (100 mg)-creatine (10 g) twice daily or celecoxib (400 mg)-creatine (10 g) twice daily for six months. The primary objective was treatment selection based on which combination best slowed deterioration in the ALS Functional Rating Scale-Revised (ALSFRS-R); the trial could be stopped after one pool if the difference between the two arms was adequately large. At trial conclusion, each arm was compared to a historical control group in a futility analysis. Safety measures were also examined. After the first patient pool, the mean six-month decline in ALSFRS-R was 5.27 (SD=5.54) in the celecoxib-creatine group and 6.47 (SD=9.14) in the minocycline-creatine group. The corresponding decline was 5.82 (SD=6.77) in the historical controls. The difference between the two sample means exceeded the stopping criterion. The null hypothesis of superiority was not rejected in the futility analysis. Skin rash occurred more frequently in the celecoxib-creatine group. In conclusion, the celecoxib-creatine combination was selected as preferable to the minocycline-creatine combination for further evaluation. This phase II design was efficient, leading to treatment selection after just 60 patients, and can be used in other phase II trials to assess different agents.

When maintained on a folate-deficient, iron-rich diet, transgenic mice lacking in apolipoprotein E (ApoE-/- mice) demonstrate impaired activity of glutathione S-transferase (GST), resulting in increased oxidative species within brain tissue despite abnormally high levels of glutathione. These mice also exhibit reduced levels of S-adenosyl methionine (SAM) and increased levels of its hydrolysis product S-adenosyl homocysteine, which inhibits SAM usage. Supplementation of the above diet with SAM restored GST activity and eliminated reactive oxygen species at the expense of stockpiled glutathione, suggesting that one or more SAM-dependent reactions were required to maintain GST activity. We examined herein the impact of SAM on GST activity using a cell-free assay. SAM stimulated GST activity in a dose-response manner when added to homogenates derived from the above ApoE-/- mice. SAM also increased activity of purified rat liver GST and recombinant GST. Filtering of SAM through a 4 kDa cutoff and systematic withholding of reaction components eliminated the possibility of any additional contaminating enzyme. These findings confirm that SAM can exert a direct effect on GST activity. Since Alzheimer's disease is accompanied by reduced GST activity, diminished SAM and increased SAH, these findings underscore the critical role of SAM in maintenance of neuronal health.

Folate deficiency increases neuronal oxidative damage and potentiates the deleterious effects of apolipoprotein E (ApoE) deficiency. Mice lacking ApoE (ApoE -/- mice) upregulate the expression and activity of another enzyme, glutathione synthase (GS), when deprived of folate, in an apparent attempt to compensate for increased oxidative damage. Herein, we examined the influence of ApoE and folate deficiency on expression and activity of several enzymes of the methionine cycle. Expression and activity of methylene tetrahydrofolate reductase was increased in the order ApoE +/+ < ApoE +/- < ApoE -/- in response to folate deprivation. Expression of cystathione beta synthase followed a similar pattern. By contrast, expression and activity of methionine synthase decreased following folate deprivation in the order ApoE +/+ < ApoE +/- < ApoE -/-. These studies demonstrate that folate deficiency induces compensatory regulation of methionine cycle genes, and that these effects are potentiated by ApoE deficiency in a gene-dosage manner. They further support the notion that latent genetic deficiencies, including those of methionine cycle, may contribute to Alzheimer's disease, especially in concert with age-related nutritional deficiencies.

Oxidative stress is an early neurodegenerative insult in Alzheimer's disease (AD). Antioxidant mechanisms, including elements of the glutathione (GSH) pathway, undergo at least a transient compensatory increase that is apparently insufficient due to continued oxidative damage during disease progression. Mice deficient in apolipoprotein E, which provide a model for some aspects of AD, undergo increased oxidative damage to brain tissue and cognitive decline when maintained on a folate-free diet, despite a compensatory increase in glutathione synthase transcription and activity as well as increased levels of GSH. Dietary supplementation with N-acetyl cysteine (1 g/kg diet), a cell-permeant antioxidant and GSH precursor, alleviated oxidative damage and cognitive decline, and restored glutathione synthase and GSH levels in ApoE-deficient mice deprived of folate to those of normal mice maintained in the presence of folate. These data support the administration of antioxidant precursors to buffer oxidative damage in neurodegenerative disorders.

Myasthenia gravis is a disorder of neuromuscular transmission, manifest by variable weakness of skeletal muscle. The disorder has a range of therapies that differ with respect to efficacy, timing, and side effects. The physician treating myasthenia gravis must be well versed in understanding the evidence basis for using these agents, as well as the trade-offs between persistent disease manifestations and their costs and expected benefits. Diagnosis of myasthenia gravis depends on recognizing the pattern of weakness, which typically involves some combination of extraocular, bulbar, facial, limb, and neck muscles. Management relies on some combination of medications that influence the function of the neuromuscular junction and treatments that alter the immune response. Thymectomy is commonly used, although trends in evidence-based medicine are leading expert clinicians to look closely at its efficacy. Plasma exchange is useful for patients in crisis, who require rapid improvement. The exact role for high-dose intravenous immunoglobulin in this setting is still being studied, although the agent is gaining popularity. Knowing that the treatments are effective is not enough. It is still important to determine the treatment that has a more rapid onset, because these patients often require intensive care or respiratory assistance.

Oxidative stress is a major contributing factor in neurodegeneration and can arise from dietary, environmental, and genetic sources. Here we examine the separate and combined impact of deprivation of folate and vitamin E, coupled with dietary iron as a prooxidant, on normal mice and transgenic mice lacking apolipoprotein E (ApoE-/- mice). Both mouse strains exhibited increased levels of glutathione when deprived of folate and vitamin E, but a substantial further increase was observed in ApoE-/- mice. To determine the mechanism(s) underlying this increase, we quantified transcription and activity of glutathione synthase (GS). Both normal and ApoE-/- mice demonstrated increased GS activity when deprived of folate and vitamin E. However, transcription was increased only in ApoE-/- mice deprived of folate and vitamin E. These findings demonstrate that deficiency in one gene can result in compensatory up-regulation in a second relevant gene and, furthermore, indicate that compensation for oxidative stress can occur in brain tissue at epigenetic and genetic levels depending on the nature and/or extent of oxidative stress., (Copyright 2004 Wiley-Liss, Inc.)

Folate deprivation induces neurotoxicity that is potentiated by additional nutritional and genetic deficiencies including vitamin E and apolipoprotein E deficiency. These deficiencies collectively induce oxidative damage, cognitive impairment, and compensatory alteration in glutathione generation. Treatment with agents that regulate distinct portions of the methionine cycle, including the S-adenosyl homocysteine hydrolase inhibitor, 3-deaza adenosine, the methyl donor S-adenosyl methionine, and the antioxidant N-acetyl cysteine, provide neuroprotection against various aspects of neurotoxicity in normal and apolipoprotein E-deficient mice and in cultured neuronal cells deprived of dietary folate and vitamin E and subjected to iron overload. Here it is demonstrated that simultaneous treatment with these agents provide superior neuroprotection by alleviating individual and overlapping neurotoxic consequences. These findings support combinatorial treatments with agents that compensate for differential insults in age-related neurodegenerative disorders.