The Oxygen Paradox, the French Paradox, and age-related diseases.

A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen "a toxic environmental poison" could be also indispensable for life (Beckman and Ames Physiol Rev 78(2):547-81, 1998; Stadtman and Berlett Chem Res Toxicol 10(5):485-94, 1997)?: the so-called Oxygen Paradox (Davies and Ursini 1995; Davies Biochem Soc Symp 61:1-31, 1995). How can French people apparently disregard the rule that high dietary intakes of cholesterol and saturated fats (e.g., cheese and paté) will result in an early death from cardiovascular diseases (Renaud and de Lorgeril Lancet 339(8808):1523-6, 1992; Catalgol et al. Front Pharmacol 3:141, 2012; Eisenberg et al. Nat Med 22(12):1428-1438, 2016)?: the so-called, French Paradox. Doubtless, the truth is not a duality and epistemological bias probably generates apparently self-contradictory conclusions. Perhaps nowhere in biology are there so many apparently contradictory views, and even experimental results, affecting human physiology and pathology as in the fields of free radicals and oxidative stress, antioxidants, foods and drinks, and dietary recommendations; this is particularly true when issues such as disease-susceptibility or avoidance, "healthspan," "lifespan," and ageing are involved. Consider, for example, the apparently paradoxical observation that treatment with low doses of a substance that is toxic at high concentrations may actually induce transient adaptations that protect against a subsequent exposure to the same (or similar) toxin. This particular paradox is now mechanistically explained as "Adaptive Homeostasis" (Davies Mol Asp Med 49:1-7, 2016; Pomatto et al. 2017a; Lomeli et al. Clin Sci (Lond) 131(21):2573-2599, 2017; Pomatto and Davies 2017); the non-damaging process by which an apparent toxicant can activate biological signal transduction pathways to increase expression of protective genes, by mechanisms that are completely different from those by which the same agent induces toxicity at high concentrations. In this review, we explore the influences and effects of paradoxes such as the Oxygen Paradox and the French Paradox on the etiology, progression, and outcomes of many of the major human age-related diseases, as well as the basic biological phenomenon of ageing itself.

Curricular factors associated with medical students' practice of the skin cancer examination: an educational enhancement initiative by the integrated skin exam consortium.

IMPORTANCE: As medical school curricula become progressively integrated, a need exists to optimize education related to the skin cancer examination (SCE) for melanoma, a relevant competency gap that influences secondary prevention efforts. OBJECTIVES: To identify curricular factors associated with medical students' confidence, intent, and performance regarding the SCE. DESIGN, SETTING, AND PARTICIPANTS: Survey-based cross-sectional study from the Integrated Skin Exam Consortium at accredited US medical schools among a volunteer sample of second-year students representing 8 geographically varied public and private institutions. Students were administered a questionnaire to assess characteristics, curricular exposures, and educational and practical experiences related to skin cancer, as well as knowledge of melanoma risk and a detection method. MAIN OUTCOMES AND MEASURES: Primary outcomes were confidence in performing the SCE, intent to perform an integrated skin examination, and actual performance of the SCE. RESULTS: Physical diagnosis session and clinical encounter were most predictive of confidence in performance of the SCE (odds ratios [ORs], 15.35 and 11.48, respectively). Other curricular factors associated with confidence included instruction time of at least 60 minutes on skin cancer (OR, 6.35), lecture on the SCE (OR, 7.54), knowledge of melanoma risk (OR, 3.71), and at least 1 opportunity to observe the SCE (OR, 2.70). Physical diagnosis session and at least 4 opportunities to observe the SCE were most predictive of intent to perform an integrated skin examination (ORs, 4.84 and 4.72, respectively). Other curricular factors associated with intent included knowledge of melanoma risk (OR, 1.83), clinical encounter (OR, 2.39), and at least 1 opportunity to observe the SCE (OR, 1.95). Clinical encounter, physical diagnosis session, and at least 1 opportunity to observe the SCE were most predictive of performance of the SCE (ORs, 21.67, 15.48, and 9.92, respectively). Other curricular factors associated with performance included instruction time of at least 60 minutes on skin cancer (OR, 2.42) and lecture on the SCE (OR, 5.04). CONCLUSIONS AND RELEVANCE: To augment the practice of the SCE among medical students, course directors may design an integrated curriculum that includes at least 60 minutes of instruction related to melanoma and the SCE, a description of the integrated skin examination as part of the physical diagnosis course, and education on high-risk demographic groups and anatomic sites specific to men and women and on the ABCDEs of melanoma, and at least 1 opportunity to observe the SCE.

Dermatology curriculum for internal medicine residents: a randomized trial.

BACKGROUND: Physicians in specialties other than dermatology care for the majority of patients with skin diseases, yet most physicians receive little training in dermatology. OBJECTIVES: The primary objective of this study was to determine whether there would be a sizable (20%) improvement in posttraining scores for internal medicine residents after completing 1 of 3 assigned curricula. A secondary objective was to determine whether there were significant differences in improvement among the 3 resident cohorts after completing their curriculum. Finally, we explored the residents' change in perceived clinical knowledge postcurriculum. METHODS: Thirty-six postgraduate year 2 internal medicine residents were randomized to complete 1 of 3 one-month dermatology curricula (didactic, clinical, or combined). The main outcome measure was performance on different sets of Medical Knowledge Self-Assessment Program (MKSAP)-15 questions at study entry and completion. A secondary outcome was self-rated performance in 3 clinical domains. RESULTS: All participants completed the study. All curricula led to an improvement in MKSAP-15 scores, but only students who completed the didactic curriculum demonstrated a 20% improvement in posttraining scores. A larger number of residents completing the clinical and didactic curricula rated their clinical performance as improved compared to those who completed the combined curriculum. CONCLUSIONS: While all 3 curricula led to improvement, as measured by a standardized assessment, a didactic curriculum in dermatology resulted in the largest improvement in knowledge as measured by a multiple-choice test.

The Integrated Skin Exam film: an educational intervention to promote early detection of melanoma by medical students.

BACKGROUND: Knowledge of the skin cancer examination (SCE) and its practice remain relevant competency gaps among medical students. OBJECTIVE: We elaborate on a method of SCE known as the Integrated Skin Exam and discuss the development of an instructional film that illustrates its principles. We assess the tool's effect on knowledge, attitudes, and perceptions related to the SCE. METHODS: Second-year students among 8 randomized schools viewed the film and completed pre-post questionnaires. RESULTS: After viewing The Integrated Skin Exam film, students demonstrated improved melanoma knowledge, including identification of high-risk demographic groups (61% vs 42.9%, P < .001), high-risk anatomic sites in women (88.6% vs 46.5%, P < .001) and men (92.1% vs 34.8%, P < .001), and the ABCDEs of melanoma (98.4% vs 91.2%, P < .001). Students demonstrated increased confidence in the SCE (66.93% vs 16.40%, P < .001) and augmented intentions to practice it (99.05% vs 13.9%, P < .001). A greater proportion (70.4% vs 41.9%, P < .001) of students thought less than 3 minutes were required to integrate SCE into the routine examination. LIMITATIONS: Longitudinal impact of the film was not assessed. CONCLUSION: The Integrated Skin Exam film introduces an integrated approach to the SCE that addresses knowledge gaps, mitigates perceived barriers, and augments intention related to practice of the SCE.

Distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases.

OBJECTIVE: To determine the prevalence of extracutaneous manifestations and autoimmunity in adult and pediatric patients with morphea. DESIGN: A retrospective review of 245 patients with morphea. SETTING: University of Texas Southwestern Medical Center-affiliated institutions. Patients Patients with clinical findings consistent with morphea. MAIN OUTCOME MEASURES: Prevalence of concomitant autoimmune diseases, prevalence of familial autoimmune disease, prevalence of extracutaneous manifestations, and laboratory evidence of autoimmunity (antinuclear antibody positivity). Secondary outcome measures included demographic features. RESULTS: In this group, adults and children were affected nearly equally, and African Americans were affected less frequently than expected. The prevalence of concomitant autoimmunity in the generalized subtype of morphea was statistically significantly greater than that found in all other subtypes combined (P = .01). Frequency of a family history of autoimmune disease showed a trend in favor of generalized and mixed subgroups. The linear subtype showed a significant association with neurologic manifestations, while general systemic manifestations were most common in the generalized subtype. Antinuclear antibody positivity was most frequent in mixed and generalized subtypes. CONCLUSIONS: High prevalences of concomitant and familial autoimmune disease, systemic manifestations, and antinuclear antibody positivity in the generalized and possibly mixed subtypes suggest that these are systemic autoimmune syndromes and not skin-only phenomena. This has implications for the management and treatment of patients with morphea.

Metastatic pleomorphic sarcoma to left atrium.

Although several thousand patients are diagnosed with sarcoma annually in the United States, metastases to the heart are very uncommon. In this case report, an overall low frequency cancer presents masquerading with common cardiac symptomology. This case illustrates the importance for detailed diagnostic cardiac evaluations and heightened suspicion by physicians to consider metastatic disease to the heart in cancer patients with cardiovascular complications. Also discussed is a review of surgical and chemotherapeutic options for this problem.