Integrative STEM education for undergraduate neuroscience: Design and implementation.

As an integrative discipline, neuroscience can serve as a vehicle for the development of integrative thinking skills and broad-based scientific proficiency in undergraduate students. Undergraduate neuroscience curricula incorporate fundamental concepts from multiple disciplines. Deepening the explicit exploration of these connections in a neuroscience core curriculum has the potential to support more meaningful and successful undergraduate STEM learning for neuroscience students. Curriculum and faculty development activities related to an integrative core curriculum can provide opportunities for faculty across disciplines and departments to advance common goals of inclusive excellence in STEM. These efforts facilitate analysis of the institutional STEM curriculum from the student perspective, and assist in creating an internal locus of accountability for diversity, equity, and inclusion within the institution. Faculty at the College of the Holy Cross have undertaken the collaborative design and implementation of an integrative core curriculum for neuroscience that embraces principles of inclusive pedagogy, emphasizes the connections between neuroscience and other disciplines, and guides students to develop broad proficiency in fundamental STEM concepts and skills.

An Integrative Approach to STEM Concepts in an Introductory Neuroscience Course: Gains in Interdisciplinary Awareness.

Neuroscience is an integrative discipline for which students must achieve broad-based proficiency in many of the sciences. We are motivated by the premise that student pursuit of proficiency in science, technology, engineering, and mathematics (STEM) can be supported by awareness of the application of knowledge and tools from the various disciplines for solving complex problems. We refer to this awareness as "interdisciplinary awareness." Faculty from biology, chemistry, mathematics/computer science, physics, and psychology departments contributed to a novel integrative introductory neuroscience course with no pre-requisites. STEM concepts were taught in "flipped" class modules throughout the semester: Students viewed brief videos and completed accompanying homework assignments independently. In subsequent class meetings, students applied the STEM concepts to understand nervous system structure and function through engaged learning activities. The integrative introduction to neuroscience course was compared to two other courses to test the hypothesis that it would lead to greater gains in interdisciplinary awareness than courses that overlap in content but were not designed for this specific goal. Data on interdisciplinary awareness were collected using previously published tools at the beginning and end of each course, enabling within-subject analyses. Students in the integrative course significantly increased their identification of scientific terms as relevant to neuroscience in a term-discipline relevance survey and increased their use of terms related to levels of analysis (e.g., molecular, cellular, systems) in response to an open-ended prompt. These gains were seen over time within the integrative introduction to neuroscience course as well as relative to the other two courses.

Malignant Melanoma on a Thermal Burn Scar with an Interval of More Than 70 Years.

Cases of malignant melanoma on thermal burn scars have occasionally been reported. We report a 78-year-old Japanese female with malignant melanoma on a thermal burn scar with an interval of more than 70 years. Our case reemphasizes the importance of regular examinations in persons with thermal burn scars.

Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab.

Nivolumab, a blockade of programmed cell death 1, is now administrated for advanced malignant melanomas. Nivolumab-associated adverse events include organ-specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin-dependent diabetes. However, predisposed persons are currently unknown. Here, we report serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab: one with Hashimoto disease and another with probable subclinical Hashimoto disease. We should verify if nivolumab-related hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid individuals with subclinical autoimmune thyroid disease.

Blue nevus with a dermoscopic appearance of peripheral streaks with branches.

Blue nevi are dermal dendritic melanocytic proliferations presenting as papules, nodules or plaques of blue, blue-gray or blue-brown color. Dermoscopic appearance commonly shows global patterns as homogeneous mono/dichromatic pigmentation and multichromatic pigmentation. Here, we report the case of a blue nevus with the dermoscopic feature of peripheral streaks with branches. With histopathologic deep sections, we confirmed that dermal dendritic melanocytes were distributed in the direction of the streaks. We emphasize that streaks are a rare but important sign of blue nevi.

Variants in melanogenesis-related genes associate with skin cancer risk among Japanese populations.

Human skin color is known to be associated with the risk of cutaneous cancer. Some reports indicated that pigmentation-related gene variants were associated with cutaneous cancer risk in Caucasian populations, but there are no similar reports in East Asian populations. This study aimed to evaluate the association between pigmentation-related genes and the risk of skin cancer in Japanese populations. We studied the associations between 12 variants of four pigmentation-related genes and melanin index variations in 198 Japanese patients with skin cancer and compared these findings to those of 500 Japanese controls by using multiple logistic regression analysis. Furthermore, we analyzed an independent sample of 107 Japanese patients with skin cancer. A non-synonymous variant, H615R in the oculocutaneous albinism 2 gene (OCA2), was associated with the risk of malignant melanoma in the Yamagata group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17-0.86; P = 0.020). Another non-synonymous variant, A481T in OCA2, was associated with the risk of squamous cell carcinoma and actinic keratosis in the Osaka group (OR, 3.16; 95% CI, 1.41-7.04; P = 0.005). In malignant melanoma cases, the minor allele in OCA2 H615R might have induced the development of lesions in sun-exposed skin (OR, 26.32; 95% CI, 1.96-333; P = 0.014). Our results suggest that some OCA2 variants are definite risk factors for the onset of cutaneous cancer in Japanese populations.

The histopathological feature of the nail isthmus in an ectopic nail.

The nail unit has a unique structure. It has been recently proposed that the nail isthmus as a transitional zone between the most distal part of the nail bed and the hyponychium. A 7-year-old Japanese boy presented with an ectopic nail, an additional and independent miniature nail on the digital pulp of the right fifth finger. We studied the expression of a series of keratin in longitudinal specimens and showed the histopathological manifestation in the nail isthmus. This region in the ectopic nail is subdivided into 2 parts: a proximal and narrow part anchored to the nail plate and a distal and wide part with a semihard keratinized structure.

Generalized vitiligo and associated autoimmune diseases in Japanese patients and their families.

BACKGROUND: Generalized vitiligo is an acquired disorder in which depigmented macules result from the autoimmune loss of melanocytes from the involved regions of skin. Generalized vitiligo is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease), rheumatoid arthritis, adult-onset type 1 diabetes mellitus, psoriasis, pernicious anemia, systemic lupus erythematosus, and Addison's disease. METHODS: One hundred and thirty-three Japanese patients with generalized vitiligo were enrolled in this study to investigate the occurrence of autoimmune diseases in Japanese patients with generalized vitiligo and their families. RESULTS: Twenty-seven of the patients with generalized vitiligo (20.3%) had autoimmune diseases, particularly autoimmune thyroid disease (sixteen patients, 12%) and alopecia areata (seven patients, 5.3%). Thirty-five patients (26.3%) had a family history of generalized vitiligo and/or other autoimmune diseases. Familial generalized vitiligo was present in fifteen (11.3%), including four families with members affected by autoimmune disorders. Twenty (15.0%) had one or more family members with only autoimmune disorders. CONCLUSIONS: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.

Phylloid hypermelanosis and melanocytic nevi with aggregated and disfigured melanosomes: causal relationship between phylloid pigment distribution and chromosome 13 abnormalities.

The mosaic pattern of phylloid hypomelanosis is mostly associated with chromosome 13 abnormalities. Recently, 1 case of hypermelanosis in a phylloid pattern has been described. We describe a 29-year-old Japanese male with mental retardation, phylloid hypermelanosis and histopathologically and ultrastructurally peculiar melanocytic nevi, which were associated with 3 aberrant chromosome 13 cell lines. The karyotyping of 30 peripheral blood lymphocytes showed 46,XY,r(13)(p11.2q34) in 21 cells, 45,XY,-13 in 7 cells and 46,XY,dic r(13)(p11.2q34) in 2 cells. Immunohistochemical staining with HMB45 showed a positive reaction to basal keratinocytes in phylloid hypermelanosis. HMB45 staining reacted to the nevus cells and keratinocytes in the melanocytic nevi. Electron microscopy of a specimen excised from a melanocytic nevus showed an unusual finding of aggregated and disfigured melanosomes in the keratinocytes. This case suggests that chromosome 13 abnormalities may be related to the development of phylloid hypermelanosis and the bizarre melanosomes in the keratinocytes of melanocytic nevi.