Idiopathic pyostomatitis-pyodermatitis vegetans with nasal obstruction: A case report.

Pyostomatitis-pyodermatitis vegetans is an uncommon mucocutaneous dermatosis of unknown etiology. It presents as erythematous pustules that coalesce to form exudative vegetating plaques on the oral mucosa and/or skin. Diagnosis is largely based on clinical assessment, although histopathology should be used as supporting evidence. Pyostomatitis-pyodermatitis vegetans is associated with inflammatory bowel disease, liver dysfunction, and others. We report a case of a 48-year-old man who presented with erythematous eroded plaques involving his nares and upper lip. Investigations revealed a dense mixed inflammatory infiltrate and pronounced peripheral eosinophilia. Uniquely, the patient did not have inflammatory bowel disease or any other systemic condition. Systemic corticosteroids were helpful in clearing mucocutaneous lesions; however, this effect was only sustained at high doses. There are few reports of pyostomatitis-pyodermatitis vegetans in the medical literature. This case highlights key aspects of this extremely rare dermatosis, especially in otherwise healthy patients without inflammatory bowel disease.

Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches.

Glioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.

Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells.

Asymmetric cell division (ACD) enables the maintenance of a stem cell population while simultaneously generating differentiated progeny. Cancer stem cells (CSCs) undergo multiple modes of cell division during tumor expansion and in response to therapy, yet the functional consequences of these division modes remain to be determined. Using a fluorescent reporter for cell surface receptor distribution during mitosis, we found that ACD generated a daughter cell with enhanced therapeutic resistance and increased coenrichment of EGFR and neurotrophin receptor (p75NTR) from a glioblastoma CSC. Stimulation of both receptors antagonized differentiation induction and promoted self-renewal capacity. p75NTR knockdown enhanced the therapeutic efficacy of EGFR inhibition, indicating that coinheritance of p75NTR and EGFR promotes resistance to EGFR inhibition through a redundant mechanism. These data demonstrate that ACD produces progeny with coenriched growth factor receptors, which contributes to the generation of a more therapeutically resistant CSC population.

Measurement of talent in volleyball: 15-month follow-up of elite adolescent players.

AIM: The purpose of this study was two-fold: first, to examine the contribution of a battery of physical and motor tests to early phases of talent detection and early development in volleyball, and second, to differentiate between and compare the motor ability of 16-year-old starter (S) and non-starter (NS) volleyball players. METHODS: Fifteen male adolescent volleyball players underwent assessment of physical and motor ability 6 times during a 15-month training program; however, not all of them took part in each testing phase. The battery was composed of 8 physical and motor tests and 2 skill tests. The physical and motor tests included 2 speed tests, an agility run, 4 explosive power tests, and an endurance test. The skill tests evaluated service accuracy at rest and following effort. RESULTS: All participants improved their results in all but 2 tests (endurance and skill tests) across testing phases. Comparisons between the S (n=8) and NS (n=7) revealed that only one physical explosive power test (vertical jump with approach), was found to be a good indicator for distinguishing between the 2 groups of players. CONCLUSION: It was concluded that the volleyball battery of tests was not sensitive enough to distinguish between the ''good'' and ''very good'' players suggesting that physical and motor tests do not reflect open skill ability in volleyball.

Measurement of talent in judo using a unique, judo-specific ability test.

AIM: Coaches of young athletes at early phases of development often use batteries of tests in order to obtain information that will be helpful in predicting their future success. However, little scientific inquiry has been conducted on the relevance of the testing process to the final selection and success of young prospects. The purpose of this study was to examine the benefits of a unique judo-specific ability test in early phases of talent development and selection. METHODS: Ten judokas (12-15 years of age) underwent assessment of general ability and specific judo ability 3 times during 1994 and 1995, at about 6-month intervals. The general ability test included: sit-ups, push-ups, and side-to-side jumps. The specific judo ability test was comprised of 10 stations in which the judokas performed physical ability and skill tasks. Following the 12-month training program the judokas were ranked by the 2 national judo coaches. Eight years after the beginning of the training program, the judokas were ranked once again by the national coaches. RESULTS: Data analysis revealed that the specific judo ability test did not correlate with either the 1995 or with the 2003 ranking. CONCLUSIONS: Because the unique judo-specific ability test was not found to be sensitive enough to accurately measure talent, it is suggested that future studies investigate the usefulness of tests reflecting a more open-skill environment.