Drug-Initiated Activity Metabolomics Identifies Myristoylglycine as a Potent Endogenous Metabolite for Human Brown Fat Differentiation.

Worldwide, obesity rates have doubled since the 1980s and in the USA alone, almost 40% of adults are obese, which is closely associated with a myriad of metabolic diseases such as type 2 diabetes and arteriosclerosis. Obesity is derived from an imbalance between energy intake and consumption, therefore balancing energy homeostasis is an attractive target for metabolic diseases. One therapeutic approach consists of increasing the number of brown-like adipocytes in the white adipose tissue (WAT). Whereas WAT stores excess energy, brown adipose tissue (BAT) can dissipate this energy overload in the form of heat, increasing energy expenditure and thus inhibiting metabolic diseases. To facilitate BAT production a high-throughput screening approach was developed on previously known drugs using human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes. The screening allowed us to discover that zafirlukast, an FDA-approved small molecule drug commonly used to treat asthma, was able to differentiate adipocyte precursors and white-biased adipocytes into functional brown adipocytes. However, zafirlukast is toxic to human cells at higher dosages. Drug-Initiated Activity Metabolomics (DIAM) was used to investigate zafirlukast as a BAT inducer, and the endogenous metabolite myristoylglycine was then discovered to mimic the browning properties of zafirlukast without impacting cell viability. Myristoylglycine was found to be bio-synthesized upon zafirlukast treatment and was unique in inducing brown adipocyte differentiation, raising the possibility of using endogenous metabolites and bypassing the exogenous drugs to potentially alleviate disease, in this case, obesity and other related metabolic diseases.

[Necrotic cervicitis for co-infection of herpes simplex virus 2 and Mycoplasma genitalium]. / Cervicitis necrótica por co-infección de virus herpes simplex 2 y Mycoplasma genitalium.

Cervicitis is a frequent condition caused mainly by sexually trans- mitted agents. The clinical spectrum varies from absence of symptoms to extensive inflammatory processes that may simulate a malignant neoplasm. We present a clinical case of an adolescent with genital ulcers and systemic disease. Speculoscopy revealed a tumoral-looking cervix. Laboratory studies confirm infection with herpes simplex virus 2 (HSV-2) and Mycoplasma genitalium, together with a histological study that ruled out neoplasia. It progresses favorably to antimicrobial treatment, with recovery of the appearance of the cervix. Cervicitis rarely presents with necrotic involvement. Co-infection with HSV-2 and M. genitalium infection may have been the determinant of cervical damage and the necrotic appearance. A thorough evaluation and study with highly sensitive and specific diagnostic tests allowed an adequate diagnosis and treatment.

Cervicitis necrótica por co-infección de virus herpes simplex 2 y Mycoplasma genitalium / Necrotic cervicitis for co-infection of herpes simplex virus 2 and Mycoplasma genitalium

Resumen Las cervicitis es una condición frecuente causada principalmente por agentes de transmisión sexual. Su presentación clínica varía desde cuadros asintomáticos hasta procesos inflamatorios extensos, que incluso asemejan un tumor maligno. Presentamos el caso de una adolescente que presentó úlceras genitales, síntomas generales y cérvix necrótico con aspecto tumoral. Los estudios de laboratorio confirmaron una co-infección por virus herpes simplex 2 (HSV-2) y Mycoplasma genitalium. El estudio histológico descartó una neo- plasia. Evolucionó favorablemente al tratamiento antimicrobiano, con recuperación progresiva del aspecto del cérvix. La cervicitis en raras ocasiones se presenta con compromiso necrótico. La co-infección por HSV-2 y M. genitalium, en este caso, pudo ser el determinante del daño cervical y la necrosis. Una evaluación acuciosa y estudio con exámenes diagnósticos de alta sensibilidad y especificidad permitieron hacer un diagnóstico y tratamiento adecuado.

Abstract Cervicitis is a frequent condition caused mainly by sexually trans- mitted agents. The clinical spectrum varies from absence of symptoms to extensive inflammatory processes that may simulate a malignant neoplasm. We present a clinical case of an adolescent with genital ulcers and systemic disease. Speculoscopy revealed a tumoral-looking cervix. Laboratory studies confirm infection with herpes simplex virus 2 (HSV-2) and Mycoplasma genitalium, together with a histological study that ruled out neoplasia. It progresses favorably to antimicrobial treatment, with recovery of the appearance of the cervix. Cervicitis rarely presents with necrotic involvement. Co-infection with HSV-2 and M. genitalium infection may have been the determinant of cervical damage and the necrotic appearance. A thorough evaluation and study with highly sensitive and specific diagnostic tests allowed an adequate diagnosis and treatment.

A longitudinal study of the learning and retention of task-specific training.

This longitudinal study evaluated the learning and retention of task-specific training during the subjects' classroom performance of a one-person pivot transfer. Twelve subjects were videotaped completing the transfer (pretest). The subjects then participated in a two-hour training session. One week later (posttest 1), and one year later (posttest 2) the subjects were videotaped again. A checklist was used to analyze the videotapes. A one-way ANOVA with repeated measures revealed that there was a statistically significant difference between the tests (F = 243.73, p-value < 0.0001). A post hoc analysis (Bonferroni procedure) indicated that the posttest 1 scores (mean = 13, SD = 0.40) were significantly higher than the pretest scores (mean = 2.96, SD = 0.39) indicating an improved score on the checklist. There was no significant difference between the scores of posttest 1 and posttest 2 (mean = 12.79, SD = 0.60) indicating that subjects continued to perform the task with proper body mechanics one year post training.