Distinct molecular profiles of skull bone marrow in health and neurological disorders.

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positron emission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases.

Spatial proteomics in three-dimensional intact specimens.

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of large biological specimens imaged in 3D are lacking. Here, we present DISCO-MS, a technology that combines whole-organ/whole-organism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultra-high-sensitivity mass spectrometry. DISCO-MS yielded proteome data indistinguishable from uncleared samples in both rodent and human tissues. We used DISCO-MS to investigate microglia activation along axonal tracts after brain injury and characterized early- and late-stage individual amyloid-beta plaques in a mouse model of Alzheimer's disease. DISCO-bot robotic sample extraction enabled us to study the regional heterogeneity of immune cells in intact mouse bodies and aortic plaques in a complete human heart. DISCO-MS enables unbiased proteome analysis of preclinical and clinical tissues after unbiased imaging of entire specimens in 3D, identifying diagnostic and therapeutic opportunities for complex diseases. VIDEO ABSTRACT.

A challenging case of an adamantinoma of fibula with soft tissue mass harboring distinct histopathology.

We present a case of adamantinoma that originated from the fibula and had a large soft tissue component measuring approximately 6 cm. Clinical, radiological, and pathological investigations initially suggested that the tumor might be a bone-invading synovial sarcoma. To the best of our knowledge, no other case of fibular adamantinoma with such a large soft tissue component has been reported in the literature.

Knowledge, Attitude, and Behavior Levels of Postmenopausal Women about Osteoporosis.

BACKGROUND: Osteoporosis can be delayed by providing accurate and adequate information to people at risk. Therefore, we aimed to determine the knowledge, attitude, and behavior levels of women in the postmenopausal period, which is the largest group at risk. METHODS: The study was conducted in a tertiary Training and Research Hospital between 1 December 2018 and 1 May 2019 in 225 postmenopausal women who applied to the Family Medicine outpatient clinic and bone mineral density (BMD) outpatient clinics for BMD measurement or had previously had this measurement at least once. A questionnaire evaluating the knowledge, attitudes, and behavior levels related to osteoporosis was applied to all patients included in the study. RESULTS: The mean age was 58.05±9.1 years. The median osteoporosis knowledge score was 7 out of 19 points. A total of 119 (52.9%) had low knowledge scores and 106 (47.1%) had higher knowledge scores. Of the individuals with high scores, 40 (37.7%) were smoking, 64 (60.4%) did not sunbathe, 89 (84%) did not consume the recommended daily amount of calcium, and 58 (54.7%) were not exercising in the recommended time. It was seen that those who were university graduates, who had previously learned about osteoporosis from a health professional, and who had a family history of osteoporosis had higher knowledge levels. CONCLUSIONS: Even in postmenopausal women who are aware that they are in the risk group and that they should have BMD, their knowledge, attitude, and behavior levels on osteoporosis were found to be quite low.

HPV-associated p16 INK4A expression and response to therapy and survival in selected head and neck cancers.

BACKGROUND: Development of squamous cell cancer of head and neck (SCCHN) is associated with human papillomavirus (HPV) infection, which in turn is closely related with expression of p16 INK4A. Loss of p16 INK4A expression by deletion, mutation, or hypermethylation is common in SCCHN. We here evaluated p16 INK4A as a prognostic marker of treatment response and survival in our SCCHN patients with laryngeal, hypopharyngeal or nasopharyngeal cancers. MATERIALS AND METHODS: 131 patients diagnosed with SCCHN between January 2,2006 and July 17, 2010 were examined for p16 INK4A. The median age was 60 years (15-82 years). Fifty one patients were stage I-II and 80 were stage III-IV. Immunohistochemical expression of p16 INK4A was analyzed in pretreatment paraffin-embedded tumor blocks. The influence of p16 INK4A status on disease-free survival, and overall survival after treatment was evaluated. RESULTS: P16 INK4A positivity was found in 58 patients (44%). Tumor-positivity for p16INK4A was correlated with improved disease free survival (70.1 months vs 59 months) and improved overall survival (2, 3 and 5-year values; 77% vs 72%, 70% vs 63% and, 63% vs 55%; respectively). On multivariate analysis, stage was determined as independent prognostic factor for disease-free survival. CONCLUSIONS: Stage was the major prognostic factor on treatment response and survival in our patients. P16 INK4A status predicts better outcome in laryngeal, hypopharyngeal or nasopharyngeal cancer cases treated with surgery plus adjuvant radiochemotherapy as well as with definitive radiation therapy and/or chemotherapy.