Jorge Trejo‐Lopez

BACKGROUND AND OBJECTIVES: Substance-related impairment among healthcare professionals has significant public health implications, but little is known regarding factors associated with substance use initiation in this group. METHODS: In this study, 105 healthcare professionals (80% male), who ranged in age from 24 to 68 years (M = 47.1 years, SD = 10.2) completed a self-report questionnaire assessing age at first use, education level at first use, means of access to substances upon first use, order of substance use initiation, and reasons for first and continued substance use. Physicians (51%), pharmacists (19.2%), dentists (11.5%), physician assistants (5.8%), and various other allied health professionals (12.7%) participated. RESULTS: Results demonstrated that 73.2% of the professionals used tobacco, 90.4% used alcohol, and 64.4% used other drugs before beginning professional school. Reasons for first use of substances paralleled those seen in the general public (e.g., curiosity, peer influence, availability), and differed from reasons for continued substance use (e.g., getting high, addiction, stress management). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Given that onset of substance use among health professionals appears to mirror that seen in the general population, their unique treatment success rates likely cannot be solely attributed to later age-of-onset of their substance use disorder. Delaying experimentation with addictive substances and improving efforts at early identification of problematic use are crucial to preventing the development of substance use disorders among healthcare professionals, as well as the public as a whole.

-synuclein (S) is the major component of several types of brain pathological inclusions that define neurodegenerative diseases termed synucleinopathies. Central nervous system (CNS) inoculation studies using either in vitro polymerized S fibrils or in vivo derived lysates containing S aggregates to induce the progressive spread of S inclusion pathology in animal disease models have supported the notion that S mediated progressive neurodegeneration can occur by a prion-like mechanism. We have previously shown that neonatal brain inoculation with preformed S fibrils in hemizygous M20 +/-transgenic mice expressing wild type human S and to a lesser extent in non-transgenic mice can result in a concentration-dependent progressive induction of CNS S pathology. Recent studies using brain lysates from patients with multiple system atrophy (MSA), characterized by S inclusion pathology in oligodendrocytes, indicate that these may be uniquely potent at inducing S pathology with prion-like strain specificity. We demonstrate here that brain lysates from MSA patients, but not control individuals, can induce S pathology following neonatal brain inoculation in transgenic mice expressing A53T human S (M83 line), but not in transgenic expressing wild type human S (M20 line) or non-transgenic mice within the timeframe of the study design. Further, we show that neuroanatomical and immunohistochemical properties of the pathology induced by MSA brain lysates is very similar to what is produced by the neonatal brain injection of preformed human S fibrils in hemizygous M83 +/-transgenic mice. Collectively, these findings reinforce the idea that the intrinsic traits of the M83 mouse model dominates over any putative prion-like strain properties of MSA S seeds that can induce pathology.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid β (Aβ)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aβ amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aβ in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.

Phosphaturic mesenchymal tumors (PMTs) are neoplasms associated with tumor-induced osteomalacia. Patients typically present with pathologic fractures in the setting of chronic hypophosphatemic hyperphosphaturic osteomalacia, as well as gradual muscle weakness, bone pain, and difficulty walking. Because of their rarity and nonspecific symptomatology, phosphaturic mesenchymal tumors often go undiagnosed for years. Even when discovered on imaging, the tumors can be diagnostically challenging for radiologists. Phosphaturic mesenchymal tumors often tend to be small and can be located nearly anywhere in the body, and, therefore, can mimic many other tumors. This case highlights the imaging and pathologic markers of a phosphaturic mesenchymal tumor, often found in a patient with tumor-induced osteomalacia.