Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.

IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 (TFAP2A, TFAP2C) and AP-1 (FOS and JUN) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD.

The Negative Effect of Social Discrimination on Pain Tolerance and the Moderating Role of Pain Catastrophizing.

This study examined the negative impact of social discrimination on the time to pain tolerance during experimentally induced cold pressor pain among healthy individuals. It was hypothesized that the degree to which one catastrophized about pain would exacerbate the negative impact of a history discriminatory experiences on pain tolerance, and that this interaction would be different between individuals of a racial and ethnic minority and non-Hispanic white individuals (thus testing catastrophizing as a moderated moderator). Higher levels of discrimination were positively related to catastrophic thinking about pain, and there was a significant negative relationship between the level of experienced discrimination and time to pain tolerance. Pain catastrophizing emerged as a significant moderator in that when pain catastrophizing levels were high, there was no association between social discrimination and pain tolerance. A history of social discrimination was significantly associated with reduced pain tolerance at low and moderate levels of pain catastrophizing. Racial minority status did not significantly alter this moderating relationship. Implications for the importance of assessing sociocultural variables, such as experiencing social discrimination in the clinical assessment of the individual with pain are outlined.

Total Synthesis and Biological Evaluation of Clavatadines C-E.

We described herein the application of a convergent and protecting-group avoidant approach that led to the first total synthesis of the marine natural products clavatadine D (4) and E (5), and the second total synthesis of clavatadine C (3). In each case, a key amide-coupling afforded an immediate precursor of each natural product in a rapid manner from structurally similar western and eastern portions that derived from an ester of l-tyrosine and butane-1,4-diamine, respectively. A deprotection step free of detectable byproducts cleanly provided the remaining known members of the clavatadine family of natural products. Each total synthesis required five steps (longest linear sequence) with overall yields of 30-37%, 26-39%, and 28-50% for clavatadine C (3), D (4), and E (5), respectively. A screen of their potential anticancer activity against the NCI-60 cell line panel revealed cytotoxicity levels up to 38% across a broad spectrum of tumor types. Although clavatadine C (3) was relatively benign, clavatadine D (4) exhibited 20-38% growth inhibition against a wide array of cancer cell types including leukemia, non-small-cell lung, colon, ovarian, and breast. Clavatadine E (5) was active against two types of human brain tumors.

Neuropsychology pilot: Dr. Carlos Porges.

This article is an interview that explores Dr. Carlos Porge's atypical job as a neuropsychologist and active airline pilot. The article aims to educate about the path and costs that go into having an atypical career in psychology. Additionally, this interview with Dr. Porges explores the challenges, considerations, and limitations of working as a neuropsychology pilot. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Changes in pharmacy students' perceptions of underserved populations after a six-week clinical rotation in a federally qualified health center clinic.

BACKGROUND AND PURPOSE: The primary objective of this study was to assess changes in pharmacy students' attitudes and perceptions toward providing care to underserved populations after a six-week clinical experience within a Federally Qualified Health Center (FQHC) clinic. EDUCATIONAL ACTIVITY AND SETTING: A pre-post survey design was utilized to evaluate third- and fourth-year pharmacy students' attitudes and perceptions before and after a six-week clinical rotation providing direct patient care to underserved patients in FQHC clinics. Results were collected via self-administered online surveys that collected information on participants' (1) demographics, (2) past experiences interacting with underserved populations, (3) type of clinical activities completed during the rotation, and (4) personal opinions and perceptions of providing care to underserved populations. FINDINGS: Responses to seven of the 18 attitudinal questions showed a statistically significant positive change from baseline, with three questions being related to educational satisfaction. Changes in attitudes for questions related to domains of personal impact and perceptions/barriers were also significant. DISCUSSION/SUMMARY: Clinical rotations within an FQHC clinic can positively impact pharmacy students' attitudes towards underserved populations. If more students are exposed to direct patient care with underserved populations throughout their experiential training, the number of graduating student pharmacists that explore job opportunities within underserved areas may increase. Clinical rotations within an FQHC clinic can positively impact pharmacy students' attitudes towards underserved populations. If more students are exposed to direct patient care with underserved populations throughout their experiential training, the number of graduating student pharmacists that explore job opportunities within underserved areas may increase.