Overcoming Barriers to Successful Climate and Health Adaptation Practice: Notes from the Field.

State and local public health agencies are at the forefront of planning and responding to the health challenges of climate hazards but face substantial barriers to effective climate and health adaptation amidst concurrent environmental and public health crises. To ensure successful adaptation, it is necessary to understand and overcome these barriers. The U.

Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts.

Aberrant hyperactivation of Wnt signaling, driven by nuclear β-catenin in the colonic epithelium, represents the seminal event in the initiation and progression of colorectal cancer (CRC). Despite its established role in CRC tumorigenesis, clinical translation of Wnt inhibitors remains unsuccessful. Late SV40 factor (LSF; encoded by TFCP2) is a transcription factor and a potent oncogene.

Factor quinolinone inhibitors disrupt spindles and multiple LSF (TFCP2)-protein interactions in mitosis, including with microtubule-associated proteins.

Factor quinolinone inhibitors (FQIs), a first-in-class set of small molecule inhibitors targeted to the transcription factor LSF (TFCP2), exhibit promising cancer chemotherapeutic properties. FQI1, the initial lead compound identified, unexpectedly induced a concentration-dependent delay in mitotic progression. Here, we show that FQI1 can rapidly and reversibly lead to mitotic arrest, even when added directly to mitotic cells, implying that FQI1-mediated mitotic defects are not transcriptionally based.

Factor quinolinone inhibitors alter cell morphology and motility by destabilizing interphase microtubules.

Factor quinolinone inhibitors are promising anti-cancer compounds, initially characterized as specific inhibitors of the oncogenic transcription factor LSF (TFCP2). These compounds exert anti-proliferative activity at least in part by disrupting mitotic spindles. Herein, we report additional interphase consequences of the initial lead compound, FQI1, in two telomerase immortalized cell lines.

Creative Anticipatory Ethical Reasoning with Scenario Analysis and Design Fiction.

This paper presents an experimental approach for engaging undergraduate STEM students in anticipatory ethical reasoning, or ethical reasoning applied to the analysis of potential mid- to long-term implications and outcomes of technological innovation. The authors implemented two variations of an approach that integrates three key components-scenario analysis, design fiction, and ethical frameworks-into five sections of an introductory course on the social contexts of science and technology that is required of STEM majors. The authors dub this approach Creative Anticipatory Ethical Reasoning, or CAER.

Co-Imagining the Futures of Implementation Precision Medicine Using Scenario Analysis and Design Fiction.

Precision medicine has a long history dating to the early 20th century when inquiries into the biochemical basis of large person-to-person variations in susceptibility to human diseases and response to medicines had first begun. Yet, personalized medicine in the 21st century is far from being "future-proof." Emerging technologies such as artificial intelligence, and changing human values and preferences, call for anticipatory, rather than reactive, approaches to the governance of precision medicine futures.

Preselection of Lung Cancer Cases Using FGFR1 mRNA and Gene Copy Number for Treatment With Ponatinib.

Introduction: Preclinically, high epidermal growth factor receptor 1 (FGFR1) messenger RNA (FGFR1-MRNA) and FGFR1 amplification (FGFR1-AMP) predicted sensitivity to fibroblast growth factor receptor inhibitors in non-small-cell lung cancer and small-cell lung cancer cell lines. KRAS mutations did not preclude sensitivity.

Patients And Methods: Metastatic EGFR- and ALK-negative lung cancers were screened for FGFR1-MRNA by in-situ hybridization (ISH) and FGFR1-AMP by silver in-situ hybridization (SISH).

Minigrants to Local Health Departments: An Opportunity to Promote Climate Change Preparedness.

Context: Human health is threatened by climate change. While the public health workforce is concerned about climate change, local health department (LHD) administrators have reported insufficient knowledge and resources to address climate change. Minigrants from state to LHDs have been used to promote a variety of local public health initiatives.

Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the positive effects of lipid-based nutrient supplements on breast-milk B vitamins.

Background: Little information is available on B vitamin concentrations in human milk or on how they are affected by maternal B vitamin deficiencies, antiretroviral therapy, or maternal supplementation.

Objective: The objective was to evaluate the effects of antiretroviral therapy and/or lipid-based nutrient supplements (LNSs) on B vitamin concentrations in breast milk from HIV-infected women in Malawi.

Design: Breast milk was collected from 537 women recruited within the Breastfeeding, Antiretrovirals, and Nutrition study at 2 or 6 wk and 24 wk postpartum.

Hydroboration-oxidation: A chemoselective route to cellulose ω-hydroxyalkanoate esters.

We describe the first synthesis of hydroxy-functionalized polysaccharide esters via chemoselective olefin hydroboration-oxidation in the presence of ester groups. Cellulose esters with terminally olefinic side chains were first synthesized by esterification of commercially available cellulose esters (e.g.

Geographic Range Expansion for Rat Lungworm in North America.

Using quantitative PCR analysis and DNA sequencing, we provide evidence for the presence of rat lungworm (Angiostrongylus cantonensis) in Oklahoma, USA, and identified a potentially novel rat host (Sigmodon hispidus). Our results indicate a geographic range expansion for this medically and ecologically relevant parasite in North America.

Global decline in suitable habitat for Angiostrongylus ( = Parastrongylus) cantonensis: the role of climate change.

Climate change is implicated in the alteration of the ranges of species worldwide. Such shifts in species distributions may introduce parasites/pathogens, hosts, and vectors associated with disease to new areas. The parasite Angiostrongylus ( = Parastrongylus) cantonensis is an invasive species that causes eosinophilic meningitis in humans and neurological abnormalities in domestic/wild animals.

Ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) for the rapid, simultaneous analysis of thiamin, riboflavin, flavin adenine dinucleotide, nicotinamide and pyridoxal in human milk.

A novel, rapid and sensitive ultra-performance liquid-chromatography tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of several B-vitamins in human milk was developed. Resolution by retention time or multiple reaction monitoring (MRM) for thiamin, riboflavin, flavin adenine dinucleotide (FAD), nicotinamide and pyridoxal (PL) has been optimized within 2 min using a gradient of 10 mM ammonium formate (aq) and acetonitrile. Thiamin-(4-methyl-¹³C-thiazol-5-yl-¹³C₃) hydrochloride, riboflavin-dioxo-pyrimidine-¹³C₄,¹⁵N₂, and pyridoxal-methyl-d₃ hydrochloride were used as internal standards.

Development of a rapid, cost-effective TaqMan Real-Time PCR Assay for identification and differentiation of Coccidioides immitis and Coccidioides posadasii.

Coccidioidomycosis is an infection caused by Coccidioides immitis or C. posadasii. We developed a TaqMan real-time PCR assay that rapidly and accurately differentiates the species.