The health benefits of reducing micro-heat islands: A 22-year analysis of the impact of urban temperature reduction on heat-related illnesses in California's major cities.

This study investigates the relationship between temporal changes in temperatures characterizing local urban heat islands (UHIs) and heat-related illnesses (HRIs) in seven major cities of California. UHIs, which are a phenomenon that arises in the presence of impervious surfaces or the lack of green spaces exacerbate the effects of extreme heat events, can be measured longitudinally using satellite products. The two objectives of this study were: (1) to identify temperature trends in local temperatures to characterize UHIs across zip code tabulation areas (ZCTAs) in the seven observed cities over a 22-year period and (2) to use propensity score and inverse probability weighting to achieve exchangeability between different types of ZCTAs and assess the difference in hospital admissions recorded as HRIs attributable to temporal changes in UHIs. We use monthly land surface temperature data derived from MODIS Terra imagery from the summer months (June-September) from 2000 to 2022. We categorized ZCTAs (into three groups) based on their monthly land surface temperature trends. Of the 216 ZCTAs included in this study, the summertime land surface temperature trends of 43 decreased, while 161 remained unchanged, and 12 increased. Los Angeles had the greatest number of decreased ZCTAs, San Diego and San Jose had the highest number of increased ZCTAs. To analyze the number of monthly HRI attributable to changes in UHI, we used inverse probability of treatment weighting to analyze the difference in HRI between the years of 2006 and 2017 which were two major extreme heat events over the entire State. We observed an average reduction of 3.2 (95 % CI: 0.5; 5.9) HRIs per month and per ZCTAs in decreased neighborhoods as compared to unchanged. This study emphasizes the importance of urban climate adaptation strategies to mitigate the intensity and prevalence of UHIs to reduce health risks related to heat.

Polymodal K+ channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

Pain and inflammation contribute immeasurably to reduced quality of life, yet modern analgesic and anti-inflammatory therapeutics can cause dependence and side effects. Here, we screened 1444 plant extracts, prepared primarily from native species in California and the United States Virgin Islands, against two voltage-gated K+ channels - T-cell expressed Kv1.3 and nociceptive-neuron expressed Kv7.2/7.3. A subset of extracts both inhibits Kv1.3 and activates Kv7.2/7.3 at hyperpolarized potentials, effects predicted to be anti-inflammatory and analgesic, respectively. Among the top dual hits are witch hazel and fireweed; polymodal modulation of multiple K+ channel types by hydrolysable tannins contributes to their dual anti-inflammatory, analgesic actions. In silico docking and mutagenesis data suggest pore-proximal extracellular linker sequence divergence underlies opposite effects of hydrolysable tannins on different Kv1 isoforms. The findings provide molecular insights into the enduring, widespread medicinal use of witch hazel and fireweed and demonstrate a screening strategy for discovering dual anti-inflammatory, analgesic small molecules.

KCNQ and KCNE Isoform-Dependent Pharmacology Rationalizes Native American Dual Use of Specific Plants as Both Analgesics and Gastrointestinal Therapeutics.

Indigenous peoples of the Americas are proficient in botanical medicine. KCNQ family voltage-gated potassium (Kv) channels are sensitive to a variety of ligands, including plant metabolites. Here, we screened methanolic extracts prepared from 40 Californian coastal redwood forest plants for effects on Kv current and membrane potential in Xenopus oocytes heterologously expressing KCNQ2/3, which regulates excitability of neurons, including those that sense pain. Extracts from 9 of the 40 plant species increased KCNQ2/3 current at -60 mV by ≥threefold (maximally, 15-fold by Urtica dioica) and/or hyperpolarized membrane potential by ≥-3 mV (maximally, -11 mV by Arctostaphylos glandulosa). All nine plants have traditionally been used as both analgesics and gastrointestinal therapeutics. Of two extracts tested, both acted as KCNQ-dependent analgesics in mice. KCNQ2/3 activation at physiologically relevant, subthreshold membrane potentials by tannic acid, gallic acid and quercetin provided molecular correlates for analgesic action of several of the plants. While tannic acid also activated KCNQ1 and KCNQ1-KCNE1 at hyperpolarized, negative membrane potentials, it inhibited KCNQ1-KCNE3 at both negative and positive membrane potentials, mechanistically rationalizing historical use of tannic acid-containing plants as gastrointestinal therapeutics. KCNE dependence of KCNQ channel modulation by plant metabolites therefore provides a molecular mechanistic basis for Native American use of specific plants as both analgesics and gastrointestinal aids.