Responses of medaka (Oryzias latipes) ammonia production and excretion to overcome acidified environments.

Anthropogenic acidification of water is an on-going environmental disaster for freshwater fishes. Fishes rely on ammonia excretion to eliminate the excess acid and mitigate the harmful effects; however, it remains largely unknown how ammoniagenesis occurs and is coordinated with ammonia excretion upon acidic stress. Medaka (Oryzias latipes) was used to examine the effects of acidic stress on ammonia production and excretion. We reveal an undiscovered ammonia-producing cell type that is rich in glutaminase (GLS) and located adjacent to the ammonia-excreting ionocytes, Na+/H+ exchanger (NHE) cells, in the gills. The gills, comparing with other ammoniagenetic organs, is the quickest to respond to the acidic stress by triggering GLS-dependent ammonia production. The unique division of labor between GLS and NHE cells in the gills allows medaka to simultaneously upregulate GLS activity and ammonia excretion shortly after exposure to acidic environments. Pharmacological experiment with a GLS inhibitor abolished the activated ammonia excretion, further suggesting the essential role of the unique feature in the responses to acidic stress. Our study shades light on a novel physiological mechanism to timely and efficiently mitigate adverse effects of acidification, providing a new way to assess the impact of on-going environmental acidification on fish.

Teleostean fishes may have developed an efficient Na+ uptake for adaptation to the freshwater system.

Understanding Na+ uptake mechanisms in vertebrates has been a research priority since vertebrate ancestors were thought to originate from hyperosmotic marine habitats to the hypoosmotic freshwater system. Given the evolutionary success of osmoregulator teleosts, these freshwater conquerors from the marine habitats are reasonably considered to develop the traits of absorbing Na+ from the Na+-poor circumstances for ionic homeostasis. However, in teleosts, the loss of epithelial Na+ channel (ENaC) has long been a mystery and an issue under debate in the evolution of vertebrates. In this study, we evaluate the idea that energetic efficiency in teleosts may have been improved by selection for ENaC loss and an evolved energy-saving alternative, the Na+/H+ exchangers (NHE3)-mediated Na+ uptake/NH4 + excretion machinery. The present study approaches this question from the lamprey, a pioneer invader of freshwater habitats, initially developed ENaC-mediated Na+ uptake driven by energy-consuming apical H+-ATPase (VHA) in the gills, similar to amphibian skin and external gills. Later, teleosts may have intensified ammonotelism to generate larger NH4 + outward gradients that facilitate NHE3-mediated Na+ uptake against an unfavorable Na+ gradient in freshwater without consuming additional ATP. Therefore, this study provides a fresh starting point for expanding our understanding of vertebrate ion regulation and environmental adaptation within the framework of the energy constraint concept.

Clinical effectiveness of beta-lactams versus fluoroquinolones as empirical therapy in patients with diabetes mellitus hospitalized for urinary tract infections: A retrospective cohort study.

BACKGROUND: Diabetic patients are at risk of severe urinary tract infections (UTIs). Due to the emerging resistance rates to fluoroquinolones and ß-lactams, we aimed to evaluate the effectiveness of ß-lactams versus fluoroquinolones as empirical therapy for diabetic patients hospitalized for UTIs. METHODS: A retrospective cohort study was conducted in a medical center in Taiwan between 2016 and 2018. Patients with type 2 diabetes, aged ≥20 and hospitalized for UTIs were enrolled. Patients with UTI diagnosis within one year before the admission, co-infections at the admission, or ≥2 pathogens in the urine cultures were excluded. The primary outcome was empiric treatment failure. RESULTS: 298 patients were followed for at least 30 days after the admission. Escherichia coli (61.07%) was the most common pathogen. The resistance rates of the pathogens to levofloxacin were 28.52% and 34.22% according to the historical Clinical and Laboratory Standards Institute (CLSI) breakpoints and the updated 2019 CLSI breakpoints, respectively. The resistance rates of ceftazidime and cefepime were 21.81% and 11.41%, respectively. Empirical ß-lactams were associated with less treatment failure compared to fluoroquinolones (adjusted OR = 0.32, 95% CI = 0.17-0.60). Beta-lactams were associated with less treatment failure than fluoroquinolones when appropriatness was determined by the pre-2019 CLSI breakpoints but not the 2019 CLSI breakpoints. CONCLUSIONS: In diabetic patients hospitalized for UTIs, ß-lactams were associated with less empiric treatment failure compared to fluoroquinolones when the resistance rate to fluoroquinolone is higher than ß-lactams. The updated 2019 CLSI breakpoint for fluoroquinolone was better than pre-2019 CLSI breakpoints to correlate with treatment outcomes for hospitalized UTIs in diabetic patients.

Fine particulate matter exposure during pregnancy and infancy and incident asthma.

BACKGROUND: Lung development is a multistage process from conception to the postnatal period, disruption of which by air pollutants can trigger later respiratory morbidity. OBJECTIVE: We sought to evaluate the effects of weekly average fine particulate matter (particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) exposure during pregnancy and infancy on asthma and identify vulnerable times to help elucidate possible mechanisms of the effects of PM2.5 on asthma symptoms. METHODS: A birth cohort study including 184,604 children born during 2004-2011 in Taichung City was retrieved from the Taiwan Maternal and Child Health Database and followed until 2014. A daily satellite-based hybrid model was applied to estimate PM2.5 exposure for each subject. A Cox proportional hazard model combined with a distributed lag nonlinear model was used to evaluate the associations of asthma with PM2.5 exposure during pregnancy and infancy. RESULTS: The birth cohort contained 34,336 asthmatic patients, and the mean age of children given a diagnosis of asthma was 3.39 ± 1.78 years. Increased exposure to PM2.5 during gestational weeks 6 to 22 and 9 to 46 weeks after birth were significantly associated with an increased incidence of asthma. The exposure-response relationship indicated that the hazard ratio (HR) of asthma increased steeply at PM2.5 exposure of greater than 93 µg/m3 during pregnancy. Additionally, the HRs remained significant with postnatal exposure to PM2.5 between 26 and 72 µg/m3 (range, 1.01-1.07 µg/m3), followed by a sharp increase in HRs at PM2.5 exposure of greater than 73 µg/m3. CONCLUSION: Both prenatal and postnatal exposures to PM2.5 were associated with later development of asthma. The vulnerable time windows might be within early gestation and midgestation and infancy.