Acute and chronic temperature dependence of Na+/H+ exchange activity of Pimephales promelas gills.

Na+/H+ exchangers (NHE) mediate at least part of Na+ entry into gill epithelia via Na+/NH4+ exchange. For homeostasis, Na+ entry into and exit via Na+/K+ ATPase from gill epithelia must balance. Na+/K+ ATPase activity is reduced in cold- compared to warm-acclimated freshwater temperate fish. We hypothesized gill NHE activity is greater in warm- than cold-acclimated fish when measured at acclimation temperatures, and NHE activity displays a temperature dependence similar to Na+/K+ ATPase. Since NHE mRNA expression does not differ, we measured the Na+-dependence of pH-induced Na+ fluxes in gill vesicles from warm- and cold-acclimated fathead minnows at 20o and 7 °C, and calculated maximum transport rates (Vmax) and Na+ K1/2s. We also measured NH4+-induced Na+ fluxes and Na+-induced H+ fluxes. In vesicles from warm-acclimated fish, NHE Vmaxs were 278 ± 33 and 149 ± 23 arbitrary unit/s (au/s) and Na+ K1/2s were 12 ± 4 and 6 ± 4 mmol/l when assayed at 20o and 7 °C (p < 0.004), respectively. In vesicles from cold-acclimated fish, Vmaxs were 288 ± 35 and 141 ± 13 au/s and Na+ K1/2s 17 ± 5 and 7 ± 2 mmol/l when assayed at 20o and 7 °C (p < 0.002), respectively. Na+-induced H+ fluxes were 98 ± 8 and 104 ± 26 au/s in warm- and cold-acclimated fish assayed at 20 °C, respectively. Na+/NH4+ exchange was 120 ± 11 and 158 ± 13 au/s in warm- and cold-acclimated fish, respectively. Conclusions: Gill NHE activity was greater in warm- than cold-acclimated fish assayed at acclimation temperatures. The temperature dependence of NHE activity was similar in both groups, but differed from that reported for Na+/K+ ATPase suggesting complex mechanisms to maintain Na+ homeostasis.

Activity changes in gill ion transporter enzymes in response to salinity and temperature in fathead minnows (Pimephales promelas).

Fathead minnows, Pimephales promelas, are found throughout the continental United States in waters in which salinity can change with tides and temperatures vary seasonally. They have been used extensively in studies of environmental toxicology and are commercially important. In a very recent study in our labs RNA Seq was used to assemble transcriptomes from the gills of fatheads acclimated to either 5° or 22 °C. By comparison with published genomes, transcripts were identified for a number of ion transporters, ion channels, and signal molecule receptors, as well as enzymes that generate ammonia. H-ATPase and Na/K-ATPase activities were measured in supernatants of gill homogenates from fish acclimated to water sodium concentrations of 1.6, 3.1 or 124 mM sodium. As the water sodium concentration increased, in vitro activities of Na/K-ATPase activity and gill glutamate dehydrogenase activity decreased while H-ATPase activity increased. In a second series of experiments minnows were acclimated to 5 °C, 12.5 °C or 22 °C. In vitro activity of Na/K-ATPase decreased but activities of H-ATPase and glutamate dehydrogenase increased as temperature increased in gill membranes. These data do not support a primary role for apical H-ATPase in sodium influx under all conditions but do suggest a role for glutamate dehydrogenase production of ammonium to act as a counter-ion for sodium uptake by NHE-3.

The COVID-19 Patient in the Surgical Intensive Care Unit.

COVID-19 continues to rampage around the world. Noncritical care-trained physicians may be deployed into the intensive care unit to manage these complex patients. Although COVID-19 is primarily a respiratory disease, it is also associated with significant pathology in the brain, heart, vasculature, lungs, gastrointestinal tract, and kidneys. This article provides an overview of COVID-19 using an organ-based, systematic approach.

Evidence and temporality of the obesity paradox in coronary bypass surgery: an analysis of cause-specific mortality.

OBJECTIVES: We evaluated the presence of an 'obesity paradox' in coronary artery bypass grafting (CABG) patients, determined its time course and ascertained whether it is associated with improved cardiovascular (CV) survival versus non-CV survival. METHODS: A retrospective analysis of 3 prospectively collected databases was conducted. A fifteen-year Kaplan-Meier analysis in 7091 CABG patients was performed and repeated in 5 body mass index [BMI (kg/m2)] cohorts [Normal (18.5-24.99 kg/m2), Overweight (25-29.99 kg/m2), Obese I (30-34.99 kg/m2), Obese II (35-39.99 kg/m2) and Obese III (≥40 kg/m2)]. Mortality hazard ratios {HR [95% confidence interval (CI)]} were derived using comprehensive multivariable competing risk Cox regression, accounting for BMI categories for overall (0-15), Early (0-1), Intermediate (1-8) and Late (8-15) postoperative years, to relax the proportional hazards assumption. The regression was repeated using BMI as a continuous variable. Mortality was classified into any, CV and non-CV. RESULTS: Obese patients were younger with more comorbidities. Fifteen-year survival was improved in the Overweight and Obese I groups (P < 0.001). Adjusted 15-year mortality was reduced in the Overweight [HR (95% CI) = 0.88 (0.79-0.98)] and Obese I [HR = 0.88 (0.78-0.99)] groups driven by improved CV and non-CV survival. This trend was noted in the early (Overweight) and intermediate postoperative periods (Overweight and Obese I) with no significance in the late period. Higher mortality in the Obese III [HR = 1.28 (1.06-1.55)] group was driven by a decreased CV survival. Using BMI as a continuous variable, a BMI of 29 kg/m2 was associated with optimal survival. CONCLUSIONS: We identified a protective partial obesity paradox in the early and intermediate postoperative periods among Overweight and mildly obese (Obese I) patients with improved CV and non-CV survival. The morbidly obese (the Obese III group) had higher early and late CV mortality.

Transcriptomic analysis of changes in gene expression of immune proteins of gill tissue in response to low environmental temperature in fathead minnows (Pimephales promelas).

In the face of ongoing climate change, it is imperative to understand better the effects of temperature on immune function in freshwater teleosts. It is unclear whether previously observed changes were caused by temperature per se. We studied changes in the gill transcriptome of fathead minnows (Pimephales promelas) at low temperature to understand better the effects of temperature on immune function. De novo assembly of the transcriptome using Trinity software resulted in 73,378 assembled contigs. Annotation using the Trinotate package yielded 58,952 Blastx hits (accessions). Expression of 194 unique mRNA transcripts changed in gill tissue of fathead minnows acclimatized to 5° compared to controls at 22 °C. At 5 °C mRNAs coding for proteins involved in innate immune responses were up-regulated. Those included proteins that block early-stage viral replication and macrophage activation. Expression of mRNAs coding for pro-inflammatory molecules and mucus secretion were also enhanced. Messenger RNAs coding for proteins associated with adaptive immune responses were down-regulated at 5 °C. Those included antigen-presenting proteins and proteins involved in immunoglobin production. Messenger RNAs coding for proteins that stimulate the cell cycle were also down-regulated at 5 °C. Histological comparison revealed that gills of cold acclimated fish had fewer mucus cells but cells contained larger mucus droplets. We conclude that decreased temperature modifies the immune systems of freshwater teleosts, leading to genome-wide upregulation of innate immunity and down regulation of adaptive immunity. Such acclimation likely evolved as an adaptive strategy against seasonal changes in infectious insults.