Moving Away from 12:12; the Effect of Different Photoperiods on Biomass Yield and Cannabinoids in Medicinal Cannabis.

The standard practice to initiate flowering in medicinal cannabis involves reducing the photoperiod from a long-day period to an equal duration cycle of 12 h light (12L)/12 h dark (12D). This method reflects the short-day flowering dependence of many cannabis varieties but may not be optimal for all. We sought to identify the effect of nine different flowering photoperiod treatments on the biomass yield and cannabinoid concentration of three medicinal cannabis varieties. The first, "Cannatonic", was a high cannabidiol (CBD)-accumulating line, whereas the other two, "Northern Lights" and "Hindu Kush", were high Δ9-tetrahydrocannabinol (THC) accumulators. The nine treatments tested, following 18 days under 18 h light/6 h dark following cloning and propagation included a standard 12L:12D period, a shortened period of 10L:14D, and a lengthened period of 14L:10D. The other six treatments started in one of the aforementioned and then 28 days later (mid-way through flowering) were switched to one of the other treatments, thus causing either an increase of 2 or 4 h, or a decrease of 2 or 4 h. Measured parameters included the timing of reproductive development; the dry weight flower yield; and the % dry weight of the main target cannabinoids, CBD and THC, from which the total g cannabinoid per plant was calculated. Flower biomass yields were highest for all lines when treatments started with 14L:10D; however, in the two THC lines, a static 14L:10D photoperiod caused a significant decline in THC concentration. Conversely, in Cannatonic, all treatments starting with 14L:10D led to a significant increase in the CBD concentration, which led to a 50-100% increase in total CBD yield. The results show that the assumption that a 12L:12D photoperiod is optimal for all lines is incorrect as, in some lines, yields can be greatly increased by a lengthened light period during flowering.

Centers for Disease Control and Prevention 2019 novel coronavirus disease (COVID-19) information management: addressing national health-care and public health needs for standardized data definitions and codified vocabulary for data exchange.

OBJECTIVE: The 2019 novel coronavirus disease (COVID-19) outbreak progressed rapidly from a public health (PH) emergency of international concern (World Health Organization [WHO], 30 January 2020) to a pandemic (WHO, 11 March 2020). The declaration of a national emergency in the United States (13 March 2020) necessitated the addition and modification of terminology related to COVID-19 and development of the disease's case definition. During this period, the Centers for Disease Control and Prevention (CDC) and standard development organizations released guidance on data standards for reporting COVID-19 clinical encounters, laboratory results, cause-of-death certifications, and other surveillance processes for COVID-19 PH emergency operations. The CDC COVID-19 Information Management Repository was created to address the need for PH and health-care stakeholders at local and national levels to easily obtain access to comprehensive and up-to-date information management resources. MATERIALS AND METHODS: We introduce the clinical and health-care informatics community to the CDC COVID-19 Information Management Repository: a new, national COVID-19 information management tool. We provide a description of COVID-19 informatics resources, including data requirements for COVID-19 data reporting. RESULTS: We demonstrate the CDC COVID-19 Information Management Repository's categorization and management of critical COVID-19 informatics documentation and standards. We also describe COVID-19 data exchange standards, forms, and specifications. CONCLUSIONS: This information will be valuable to clinical and PH informaticians, epidemiologists, data analysts, standards developers and implementers, and information technology managers involved in the development of COVID-19 situational awareness and response reporting and analytics.

The 11-Item Modified Frailty Index as a Tool to Predict Unplanned Events in Traumatic Brain Injury.

BACKGROUND: Frailty has been studied extensively in trauma, but there is minimal research detailing its impact on traumatic brain injury (TBI). We hypothesized that the 11-item modified frailty index (mFI-11) would predict complications and discharge outcomes in patients with TBI. METHODS: A retrospective review of our trauma quality improvement program (TQIP) registry was conducted for all patients with TBI. The mFI-11 score was calculated for each patient. Multivariable logistic regression was used to assess the relationship between mFI-11 and cardiovascular, infectious, pulmonary, renal, thromboembolic, and unplanned complications (ie, unplanned intensive care unit [ICU] admission, intubation, or return to the operating room). RESULTS: There were 2352 patients with TBI of whom 61.6% (n = 1450) were not frail, 19.3% (n = 454) were mildly frail, and 19.1% (n = 448) were moderately to severely frail. Higher frailty scores were associated with increasing age (P < .0001) and decreasing injury severity score [ISS] (P = 0.001). Higher frailty scores also correlated with increasing rates of a skilled nursing facility/long-term acute care hospital/rehabilitation discharge (P = .0002). On multivariable logistic regression adjusting for age, Glasgow Coma Scale (GCS) score, ISS, mechanism, and sex, moderate to severe frailty increased the odds of acute kidney injury (odds ratio [OR] 2.06, 95% CI 1.07-3.99, P = .03) and any unplanned event (OR 1.6, 95% CI 1.1-2.3, P = .01). CONCLUSION: Frailty measured by the mFI-11 is associated with greater rates of discharge to unfavorable locations and increased odds of acute kidney injury and unplanned events among patients with TBI. These findings suggest that frail patients with TBIs require greater vigilance to avoid such unanticipated outcomes.

Cardioprotective mitochondrial binding by hexokinase I is induced by a hyperoxic acute thermal insult in the rainbow trout (Oncorhynchus mykiss).

Due to the substantial photosynthetic biomass in their habitat, salmonids such as the rainbow trout (Oncorhynchus mykiss) can be subject to hyperoxia in addition to high temperatures associated with climate change. Both stressful conditions increase the incidence of damaging reactive oxygen species (ROS). The mitochondrial association of hexokinase has been shown to increase in the hearts of certain fish experiencing hypoxia in a putative cardioprotective response to oxidative stress. In this study, the mitochondrial association of hexokinase I (HKI) and markers of oxidative damage and metabolic stress were probed to elucidate the cardioprotective role of hexokinase in the rainbow trout. Results showed that the co-administration of hyperoxia and hyperthermia increased the ventricular mitochondrially-bound fraction of HKI, whereas exposure to hyperthermia in normoxia had no effect; in the combined condition there was little evidence of increased stress. A second in vitro study using ventricular strips and isolated cardiomyocytes was undertaken to reconcile the cardioprotective role of HK in the rainbow trout with findings in mammalian studies, confirming that mitochondrial association of HK maintains aerobic efficiency and inhibits apoptosis. Finally, protein sequence analysis suggested that the physiological contributions of HKI and HKII in salmonids vary from those in mammals, further explaining the dynamic nature of the traditionally-inert HKI. Together, these findings help to explain the broader functions of HKI in the salmonid heart, and illustrate the role of complex environmental conditions in defining physiological responses.

Nanoparticulate-specific effects of silver on teleost cardiac contractility.

Silver nanoparticles (nAg), due to their biocidal properties, are common in medical applications and are used in more consumer products than any other engineered nanomaterial. This growing abundance, combined with their ability to translocate across the epithelium and bioaccumulate, suggests that internalized nAg may present a risk of toxicity to many organisms in the future. However, little experimentation has been devoted to cardiac responses to acute nAg exposure, even though nAg is known to disrupt ion channels even when ionic Ag+ does not. In this study, we examined the cardiac response to nAg exposure relative to a sham and an ionic AgNO3 control across cardiomyocyte survival and homeostasis, ventricular contractility, and intrinsic pacing rates of whole hearts. Our results suggest that nAg, but not Ag+ alone, inhibits force production by the myocardium, that Ag in any form disrupts normal pacing of cardiac contractions, and that these responses are likely not due to cytotoxicity. This evidence of nanoparticle-specific effects on physiology should encourage further research into nAg cardiotoxicity and other potential sublethal effects.

Environmentally relevant concentrations of amine-functionalized copper nanoparticles exhibit different mechanisms of bioactivity in Fundulus Heteroclitus in fresh and brackish water.

The bioavailability of engineered nanomaterials should be limited in marine environments, but uptake and toxicity has been noted in marine fish and invertebrates, albeit at exposure doses far exceeding predicted environmental levels. We examined the bioactivity of amine functionalized copper nanoparticles (nCu; 5-10 nm core diameter) to the euryhaline killifish, Fundulus heteroclitus, in fresh (FW) and brackish water (BW). Free copper dissolution was undetectable in either water type and nCu remained relatively well dispersed in BW, despite the high ionic strength. Exposure to an environmentally relevant concentration of nCu (10 µg L-1) for 48 h significantly increased the maximum rate of oxygen consumption and aerobic scope in BW killifish. This effect was associated with gill remodeling which likely increased surface area and scope for oxygen uptake. In contrast, nCu exposure had no effect on oxygen consumption in FW killifish, but gill Na+/K+-ATPase activity was reduced by >40%, an effect not seen in BW. Osmotic and ionic homeostasis were protected and no indications of physiological or oxidative stress were observed in either FW and BW exposure groups. The results show that functionalized nCu formulations can exhibit bioactivity in both FW and BW and that the underlying mechanisms are different between water types.

Ecophysiological perspectives on engineered nanomaterial toxicity in fish and crustaceans.

Engineered nanomaterials (ENMs) are incorporated into numerous industrial, clinical, food, and consumer products and a significant body of evidence is now available on their toxicity to aquatic organisms. Environmental ENM concentrations are difficult to quantify, but production and release estimates suggest wastewater treatment plant effluent levels ranging from 10-4 to >101µgL-1 for the most common formulations by production volume. Bioavailability and ENM toxicity are heavily influenced by water quality parameters and the physicochemical properties and resulting colloidal behaviour of the particular ENM formulation. ENMs generally induce only mild acute toxicity to most adult fish and crustaceans under environmentally relevant exposure scenarios; however, sensitivity may be considerably higher for certain species and life stages. In adult animals, aquatic ENM exposure often irritates respiratory and digestive epithelia and causes oxidative stress, which can be associated with cardiovascular dysfunction and the activation of immune responses. Direct interactions between ENMs (or their dissolution products) and proteins can also lead to ionoregulatory stress and/or developmental toxicity. Chronic and developmental toxicity have been noted for several common ENMs (e.g. TiO2, Ag), however more data is necessary to accurately characterize long term ecological risks. The bioavailability of ENMs should be limited in saline waters but toxicity has been observed in marine animals, highlighting a need for more study on possible impacts in estuarine and coastal systems. Nano-enabled advancements in industrial processes like water treatment and remediation could provide significant net benefits to the environment and will likely temper the relatively modest impacts of incidental ENM release and exposure.

Metabolic Adjustments to Short-Term Diurnal Temperature Fluctuation in the Rainbow Trout (Oncorhynchus mykiss).

In rainbow trout, warmer temperatures increase metabolic rate, which can be energetically stressful. Diel fluctuations in water temperatures are common in rivers, raising the question of whether fish experience metabolic preconditioning with repeated heat stress. In this study, rainbow trout (Oncorhynchus mykiss Walbaum, 1792) were subjected to three temperature treatments consisting of either a constant exposure to 16°C, a single exposure to 24°C, or three cycles between 16° and 24°C. Metabolic responses were investigated, including patterns of regulation of adenosine monophosphate-activated protein kinase and its substrates, key metabolic enzymes, and several relevant metabolites. In liver and, to a lesser extent, in heart, patterns of signal transduction suggest an increasingly anabolic phenotype with successive heat cycles. Inhibition of Raptor in the heart suggests lowered gross protein synthesis after multiple heat cycles. Fish also showed recovery of glycogen stores and lipid synthesis after multiple thermal cycles, while they maintained baseline plasma glucose levels. The animals showed no evidence of hypoxemia, and our results suggest rainbow trout exposed to repeated thermal cycles were not at risk of metabolic substrate depletion. Collectively, our data indicate that, when exposed to fluctuating but noncritical thermal cycles, rainbow trout may adopt a new metabolic phenotype to sequester readily accessible metabolic substrates in the liver in preparation for more severe or sustained thermal exposures.

Assessment of the toxic potential of engineered metal oxide nanomaterials using an acellular model: citrated rat blood plasma.

Citrated Sprague-Dawley rat blood plasma was used as a biologically relevant exposure medium to assess the acellular toxic potential of two metal oxide engineered nanomaterials (ENMs), zinc oxide (nZnO), and cerium oxide (nCeO2). Plasma was incubated at 37 °C for up to 48 h with ENM concentrations ranging between 0 and 200 mg/L. The degree of ENM-induced oxidation was assessed by assaying for reactive oxygen species (ROS) levels using dichlorofluorescein (DCF), pH, ferric reducing ability of plasma (FRAP), lipase activity, malondialdehyde (MDA), and protein carbonyls (PC). Whereas previous in vitro studies showed linear-positive correlations between ENM concentration and oxidative damage, our results suggested that low concentrations were generally pro-oxidant and higher concentrations appeared antioxidant or protective, as indicated by DCF fluorescence trends. nZnO and nCeO2 also affected pH in a manner dependent on concentration and elemental composition; higher nZnO concentrations maintained a more alkaline pH, while nCeO2 tended to decrease pH. No other biomarkers of oxidative damage (FRAP, MDA, PC, lipase activity) showed changes at any ENM concentration or time-point tested. Differential dissolution of the two ENMs was also observed, where as much as ∼31.3% of nZnO was instantaneously dissolved to Zn2+ and only negligible nCeO2 was degraded. The results suggest that the direct oxidative potential of nZnO and nCeO2 in citrated rat blood plasma is low, and that a physiological or immune response is needed to generate appreciable damage biomarkers. The data also highlight the need for careful consideration when selecting a model for assessing ENM toxicity.

A fluorescent Arg-Gly-Asp (RGD) peptide-naphthalenediimide (NDI) conjugate for imaging integrin α(v)ß(3) in vitro.

We have developed a fluorescent peptide conjugate (TrpNDIRGDfK) based on the coupling of cyclo(RGDfK) to a new tryptophan-tagged amino acid naphthalenediimide (TrpNDI). Confocal fluorescence microscopy coupled with fluorescence lifetime imaging (FLIM) mapping, single and two-photon fluorescence excitation, lifetime components and corresponding decay profiles were used as parameters able to investigate qualitatively the cellular behavior regarding the molecular environment and biolocalisation of TrpNDI and TrpNDI-RGDfK in cancer cells.

Cardiorespiratory toxicity of environmentally relevant zinc oxide nanoparticles in the freshwater fish Catostomus commersonii.

The inhalation of zinc oxide engineered nanomaterials (ENMs) has been linked to cardiorespiratory dysfunction in mammalian models but the effects of aquatic ENM exposure on fish have not been fully investigated. Nano-zinc oxide (nZnO) is widely used in consumer products such as sunscreens and can make its way into aquatic ecosystems from domestic and commercial wastewater. This study examined the impact of an environmentally relevant nZnO formulation on cardiorespiratory function and energy metabolism in the white sucker (Catostomus commersonii), a freshwater teleost fish. Evidence of oxidative and cellular stress was present in gill tissue, including increases in malondialdehyde levels, heat shock protein (HSP) expression, and caspase 3/7 activity. Gill Na(+)/K(+)-ATPase activity was also higher by approximately three-fold in nZnO-treated fish, likely in response to increased epithelial permeability or structural remodeling. Despite evidence of toxicity in gill, plasma cortisol and lactate levels did not change in animals exposed to 1.0 mg L(-1) nZnO. White suckers also exhibited a 35% decrease in heart rate during nZnO exposure, with no significant changes in resting oxygen consumption or tissue energy stores. Our results suggest that tissue damage or cellular stress resulting from nZnO exposure activates gill neuroepithelial cells, triggering a whole-animal hypoxic response. An increase in parasympathetic nervous signaling will decrease heart rate and may reduce energy demand, even in the face of an environmental toxicant. We have shown that acute exposure to nZnO is toxic to white suckers and that ENMs have the potential to negatively impact cardiorespiratory function in adult fish.

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response.

RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo.

Physiological hepatic response to zinc oxide nanoparticle exposure in the white sucker, Catostomus commersonii.

Liver toxicity of commercially relevant zinc oxide nanoparticles (nZnO) was assessed in a benthic freshwater cypriniform, the white sucker (Catostomus commersonii). Exposure to nZnO caused several changes in levels of liver enzyme activity, antioxidants, and lipid peroxidation end products consistent with an oxidative stress response. Aconitase activity decreased by ~65% but tended to be restored to original levels upon supplementation with Fe(2+), indicating oxidative inactivation of the 4Fe-4S cluster. Furthermore, glucose-6-phosphate dehydrogenase activity decreased by ~29%, and glutathione levels increased by ~56%. Taken together, these suggest that nZnO induces hepatic physiological stress. Each assay was then validated by using a single liver homogenate or plasma sample that was partitioned and treated with nZnO or Zn(2+), the breakdown product of nZnO. It was found that Zn(2+), but not nZnO, increased detected glutathione reductase activity by ~14% and decreased detected malondialdehyde by ~39%. This indicates that if appreciable nZnO dissolution occurs in liver samples during processing and assay, it may skew results, with implications not only for this study, but also for a wide range of nanotoxicology studies focusing on nZnO. Finally, in vitro incubations of cell-free rat blood plasma with nZnO failed to generate any significant increase in malondialdehyde or protein carbonyl levels, or any significant decrease in ferric reducing ability of plasma. This suggests that at the level tested, any oxidative stress caused by nZnO is the result of a coordinated physiological response by the liver.

Carbohydrate management, anaerobic metabolism, and adenosine levels in the armoured catfish, Liposarcus pardalis (castelnau), during hypoxia.

The armoured catfish, Liposarcus pardalis, tolerates severe hypoxia at high temperatures. Although this species can breathe air, it also has a strong anaerobic metabolism. We assessed tissue to plasma glucose ratios and glycogen and lactate in a number of tissues under "natural" pond hypoxia, and severe aquarium hypoxia without aerial respiration. Armour lactate content and adenosine in brain and heart were also investigated. During normoxia, tissue to plasma glucose ratios in gill, brain, and heart were close to one. Hypoxia increased plasma glucose and decreased tissue to plasma ratios to less than one, suggesting glucose phosphorylation is activated more than uptake. High normoxic white muscle glucose relative to plasma suggests gluconeogenesis or active glucose uptake. Excess muscle glucose may serve as a metabolic reserve since hypoxia decreased muscle to plasma glucose ratios. Mild pond hypoxia changed glucose management in the absence of lactate accumulation. Lactate was elevated in all tissues except armour following aquarium hypoxia; however, confinement in aquaria increased armour lactate, even under normoxia. A stress-associated acidosis may contribute to armour lactate sequestration. High plasma lactate levels were associated with brain adenosine accumulation. An increase in heart adenosine was triggered by confinement in aquaria, although not by hypoxia alone.