Days Of Recovery Research Articles

Abstract P157: Acute GPER1 Activation Reduces Blood Pressure during the Inactive Period in Aged Female Mice

Non-dipping of blood pressure (BP) during the nighttime is an independent risk factor for hypertension. Importantly, BP dipping is diminished in postmenopausal women, suggesting that the female sex hormones may contribute to the circadian rhythm of BP. Estradiol, activates the G protein-coupled estrogen receptor 1 (GPER1), which elicits protective actions within the cardiovascular system. However, little is known about the GPER1 effect on circadian BP regulation in aged females. Taken together, we hypothesized that systemic GPER1 activation lowers BP and regulates circadian rhythm of BP in aged females. To test the hypothesis, 23-24 months-old C57BL/6J female mice (n=6) were implanted with radio-telemeters for BP recording. After 21 days of postsurgical recovery, BP was recorded. Mice were then given vehicle intraperitoneally daily for 3 consecutive days, followed by the selective GPER1 agonist (LNS8801, 400 µg/kg/day) for an additional 3 days. Data were collected over 24-hour periods according to the 12-hour active period and the 12-hour inactive period. GPER1 activation lowered 24-hour mean arterial pressure (MAP) compared to vehicle control values (113±3 vs. 117±3 mmHg; p=0.01). Similar to MAP, 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower in LNS8801-treated mice compared to corresponding vehicle-treated mice. However, there was not a significant difference in 24-hour heart rate (HR). Interestingly, MAP during the inactive period was lower in LNS8801-treated mice compared to corresponding vehicle-treated mice (104±2 vs. 110±3, respectively, p=0.02). Whereas, GPER1 activation did not elicit significant changes in MAP during the active period. Similarly, LNS8801 reduced DBP during the inactive period (88±4 vs. 96±4 mmHg; p=0.04). We extended the study in aged female mice (14–16 months) with genetic deletion of GPER1 (GPER1 KO; n=6) and wildtype littermates (WT; n=5). Genetic deletion of GPER1 increased 24-hour MAP, SBP, and DBP, whereas HR was not significantly different between genotypes. Noteworthy, GPER1 KO increased MAP during the active period (126±2 vs. 114±1 mmHg; p=0.009) and during the inactive period, compared to WT (110±3 vs. 101±1 mmHg; p=0.01). The results indicate that GPER1 activity lowers BP. Interestingly, LNS8801 acutely improves BP dipping during the inactive period. Overall, GPER1 activation elicits BP-lowering effects in aged female mice, possibly by regulating the circadian BP rhythm.

Macrophages modulate skeletal muscle wasting and recovery in acute lung injury in mice.

Skeletal muscle dysfunction in critical illnesses leaves survivors weak and functionally impaired. Macrophages infiltrate muscles; however, their functional role is unclear. We aim to examine muscle leukocyte composition and the effect of macrophages on muscle mass and function in the murine acute lung injury (ALI)-associated skeletal muscle wasting model. We performed flow cytometry of hindlimb muscle to identify myeloid cells pre-injury and time points up to 29 days after intratracheal lipopolysaccharide ALI. We evaluated muscle force and morphometrics after systemic and intramuscular clodronate-induced macrophage depletions between peak lung injury and recovery (day 5-6) versus vehicle control. Our results show muscle leukocytes changed over ALI course with day 3 neutrophil infiltration (130.5 ± 95.6cells/mg control to 236.3 ± 70.6cells/mg day 3) and increased day 10 monocyte abundance (5.0 ± 3.4%CD45+CD11b+ day 3 to 14.0 ± 2.6%CD45+CD11b+ day 10, p = 0.005). Although macrophage count did not significantly change, pro-inflammatory (27.0 ± 7.2% day 3 to 7.2 ± 3.8% day 10, p = 0.02) and anti-inflammatory (30.5 ± 11.1% day 3 to 52.7 ± 9.7% day 10, p = 0.09) surface marker expression changed over the course of ALI. Macrophage depletion following peak lung injury increased muscle mass and force generation. These data suggest muscle macrophages beyond peak lung injury limit or delay muscle recovery. Targeting macrophages could augment muscle recovery following lung injury.

Recovery resilience framework of replaceable AB-BRB for seismic strengthening during the aftershock stage

Earthquakes cause serious damage to structures, and seismic strengthening is an effective solution to improving structural capacity. With the development of prefabricated technology, the assembled buckling-restrained braces (BRBs) have garnered significant attention in structural engineering due to their potentials to enhance seismic resilience and to guarantee recoverability behavior. At this stage, research on the replaceable performance of assembled BRBs is limited in the current body of literature. The specific focus on the replaceability aspect of assembled BRBs, including the ease of replacing individual components or the entire brace system, has not been extensively explored. Meanwhile, research on earthquake resilience during the aftershock stage is relatively limited at present. Despite the recognition of the significant and prolonged impact of aftershocks on communities and infrastructure, there is a paucity of comprehensive studies specifically focusing on the resilience strategies and measures required during this stage. The authors formerly proposed a novel assembled bolt-connected BRB (AB-BRB), and experiments have been conducted to verify its hysteretic and replaceable behaviors. In this paper, the recovery resilience of the proposed replaceable AB-BRB for seismic strengthening is further assessed, especially during the aftershock stage. The replacement realization of AB-BRB in analysis is first introduced. Then the recovery resilience framework for assessment during the aftershock stage is proposed. Finally an implementary example is given to perform the recovery resilience framework, in which two cases and three scenarios are discussed in detail. In general, after using the AB-BRB for seismic strengthening, the recovery time obviously decreases and the resilience index obviously increases when compared with the results in un-strengthened scenario (scenario 3), which demonstrates that the retrofitted system possesses a better resilience recovery capacity. For EEL in case 1, the recovery days are given to be 298.7446 before strengthening (scenario 3), and the results drop to 165.4133 (scenario 1) and 147.0295 (scenario 2) after strengthening. Correspondingly, the resilience index is calculated as 0.5022 before strengthening (scenario 3), and the results increase to 0.7101 (scenario 1) and 0.7411 (scenario 2) after strengthening. Similar conclusions can be given for case 2 and other intensity levels. Meanwhile, after performing the replacement operation of AB-BRB (scenario 2), the seismic performance of the retrofitted system further enhances during the aftershock stage (i.e., less recovery days and larger resilience index). For case 1 and recovery form 1, the resilience index for 1 month is signified as 0.6272, 0.6869 and 0.2066 from scenario 1 to 3, and the resilience index for 3 months is signified as 0.8182, 0.8561 and 0.4965 from scenario 1 to 3. Compared with scenario 1, the recovery ability in scenario 2 is further ensured and the potential risk is further controlled, which demonstrates the importance of replaceable capacity of AB-BRB for resilience improvement especially during the aftershock stage.

Bivalves under extreme weather events: A comparative study of five economically important species in the South China sea during marine heatwaves

Marine heatwaves (MHWs) are increasing in frequency and intensity, threatening marine organisms and ecosystems they support. Yet, little is known about impacts of intensifying MHWs on ecologically and economically important bivalves cultured in the South China Sea. Here, we compared survival and physiological responses of five bivalve species, Pinctada fucata, Crassostrea angulata, Perna viridis, Argopecten irradians and Paphia undulata, to two consecutive MHWs events (3 days of thermal exposure to + 4 °C or + 8 °C, following 3 days of recovery under ambient conditions). While P. fucata, P. viridis, and P. undulata are native to the South China Sea region, C. angulata and A. irradians are not. Individuals of P. fucata, C. angulata and P. viridis had higher stress tolerance to MHWs than A. irradians and P. undulata, the latter already experiencing 100% mortality under +8 °C conditions during the first event. With increasing intensity of MHWs, standard metabolic rates of all five species increased significantly, in line with significant depressions of function-related energy-metabolizing enzymes (CMA, NKA, and T-ATP). Likewise, activities of antioxidant enzymes (SOD, CAT, and MDA) and shell mineralization-related enzymes (AKP and ACP) responded significantly to MHWs, despite species-specific performances observed. These findings demonstrate that some bivalve species can likely fail to accommodate intensifying MHWs events in the South China Sea, but some may persist. If this is the case, then one would expect substantial loss of fitness in bivalve aquaculture in the South China Sea under intensifying MHWs conditions.

Transcriptomic and physiological responses of Quercus acutissima and Quercus palustris to drought stress and rewatering.

Establishment of oak seedlings, which is an important factor in forest restoration, is affected by drought that hampers the survival, growth, and development of seedlings. Therefore, it is necessary to understand how seedlings respond to and recover from water-shortage stress. We subjected seedlings of two oak species, Quercus acutissima and Quercus palustris, to drought stress for one month and then rewatered them for six days to observe physiological and genetic expression changes. Phenotypically, the growth of Q. acutissima was reduced and severe wilting and recovery failure were observed in Q. palustris after an increase in plant temperature. The two species differed in several physiological parameters during drought stress and recovery. Although the photosynthesis-related indicators did not change in Q. acutissima, they were decreased in Q. palustris. Moreover, during drought, content of soluble sugars was significantly increased in both species, but it recovered to original levels only in Q. acutissima. Malondialdehyde content increased in both the species during drought, but it did not recover in Q. palustris after rewatering. Among the antioxidant enzymes, only superoxide dismutase activity increased in Q. acutissima during drought, whereas activities of ascorbate peroxidase, catalase, and glutathione reductase increased in Q. palustris. Abscisic acid levels were increased and then maintained in Q. acutissima, but recovered to previous levels after rewatering in Q. palustris. RNA samples from the control, drought, recovery day 1, and recovery day 6 treatment groups were compared using transcriptome analysis. Q. acutissima exhibited 832 and 1076 differentially expressed genes (DEGs) related to drought response and recovery, respectively, whereas Q. palustris exhibited 3947 and 1587 DEGs, respectively under these conditions. Gene ontology enrichment of DEGs revealed "response to water," "apoplast," and "Protein self-association" to be common to both the species. However, in the heatmap analysis of genes related to sucrose and starch synthesis, glycolysis, antioxidants, and hormones, the two species exhibited very different transcriptome responses. Nevertheless, the levels of most DEGs returned to their pre-drought levels after rewatering. These results provide a basic foundation for understanding the physiological and genetic expression responses of oak seedlings to drought stress and recovery.

Fast-track surgery with three-port versus conventional perioperative management of bladder cancer associated laparoscopic radical cystectomy and Ileal conduit diversion: Chinese experience

ObjectiveThis study seeks to explore the impact of fast track surgery (FTS) with three-port in patients treated with laparoscopic radical cystectomy and ileal conduit on postoperative recovery, hospital stay and the complications.MethodsThis retrospective study analyzed 230 patients with invasive bladder cancer who underwent laparoscopic radical cystectomy at the Second Hospital of Anhui Medical University between December 2011 to January 2023. 50 patients received conventional surgery (CS) and 180 patients received FTS with three-port. Patients were assessed for time to normal diet consumption, time to passing first flatus, number of postoperative recovery days and complications. Trends of serum C-reactive protein levels were monitored preoperatively and on postoperative days 1, 3 and 7.ResultsPatients who underwent FTS with three-port had a shorter duration to first flatus (P < 0.05). And number of postoperative hospital days and the length of hospital stay were notably shorter in contrast to the CS group (P < 0.05). Serum CRP levels on postoperative day 7 were markedly reduced in those of the FTS group compared to the CS group (P < 0.05). Those of the CS group experienced more frequent rates of complications compared to those of the FTS with three-port group (P < 0.05).ConclusionOur findings demonstrate that the FTS with three-port program hastens postoperative recovery and reduces duration of hospital stay. It is safer and more effective than the CS program in the Chinese population undergoing laparoscopic radical cystectomy.

Longitudinal importance of the soluble receptor for advanced glycation end-products in nonintubated hospitalized patients with COVID-19 pneumonia.

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of alveolar type I cell injury associated with outcomes in COVID-19 pneumonia. How plasma sRAGE changes over time and whether it remains associated with long-term clinical outcomes beyond a single measurement in COVID-19 have not been well studied. We studied two cohorts in randomized clinical trials of monoclonal antibody treatment for COVID-19 (bamlanivimab and tixagevimab/cilgavimab). We first studied the association between baseline plasma sRAGE and 90-day clinical outcomes, which had been previously demonstrated in the bamlanivimab cohort, among hospitalized patients with COVID-19 supported with high-flow nasal oxygen (HFNO) or noninvasive ventilation (NIV) in the tixagevimab/cilgavimab study. Next, we investigated the relationship between day 3 sRAGE and 90-day outcomes and how plasma sRAGE changes over the first 3 days of hospitalization in both clinical trial cohorts. We found that plasma sRAGE in the highest quartile in the HFNO/NIV participants in the tixagevimab/cilgavimab trial was associated with a significantly lower rate of 90-day sustained recovery [recovery rate ratio = 0.31, 95% confidence interval (CI) = 0.14-0.71, P = 0.005] and with a significantly higher rate of 90-day mortality (hazard ratio = 2.49, 95% CI = 1.15-5.43, P = 0.021) compared with the lower three quartiles. Day 3 plasma sRAGE in both clinical trial cohorts remained associated with 90-day clinical outcomes. The trajectory of sRAGE was not influenced by treatment assignment. Our results indicate that plasma sRAGE is a valuable prognostic marker in COVID-19 up to 3 days after initial hospital presentation.NEW & NOTEWORTHY The soluble receptor for advanced glycation end-products (sRAGE) is a marker of alveolar type I epithelial cell injury associated with clinical outcomes in acute respiratory distress syndrome and, more recently, in hospitalized subjects with COVID-19. How plasma sRAGE changes over time and whether plasma sRAGE remains associated with long-term clinical outcomes beyond a single baseline measurement in patients with COVID-19 have not been well studied.

Shallow water seeding cultivation enhances cold tolerance in tobacco seedlings

Cold stress can impact plant biology at both the molecular and morphological levels. We cultivated two different types of tobacco seedlings using distinct seeding methods, observing significant differences in their cold tolerance at 4 °C. After 12 h cold stress, shallow water seeding cultivation treatment demonstrates a relatively good growth state with slight wilting of the leaves. Tobacco grown using the float system exhibited short, thick roots, while those cultivated through shallow water seeding had elongated roots with more tips and forks. After cold stress, the shallow water seeding cultivation treatment demonstrated higher antioxidant enzyme activity, and lower malondialdehyde (MDA) content.Transcriptome analysis was performed on the leaves of these tobacco seedlings at three stages of cold treatment (before cold stress, after cold stress, and after 3 days of recovery). Upon analyzing the raw data, we found that the shallow water seeding cultivation treatment was associated with significant functional enrichment of nicotinamide adenine dinucleotide (NAD) biosynthesis and NAD metabolism before cold stress, enrichment of functions related to the maintenance of cellular structure after cold stress, and substantial functional enrichment related to photosynthesis during the recovery period. Weighted gene co-expression network analysis (WGCNA) was conducted, identifying several hub genes that may contribute to the differences in cold tolerance between the two tobacco seedlings. Hub genes related to energy conversion were predominantly identified in shallow water seeding cultivation treatment during our analysis, surpassing findings in other areas. These include the AS gene, which controls the synthesis of NAD precursors, the PED1 gene, closely associated with fatty acid β-oxidation, and the RROP1 gene, related to ATP production.Overall, our study provides a valuable theoretical basis for exploring improved methods of cultivating tobacco seedlings. Through transcriptome sequencing technology, we have elucidated the differences in gene expression in different tobacco seedlings at three time points, identifying key genes affecting cold tolerance in tobacco and providing possibilities for future gene editing.

Preclinical Safety Evaluation of Etripamil Nasal Spray in Cynomolgus Macaques (Macaca fascicularis) to Assess for Safety in Patients With Paroxysmal Supraventricular Tachycardia.

Etripamil is a calcium channel blocker currently in Phase 3 trials for the treatment of paroxysmal supraventricular tachycardia (PSVT). Systemic and local toxicity following once-weekly intranasal administration of etripamil was evaluated in cynomolgus macaques to support clinical development. Groups of animals (N = 8, 4 males and 4 females) were administered etripamil into the left nostril weekly at dose levels of 0 (vehicle), 1.9, 3.8, or 5.7mg/kg/dose for 26 doses. Persistence, reversibility, and progression of findings were examined following a 28-day recovery period. Clinical signs were transient and were related to the intranasal administration (e.g., nasal discharge, sneezing, etc.) of etripamil. There were no macroscopic or systemic microscopic findings at any dose. Etripamil-related adaptive and reactive local changes affecting the nasal cavity, larynx, and nasopharynx were observed at ≥1.9mg/kg/dose. Minimal to severe dose-dependent nasal epithelial damage was observed, mainly affecting respiratory and transitional epithelium. Following the 28-day recovery period, microscopic changes were confined to the left nasal cavity and nasopharynx. These changes were significantly lower in incidence and severity, with noticeable reversal of the adaptive and reactive changes, indicating partial to complete recovery of the epithelial lining. Based on the lack of systemic toxicity and the minimal and transient nasal changes, the systemic, no observable adverse effect level (NOAEL) of etripamil in monkeys was the high dose, 5.7mg/kg/dose. The NOAEL for local toxicity was 1.9mg/kg/dose. Collectively, these data support further study of etripamil in human trials as a potential treatment for PSVT.

Stress and recovery of yellowtail kingfish (Seriola aureovittata) during Sea-land relay transportation: Biochemical, microecological and transcriptomic responses

Sea-land relay transportation (SRT) is a key part of the “land-based greenhouse + offshore net cage” mariculture system for yellowtail kingfish. In this study, the physiological status of yellowtail kingfish during SRT was assessed by determining serum biochemical indexes (levels of cortisol, glucose, and malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and catalase (CAT)), the composition of intestinal microflora, and the liver transcriptome before (control), during, and after transportation (T1 and T2) and after recovery for 6 hours (6 h), 12 hours (12 h), 1 day (D1), 3 days (D3), and 7 days (D7). The results show that the serum cortisol and glucose levels, MDA level, and activities of SOD and CAT significantly increased during transportation, and decreased to similar levels to those in the control after 1 day of recovery. Bacteria including Acinetobacter, Enterobacter, and Comamonas accounted for more than 91 % of the microbial community in the gut of yellowtail kingfish, and these genera were associated with changes in serum glucose levels, indicating that they may help to alleviate the effects of transportation stress. Analyses of liver transcriptome data showed that significantly differentially expressed genes (DEGs) in the T2, D1, D3 and D7 groups were significantly enriched in the “Protein processing in the endoplasmic reticulum (ER)” pathway. At the end of transportation (T2 group), the ER-associated degradation (ERAD) pathway was activated, with up-regulation of hsp40, hsp70, and hsp90α. The transcript levels of these genes gradually returned to levels similar to those in the control during the recovery period. At the first day of recovery, the unfolded protein response imposed stress upon the ER, accompanied by significant down-regulation of PEPK and Calmin and significant up-regulation of CRT. The DEGs in the D3 group were enriched in the “ER”, “Steroid biosynthesis”, “Fatty acid degradation”, “PPAR signaling”, and “Fat digestion and absorption” pathways, whereas the number of DEGs related to lipid metabolism and stress pathways was significantly decreased in the D7 group. Our results indicate that hsp70 and hsp90α can be used as stress markers, and hsp40 can be used as a physio-metabolic recovery marker for yellowtail kingfish. These results show that, although serum indices recovered 24 hours after transportation, up to 3 days after transportation is an important period for recovery from transportation stress at the transcriptome level. “Protein processing in the ER pathway” is an important pathway regulating stress and recovery in yellowtail kingfish.

Start-up and Recovery Performance of ANAMMOX Reactors Under Long-term Starvation

The application of ANAMMOX technology is constrained by sluggish growth and difficulty in enriching ANAMMOX bacteria. Long-term starvation of functioning bacteria due to limited substrate supply makes the steady operation of ANAMMOX reactors more difficult. Re-examining the start-up and recovery performance of the ANAMMOX reactor and identifying its resistance mechanism are important from the standpoint of long-term starvation. By inoculating nitrifying and denitrifying sludge under various operating circumstances, the ANAMMOX reactors were successfully started. Under various start-up procedures, the tolerance mechanism and recovery performance were examined. The outcomes demonstrated that the denitrifying sludge-inoculated reactor operated steadily with a high substrate concentration and low flow rate. After 85 days of operation, the removal efficiencies of NH4+-N, NO2--N, and total nitrogen reached 98.7%, 99.3%, and 89.3%, respectively. After 144 days of starvation and 30 days of recovery, the better nitrogen removal performance was achieved at a low substrate concentration and high flow rate, and the removal efficiencies were 99.8% （NH4+-N）, 99.8% （NO2--N）, and 93.6% （total nitrogen）. During the starvation, extracellular polymeric substances wrapped the ANAMMOX bacteria and kept them intact to resist long-term starvation stress. The expression of nirS, hzsA, and hdh genes ensured the synthesis of nitrite/nitric oxide oxidoreductase, hydrazine synthase, and hydrazine dehydrogenase to maintain ANAMMOX activity. There was no significant difference in the relative abundance of ANAMMOX bacteria before and after starvation recovery. Candidatus Kuenenia had better anti-hunger ability, and the relative abundance increased by more than 86% after 30 days of recovery, confirming its tolerance to long-term starvation.

A - 40 The Impact of Early Access on Sports-Related Concussions in Youth Hockey Players

Abstract Purpose Sports-related concussions are the most common setting for adolescents to sustain a concussion. Delayed access to care is a risk factor for recovery and youth athletes have limited access to early intervention often due to lack of athletic trainer coverage. The purpose of this study was to evaluate the effect of early access on sports-related concussions in youth hockey players. Method Participants (n = 67) included youth athletes from hockey organizations who partnered with a local specialty concussion clinic. Athletes presented to clinic for care (median = 2 days) after sustaining a concussion. We examined whether the number of days since injury to initial exam (DSI) significantly predicted recovery time while controlling for common injury modifiers, such as symptom severity, anxiety sensitivity, and age. Recovery was measured in number of days since injury to the date of medical clearance. Results Multivariate general linear analyses indicated that DSI (M = 4.96, SD = 8.90), significantly predicted the number of recovery days (M = 12.85, SD = 9.47), with each day earlier to initial exam predicting almost one day faster recovery (B = 0.92; p &amp;lt; 0.001; ηp2 = 0.813). Variables of age (M = 13.78, SD = 2.59), anxiety sensitivity (M = 8.91, SD = 9.69), and concussion severity (M = 19.22, SD = 8.90), were not predictive recovery. Conclusions Early access resulted in faster medical clearance. This sample of youth hockey players do not have access to an athletic trainer to provide early intervention. Our results suggest that the ability to have early intervention through a specialty concussion clinic partnership resulted in faster recovery, highlighting the importance of continuing to explore and cultivate these relationships with youth sports.

Topical Polyethylene Glycol-Phage Ointment as a Therapy to Treat Burn-Wound Infection Using Mice Model

Background: One of the most significant problems facing public health today is antimicrobial resistance. Pseudomonas aeruginosa is considered one of the most prevalent causes of healthcare-associated illnesses. Objective: The use of phages as a potential alternative therapeutic method for treating bacterial infections has been the subject of significant research to solve this predicament. Methods: The P. aeruginosa isolates that caused infections of burn wounds were collected from three hospitals in Baghdad. The VITEK system diagnosed and examined the isolates for their antibiotic sensitivity. As well as the phages were isolated and purified from sewage water samples from different sewer stations. After these steps, phages were examined by transmission electron microscopy to ensure the order and the families of these phages, and the tests of lytic activities of phages on the P. aeruginosa isolates were done to determine the best lytic ability of them to use for treatment wounds infections. Results: Burn-wound infections swabs culture showed a positive culture for 109 isolates as the following P. aeruginosa in 76(69.72%), Staphylococcus aureus16(14.67%), Acinetobacter baumannii 9(8.25%), Klebsiella pneumoniae 5(4.58%), Escherichia .coli 3(2.75%) obtained from burn wound infections, had a significant level of resistance to several antibiotics. Four bacteriophages were isolated: KM1, KM2, KM3, KM4 and KM5. KM5 is a mixture of phages referred to as a cocktail. The four phages and their cocktail exhibited significant lytic activity against P. aeruginosa. A total of four monophages and a cocktail were utilized in the preparation of the PEG-phage ointment. Conclusions: All monophages and their cocktail could completely clear bacterial infection in 17 days. KM3 and KM4 PEG-phage ointments demonstrated more potent healing activity than standard, which required 12 days for full recovery, while the cocktail took 15 days (KM5). However, KM1 and KM2 took the same time as the standard, which is 17 days for burn wound infection treated with PEG-phage ointments, while the control, which did not receive any treatment, took 23 days to recover. KM1 and KM2 show less activity for healing burn wound infections from all five phage ointments.

Comprehensive Modulation of Secondary Metabolites in Terpenoid-Accumulating Mentha spicata L. via UV Radiation.

In plants, secondary metabolites change in response to environmental conditions. These changes co-regulate resilience to stressful environmental conditions, plant growth and development, and interactions between plants and the wider ecosystem, while also affecting soil carbon storage and atmospheric and climatic conditions. The objective of this study was to determine the association between UV exposure and the contents of key metabolites, including amino acids, phenolics, flavonoids, terpenoids, carotenoids, tocopherols, and phytosterols. Mentha spicata plantlets were grown in tissue culture boxes for 30 days and then exposed to a low dose of broadband UV-B (291-315 nm; 2.8 kJm-2 biologically effective UV) enriched light for eight days. Metabolite contents were quantified either immediately after the final UV exposure, or after seven days of recovery under photosynthetically active radiation. It was found that UV promoted the production of flavonoids (1.8-fold) ahead of phenolic acids (unchanged). Furthermore, the majority of monoterpenes and sesquiterpenes, constituents of valuable mint essential oil, were significantly increased through UV treatment (up to 90-fold for α-linalool). In contrast, the contents of carotenoids and tocopherols did not increase following UV exposure. A comparison between plants sampled immediately after UV exposure and after seven days of recovery showed that there was an overall increase in the content of carotenoids, mono- and sesquiterpenes, phenolics, and amino acids following recovery, while the contents of sterols and tocopherols decreased. These UV-induced changes in metabolite profile may have important consequences for agriculture, ecology, and even the global climate, and they also provide an exciting opportunity to enhance crop value, facilitating the development of improved products with higher levels of essential oils and added benefits of enhanced flavour, colour, and bioactive content.

Repeat treatment of organotypic airway cultures with ethyl methanesulfonate causes accumulation of somatic cell mutations without expansion of bronchial-carcinoma-specific cancer driver mutations

The human in vitro organotypic air-liquid-interface (ALI) airway tissue model is structurally and functionally similar to the human large airway epithelium and, as a result, is being used increasingly for studying the toxicity of inhaled substances. Our previous research demonstrated that DNA damage and mutagenesis can be detected in human airway tissue models under conditions used to assess general and respiratory toxicity endpoints. Expanding upon our previous proof-of-principle study, human airway epithelial tissue models were treated with 6.25–100 µg/mL ethyl methanesulfonate (EMS) for 28 days, followed by a 28-day recovery period. Mutagenesis was evaluated by Duplex Sequencing (DS), and clonal expansion of bronchial-cancer-specific cancer-driver mutations (CDMs) was investigated by CarcSeq to determine if both mutation-based endpoints can be assessed in the same system. Additionally, DNA damage and tissue-specific responses were analyzed during the treatment and following the recovery period. EMS exposure led to time-dependent increases in mutagenesis over the 28-day treatment period, without expansion of clones containing CDMs; the mutation frequencies remained elevated following the recovery. EMS also produced an increase in DNA damage measured by the CometChip and MultiFlow assays and the elevated levels of DNA damage were reduced (but not eliminated) following the recovery period. Cytotoxicity and most tissue-function changes induced by EMS treatment recovered to control levels, the exception being reduced proliferating cell frequency. Our results indicate that general, respiratory-tissue-specific and genotoxicity endpoints increased with repeat EMS dosing; expansion of CDM clones, however, was not detected using this repeat treatment protocol. DisclaimerThis article reflects the views of its authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation.

Neuroprotection provided by hypothermia initiated with high transnasal flow with ambient air in a model of pediatric cardiac arrest.

Clinical trials of hypothermia after pediatric cardiac arrest (CA) have not seen robust improvement in functional outcome, possibly because of the long delay in achieving target temperature. Previous work in infant piglets showed that high nasal airflow, which induces evaporative cooling in the nasal mucosa, reduced regional brain temperature uniformly in half the time needed to reduce body temperature. Here, we evaluated whether initiation of hypothermia with high transnasal airflow provides neuroprotection without adverse effects in the setting of asphyxic CA. Anesthetized piglets underwent sham-operated procedures (n = 7) or asphyxic CA with normothermic recovery (38.5°C; n = 9) or hypothermia initiated by surface cooling at 10 (n = 8) or 120 (n = 7) min or transnasal cooling initiated at 10 (n = 7) or 120 (n = 7) min after resuscitation. Hypothermia was sustained at 34°C with surface cooling until 20 h followed by 6 h of rewarming. At 4 days of recovery, significant neuronal loss occurred in putamen and sensorimotor cortex. Transnasal cooling initiated at 10 min significantly rescued the number of viable neurons in putamen, whereas levels in putamen in other hypothermic groups remained less than sham levels. In sensorimotor cortex, neuronal viability in the four hypothermic groups was not significantly different from the sham group. These results demonstrate that early initiation of high transnasal airflow in a pediatric CA model is effective in protecting vulnerable brain regions. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be deployed in the field or emergency room for early initiation of brain cooling after pediatric CA.NEW & NOTEWORTHY The onset of therapeutic hypothermia after cardiac resuscitation is often delayed, leading to incomplete neuroprotection. In an infant swine model of asphyxic cardiac arrest, initiation of high transnasal airflow to maximize nasal evaporative cooling produced hypothermia sufficient to provide neuroprotection that was not inferior to body surface cooling. Because of its simplicity and portability, this technique may be of use in the field or emergency room for rapid brain cooling in pediatric cardiac arrest victims.

Repeated caffeine intake suppresses cerebral grey matter responses to chronic sleep restriction in an A1 adenosine receptor-dependent manner: a double-blind randomized controlled study with PET-MRI

Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A2A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [18F]-CPFPX to quantify the baseline availability of A1 adenosine receptors (A1R) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical A1R availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors in CSR-induced GM plasticity are warranted.

Changes of physiological traits on red chili pepper (Capsicum annum L.) exposed by short-term waterlogging

Abstract Tropical riparian wetland known as non-tidal lowland is potential land for agriculture, especially for vegetable cultivation such as red chili pepper (Capsicum annum L.). Transitional period (dry to rainy season) has a chance for red chili pepper cultivation in the field (at low tide conditions), but has risk of experiencing dynamic water table to waterlogging in early rainy season. The aim of this research was to determine the effects of physiological traits of red chili pepper exposure on short-term (4 days) waterlogging. This study was done at the Tropical Crop Science Laboratory, Kagoshima University, Japan. The experiment was designed as a completely randomized factorial design. The first factor was control/field capacity and waterlogging (entire growing media was submerged). The second factor was chili variety, consisting of Laris and Romario. Treatments began 14 days after transplanting, lasted four days, then followed by seven days of recovery. The results of this study showed that there were changes in photosynthetic characters between before waterlogging, after waterlogging and after recovery time, between control and waterlogging, and also between Laris and Romario. Photosynthetic and transpiration rates decreased sharply under waterlogging in after waterlogging, but increased in after recovery period on Laris, opposite on Romario. Changes occur were associated with the decline in stomatal conductance and chlorophyll fluorescence as a response to waterlogging stress. Laris as a resistant variety has the ability to recover under short-term stress conditions, so it needs to be further developed for cultivation in tropical riparian wetlands.

A refined rodent model of anorexia nervosa: Simulating state‐specific effects of caloric restriction and weight restoration

AbstractCurrent rodent models of anorexia nervosa (AN) often have accelerated weight loss that often do not allow for investigation of physiological ramifications of prolonged low weight status characteristic of AN. The purpose of this project was to refine a rodent model of AN to extend the duration of low weight status and allow for investigation of recovery. Eight‐week‐old female Sprague Dawley rats underwent 50%–60% food restriction for 30 days. Rats were group‐housed except during feeding, where AN rats were individually housed and given up to 2 h to consume food. Control (CON) rats were allowed to consume food ad libitum. To simulate recovery, a separate cohort of animals underwent the same food restriction protocol for 30 days, then rats (AN‐R) were allowed to consume food ad libitum to facilitate weight recovery for an additional 30 days. AN‐R rats were compared to age matched controls (CON‐R). AN rats lost ~15% bodyweight and were ~30% lighter than CON. Compared to CON, AN rats had ~35% lower fat content, ~18% lower bone mineral density, ~22% smaller plantaris muscle mass and ~52% smaller ovaries. Upon reintroduction of food, AN‐R rats achieved comparable bodyweights to CON‐R rats after ~10 days. However, after 30 days of recovery, AN‐R rats still had ~14% lower bone mineral density and ~11% smaller plantaris mass and ~21% smaller ovaries. This refinement of rodent AN results in physiological side effects of AN without reaching excessive weight loss requiring euthanasia. Moreover, some physiological consequences of simulated AN are not resolved with weight restoration.

#59 Fibroblast Growth factor 23 for prediction of outcome in community-acquired acute kidney injury: a prospective observational study

Abstract Background and Aims Serum FGF23 level has been found to be elevated in AKI through multiple previous studies. Moreover, higher FGF23 level was associated with mortality and adverse outcomes in critically ill patients and patients undergoing cardiac surgery who developed AKI suggesting that FGF23 can have a prognostic value in AKI. The current study aims to investigate the association of serum FGF23 levels with morbidity and mortality in patients with community-acquired AKI. Method A longitudinal prospective study was carried out that included 64 patients who presented with community-acquired AKI to Mansoura Nephrology and Dialysis Unit (MNDU) at Mansoura University Hospital. Serum intact FGF23 level was measured after admission. patients were followed up during hospital stay and then at 90-day after admission. The primary outcomes were hospital and 90-day mortality and renal recovery. Results In this study, nine of the studied 64 AKI patients (14.1%) died during hospital admission and 18 out of 62 AKI patients (29%) died during the 90-day follow up period including those who died during hospital admission. Hospital mortality was significantly higher in patients with shock, sepsis, hypoalbuminemia, or high FGF23 in univariate analysis (p &amp;lt; 0.05). However, when binary logistic regression was carried out, shock was the only significant independent predictor for mortality [p value = 0.015; adjusted odds ratio = 12.465], while serum FGF23 did not independently predict in-hospital [p value = 0.589; adjusted odds ratio = 1.001] or 90-day mortality [p value = 0.055; adjusted odds ratio = 1.003] when entered in the regression equation together with the other confounders. Serum FGF23 in this study was not also associated with renal recovery, need for renal replacement, or the duration from peak serum creatinine to renal recovery (p &amp;gt; 0.05). Conclusion This research showed that serum iFGF23 could not predict mortality, renal recovery, or need for renal replacement therapy in patients with community-acquired AKI.