Search

Hypoxia is a widespread environmental stressor that shapes fish physiology and morphology. Plasticity in traits that improve oxygen uptake and delivery or reduce oxygen requirements may be critical for fish to cope with fluctuating dissolved oxygen (DO) conditions in their natural habitat or adapt to new environments. In this study, we characterized a suite of morpho-physiological respiratory traits of a naturally hypoxia-acclimated weakly electric mormyrid fish, Petrocephalus degeni, and quantified their plasticity in response to long-term normoxia exposure. We captured P. degeni from a hypoxic swamp habitat (PO2 = 2.43 ± 1.85 kPa) surrounding Lake Nabugabo, Uganda, and acclimated them to normoxia (PO2 > 16 kPa) for up to 75 days. At various time points throughout normoxia exposure, we measured blood hemoglobin and lactate concentration, gill size, routine metabolic rate (RMR), regulation index (RI), and critical oxygen tension (Pcrit). We found that 62–75 days of normoxia exposure significantly reduced blood hemoglobin concentration (− 17%), gill filament length (− 14%), and hemibranch area (− 18%), whereas RMR, RI, Pcrit, and blood lactate showed no significant change. Our results support earlier findings that swamp-dwelling P. degeni are well adapted to life in chronic and severe hypoxia and indicate that they possess a limited capacity for phenotypic plasticity in response to a change in their DO environment.

The generation of photon pairs from nanoscale structures with high rates is still a challenge for the integration of quantum devices, as it suffers from parasitic signals from the substrate. In this work, we report type-0 spontaneous parametric down-conversion at 1550 nm from individual bottom-up grown zinc-blende GaAs nanowires with lengths of up to 5 mu m and diameters of up to 450 nm. The nanowires were deposited on a transparent ITO substrate, and we measured a background-free coincidence rate of 0.05 Hz in a Hanbury-Brown-Twiss setup. Taking into account transmission losses, the pump fluence, and the nanowire volume, we achieved a biphoton generation of 60 GHz/ Wm, which is at least 3 times higher than that of previously reported single nonlinear micro-and nanostructures. We also studied the correlations between the second-harmonic generation and the spontaneous parametric down-conversion intensities with respect to the pump polarization and in different individual nanowires., Nano Letters, 23 (8), ISSN:1530-6984, ISSN:1530-6992

Stereochemical control of photochemical reactions that occur via triplet energy transfer remains a challenge. Suppressing off-catalyst stereorandom reactivity is difficult for highly reactive open-shell intermediates. Strategies for suppressing racemate-producing, off-catalyst pathways have long focused on formation of ground state, substrate-catalyst chiral complexes that are primed for triplet energy transfer via a photocatalyst in contrast to their off-catalyst counterparts. Herein, we describe a strategy where both a chiral catalyst-associated vinylpyridine and a nonassociated, free vinylpyridine substrate can be sensitized by an Ir(III) photocatalyst, yet high levels of diastereo- and enantioselectivity in a [2 + 2] photocycloaddition are achieved through a preferred, highly organized transition state. This mechanistic paradigm is distinct from, yet complementary to current approaches for achieving high levels of stereocontrol in photochemical transformations.

Moderate haemophilia has traditionally been associated with less complications than severe haemophilia. Changes in treatment recommendations have highlighted the burden of moderate haemophilia with a subset of patients with a severe bleeding phenotype. The ankle joint is disproportionally affected by ankle haemarthropathy however the impact has not been evaluated in moderate haemophilia, nor the effect on health related quality of life (HRQoL) or foot and ankle outcomes.To establish the impact of ankle haemarthropathy in patients with moderate haemophilia.A multicentre questionnaire study recruited patients from 11 haemophilia centres in England, Scotland and Wales. The HAEMO-QoL-A and Manchester-Oxford foot and ankle questionnaire (MOXFQ) with total and domain scores measured impact. Measures of pain and ankle haemophilia joint health (HJHS) scores were also collected.Twenty-nine participants were recruited. HAEMO-QoL A mean (SD) total scores of 10.8 (5.2) of 100 (best health) and foot and ankle specific MOXFQ total scores of 45.5 (24.7) above zero (best outcome) indicate poor HRQoL and foot and ankle outcomes. Average ankle pain over past 6 months of (0-10) 5.5 (SD2.5) was reported and median (IQR) ankle HJHS of 3.0 (1;12.5) to 4.5 (0;9.5) for the left and right ankles.HRQoL and foot and ankle specific outcomes are poor in patients with moderate haemophilia and ankle haemarthropathy, driven by chronic levels of ankle joint pain. Despite moderate haemophilia being considered less affected by haemarthrosis and haemarthropathy, patients with a bleeding or haemarthropathy phenotype are clinically similar to patients with severe haemophilia A.

The development of novel lysergamides continues to occur, based on both the needs of psychedelic medicine and commercial interest in new recreational substances. The present study continues the authors' research on novel lysergamides and describes the analytical profile of 1-cyclopropanoyl-AL-LAD (IUPAC name: 1-(cyclopropanecarbonyl)-N,N-diethyl-6-(prop-2-en-1-yl)-9,10-didehydroergoline-8β-carboxamide; 1cP-AL-LAD), using various chromatographic, mass spectrometric, and spectroscopic methods. Analysis of a powdered sample of 1cP-AL-LAD, obtained from an online vendor, by high performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry in full scan/AutoMS/MS mode revealed the detection of 17 impurities based on high-resolution tandem mass spectral data; tentative determination of their identity was based on mass spectral grounds alone, though detection of AL-LAD and 1P-AL-LAD was confirmed using available reference standards. Other tentative compound identifications included 1-acetyl-AL-LAD and several other substances potentially reflecting oxidation of the N

Protein kinase D (PKD) is a serine/threonine kinase family with three isoforms (PKD1–3) that are expressed in most cells and implicated in a wide array of signaling pathways, including cell growth, differentiation, transcription, secretion, polarization and actin turnover. Despite growing interest in PKD, relatively little is known about the role of PKD in immune responses. We recently published that inhibiting PKD limits proinflammatory cytokine secretion and leukocyte accumulation in mouse models of viral infection, and that PKD3 is highly expressed in the murine lung and immune cell populations. Here we focus on the immune-related phenotypes of PKD3 knockout mice. We report that PKD3 is necessary for maximal neutrophil accumulation in the lung following challenge with inhaled polyinosinic: polycytidylic acid, a double-stranded RNA, as well as following influenza A virus infection. Using reciprocal bone marrow chimeras, we found that PKD3 is required in the hematopoietic compartment for optimal neutrophil migration to the lung. Ex vivo transwell and chemokinesis assays confirmed that PKD3(−/−) neutrophils possess an intrinsic motility defect, partly because of reduced surface expression of CD18, which is critical for leukocyte migration. Finally, the peak of neutrophilia was significantly reduced in PKD3(−/−) mice after lethal influenza A virus infection. Together, these results demonstrate that PKD3 has an essential, and nonredundant, role in promoting neutrophil recruitment to the lung. A better understanding of the isoform-specific and cell type–specific activities of PKD has the potential to lead to novel therapeutics for respiratory illnesses.

Falls are the second leading cause of trauma-related deaths worldwide. Identifying fall risk patients and initiating interventions reduces injuries and mortality, particularly in the elderly. The primary aim of this retrospective study was to identify missed opportunities for fall risk identification and intervention for geriatric trauma patients.In this retrospective observational cohort study, the trauma registry was queried to identify geriatric patients admitted for a fall over 36 months. The electronic medical record (EMR) was reviewed to evaluate patients' fall risk in the 12 months prior to the index fall admission. The EMR was also queried for repeat falls within 12 months after discharge, and to determine if fall prevention education was provided at discharge.597 patients met inclusion criteria; 68.3% were female. 64.7% were at risk for falling in the year before admission. 2% had documented fall prevention education at discharge. 32% of patients fell again within a year of discharge and 19.4% were readmitted for a repeat fall. Patients at high risk for falls (on the Hester-Davis scale) were significantly more likely to be readmitted (p = 0.005) and expire within six months (p = 0.033) than moderate risk patients. Mortality at 12 months post-admission for all patients was 19.4%.This large study demonstrated that geriatric trauma patients admitted for a fall were already at risk for falling in the 12 months prior to admission. This is a novel finding that presents a substantial prevention opportunity for healthcare systems. Education and implementation of proven techniques to prevent falls as soon as at-risk patients are identified has the potential to change the course for a patient who may not only fall, but also fall again. This proactive approach could significantly impact the fall epidemic in our elderly population.

In critical illness, enteral nutrition (EN) is frequently limited by gastrointestinal (GI) dysfunction. The aim of this systematic review and meta-analysis was to determine relationships between enteral calorie delivery and GI dysfunction in critically ill adults.MEDLINE, EMCARE, EMBASE, and CINAHL databases were searched from 1 January 2000 to 11 August 2021 to identify parallel group randomised controlled trials of an EN intervention that resulted in a significant difference in calorie delivery between groups and reported at least one outcome relating to GI dysfunction. Study groups were categorised as 'higher' or 'lower' calorie delivery and data were extracted on study interventions, GI dysfunction and clinical outcomes. Extracted data were aggregated using a random effects model and presented as risk ratio with 95% confidence intervals. A P-value0.05 was considered significant. The risk of publication bias was assessed graphically using a funnel plot.From 13 studies involving 6824 patients the mean calorie delivery in the higher calorie group was 1673 ± 468 kcal/day compared to 1121 ± 312 kcal/day in the lower calorie group. The higher calorie group had an increased risk of a large (any volume ≥300 ml) gastric residual volume (GRV) (RR 1.40; 95% CI 1.09, 1.80; P = 0.009) and prokinetic administration (RR 1.18; 95% CI 1.11, 1.27; P 0.00001). There were no between group differences in the presence of vomiting/regurgitation (RR 0.93; 95% CI 0.58, 1.49; P = 0.76), diarrhoea (RR 1.12; 95% CI 0.93, 1.35; P = 0.22) or abdominal distension (RR 0.71; 95% CI 0.49, 1.04; P = 0.08). There was no evidence of publication bias.Higher calorie delivery is associated with increased rates of GRV≥300 ml and prokinetic administration, but not vomiting/regurgitation, diarrhoea or abdominal distension.No funding was received for the conduct of this systematic review and meta-analysis. The protocol was prospectively registered with PROSPERO (CRD42021268876).

Rationale: Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives: To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods: Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m-2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m-2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h-1 vs. 0.034 ± 0.016% h-1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h-1 vs. 0.043 ± 0.018% h-1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions: The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.

The use of medium-chain triglyceride (MCT) oil has increased due to its potential for therapeutic and ergogenic properties. Although recent evidence has suggested that MCT oil supplementation may lead to an improvement in endurance and substrate utilization, contradicting studies have reported the ergogenic benefits of MCT oil toward exercise performance.An extensive systematic review was conducted to assess the role of MCT oil as an ergogenic aid in exercise performance. Moreover, this study examined any alterations in substrate utilization and various physiological components while using MCT oil. The databases searched in this review were PubMed, Embase, CINAHL, and the Cochrane Library.Most studies reported that MCT oil did not improve exercise performance and had no effect on respiratory exchange ratio, glucose concentration, fat and carbohydrate oxidation, and lactate concentration. Although ketones were increased when supplementing with MCTs, most studies demonstrated that the body could not utilize the MCT oil-induced ketones as its primary energy source during an acute bout of endurance exercise. Thirty grams of MCTs seems to be the safe maximal dosage to minimize adverse reactions during or after exercise.MCT oil showed very little to no ergogenic effects on exercise performance and substrate utilization in healthy populations. Future research is needed to examine the effects of long-term intake of MCT oil alongside various diets, perhaps a ketogenic diet, on exercise performance within different sports/exercises in a variety of populations.

Physical review / E 107(2), 025206 (2023). doi:10.1103/PhysRevE.107.025206, Published by APS, Woodbury, NY

In marine ecosystems, increased global-scale transportation creates opportunities for rapid introduction of invasive parasitic species that, in some cases, result in dramatic shifts within the native communities. A lack of detailed knowledge regarding the ecology of invasive marine parasites hinders our ability to develop effective conservation strategies and avoid unforeseen ecological consequences. We examined co-infestation patterns of a highly pathogenic, introduced parasitic isopod (Orthione griffenis) and a native symbiotic clam (Neaeromya rugifera) on the North American native blue mud shrimp Upogebia pugettensis. Our comparisons included infestations of O. griffenis and N. rugifera among 447 U. pugettensis hosts over 3 study years and were designed to statistically assess whether the 2 symbionts exhibited significant associations with one another. Our results indicate that infestations by the 2 symbiont species are positively correlated, such that the presence of one symbiont is a strong, positive predictor for the presence of the other. For both symbionts, host size is an important factor that drives the observed correlation. Host sex is also influential for O. griffenis. Interestingly, even after accounting for these host attributes, the infestations by the 2 symbionts continue to correlate positively, particularly among older (second-year and beyond) symbionts, highlighting the likely influence of additional host and environmental factors in driving the symbiont correlation post-settlement. We consider potential mechanisms, including differential energetic reserves and longevities between infested and co-infested hosts, in detail. These results offer insights into the ecological drivers of symbiont co-infestation, which have important implications for understanding host-parasite interactions and future conservation measures.

ispartof: PEOPLE AND NATURE vol:4 issue:5 pages:1319-1338 status: published

Introduction: Patients with traumatic brain injury (TBI) are at risk for seizures and other abnormalities that can have permanent adverse effects on the brain. We aimed to report the incidence of seizures and continuous EEG (cEEG) abnormalities after TBI and identify any risk factors associated with the development of these abnormalities. Materials and Methods: This retrospective study identified 245 adult patients with mild to severe TBI who had a cEEG performed within one week of admission to a Midwest Level 1 Trauma Center between July 2014 and July 2019. Trauma registry and electronic medical record (EPIC) data were extracted. Results: Twelve percent of patients with TBI developed seizures and an additional 23% demonstrated electrographic patterns that are correlated with risk for seizures (such as lateralized periodic patterns and sporadic epileptiform discharges). Fifty three percent of seizures would have been missed unless a cEEG was performed. Age, history of epilepsy or prior TBI, hypertension, bleeding disorder, and dementia were associated with an increased risk of developing seizures or higher risk patterns. Conclusions: Thirty-five percent of patients who presented with TBI were noted to have seizures or electrographic patterns associated with a higher risk of seizures. The incidence of cEEG abnormalities in this study is higher than previously reported and these patients are at risk for permanent neurological injury. We recommend the routine use of cEEG for all critically ill patients with TBI as over half of the seizures would have been missed if cEEG was not employed.

AMSTAR-2 is a critical appraisal instrument for systematic reviews and may have a role in editorial processes. This study explored whether associations exist between AMSTAR-2 assessments and editorial decisions. A retrospective, cross-sectional study of manuscripts submitted to a single journal between 2015 and 2017 was undertaken. All submissions that reported an eligible systematic review were assessed using AMSTAR-2 by two assessors. Inter-rater agreement (IRR) was calculated for all AMSTAR-2 items. Associations between AMSTAR-2 assessments and the editorial decision, final publication status in any journal, and measures of impact were explored. One hundred and twenty-two manuscripts were included. Across all AMSTAR-2 items, the IRR varied from 0.03 (slight agreement) to 0.82 (substantial agreement). All submissions contained at least two critical methodological weaknesses. There was no difference in the number of weaknesses (median: 4; IQR: 3–5 vs. median: 4; IQR: 3.5–4.5; p = 0.482) between accepted and rejected submissions. Neither was there a difference between rejected submissions published elsewhere and those which remained unpublished (median: 4; IQR: 3.5–4.5 vs. median: 4; IQR: 4.5–5; p = 0.103). The number of weaknesses was not associated with academic impact. There was no association with AMSTAR-2 assessments and editorial outcomes. Further work is required to explore whether the instrument can be prospectively operationalized for use during editorial processes.

Background Ependymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and the worst prognosis of all EPN molecular groups. At relapse, it is typically incurable even with re-resection and re-irradiation. The biology of recurrent PFA remains largely unknown, however, the increasing use of surgery at first recurrence has now provided access to clinical samples to facilitate a better understanding of this. Methods In this large longitudinal international multicenter study, we examined matched samples of primary and recurrent disease from PFA patients to investigate the biology of recurrence. Results DNA methylome derived copy number variants (CNVs) revealed large scale chromosome gains and losses at recurrence. CNV changes were dominated by chromosome 1q gain and/or 6q loss, both previously identified as high-risk factors in PFA, which were present in 23% at presentation but increased to 61% at 1 st recurrence. Multivariate survival analyses of this cohort showed that cases with 1q gain or 6q loss at 1 st recurrence were significantly more likely to recur again. Predisposition to 1q+/6q- CNV changes at recurrence correlated with hypomethylation of heterochromatin-associated DNA at presentation. Cellular and molecular analyses revealed that 1q+/6q- PFA had significantly higher proportions of proliferative neuroepithelial undifferentiated progenitors and decreased differentiated neoplastic subpopulations. Conclusions This study provides clinically and preclinically-actionable insights into the biology of PFA recurrence. The hypomethylation predisposition signature in PFA is a potential risk-classifier for trial stratification. We show that the cellular heterogeneity of PFAs evolves largely because of genetic evolution of neoplastic cells.