Publications by authors named "Michael Jones"

1,250 Publications

  • Page 1 of 1

Pharmacokinetics of a Single Intramuscular Injection of Ceftiofur Crystalline Free Acid in Bald Eagles ().

J Avian Med Surg 2021 Sep;35(3):290-294

Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN 37996, USA.

The objective of this study was to evaluate the pharmacokinetic properties of ceftiofur crystalline free acid (CCFA) administered intramuscularly at dosages of 10 and 20 mg/kg in bald eagles (BAEAs) (). Ceftiofur crystalline free acid is a long-acting, injectable, third-generation cephalosporin antibiotic drug. A prospective, randomized, complete crossover design was used for this pharmacokinetic investigation. CCFA (10 or 20 mg/kg) was administered intramuscularly, and blood samples were obtained from 6 adult, nonreleasable, healthy BAEAs at predetermined sampling times. After a 4-week washout period, the protocol was repeated with each bird receiving the dose not given during the initial sample collection according to the randomized crossover design. Plasma ceftiofur free acid equivalents were quantified and data were analyzed by a noncompartmental pharmacokinetic approach. The mean observed peak plasma concentrations were 9.23 µg/mL and 15.08 µg/mL for 10 and 20 mg/kg CCFA IM administration, respectively. The mean observed time to maximum plasma concentration was 18 and 17.6 hours, and the mean terminal elimination half-life was 32.38 and 38.08 hours for intramuscular administration of 10 and 20 mg/kg CCFA, respectively, in the BAEAs. Reported minimum inhibitory concentrations of raptor bacterial isolates from a prior study was used to determine the target minimum inhibitory concentration of 1 µg/mL selected for this investigation. From the previously published information, a target plasma concentration of 4 µg/mL was determined for the CCFA in the BAEAs. From the results of this study, CCFA may be dosed every 60 and 110 hours at 10 mg/kg IM, and every 80 and 160 hours at 20 mg/kg IM in BAEAs.
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http://dx.doi.org/10.1647/20-00038DOI Listing
September 2021

Melatonin ameliorates aging-related impaired angiogenesis in gastric endothelial cells via local actions on mitochondria & VEGF-survivin signaling.

Am J Physiol Gastrointest Liver Physiol 2021 Oct 20. Epub 2021 Oct 20.

Medical and Research Services, Veterans Affairs Long Beach Healthcare System (VALBHS), Long Beach, California, United States.

Background & Aims: Tissue injury healing is impaired in aging, and this impairment is caused in part by reduced angiogenesis. Melatonin, a neuroendocrine hormone that regulates sleep and circadian rhythm is also produced in the gastrointestinal tract. The expression of melatonin receptors - MT1 and MT2 in gastric endothelial cells, and their roles in aging-related impairment of gastric angiogenesis, have not been examined. We hypothesized that MT1 and MT2 expression is reduced in gastric endothelial cells of aging rats and that melatonin treatment can upregulate their expression and improve angiogenesis.

Methods: We examined the expression of MT1 and MT2 in gastric endothelial cells (GECs) isolated from young and aging rats. We also examined the effects of melatonin treatment on angiogenesis, GEC mitochondrial function, expression of vascular endothelial growth factor (VEGF), its signaling receptor (VEGFR-2), and the inhibitor of apoptosis protein, survivin.

Results: Young and aging GECs expressed MT1 (in the cytoplasm and mitochondria) and MT2 (in nucleus and mitochondria). In aging GECs, MT1 and MT2 levels, in vitro angiogenesis, and mitochondrial membrane potential were significantly reduced (by 1.5-fold, 1.9-fold, 3.1-fold, 1.63-fold, respectively) vs. young GECs. Melatonin treatment of aging GECs significantly increased MT1 and MT2 expression vs. controls, induced nuclear translocation of MT1, and significantly ameliorated the aging-related impairment of angiogenesis and mitochondrial function.

Conclusions: Aging GECs have significantly reduced MT1 and MT2 expression, angiogenesis, and mitochondrial membrane potential vs. young GECs. Treatment of aging GECs with melatonin increases expression of VEGF receptor and survivin and ameliorates aging-related impaired angiogenesis and mitochondrial function.
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http://dx.doi.org/10.1152/ajpgi.00101.2021DOI Listing
October 2021

Effects of turnover and stability of health staff on quality of care in remote communities of the Northern Territory, Australia: a retrospective cohort study.

BMJ Open 2021 Oct 19;11(10):e055635. Epub 2021 Oct 19.

Menzies School of Health Research, Charles Darwin University, Alice Springs, Northern Territory, Australia.

Objectives: To evaluate the relationship between markers of staff employment stability and use of short-term healthcare workers with markers of quality of care. A secondary objective was to identify clinic-specific factors which may counter hypothesised reduced quality of care associated with lower stability, higher turnover or higher use of short-term staff.

Design: Retrospective cohort study (Northern Territory (NT) Department of Health Primary Care Information Systems).

Setting: All 48 government primary healthcare clinics in remote communities in NT, Australia (2011-2015).

Participants: 25 413 patients drawn from participating clinics during the study period.

Outcome Measures: Associations between independent variables (resident remote area nurse and Aboriginal Health Practitioner turnover rates, stability rates and the proportional use of agency nurses) and indicators of health service quality in child and maternal health, chronic disease management and preventive health activity were tested using linear regression, adjusting for community and clinic size. Latent class modelling was used to investigate between-clinic heterogeneity.

Results: The proportion of resident Aboriginal clients receiving high-quality care as measured by various quality indicators varied considerably across indicators and clinics. Higher quality care was more likely to be received for management of chronic diseases such as diabetes and least likely to be received for general/preventive adult health checks. Many indicators had target goals of 0.80 which were mostly not achieved. The evidence for associations between decreased stability measures or increased use of agency nurses and reduced achievement of quality indicators was not supported as hypothesised. For the majority of associations, the overall effect sizes were small (close to zero) and failed to reach statistical significance. Where statistically significant associations were found, they were generally in the hypothesised direction.

Conclusions: Overall, minimal evidence of the hypothesised negative effects of increased turnover, decreased stability and increased reliance on temporary staff on quality of care was found. Substantial variations in clinic-specific estimates of association were evident, suggesting that clinic-specific factors may counter any potential negative effects of decreased staff employment stability. Investigation of clinic-specific factors using latent class analysis failed to yield clinic characteristics that adequately explain between-clinic variation in associations. Understanding the reasons for this variation would significantly aid the provision of clinical care in remote Australia.
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http://dx.doi.org/10.1136/bmjopen-2021-055635DOI Listing
October 2021

Limited evidence of moderation of the association between gastrointestinal symptoms and prospective healthcare utilisation by quality of life.

Aliment Pharmacol Ther 2021 Oct 19. Epub 2021 Oct 19.

School of Psychological Sciences, Macquarie University, Sydney, NSW, Australia.

Background: An individual's drive to seek medical help remains a complex behavioural process, incorporating psychological, social and symptom-specific factors. Within irritable bowel syndrome (IBS), gastrointestinal symptoms only predict a small portion of the high healthcare-seeking experienced.

Aim: To examine the moderating role of quality of life (QoL) domains on this relationship to help explain the variance observed.

Methods: This is an analysis of a Swedish population-based prospective study of healthcare use over a 12-year period. At baseline, gastrointestinal symptoms were measured with the valid Gastrointestinal Symptom Rating Scale, and QoL via the SF-36. 1159 subjects (57% female; mean age 48.6 years) had their health records matched with the initial survey. 164 were classified as IBS by Rome II criteria. Negative binomial or logistic models were fit to evaluate the moderating effect of particular QoL domains on the relationship between gastrointestinal symptoms and prospective healthcare utilisation.

Results: Gastrointestinal symptoms were associated with prospective healthcare use, but moderation in this relationship by particular QoL domains was not supported; most models did not reach statistical significance. Furthermore, the impact of IBS status did not alter the moderation hypotheses.

Conclusions: Particular QoL domains did not impact the relationship between gastrointestinal symptoms on prospective healthcare seeking. Future research should continue to examine other psychological, social and symptom variables to identify predictors of high healthcare consumers in IBS.
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http://dx.doi.org/10.1111/apt.16651DOI Listing
October 2021

Swarm intelligence begins now or never.

Proc Natl Acad Sci U S A 2021 Oct;118(42)

Science, Mathematics and Technology Cluster, Singapore University of Technology and Design, Singapore 487372.

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http://dx.doi.org/10.1073/pnas.2113678118DOI Listing
October 2021

Antibiotic use but not gastrointestinal infection frequently precedes first diagnosis of functional gastrointestinal disorders.

United European Gastroenterol J 2021 Oct 15. Epub 2021 Oct 15.

College of Health, Medicine and Well Being, University of Newcastle, Newcastle, New South Wales, Australia.

Introduction: While the etiopathogenesis of functional gastrointestinal disorders (FGIDs) is not completely understood, alterations of the intestinal microbiome have been observed. Antibiotics can induce dysbiosis, but whether antibiotics are a risk factor for the onset of FGIDs is uncertain. Antibiotics have been reported as both a risk factor for new onset FGID but also as a therapy for existing FGID. This study aimed to estimate the fraction of cases where antibiotics provoked the onset of FGID.

Method: Electronic medical records were obtained from general practices (primary care) in the United Kingdom. Dates of antibiotic prescription (AP) were compared with first date of FGID diagnosis and contrasted across three prevalent FGIDs and controls without gastrointestinal disorders.

Results: There were 10,926 GI healthy controls, 4326 IBS alone, 3477 FD alone, 340 chronic constipation and 4402 with overlap of multiple conditions. Both the prevalence of AP and rate were higher in FGID patients and increased with diagnosis of multiple FGIDs. 7%-14% of FGID patients were prescribed their first recorded antibiotic in the 12 months prior to their first FGID diagnosis and 20%-33% were prescribed an antibiotic in the same period. Differences between FGID groups were not accounted for by social deprivation and only rate of AP was moderated by social deprivation. In contrast, only 5%-10% of patients ever had a gastrointestinal infection recorded and only 1.5%-3.5% prior to their first FGID diagnosis.

Conclusion: These data indicate that antibiotics are prescribed prior to FGID diagnosis in a significant minority of care-seeking FGID patients, opening the potential for this medication to contribute to the pathophysiology. APs appears to mostly be for non-gastrointestinal conditions.
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http://dx.doi.org/10.1002/ueg2.12164DOI Listing
October 2021

Determining Sequence-Dependent DNA Oligonucleotide Hybridization and Dehybridization Mechanisms Using Coarse-Grained Molecular Simulation, Markov State Models, and Infrared Spectroscopy.

J Am Chem Soc 2021 Oct 13. Epub 2021 Oct 13.

Pritzker School of Molecular Engineering, The University of Chicago, 5640 South Ellis Avenue, Chicago, Illinois 60637, United States.

A robust understanding of the sequence-dependent thermodynamics of DNA hybridization has enabled rapid advances in DNA nanotechnology. A fundamental understanding of the sequence-dependent kinetics and mechanisms of hybridization and dehybridization remains comparatively underdeveloped. In this work, we establish new understanding of the sequence-dependent hybridization/dehybridization kinetics and mechanism within a family of self-complementary pairs of 10-mer DNA oligomers by integrating coarse-grained molecular simulation, machine learning of the slow dynamical modes, data-driven inference of long-time kinetic models, and experimental temperature-jump infrared spectroscopy. For a repetitive ATATATATAT sequence, we resolve a rugged dynamical landscape comprising multiple metastable states, numerous competing hybridization/dehybridization pathways, and a spectrum of dynamical relaxations. Introduction of a G:C pair at the terminus (GATATATATC) or center (ATATGCATAT) of the sequence reduces the ruggedness of the dynamics landscape by eliminating a number of metastable states and reducing the number of competing dynamical pathways. Only by introducing a G:C pair midway between the terminus and the center to maximally disrupt the repetitive nature of the sequence (ATGATATCAT) do we recover a canonical "all-or-nothing" two-state model of hybridization/dehybridization with no intermediate metastable states. Our results establish new understanding of the dynamical richness of sequence-dependent kinetics and mechanisms of DNA hybridization/dehybridization by furnishing quantitative and predictive kinetic models of the dynamical transition network between metastable states, present a molecular basis with which to understand experimental temperature jump data, and furnish foundational design rules by which to rationally engineer the kinetics and pathways of DNA association and dissociation for DNA nanotechnology applications.
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http://dx.doi.org/10.1021/jacs.1c05219DOI Listing
October 2021

3D printing lifts the lid on black box instruments.

Anal Bioanal Chem 2021 Oct 11. Epub 2021 Oct 11.

Department of Chemistry, Whitworth University, Spokane, WA, 99251, USA.

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http://dx.doi.org/10.1007/s00216-021-03681-1DOI Listing
October 2021

Prevalence, symptoms and risk factor profile of rumination syndrome and functional dyspepsia: a population-based study.

Aliment Pharmacol Ther 2021 Oct 9. Epub 2021 Oct 9.

Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia.

Background: Rumination syndrome is a functional gastroduodenal disorder characterised by effortless regurgitation of recently ingested food. Emerging evidence reports duodenal eosinophilic inflammation in a subset, suggesting a shared pathophysiology with functional dyspepsia (FD).

Aim: To assess the clinical features of rumination syndrome and FD in a community-based study.

Methods: We mailed a survey assessing gastrointestinal symptoms, diet and psychological symptoms to 9835 residents of Olmsted County, MN, USA in 2017-2018; diagnostic codes were obtained from linked clinical records. The two disorders were assessed as mutually exclusive in 'pure' forms with a separate overlap group, all compared to a control group not meeting criteria for either. Prevalence of associations, and univariate and independent associations with predictors were assessed by logistic regression.

Results: Prevalence of rumination syndrome and FD were 5.8% and 7.1%, respectively; the overlap was 3.83-times more likely than expected by chance. Independent predictors for rumination (odds ratio (OR), 95% confidence interval (CI)) were female gender (1.79, 1.21-2.63), smoking (1.89, 1.28-2.78), gluten-free diet (1.58, 1.14-2.19), allergic rhinitis (1.45, 1.01-2.08) and depression (1.10, 1.05-1.16). FD was independently associated with female gender, depression, non-coeliac wheat sensitivity, migraine, irritable bowel syndrome and somatic symptoms. A similar reported efficacy (≥54%) of low fat or dairy-free diets was found with both disorders (P = 0.53 and P = 1.00, respectively). The strongest independent associations with overlapping FD and rumination syndrome were a history of rheumatoid arthritis (3.93, 1.28-12.06) and asthma (3.02, 1.44-6.34).

Conclusion: Rumination syndrome overlaps with FD with a shared risk factor profile, suggesting a common pathophysiology.
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http://dx.doi.org/10.1111/apt.16630DOI Listing
October 2021

Volumetric Rectal Perception Testing: Is It Clinically Relevant? Results From a Large Patient Cohort.

Am J Gastroenterol 2021 Oct 5. Epub 2021 Oct 5.

Neurogastroenterology Unit and Department of Gastroenterology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Introduction: Rectal perception testing is a recommended component of anorectal physiology testing. Although recent consensus (London) guidelines suggested criteria for categorizing hyporectal and hyper-rectal sensitivity, these were based on scant evidence. Moreover, data regarding diagnostic capabilities and clinical utility of rectal perception testing are lacking. The aims of this study were to determine the association between rectal perception testing and both clinical and physiological variables to enhance the analysis and interpretation of real-life test results.

Methods: Prospectively documented data from 1,618 (92% female) patients referred for anorectal physiology testing were analyzed for 3 rectal perception thresholds (first, urge, and maximal tolerated). Normal values derived from healthy female subjects were used to categorize each threshold into hyposensitive and hypersensitive to examine the clinical relevance of this categorization.

Results: There was poor to moderate agreement between the 3 thresholds. Older age, male sex, and constipation were associated with higher perception thresholds, whereas irritable bowel syndrome, fecal incontinence, connective tissue disease, and pelvic radiation were associated with lower perception thresholds to some, but not all, thresholds (P < 0.01 on multivariate analysis for all). The clinical utility and limitations of categorizing thresholds into "hypersensitivity" and "hyposensitivity" were determined.

Discussion: Commonly practiced rectal perception testing is correlated with several disease states and thus has clinical relevance. However, most disease states were correlated with 2 or even only 1 abnormal threshold, and agreement between thresholds was limited. This may suggest each threshold measures different pathophysiological pathways. We suggest all 3 thresholds be measured and reported separately in routine clinical testing.
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http://dx.doi.org/10.14309/ajg.0000000000001526DOI Listing
October 2021

Effects of Peer Mentoring for Caregivers of Patients With Acquired Brain Injury: A Preliminary Investigation of Efficacy.

Arch Rehabil Res Clin Transl 2021 Sep 25;3(3):100149. Epub 2021 Jul 25.

Virginia C. Crawford Research Institute, Shepherd Center, Atlanta, GA.

Objective: To evaluate effectiveness of a peer mentor intervention for caregivers of patients with acquired brain injury (ABI) in encouraging caregiver participation in support services to prepare them for the role of caregiving and in reducing caregiver stress and depression.

Design: Controlled trial with participants randomized to either usual care or 1-to-1 visits with a family caregiver peer mentor during the ABI inpatient rehabilitation stay.

Setting: Nonprofit rehabilitation hospital specializing in care of persons with brain and spinal cord injury.

Participants: Caregivers (N=36) of patients with ABI admitted for rehabilitation whose discharge location was home with care provided by family members (caregivers: 93% female; 58% White; mean age, 48±10.4y).

Interventions: One-to-one peer mentoring visits during the inpatient stay with a trained peer mentor who is also a family caregiver of a survivor of brain injury.

Main Outcome Measures: Frequency of participation in support services for family caregivers, reported caregiver stress, and reported caregiver depressive symptoms.

Results: There was no difference between groups in participation in support services for family caregivers. Participants in the peer mentor intervention group reported significantly greater improvement in caregiver stress at discharge and 30 days post discharge than participants in the usual care group. Reported depressive symptoms were also lower for the intervention group, but change scores did not achieve statistical significance at discharge or 30-day follow-up.

Conclusions: Peer mentoring appears to improve caregivers' ability to handle the stress of caregiving and reduces reported depressive symptoms. There was no between-group difference noted in participation in support services for families; however, participation was adversely affected by restrictions imposed during the coronavirus disease 2019 pandemic, which may have masked any effect.
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http://dx.doi.org/10.1016/j.arrct.2021.100149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463468PMC
September 2021

The Beverage Hydration Index: Influence of Electrolytes, Carbohydrate and Protein.

Nutrients 2021 Aug 25;13(9). Epub 2021 Aug 25.

Exercise Physiology Laboratory, Georgia Institute of Technology, Atlanta, GA 30332, USA.

The beverage hydration index (BHI) facilitates a comparison of relative hydration properties of beverages using water as the standard. The additive effects of electrolytes, carbohydrate, and protein on rehydration were assessed using BHI. Nineteen healthy young adults completed four test sessions in randomized order: deionized water (W), electrolytes only (E), carbohydrate-electrolytes (C + E), and 2 g/L dipeptide (alanyl-glutamine)-electrolytes (AG + E). One liter of beverage was consumed, after which urine and body mass were obtained every 60 min through 240 min. Compared to W, BHI was higher ( = 0.007) for C + E (1.15 ± 0.17) after 120 min and for AG + E ( = 0.021) at 240 min (1.15 ± 0.20). BHI did not differ ( > 0.05) among E, C + E, or AG + E; however, E contributed the greatest absolute net effect (>12%) on BHI relative to W. Net fluid balance was lower for W ( = 0.048) compared to C + E and AG + E after 120 min. AG + E and E elicited higher ( < 0.001) overall urine osmolality vs. W. W also elicited greater reports of stomach bloating ( = 0.02) compared to AG + E and C + E. The addition of electrolytes alone (in the range of sports drinks) did not consistently improve BHI versus water; however, the combination with carbohydrate or dipeptides increased fluid retention, although this occurred earlier for the sports drink than the dipeptide beverage. Electrolyte content appears to make the largest contribution in hydration properties of beverages for young adults when consumed at rest.
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http://dx.doi.org/10.3390/nu13092933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465972PMC
August 2021

Electroencephalographic evidence of unconscious and conscious attentional bias in people with functional gastrointestinal disorders: A pilot study.

Int J Psychophysiol 2021 Sep 21;170:30-42. Epub 2021 Sep 21.

Department of Psychology, Macquarie University, Sydney, Australia.

Debate continues as to whether an attentional bias towards threat displayed by sufferers of functional gastrointestinal disorders (FGIDs) is conscious and, thus, more amenable to change through psychological therapy. We compared the amplitudes of early (unconscious) and later (conscious) electroencephalographic (EEG) event-related potentials following silent reading of symptom-related, emotionally neutral, and emotionally negative nouns across two participant groups: 30 female FGID-sufferers who met diagnostic criteria for irritable bowel syndrome or functional dyspepsia, and 30 female healthy controls. Analogous indices based on alpha desynchronization were also examined, as were correlations between the EEG-based indices and a range of psychosocial variables. FGID-sufferers displayed marginally significantly higher occipital EPN amplitudes for all nouns, indicating marginally higher levels of unconscious attention in the task. FGID-sufferers also displayed, for negative as compared to neutral nouns, significantly lower central N400 amplitudes indicative of higher conscious attention. The result was only apparent in post-hoc pairwise comparisons, however. Uniquely among FGID-sufferers, central N400 was strongly negatively correlated with a range of negative psychosocial traits and states. The findings provide preliminary evidence of hypervigilance to general (as opposed to symptom-specific) threat among FGID-sufferers. Amidst concerns over Type I error, recommendations are made for fine-tuning the operationalisation of unconscious and conscious attentional bias in this population.
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http://dx.doi.org/10.1016/j.ijpsycho.2021.09.006DOI Listing
September 2021

Rapid discrimination of Curcuma longa and Curcuma xanthorrhiza using Direct Analysis in Real Time Mass Spectrometry and Near Infrared Spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Sep 2;265:120347. Epub 2021 Sep 2.

Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.

This study describes a newly developed method for the fast and straightforward differentiation of two turmeric species using Direct Analysis in Real Time mass spectrometry and miniaturized Near Infrared spectroscopy. Multivariate analyses (PCA and LDA) were performed on the mass spectrometric data, thus creating a powerful model for the discrimination of Curcumalonga and Curcumaxanthorrhiza. Cross-validation of the model revealed correctness-scores of 100% with 20-fold as well as leave-one-out validation techniques. To further estimate the models prediction power, seven retail samples of turmeric powder were analyzed and assorted to a species. Looking for a fast, non-invasive, cost-efficient and laboratory independent method, miniaturized NIR spectrometers offer an alternative for quality control of turmeric species. However, different technologies implemented to compensate for their small size, lead to different applicability of these spectrometers. Therefore, we investigated the three handheld spectrometers microPHAZIR, MicroNIR 2200 and MicroNIR 1700ES for their application in spice analysis in hyphenation to PCA, LDA and ANN methods used for the discriminant analysis. While microPHAZIR proved to be the most valuable device for differentiating C.longa and C.xanthorrhiza, MicroNIR 1700ES offered the worst results. These findings are interpreted on the basis of a quantum chemical simulation of the NIR spectrum of curcumin as the representative constituent. It was found that the information accessible to MicroNIR 1700ES that is relevant to the analyzed constituents is located in the spectral region prone to interferences with the matrix, likely limiting the performance of this spectrometer in this analytical scenario.
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http://dx.doi.org/10.1016/j.saa.2021.120347DOI Listing
September 2021

Hospital outcomes in pediatric patients with Prader-Willi syndrome (PWS) undergoing orthopedic surgery: A 12-year analysis of national trends in surgical management and inpatient hospital outcomes.

J Orthop Sci 2021 Sep 13. Epub 2021 Sep 13.

Department of Orthopedics, Phoenix Children Hospital, Phoenix, 1919 E Thomas Rd, Phoenix, AZ, 85016, USA.

Background: The incidence of orthopedic disorders amongst patients with Prader-Willi Syndrome (PWS) is high when compared to the general pediatric population. The purpose of this retrospective study was to define the most commonly performed orthopedic procedures in pediatric patients with PWS and to characterize the peri-operative outcomes of these patients.

Methods: The Kids Inpatient Database (KID) was queried to collect data and identify all pediatric patients with PWS who underwent orthopedic procedures from 2001 to 2012. A total of 3684 patients with PWS were identified, 334 of who underwent an orthopedic procedure. Population demographics, comorbidities, and specific procedures undergone were defined. The incidences of postoperative complications and length of associated hospital stay were additionally evaluated.

Results: Mean age of patients in this sample was 10.33 years (SD 4.5). The most common comorbidities included obesity (18.1%), chronic pulmonary disease (14.1%), hypothyroidism (5.1%), hypertension (5.1%), and uncomplicated diabetes (4%). Common procedures were spinal fusion (165/334, 49%) and lower extremity procedures (50/334, 15%). Complications included acute blood loss anemia, device related complications, pneumonia, sepsis, and urinary tract infections. The overall complication rate was 35.6%. Average hospital lengths of stay for patients undergoing spinal fusion was 6.68 days (SD 4.13), lower extremity orthopedic procedure was 5.65 days (SD 7.4), and all other orthopedic procedures was 7.74 days (SD 16.3).

Conclusions: Orthopedic disorders are common in patients with PWS. Consequently, spinal fusions and lower extremity procedures are commonly performed in this patient population. Associated comorbid conditions may negatively impact surgical outcomes in these patients. This information should prove useful in the peri-operative management of patients with PWS undergoing orthopedic surgery and for shared decision making with families.
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http://dx.doi.org/10.1016/j.jos.2021.08.005DOI Listing
September 2021

Measuring the impact of gastrointestinal inconvenience and symptoms on perceived health in the general population - validation of the Short Health Scale for gastrointestinal symptoms (SHS-GI).

Scand J Gastroenterol 2021 Sep 14:1-8. Epub 2021 Sep 14.

School of Psychological Sciences, Macquarie University, North Ryde, Australia.

Objectives: Gastrointestinal (GI) symptoms are intimately related to our wellbeing. The Short Health Scale for GI symptoms (SHS-GI) is a simple questionnaire to measure the impact of GI inconvenience and symptoms on quality of life. The aim was to validate the SHS-GI in a general population sample and to compare it with SHS-data across different patient groups.

Method: A subsample of 170 participants from a population-based colonoscopy study completed the Rome II questionnaire, GI diaries, psychological questionnaire (hospital anxiety and depression scale) and SHS-GI at follow-up investigation. Psychometric properties of SHS-GI as an overall score were determined by performing a confirmatory factor analysis (CFA). Spearman correlation between SHS total score and symptoms was calculated in the general population sample. SHS-GI data was compared with SHS data from patients with inflammatory bowel disease (IBD) and fecal incontinence (FI).

Results: As expected, the general population rated their impact of GI inconvenience on quality of life as better than the patient populations in terms of all aspects of the SHS-GI. The CFA showed a good model fit meeting all fit criteria in the general population. Cronbach's alpha for the total scale was 0.80 in the general population sample and ranged from 0.72 in the FI sample to 0.88 and 0.89 in the IBD samples.

Conclusions: SHS-GI demonstrated appropriate psychometric properties in a sample of the normal population. We suggest that SHS-GI is a valid simple questionnaire suitable for measuring the impact of GI symptoms and inconvenience on quality of life in both general and patient populations.
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http://dx.doi.org/10.1080/00365521.2021.1974087DOI Listing
September 2021

Functional Characterization of Target Genes Associated with Insecticide Resistance of the Green Peach Aphid, Myzus persicae.

Methods Mol Biol 2022 ;2360:187-208

Crop Biotechnology Research Group, College of Science, Health, Engineering and Education, Murdoch University, Perth, WA, Australia.

Identifying genes responsive to insecticide treatment is the first step towards understanding the mechanism(s) of insecticide resistance and the development of effective insecticides against economic insect pests such as the Green peach aphid (GPA). Functional and Reverse Genetics approaches such as the RNA interference (RNAi) technology can be used to assess the possible involvement of genes whose expression is associated with an insecticide treatment. For GPA, this can be done by comparing the behavior and development of the insect following RNAi of a putative gene associated with insecticide treatment and exposure of the RNAi-treated insects to lethal doses of insecticides. In a case where knockdown of a gene or genes increases the susceptibility of RNAi-treated populations compared to controls, the target gene may have a direct role in the development of resistance to the insecticide or the gene may be involved in other metabolic processes that may be required for resilience against the insecticide.
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http://dx.doi.org/10.1007/978-1-0716-1633-8_15DOI Listing
January 2022

Genome-Wide Identification and Validation of Target Genes Associated with Insecticide Treatment of the Green Peach Aphid, Myzus persicae.

Methods Mol Biol 2022 ;2360:119-138

Crop Biotechnology Research Group, College of Science, Health, Engineering and Education, Murdoch University, Perth, WA, Australia.

Next-generation sequencing and analyses of whole-genome transcripts can be used to identify genes and potential mechanisms that may be responsible for the development of resistance to insecticides. Such genes can be identified by isolating and sequencing high-quality messenger RNA and identifying differentially expressed genes (DEGs), and gene variants from insecticide-treated and untreated colonies of the Green peach aphid (GPA) or resistant and susceptible GPA populations. Datasets generated would reveal a set of genes whose expression may be associated with the insecticide treatment. The DEGs can then be validated using quantitative PCR assays.
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http://dx.doi.org/10.1007/978-1-0716-1633-8_11DOI Listing
January 2022

An integrated mass spectrometry imaging and digital pathology workflow for objective detection of colorectal tumours by unique atomic signatures.

Chem Sci 2021 Aug 29;12(30):10321-10333. Epub 2021 Jun 29.

Melbourne Dementia Research Centre at the Florey Institute of Neuroscience and Mental Health, The University of Melbourne Parkville Victoria 3010 Australia.

Tumours are abnormal growths of cells that reproduce by redirecting essential nutrients and resources from surrounding tissue. Changes to cell metabolism that trigger the growth of tumours are reflected in subtle differences between the chemical composition of healthy and malignant cells. We used LA-ICP-MS imaging to investigate whether these chemical differences can be used to spatially identify tumours and support detection of primary colorectal tumours in anatomical pathology. First, we generated quantitative LA-ICP-MS images of three colorectal surgical resections with case-matched normal intestinal wall tissue and used this data in a Monte Carlo optimisation experiment to develop an algorithm that can classify pixels as tumour positive or negative. Blinded testing and interrogation of LA-ICP-MS images with micrographs of haematoxylin and eosin stained and Ki67 immunolabelled sections revealed Monte Carlo optimisation accurately identified primary tumour cells, as well as returning false positive pixels in areas of high cell proliferation. We analysed an additional 11 surgical resections of primary colorectal tumours and re-developed our image processing method to include a random forest regression machine learning model to correctly identify heterogenous tumours and exclude false positive pixels in images of non-malignant tissue. Our final model used over 1.6 billion calculations to correctly discern healthy cells from various types and stages of invasive colorectal tumours. The imaging mass spectrometry and data analysis methods described, developed in partnership with clinical cancer researchers, have the potential to further support cancer detection as part of a comprehensive digital pathology approach to cancer care through validation of a new chemical biomarker of tumour cells.
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http://dx.doi.org/10.1039/d1sc02237gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386113PMC
August 2021

New design yields robust large-area framing camera.

Rev Sci Instrum 2021 Aug;92(8):083103

Sandia National Laboratories, HI Sensor uSystems and FA, 1515 Eubank Blvd. SE, Albuquerque, New Mexico 87123, USA.

Framing cameras provide a discrete series of images over a short period of time in a manner that mimics a high-speed movie camera but with individual shutter times that must be extremely short in order to capture freeze-frame images of rapidly evolving phenomena such as high-explosive shock-driven ejecta, dynamic compression of metals, and high-velocity fluid flow. The Nevada National Security Site has designed and fielded a new, large-area, gated framing camera called Kraken. The camera design emphasized manufacturability and flexibility by improving imager yield and creating a camera architecture to shorten design cycles. Design strategies and field data are presented.
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http://dx.doi.org/10.1063/5.0049110DOI Listing
August 2021

Can an ECG performed during emergency department triage and interpreted as normal by computer analysis safely wait for clinician review until the time of patient assessment? A pilot study.

J Electrocardiol 2021 Sep-Oct;68:145-149. Epub 2021 Aug 19.

REMEDY (Research Emergency Medicine Derby), Royal Derby Hospital, Uttoxeter Road, Derby DE22 3NE, UK.

Introduction: Electrocardiograms (ECGs) are frequently performed during patient triage in Emergency Departments (EDs). Emergency Physicians (EPs) are interrupted during other tasks to review ECGs. Critics believe this practice could lead to distraction with consequent medical error and decision fatigue. ECGs can be interpreted by computer software at the time of capture; some evidence exists to suggest that an ECG performed during ED triage with an immediate computer interpretation (ICI) of 'normal' will seldom contain information necessitating a change to triage management.

Material And Methods: All ED triage ECGs performed in the Royal Derby Hospital between 13th July 2017 and 12th July 2018 in patients without chest pain and with an ICI of 'normal' were identified through a database search. Forty were randomly selected and reviewed by two EPs (blinded to patient details, ICI and outcome) who were asked to identify those that required a change to triage management.

Results: The study processes were feasible. At least one of the two EP reviewers felt that a change to triage management was required in 48% of cases (e.g. "review patient", "obtain blood gas", "review old ECGs"); they agreed on the need for change of management in 13% of cases. An ICI of normal had a NPV of 53% (95% CI 37-67%) for the need for a change to triage management based upon ECG findings. Inter-observer agreement was poor (kappa = 0.17).

Conclusions: Based on these results, ED triage ECGs should still be presented to EPs for immediate review regardless of the ICI. Inter-observer agreement between EPs was poor. Further research is required to link triage ECG interpretation, need for intervention and patient outcome.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.08.006DOI Listing
October 2021

Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial.

Stroke 2021 Aug 26:STROKEAHA120032972. Epub 2021 Aug 26.

Department of Biostatistics, University of Alabama School of Public Health (G.H.).

Background And Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort.

Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of scores less than the anticipated deviate for the population-based cohort for representative percentiles.

Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall score for patients was significantly below expected for higher percentiles (<0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile (=0.015). Lower performance was attributed largely to Word List Recall (<0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, ≤0.01). The scores for left versus right carotid disease were similar.

Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02089217.
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http://dx.doi.org/10.1161/STROKEAHA.120.032972DOI Listing
August 2021

Understanding and responding to the cost and health impact of short-term health staffing in remote and rural Aboriginal and Torres Strait Islander community-controlled health services: a mixed methods study protocol.

BMJ Open 2021 08 18;11(8):e043902. Epub 2021 Aug 18.

Menzies School of Health Research, Charles Darwin University, Alice Springs, Northern Territory, Australia

Introduction: Access to high-quality primary healthcare is limited for remote residents in Australia. Increasingly, remote health services are reliant on short-term or 'fly-in, fly-out/drive-in, drive-out' health workforce to deliver primary healthcare. A key strategy to achieving health service access equity, particularly evident in remote Australia, has been the development of Aboriginal Community Controlled Health Services (ACCHSs). This study aims to generate new knowledge about (1) the impact of short-term staffing in remote and rural ACCHSs on Aboriginal and Torres Strait Islander communities; (2) the potential mitigating effect of community control; and (3) effective, context-specific evidence-based retention strategies.

Methods And Analysis: This paper describes a 3-year, mixed methods study involving 12 ACCHSs across three states. The methods are situated within an evidence-based programme logic framework for rural and remote primary healthcare services. Quantitative data will be used to describe staffing stability and turnover, with multiple regression analyses to determine associations between independent variables (population size, geographical remoteness, resident staff turnover and socioeconomic status) and dependent variables related to patient care, service cost, quality and effectiveness. Qualitative assessment will include interviews and focus groups with clinical staff, clinic users, regionally-based retrieval staff and representatives of jurisdictional peak bodies for the ACCHS sector, to understand the impact of short-term staff on quality and continuity of patient care, as well as satisfaction and acceptability of services.

Ethics And Dissemination: The study has ethics approval from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (project number DR03171), Central Australian Human Research Ethics Committee (CA-19-3493), Western Australian Aboriginal Health Ethics Committee (WAAHEC-938) and Far North Queensland Human Research Ethics Committee (HREC/2019/QCH/56393). Results will be disseminated through peer-reviewed journals, the project steering committee and community/stakeholder engagement activities to be determined by each ACCHS.
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http://dx.doi.org/10.1136/bmjopen-2020-043902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375723PMC
August 2021

Understanding and responding to the cost and health impact of short-term health staffing in remote and rural Aboriginal and Torres Strait Islander community-controlled health services: a mixed methods study protocol.

BMJ Open 2021 08 18;11(8):e043902. Epub 2021 Aug 18.

Menzies School of Health Research, Charles Darwin University, Alice Springs, Northern Territory, Australia

Introduction: Access to high-quality primary healthcare is limited for remote residents in Australia. Increasingly, remote health services are reliant on short-term or 'fly-in, fly-out/drive-in, drive-out' health workforce to deliver primary healthcare. A key strategy to achieving health service access equity, particularly evident in remote Australia, has been the development of Aboriginal Community Controlled Health Services (ACCHSs). This study aims to generate new knowledge about (1) the impact of short-term staffing in remote and rural ACCHSs on Aboriginal and Torres Strait Islander communities; (2) the potential mitigating effect of community control; and (3) effective, context-specific evidence-based retention strategies.

Methods And Analysis: This paper describes a 3-year, mixed methods study involving 12 ACCHSs across three states. The methods are situated within an evidence-based programme logic framework for rural and remote primary healthcare services. Quantitative data will be used to describe staffing stability and turnover, with multiple regression analyses to determine associations between independent variables (population size, geographical remoteness, resident staff turnover and socioeconomic status) and dependent variables related to patient care, service cost, quality and effectiveness. Qualitative assessment will include interviews and focus groups with clinical staff, clinic users, regionally-based retrieval staff and representatives of jurisdictional peak bodies for the ACCHS sector, to understand the impact of short-term staff on quality and continuity of patient care, as well as satisfaction and acceptability of services.

Ethics And Dissemination: The study has ethics approval from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (project number DR03171), Central Australian Human Research Ethics Committee (CA-19-3493), Western Australian Aboriginal Health Ethics Committee (WAAHEC-938) and Far North Queensland Human Research Ethics Committee (HREC/2019/QCH/56393). Results will be disseminated through peer-reviewed journals, the project steering committee and community/stakeholder engagement activities to be determined by each ACCHS.
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http://dx.doi.org/10.1136/bmjopen-2020-043902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375723PMC
August 2021

Concomitant Irritable Bowel Syndrome Does Not Influence the Response to Antimicrobial Therapy in Patients with Functional Dyspepsia.

Dig Dis Sci 2021 Aug 14. Epub 2021 Aug 14.

Faculty of Medicine, University of Queensland, St. Lucia, QLD, Australia.

Background And Aims: Antimicrobial therapy improves symptoms in patients with irritable bowel syndrome (IBS), but the efficacy in functional dyspepsia (FD) is largely unknown. While FD and IBS frequently overlap, it is unknown if concomitant IBS in FD alters the response to antimicrobial therapy in FD. Thus, we aimed to assess and compare the effect of antimicrobial therapy on visceral sensory function and symptom improvement in FD patients with and without IBS.

Methods: Adult patients with FD with or without IBS received rifaximin 550 mg BD for 10 days, followed by a 6-week follow-up period. The total gastrointestinal symptom score as measured by the SAGIS (Structured Assessment of Gastrointestinal Symptoms) questionnaire and subscores (dyspepsia, diarrhea, and constipation), symptom response to a standardized nutrient challenge and normalization of the glucose breath tests were measured.

Results: Twenty-one consecutive adult patients with FD and 14/21 with concomitant IBS were recruited. Treatment with rifaximin resulted in a significant (p = 0.017) improvement in the total SAGIS score from 34.7 (± 15.4) at baseline to 26.0 (± 16.8) at 2 weeks and 25.6 (± 17.8) at 6 weeks post-treatment. Similarly, compared to baseline there was a statistically significant improvement in SAGIS subscores for dyspepsia and diarrhea (all p < 0.05) and effects persisted for 6 weeks post-treatment. Similarly, the symptom score (and subscores) following a standardized nutrient challenge improved significantly (p < 0.001) 2 weeks post-treatment. The presence of concomitant IBS did not significantly influence the improvement of symptoms after antibiotic therapy (all p > 0.5).

Conclusions: In FD patients, the response to antimicrobial therapy with rifaximin is not influenced by concomitant IBS symptoms.
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http://dx.doi.org/10.1007/s10620-021-07149-1DOI Listing
August 2021

Depression, Anxiety, and Other Mental Disorders in Patients With Cancer in Low- and Lower-Middle-Income Countries: A Systematic Review and Meta-Analysis.

JCO Glob Oncol 2021 07;7:1233-1250

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Purpose: Cancer is a growing public health issue in low- and lower-middle-income countries (LLMICs), but the mental health consequences in this setting have not been well-characterized. We aimed to systematically evaluate the available literature on the prevalence, associates, and treatment of mental disorders in patients with cancer in LLMICs.

Methods: We systematically searched Medline, PsycINFO, EMBASE, and CINAHL. We performed a random effects meta-analysis to determine the pooled prevalence of major depression or anxiety disorders in this population, defined by Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria. We qualitatively reviewed studies that examined the prevalence of depressive or anxiety disorders defined by self-report tools, the prevalence of other mental disorders, associated factors of depressive and anxiety symptoms, and the treatment of mental disorders in this population.

Results: Forty studies spanning a 15-year period were included in the review. The pooled prevalence defined by Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria was 21% for major depression (95% CI, 15 to 28) and 18% for anxiety disorders (95% CI, 8 to 30). Depressive and anxiety symptoms were most frequently associated with advanced disease and low levels of education. Among the four studies evaluating treatment, three evaluated the effectiveness of psychotherapy and one evaluated a yoga program.

Conclusion: The prevalence of depression and anxiety in patients with cancer generally appears higher in LLMICs than in upper-income countries. Our findings demonstrate the existence of a significant and underappreciated disease burden. We suggest that clinicians remain vigilant to psychiatric symptoms. Improved screening and treatment are likely to improve quality of life and reduce both morbidity and mortality.
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http://dx.doi.org/10.1200/GO.21.00056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457869PMC
July 2021

Impact of Orientational Glass Formation and Local Strain on Photo-Induced Halide Segregation in Hybrid Metal-Halide Perovskites.

J Phys Chem C Nanomater Interfaces 2021 Jul 30;125(27):15025-15034. Epub 2021 Jun 30.

Cavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, U.K.

Band gap tuning of hybrid metal-halide perovskites by halide substitution holds promise for tailored light absorption in tandem solar cells and emission in light-emitting diodes. However, the impact of halide substitution on the crystal structure and the fundamental mechanism of photo-induced halide segregation remain open questions. Here, using a combination of temperature-dependent X-ray diffraction and calorimetry measurements, we report the emergence of a disorder- and frustration-driven orientational glass for a wide range of compositions in CHNHPb(Cl Br ). Using temperature-dependent photoluminescence measurements, we find a correlation between halide segregation under illumination and local strains from the orientational glass. We observe no glassy behavior in CsPb(Cl Br ), highlighting the importance of the A-site cation for the structure and optoelectronic properties. Using first-principles calculations, we identify the local preferential alignment of the organic cations as the glass formation mechanism. Our findings rationalize the superior photostability of mixed-cation metal-halide perovskites and provide guidelines for further stabilization strategies.
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http://dx.doi.org/10.1021/acs.jpcc.1c03169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287560PMC
July 2021

Amino acid metabolism as a therapeutic target in cancer: a review.

Amino Acids 2021 Aug 22;53(8):1169-1179. Epub 2021 Jul 22.

Faculty of Health and Life Sciences, University of the West of England, Coldharbour Lane, Bristol, BS16 1QY, UK.

Malignant cells often demonstrate a proliferative advantage when compared to non-malignant cells. However, the rapid growth and metabolism required for survival can also highlight vulnerabilities specific to these malignant cells. One such vulnerability exhibited by cancer is an increased demand for amino acids (AAs), which often results in a dependency on exogenous sources of AAs or requires upregulation of de novo synthesis. These metabolic alterations can be exploited by therapy, which aims to improve treatment outcome and decrease relapse and reoccurrence. One clinically utilised strategy targeting AA dependency is the use of asparaginase in the treatment of acute lymphoblastic leukaemia (ALL), which results in a depletion of exogenous asparagine and subsequent cancer cell death. Examples of other successful strategies include the exploitation of arginine deiminase and methioninase, nutrient restriction of methionine and the inhibition of glutaminase. In this review, we summarise these treatment strategies into three promising avenues: AA restriction, enzymatic depletion and inhibition of metabolism. This review provides an insight into the complexity of metabolism in cancer, whilst highlighting these three current research avenues that have support in both preclinical and clinical settings.
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http://dx.doi.org/10.1007/s00726-021-03052-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325646PMC
August 2021

Structural Origins of Voltage Hysteresis in the Na-Ion Cathode P2-Na[MgMn]O: A Combined Spectroscopic and Density Functional Theory Study.

Chem Mater 2021 Jul 21;33(13):4890-4906. Epub 2021 Jun 21.

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.

P2-layered sodium-ion battery (NIB) cathodes are a promising class of Na-ion electrode materials with high Na mobility and relatively high capacities. In this work, we report the structural changes that take place in P2-Na[MgMn]O. Using X-ray diffraction, Mn -edge extended X-ray absorption fine structure, and Na NMR spectroscopy, we identify the bulk phase changes along the first electrochemical charge-discharge cycle-including the formation of a high-voltage " phase", an intergrowth of the OP4 and O2 phases. Our transition state searches reveal that reversible Mg migration in the phase is both kinetically and thermodynamically favorable at high voltages. We propose that Mg migration is a significant contributor to the observed voltage hysteresis in Na[MgMn]O and identify qualitative changes in the Na ion mobility.
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http://dx.doi.org/10.1021/acs.chemmater.1c00248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280737PMC
July 2021
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