Publications by authors named "Robert Walker"

642 Publications

Key components of recovery predict occupational performance and health in peer support specialists.

Psychiatr Rehabil J 2021 Sep 22;44(3):212-218. Epub 2021 Apr 22.

Geisel School of Medicine, Dartmouth College.

The primary purpose of the study was to explore and identify how components of recovery are associated with occupational performance and health among peer support specialists. One hundred and twenty-one peer support specialists were recruited from statewide peer certification training programs and the International Association of Peer Supporters. Study respondents completed a survey package including demographic questions and psychometrically sound self-report measures. Two hierarchical multivariable linear regression models were conducted to evaluate whether the recovery components of the process of recovery, social support for recovery, and work self-determination (i.e., work autonomy, work competence, and work relatedness) were associated with indicators of occupational performance (i.e., work engagement) and health (i.e., job satisfaction). Work autonomy was associated with the occupational performance indicator, while the process of recovery and social support for recovery were the only recovery components associated with the indicator for occupational health. Findings support the importance of work self-determination and social support and recovery for occupational performance and health among peer support specialists. Mental health and rehabilitation professionals should address these key components of recovery when working with and supporting the work well-being of peer support specialists. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/prj0000479DOI Listing
September 2021

Gluconeogenesis in Plants: A Key Interface between Organic Acid/Amino Acid/Lipid and Sugar Metabolism.

Molecules 2021 Aug 24;26(17). Epub 2021 Aug 24.

Dipartimento di Scienze Agrarie, Alimentari e Ambientali, Università degli Studi di Perugia, 06123 Perugia, Italy.

Gluconeogenesis is a key interface between organic acid/amino acid/lipid and sugar metabolism. The aims of this article are four-fold. First, to provide a concise overview of plant gluconeogenesis. Second, to emphasise the widespread occurrence of gluconeogenesis and its utilisation in diverse processes. Third, to stress the importance of the vacuolar storage and release of Krebs cycle acids/nitrogenous compounds, and of the role of gluconeogenesis and malic enzyme in this process. Fourth, to outline the contribution of fine control of enzyme activity to the coordinate-regulation of gluconeogenesis and malate metabolism, and the importance of cytosolic pH in this.
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http://dx.doi.org/10.3390/molecules26175129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434439PMC
August 2021

Experiences of New Zealand Haemodialysis Patients in Relation to Food and Nutrition Management: A Qualitative Study.

Nutrients 2021 Jul 3;13(7). Epub 2021 Jul 3.

Ngāi Tahu Māori Health Research Unit, Dunedin School of Medicine, University of Otago, 18 Frederick St, Dunedin 9016, New Zealand.

People receiving haemodialysis have considerable and complex dietary and healthcare needs, including co-morbidities. A recent New Zealand study has shown that few patients on haemodialysis are able to meet nutritional requirements for haemodialysis. This study aims to describe the perspectives and experiences of dietary management among patients on haemodialysis in New Zealand. This exploratory qualitative study used in-depth semi-structured interviews. Purposive sampling was used to recruit participants from different ethnic groups. Forty interviews were conducted, audio-recorded and transcribed verbatim. An inductive approach was taken using thematic analysis. Forty participants were interviewed. Participants spoke of major disruption to their lives as a result of their chronic kidney disease and being on haemodialysis, including loss of employment, financial challenges, loss of independence, social isolation and increased reliance on extended family. Most had received adequate dietary information, although some felt that more culturally appropriate support would have enabled a healthier diet. These findings show that further support to make the recommended dietary changes while on haemodialysis should focus on socio-cultural factors, in addition to the information already provided.
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http://dx.doi.org/10.3390/nu13072299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308339PMC
July 2021

Sucrose Metabolism and Transport in Grapevines, with Emphasis on Berries and Leaves, and Insights Gained from a Cross-Species Comparison.

Int J Mol Sci 2021 Jul 21;22(15). Epub 2021 Jul 21.

Dipartimento di Scienze Agrarie, Alimentari e Ambientali, Università degli Studi di Perugia, 06121 Perugia, Italy.

In grapevines, as in other plants, sucrose and its constituents glucose and fructose are fundamentally important and carry out a multitude of roles. The aims of this review are three-fold. First, to provide a summary of the metabolism and transport of sucrose in grapevines, together with new insights and interpretations. Second, to stress the importance of considering the compartmentation of metabolism. Third, to outline the key role of acid invertase in osmoregulation associated with sucrose metabolism and transport in plants.
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http://dx.doi.org/10.3390/ijms22157794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345980PMC
July 2021

Kidney failure in Samoa.

Lancet Reg Health West Pac 2020 Dec 20;5:100058. Epub 2020 Nov 20.

Department of Medicine, Otago Medical School, University of Otago, Dunedin, New Zealand.

Background: There is limited literature on kidney disease in the Pacific Region, despite it being recognised as a leading cause of death in some Pacific Island nations. Kidney replacement therapy is only available in a handful of Pacific Islands. This paper reports the epidemiology of haemodialysis patients in Samoa.

Methods: Registry data from the National Kidney Foundation of Samoa was analysed to estimate the incidence and prevalence rates of kidney failure from the rates of haemodialysis in Samoa and to explore some of the demographic features related to kidney failure in Samoa.

Findings: In total, 393 patients have received long-term haemodialysis in the National Kidney Foundation of Samoa since its inception in 2005 until August 2019. 43% of the haemodialysis population were women and the mean age of people dialysed was 54.9 years. The crude mean incidence rate of kidney failure in Samoa, based on treated kidney failure cases, is 224 patients per million population with a crude prevalence of 629 patients per million population. Diabetic nephropathy (69.4%) was the leading cause of kidney failure.

Interpretation: This is the first paper to report the epidemiology of haemodialysis patients in Samoa and reveals an urgent need for further studies on the extent of chronic kidney disease, and kidney failure, in Samoa to develop country specific prevention strategies to mitigate this growing burden and optimise care for kidney failure patients in Samoa.

Funding: : No funding was received for this study.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315401PMC
December 2020

Mutant Idh2 cooperates with a NUP98-HOXD13 fusion to induce early immature thymocyte precursor ALL.

Cancer Res 2021 Jul 28. Epub 2021 Jul 28.

Genetics Branch, NIH/NCI

Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are frequently observed in a wide variety of hematologic malignancies, including myeloid and T-cell leukemias. In this study, we generated Idh2R140Q transgenic mice to examine the role of the Idh2R140Q mutation in leukemia. No leukemia developed in Idh2R140Q transgenic mice, suggesting a need for additional genetic events for leukemia development. Since myeloid cells from NUP98-HOXD13 fusion (NHD13) transgenic mice frequently acquire somatic Idh mutations when they transform to AML, we generated Idh2R140Q/NHD13 double transgenic mice. Idh2R140Q/NHD13 transgenic mice developed an immature T cell leukemia with an immunophenotype similar to double-negative 1 (DN1) or DN2 thymocytes. Idh2R140Q/NHD13 leukemic cells were enriched for an early thymic precursor transcriptional signature, and the gene expression profile for Idh2R140Q/NHD13 DN1/DN2 T-ALL closely matched that of human early/immature T cell precursor (EITP) ALL. Moreover, recurrent mutations found in EITP ALL patients, including KRAS, PTPN11, JAK3, SH2B3, and EZH2 were also found in Idh2R140Q/NHD13 DN1/DN2 T-ALL. In vitro treatment of Idh2R140Q/NHD13 thymocytes with enasidenib, a selective inhibitor of mutant IDH2, led to a marked decrease in leukemic cell proliferation. These findings demonstrate that Idh2R140Q/NHD13 mice can serve as a useful in vivo model for the study of EITP ALL development and therapy.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-1027DOI Listing
July 2021

Amino acids change solute affinity for lipid bilayers.

Biophys J 2021 Sep 24;120(17):3676-3687. Epub 2021 Jul 24.

Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana; Montana Materials Science Program, Montana State University, Bozeman, Montana. Electronic address:

Time-resolved fluorescence and differential scanning calorimetry (DSC) were used to examine how two amino acids, L-phenylalanine (L-PA) and N-acetyl-DL-tryptophan (NAT), affect the temperature-dependent membrane affinity of two structurally similar coumarin solutes for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles. The 7-aminocoumarin solutes, coumarin 151 (C151) and coumarin 152 (C152), differ in their substitution at amine position-C151 is a primary amine, and C152 is a tertiary amine-and both solutes show different tendencies to associate with lipid bilayers consistent with differences in their respective log-P-values. Adding L-PA to the DPPC vesicle solution did not change C151's propensity to remain freely solvated in aqueous solution, but C152 showed a greater tendency to partition into the hydrophobic bilayer interior at temperatures below DPPC's gel-liquid crystalline transition temperature (T). This finding is consistent with L-PA's ability to enhance membrane permeability by disrupting chain-chain interactions. Adding NAT to DPPC-vesicle-containing solutions changed C151 and C152 affinity for the DPPC membranes in unexpected ways. DSC data show that NAT interacts strongly with the lipid bilayer, lowering T by up to 2°C at concentrations of 10 mM. These effects disappear when either C151 or C152 is added to solution at concentrations below 10 μM, and T returns to a value consistent with unperturbed DPPC bilayers. Together with DSC results, fluorescence data imply that NAT promotes coumarin adsorption to the vesicle bilayer surface. NAT's effects diminish above T and imply that unlike L-PA, NAT does not penetrate into the bilayer but instead remains adsorbed to the bilayer's exterior. Taken in their entirety, these discoveries suggest that amino acids-and by inference, polypeptides and proteins-change solute affinity for lipid bilayers with specific effects that depend on individualized amino-acid-lipid-bilayer interactions.
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http://dx.doi.org/10.1016/j.bpj.2021.07.021DOI Listing
September 2021

Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma.

Cancers (Basel) 2021 Jul 6;13(14). Epub 2021 Jul 6.

School of Cancer Sciences, Cancer Research UK Centre, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.

Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal adenocarcinoma (EAC). Unfortunately, response to neoadjuvant chemotherapy (NAC) is poor (20-37%), as is the overall survival benefit at five years (9%). The EAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance. To identify associations between genomic events and response to NAC in EAC, a comparative genomic analysis was performed in 65 patients with extensive clinical and pathological annotation using whole-genome sequencing (WGS). We defined response using Mandard Tumor Regression Grade (TRG), with responders classified as TRG1-2 ( = 27) and non-responders classified as TRG4-5 ( =38). We report a higher non-synonymous mutation burden in responders (median 2.08/Mb vs. 1.70/Mb, = 0.036) and elevated copy number variation in non-responders (282 vs. 136/patient, < 0.001). We identified copy number variants unique to each group in our cohort, with cell cycle (, ), c-Myc (), RTK/PIK3 (, ) and gastrointestinal differentiation () pathway genes being specifically altered in non-responders. Of note, mutations were exclusively present in the non-responder group with a frequency of 22%. Thus, lower mutation burden, higher chromosomal instability and specific copy number alterations are associated with resistance to NAC.
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http://dx.doi.org/10.3390/cancers13143394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308111PMC
July 2021

Renal manifestations of syphilis.

Intern Med J 2021 07;51(7):1160-1167

Medicine, University of Otago, Dunedin, New Zealand.

Syphilis is a sexually transmitted disease caused by spirochaete Treponema pallidum. The incidence of syphilis is rising across the globe. It has been described in the literature as a great imitator due to the vast range of clinical manifestations that can occur in the disease. Renal manifestations are rare but a feature of secondary syphilis. It can cause glomerulopathies, tubular pathology and vasculitic lesions in the kidney. Membranous nephropathy is the most commonly reported glomerular lesion associated with syphilis. With two recent cases of secondary membranous nephropathy due to syphilis, it is timely to review the current state of knowledge, and discuss the different renal manifestation of syphilis, its pathology and treatment options.
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http://dx.doi.org/10.1111/imj.15407DOI Listing
July 2021

Microbial Phosphorus Mobilization Strategies Across a Natural Nutrient Limitation Gradient and Evidence for Linkage With Iron Solubilization Traits.

Front Microbiol 2021 23;12:572212. Epub 2021 Jun 23.

Ecology Department, Climate and Ecosystem Sciences Division, Earth and Environmental Sciences Area, Lawrence Berkeley National Laboratory, Berkeley, CA, United States.

Microorganisms have evolved several mechanisms to mobilize and mineralize occluded and insoluble phosphorus (P), thereby promoting plant growth in terrestrial ecosystems. However, the linkages between microbial P-solubilization traits and the preponderance of insoluble P in natural ecosystems are not well known. We tested the P solubilization traits of hundreds of culturable bacteria representative of the rhizosphere from a natural gradient where P concentration and bioavailability decline as soil becomes progressively more weathered. Aluminum, iron phosphate and organic P (phytate) were expected to dominate in more weathered soils. A defined cultivation medium with these chemical forms of P was used for isolation. A combination of soil chemical, spectroscopic analyses and 16S rRNA gene sequencing were used to understand the ability for solubilization of these predominant forms of P. Locations with more occluded and organic P harbored the greatest abundance of P-mobilizing microorganisms, especially ( and spp.). Nearly all bacteria utilized aluminum phosphate, however fewer could subsist on iron phosphate (FePO) or phytate. Microorganisms isolated from phytic acid were also most effective at solubilizing FePO, suggesting that phytate solubilization may be linked to the ability to solubilize Fe. Significantly, we observed Fe to be co-located with P in organic patches in soil. Siderophore addition in lab experiments reinstated phytase mediated P-solubilization from Fe-phytate complexes. Taken together, these results indicate that metal-organic-P complex formation may limit enzymatic P solubilization from phytate in soil. Additionally, the linked traits of phytase and siderophore production were mostly restricted to specific clades within the . We propose that Fe complexation of organic P (e.g., phytate) represents a major constraint on P turnover and availability in acidic soils, as only a limited subset of bacteria appear to possess the traits required to access this persistent pool of soil P.
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http://dx.doi.org/10.3389/fmicb.2021.572212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261140PMC
June 2021

LID Study: Plasma lidocaine levels following airway topicalisation for paediatric microlaryngobronchoscopy (MLB).

Clin Otolaryngol 2021 Jul 2. Epub 2021 Jul 2.

Department of Paediatric Otolaryngology, Royal Manchester Children's Hospital, Manchester, UK.

Background: A dose of 5mg/kg lidocaine is considered appropriate for paediatric airway topicalisation. Existing literature suggests younger children are susceptible to toxic lidocaine plasma levels and achieve this at a faster rate.

Aims: The primary outcome of this study was to ascertain peak plasma lidocaine levels after topicalisation for airway endoscopy. Secondary endpoints included: time to peak lidocaine plasma levels, signs of lidocaine toxicity (restricted to ECG changes or seizures when under anaesthesia) and clinical adverse events of laryngospasm, coughing or desaturation during the procedure.

Methods: Data was collected prospectively over 18 months at Royal Manchester Children's Hospital. Children aged 0-8 years undergoing elective diagnostic or therapeutic airway endoscopy were included within the study. Standardised 2% lidocaine was used for airway topicalisation. Dose varied depending upon practitioner usual practice. Venous blood sampling occurred at 5, 10, 15 and 20 minutes post administration and plasma lidocaine levels (ng/ml) analysed.

Results: A significant relationship exists between higher peak plasma levels and ages <18 months (p=0.00973). Strong linear correlation exists between body weight and age for our cohort (r=0.88). Higher peak plasma lidocaine levels occur with total dose volumes between 2 and 3mls of 2% lidocaine local anaesthetic (p=0.03) compared with <2ml total dose volumes. Data suggests a potential relationship of lower body weights achieving higher peak plasma levels (p=0.0516). Reduced IQR variation of peak plasma lidocaine levels exists when lidocaine dosing is <5mg/kg.

Conclusions: Age and total dose volume of topicalised lidocaine have a significant relationship with plasma lidocaine levels. A dose of 5mg/kg topicalised lidocaine for paediatric airway endoscopy is safe and provides good operating conditions. Lower patient body weights trend toward higher peak lidocaine plasma concentrations and require further investigation.
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http://dx.doi.org/10.1111/coa.13833DOI Listing
July 2021

Cerebral Oximetry during Out-of-Hospital Resuscitation: Pilot Study of First Responder Implementation.

Prehosp Emerg Care 2021 Jul 27:1-5. Epub 2021 Jul 27.

Received February 22, 2021 from Emergency Medical Services Division of Public Health, Seattle & King County, Seattle, WA (JS, JB, PK, TR); Stryker, Redmond, WA (RW, FC); Nonin Medical, Inc, Plymouth, MN (JC); Department of Medicine, University of Washington, Seattle, WA (PK, TR). Revised received June 8, 2021; accepted for publication June 21, 2021.

Anoxic brain injury is a common mode of death following out-of-hospital cardiac arrest (OHCA). We assessed the course of regional cerebral oxygen saturation (rSO) at the outset and during first responder resuscitation to understand its relationship with return of spontaneous circulation (ROSC) and functional survival. We undertook a prospective observational investigation of adult OHCA patients treated by a first-responder EMS agency in King County, WA. Cerebral oximetry was performed using the SenSmart® Model X-100 Universal Oximetry System (Nonin Medical, Inc). We determined cerebral oximetry rSO overall and stratified according to ROSC and favorable survival status defined by Cerebral Performance Category (CPC) of 1-2. Among the 59 OHCA cases enrolled, 47% ( = 28) achieved ROSC and 14% ( = 8) survived with CPC 1-2. On average, initial rSO cerebral oximetry was 41% and was not different at the outset according to return of spontaneous circulation (ROSC) or survival status. Within 5 minutes of first responder resuscitation, those who would subsequently achieve ROSC had a higher rSO than those who would not achieve ROSC (51% vs. 43%,  = 0.03). Among patients who achieved ROSC, those who would survive with CPC 1-2 had a higher rSO cerebral oximetry following ROSC than nonsurvivors (74% vs. 60%,  = 0.04 at 5 minutes post ROSC), a difference that was not evident in the minutes prior to ROSC (55% vs. 51% at 3 minutes prior to ROSC,  = 0.5). In this observational study, where first responders applied cerebral oximetry, higher rSO during the course of care predicted ROSC among all patients and predicted favorable survival among those who achieved ROSC. Future investigation should evaluate whether and how treatments might modify rSO and in turn may influence prognosis.
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http://dx.doi.org/10.1080/10903127.2021.1948647DOI Listing
July 2021

New-onset type 1 diabetes complicated by diabetic ketoacidosis and severe sepsis requiring extracorporeal membrane oxygenation and kidney replacement therapy.

J Diabetes Metab Disord 2021 Jun 22;20(1):1075-1079. Epub 2021 Jan 22.

Department of Women's and Children's Health, Otago Medical School - Dunedin Campus, University of Otago, PO Box 56, Dunedin, 9054 New Zealand.

Diabetic ketoacidosis (DKA) accounts for up to a third of all new presentations of Type 1 Diabetes Mellitus (T1DM) in children and adolescents. While most cases are relatively uncomplicated new onset presentations, if DKA is compounded with an additional underlying severe illness, such as appendicitis or severe infection, diagnostic delays may be experienced, and treatment response and outcomes may be compromised. We report an atypical case of new onset diabetes with severe DKA and underlying severe sepsis, which responded poorly to traditional therapy resulting in maximal intensive care management including mechanical ventilation, inotropes, extracorporeal membrane oxygenation (ECMO) for cardiorespiratory support, and kidney replacement therapy.
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http://dx.doi.org/10.1007/s40200-021-00736-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212357PMC
June 2021

Predictors of Health Deterioration Among Older New Zealanders Undergoing Dialysis: A Three-Year Accelerated Longitudinal Cohort Study.

Can J Kidney Health Dis 2021 13;8:20543581211022207. Epub 2021 Jun 13.

Department of Medicine, Otago Medical School, University of Otago, Dunedin, New Zealand.

Background: Patient involvement in dialysis decision-making is crucial, yet little is known about patient-reported outcomes over time on dialysis.

Objective: To examine health-related outcomes over 24 and 36 months in an older cohort of dialysis patients.

Design: The "Dialysis outcomes in those aged ≥65 years study" is a prospective longitudinal cohort study of New Zealanders with kidney failure.

Setting: Three New Zealand nephrology units.

Patients: Kidney failure (dialysis and predialysis) patients aged 65 or above. We have previously described outcomes after 12 months of dialysis therapy relative to baseline.

Measurements: Patient-reported social and health factors using the SF-36, EQ-5D, and Kidney Symptom Score questionnaires.

Methods: This article describes and compares characteristics of 120 older kidney failure patients according to whether they report "Same/better" or "Worse" health 24 and 36 months later, and identifies predictors of "worse health." Modified Poisson regression modeling estimated relative risks (RR) of worse health.

Results: Of 120 patients at 12 months, 47.5% had worse health or had died by 24 months. Of those surviving at 24 months (n = 80), 40% had "Worse health" or had died at 36 months. Variables independently associated with reduced risk of "Worse health" (24 months) were as follows: Māori ethnicity (RR = 0.44; 95% CI = 0.26-0.75), Pacific ethnicity (RR = 0.39; 95% CI = 0.33-0.46); greater social satisfaction (RR = 0.57; 95% CI = 0.46-0.7). Variables associated with an increased risk of "Worse health" were as follows: problems with usual activities (RR = 1.32; 95% CI = 1.04-1.37); pain or discomfort (RR = 1.48; 95% CI = 1.34, 1.63). At 36 months, lack of sense of community (RR = 1.41; 95% CI = 1.18-1.69), 2 or more comorbidities (RR = 1.21; 95% CI = 1.13-1.29), and problems with poor health (RR = 1.47; 95% CI = 1.41-1.54) were associated with "Worse health."

Limitations: Participant numbers restricted the number of variables able to be included in the multivariable model, and hence there may have been insufficient power to detect certain associations.

Conclusions: In this study, the majority of older dialyzing patients report "Same/better health" at 24 and 36 months. Māori and Pacific people report better outcomes on dialysis. Social and/or clinical interventions aimed at improving social satisfaction, sense of community, and help with usual activities may impact favorably on the experiences for older dialysis patients.

Trial Registration: Australian and New Zealand clinical trials registry: ACTRN12611000024943.
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http://dx.doi.org/10.1177/20543581211022207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207284PMC
June 2021

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

Ann Intern Med 2021 08 15;174(8):1151-1158. Epub 2021 Jun 15.

National Institutes of Health, Bethesda, Maryland (K.S., A.K.P., H.C.L., H.M.).

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.
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http://dx.doi.org/10.7326/M21-1647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252833PMC
August 2021

Plant metabolomics integrated with transcriptomics and rhizospheric bacterial community indicates the mitigation effects of Klebsiella oxytoca P620 on p-hydroxybenzoic acid stress in cucumber.

J Hazard Mater 2021 08 26;415:125756. Epub 2021 Mar 26.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, Shandong 271018, PR China. Electronic address:

Accumulation of p-hydroxybenzoic acid (PHBA) in soil causes autotoxicity stress in cucumber. When the stress is mitigated by PHBA-degrading bacteria, plant metabolites have not been detected. To explore mechanisms underlining the mitigation, plant metabolites have not been combined with rhizospheric microbes, antioxidant and soil enzymes. In this study, a strain P620 of Klebsiella decomposed PHBA to acetyl CoA. Cucumber was sown into soil supplemented with P620 and/or PHBA. After addition with P620, P620 colonization and the enriched bacterial genera were observed in rhizosphere. Compared to PHBA stress alone, the combination of P620 application and PHBA stress improved plant growth, decreased PHBA concentration in soil, and increased the activities of five soil enzymes and eight antioxidant enzymes in leaves. Metabolomic and transcriptomic analysis highlighted that P620 application decreased the intensities of MAG(18:3) isomer 4, MAG(18:3) isomer 2, lysoPC 18:3 (2n isomer), 2'-deoxyadenosine-5'-monophosphate, pyridoxine, and glucarate O-phosphoric acid in PHBA-stressed leaves and down-regulated the expression of genes related to these metabolites. We propose a mechanism that P620 application alters microbial communities in PHBA-contaminated soil. Thus, the application reduces PHBA concentration in soil, activates antioxidant and soil enzymes, and also influences metabolites in leaves by affecting plant transcriptome, mitigating PHBA stress in cucumber.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125756DOI Listing
August 2021

Models of immunogenicity in preclinical assessment of tissue engineered heart valves.

Acta Biomater 2021 May 31. Epub 2021 May 31.

Department of Medicine, University of Auckland, Grafton, Auckland 1024, New Zealand.

Tissue engineered heart valves may one day offer an exciting alternative to traditional valve prostheses. Methods of construction vary, from decellularised animal tissue to synthetic hydrogels, but the goal is the same: the creation of a 'living valve' populated with autologous cells that may persist indefinitely upon implantation. Previous failed attempts in humans have highlighted the difficulty in predicting how a novel heart valve will perform in vivo. A significant hurdle in bringing these prostheses to market is understanding the immune reaction in the short and long term. With respect to innate immunity, the chronic remodelling of a tissue engineered implant by macrophages remains poorly understood. Also unclear are the mechanisms behind unknown antigens and their effect on the adaptive immune system. No silver bullet exists, rather researchers must draw upon a number of in vitro and in vivo models to fully elucidate the effect a host will exert on the graft. This review details the methods by which the immunogenicity of tissue engineered heart valves may be investigated and reveals areas that would benefit from more research. STATEMENT OF SIGNIFICANCE: Both academic and private institutions around the world are committed to the creation of a valve prosthesis that will perform safely upon implantation. To date, however, no truly non-immunogenic valves have emerged. This review highlights the importance of preclinical immunogenicity assessment, and summarizes the available techniques used in vitro and in vivo to elucidate the immune response. To the authors knowledge, this is the first review that details the immune testing regimen specific to a TEHV candidate.
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http://dx.doi.org/10.1016/j.actbio.2021.05.049DOI Listing
May 2021

Does the intact nephron hypothesis provide a reasonable model for metformin dosing in chronic kidney disease?

Br J Clin Pharmacol 2021 May 18. Epub 2021 May 18.

School of Pharmacy, University of Otago, Dunedin, New Zealand.

This research explored the intact nephron hypothesis (INH) as a model for metformin dosing in patients with chronic kidney disease (CKD). The INH assumes that glomerular filtration rate (GFR) will account for all kidney drug handling even for drugs eliminated by tubular secretion like metformin. We conducted two studies: (1) a regression analysis to explore the relationship between metformin clearance and eGFR metrics, and (2) a joint population pharmacokinetic analysis to test the relationship between metformin renal clearance and gentamicin clearance. The relationship between metformin renal clearance and eGFR metrics and gentamicin clearance was found to be linear, suggesting that a proportional dose reduction based on GFR in patients with CKD is reasonable.
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http://dx.doi.org/10.1111/bcp.14919DOI Listing
May 2021

Mental Health App Evaluation: Updating the American Psychiatric Association's Framework Through a Stakeholder-Engaged Workshop.

Psychiatr Serv 2021 Sep 22;72(9):1095-1098. Epub 2021 Apr 22.

Division of Digital Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Lagan, Torous); College of Nursing, University of Nebraska Medical Center, Omaha (Emerson); Department of Psychiatry, Utah Southwestern Medical Center, Dallas (King); Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee (Matwin); U.S. Department of Veterans Affairs Palo Alto Health Care System, and Department of Psychiatry, Stanford Medical Center, Palo Alto, California (Chan); Behavioral Health Informatics, Children's Hospital of Philadelphia, Philadelphia (Proctor); Department of Psychiatry, Northwell Health, New York City (Tartaglia); Department of Psychiatry, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire (Fortuna); Department of Psychiatry, Lahey Hospital and Medical Center, Boston (Aquino); Department of Mental Health, Office of Recovery and Empowerment, Boston (Walker); Department of Practice Management and Delivery Systems Policy (Dirst) and Department of Digital Health (Tatro), American Psychiatric Association, Washington, D.C.; Department of Psychiatry, McLean Hospital, Belmont, Massachusetts (Benson); Los Angeles County Department of Mental Health, Los Angeles (Myrick); Scarborough Hospital Toronto, and Department of Psychiatry, University of Toronto, Toronto (Gratzer). Dror Ben-Zeev, Ph.D., is editor of this column.

The app evaluation framework of the American Psychiatric Association (APA) has emerged as an adaptable tool for those seeking to navigate the ever-growing space of mental health apps. The authors describe a meeting convened in December 2019 to refine the APA framework. The expert panel comprised 16 individuals across health care fields, with representation from psychiatry, psychology, social work, nursing, clinical informatics, peer support specialists, and individuals with lived mental health experience. This meeting resulted in an update to the APA framework with the addition of clearer question descriptions and the release of an eight-question screener that may be useful in clinical settings.
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http://dx.doi.org/10.1176/appi.ps.202000663DOI Listing
September 2021

Out-of-hospital resuscitation of a 3 month old boy presenting with recurrent ventricular fibrillation cardiac arrest: a case report.

Scand J Trauma Resusc Emerg Med 2021 Apr 13;29(1):58. Epub 2021 Apr 13.

London Ambulance Service NHS Trust, London Ambulance Service, 220 Waterloo Road, London, SE1 8SD, UK.

A 3 month old boy, with no known health conditions, suffered a sudden collapse at home. On first EMS arrival, ventricular fibrillation (VF) cardiac arrest was identified and resuscitation following UK national guidelines was initiated. He remained in cardiac arrest for over 25 min, during which he received 10 defibrillation shocks, each effective, but with VF reoccurring within a few seconds of each of the first 9. A return of spontaneous circulation (ROSC) was achieved after the 10th shock. The resuscitation was conducted fully in his home, with the early involvement of Advanced Paramedic Practitioners specialising in critical care (APP- CC). Throughout his resuscitation, there remained a strong focus on delivering quality resuscitation in situ, rather than a 'load and go' approach that would have resulted in very early conveyance to hospital with on-going CPR.The patient was subsequently discharged home and is making an excellent recovery. The arrest was later determined to have been caused by a primary arrhythmia as a result of a previously unidentified non-obstructive variant hypertrophic cardiomyopathy.We present data downloaded from the defibrillator used during the resuscitation that illustrates clearly the recurrent nature of his fibrillation.
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http://dx.doi.org/10.1186/s13049-021-00871-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045223PMC
April 2021

Grape Berry Secondary Metabolites and Their Modulation by Abiotic Factors in a Climate Change Scenario-A Review.

Front Plant Sci 2021 22;12:643258. Epub 2021 Mar 22.

Faculty of Land and Food Systems, Wine Research Centre, The University of British Columbia, Vancouver, BC, Canada.

Temperature, water, solar radiation, and atmospheric CO concentration are the main abiotic factors that are changing in the course of global warming. These abiotic factors govern the synthesis and degradation of primary (sugars, amino acids, organic acids, etc.) and secondary (phenolic and volatile flavor compounds and their precursors) metabolites directly, via the regulation of their biosynthetic pathways, or indirectly, via their effects on vine physiology and phenology. Several hundred secondary metabolites have been identified in the grape berry. Their biosynthesis and degradation have been characterized and have been shown to occur during different developmental stages of the berry. The understanding of how the different abiotic factors modulate secondary metabolism and thus berry quality is of crucial importance for breeders and growers to develop plant material and viticultural practices to maintain high-quality fruit and wine production in the context of global warming. Here, we review the main secondary metabolites of the grape berry, their biosynthesis, and how their accumulation and degradation is influenced by abiotic factors. The first part of the review provides an update on structure, biosynthesis, and degradation of phenolic compounds (flavonoids and non-flavonoids) and major aroma compounds (terpenes, thiols, methoxypyrazines, and C13 norisoprenoids). The second part gives an update on the influence of abiotic factors, such as water availability, temperature, radiation, and CO concentration, on berry secondary metabolism. At the end of the paper, we raise some critical questions regarding intracluster berry heterogeneity and dilution effects and how the sampling strategy can impact the outcome of studies on the grapevine berry response to abiotic factors.
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http://dx.doi.org/10.3389/fpls.2021.643258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020818PMC
March 2021

Faster chemistry at surfaces.

Authors:
Robert A Walker

Nat Chem 2021 04;13(4):296-297

Chemistry and Biochemistry Department, Montana Materials Science Program, Montana State University, Bozeman, MT, USA.

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http://dx.doi.org/10.1038/s41557-021-00672-8DOI Listing
April 2021

Biosynthesis and Cellular Functions of Tartaric Acid in Grapevines.

Front Plant Sci 2021 4;12:643024. Epub 2021 Mar 4.

College of Science and Engineering, Flinders University, Bedford Park, SA, Australia.

Tartaric acid (TA) is an obscure end point to the catabolism of ascorbic acid (Asc). Here, it is proposed as a "specialized primary metabolite", originating from carbohydrate metabolism but with restricted distribution within the plant kingdom and lack of known function in primary metabolic pathways. Grapes fall into the list of high TA-accumulators, with biosynthesis occurring in both leaf and berry. Very little is known of the TA biosynthetic pathway enzymes in any plant species, although recently some progress has been made in this space. New technologies in grapevine research such as the development of global co-expression network analysis tools and genome-wide association studies, should enable more rapid progress. There is also a lack of information regarding roles for this organic acid in plant metabolism. Therefore this review aims to briefly summarize current knowledge about the key intermediates and enzymes of TA biosynthesis in grapes and the regulation of its precursor, ascorbate, followed by speculative discussion around the potential roles of TA based on current knowledge of Asc metabolism, TA biosynthetic enzymes and other aspects of fruit metabolism.
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http://dx.doi.org/10.3389/fpls.2021.643024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970118PMC
March 2021

Preparing nurses for palliative and end of life care: A survey of New Zealand nursing schools.

Nurse Educ Today 2021 May 23;100:104822. Epub 2021 Feb 23.

School of Population Health, University of Auckland, Auckland, New Zealand.

Background: Nurses play a vital role in the care of people with advanced life-limiting illnesses, so palliative and end of life care is an essential skill nurses need to learn. Despite numerous reports in the international literature about educational developments in this area, there are widespread inconsistencies in undergraduate education, and graduates continue to report feeling unprepared for this part of their work. Little is known about how New Zealand nursing students learn about this important area of clinical practice.

Objectives: To obtain information about teaching content, organisation, delivery, assessment and clinical learning opportunities in palliative and end of life care in undergraduate nurse education in New Zealand.

Design: Quantitative descriptive cross sectional study.

Settings: Tertiary education institutions that provide the Bachelor of Nursing programme in New Zealand.

Participants: Academic leads and course coordinators.

Methods: National online survey.

Results: A total of 13/18 (72%) educational institutions completed the survey. All integrate palliative and end of life care in their teaching with an identified coordinator at 12 (92%) institutions. Between 1 and 10 h of formal teaching is provided at 11 (85%) institutions where lectures and tutorials are most comon. Clinical placements with specialist palliative care providers are scarce and limited to senior students as elective placements. Assessment of student learning in palliative and end of life care is carried out at seven (54%) institutions, and formally evaluated at 12 (92%). Lack of teaching time and clinical placements with palliative care providers are barriers to increased learning opportunities in palliative and end of life care.

Conclusions: This article provides comprehensive information about palliative and end of life care teaching in undergraduate nurse education in New Zealand. Teaching on this subject is not a mandatory requirement so there are inconsistencies in the teaching provided between educational institutions, and significant barriers to development. Mandatory competencies need to be introduced to ensure graduates have the knowledge, skills and attitudes required to provide optimal care for people near the end of life.
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http://dx.doi.org/10.1016/j.nedt.2021.104822DOI Listing
May 2021

Fiber Bragg Grating Wavelength Drift in Long-Term High Temperature Annealing.

Sensors (Basel) 2021 Feb 19;21(4). Epub 2021 Feb 19.

National Research Council Canada, 100 Sussex Drive, Ottawa, ON K1A 0R6, Canada.

High-temperature-resistant fiber Bragg gratings (FBGs) are the main competitors to thermocouples as sensors in applications for high temperature environments defined as being in the 600-1200 °C temperature range. Due to their small size, capacity to be multiplexed into high density distributed sensor arrays and survivability in extreme ambient temperatures, they could provide the essential sensing support that is needed in high temperature processes. While capable of providing reliable sensing information in the short term, their long-term functionality is affected by the drift of the characteristic Bragg wavelength or resonance that is used to derive the temperature. A number of physical processes have been proposed as the cause of the high temperature wavelength drift but there is yet no credible description of this process. In this paper we review the literature related to the long-term wavelength drift of FBGs at high temperature and provide our recent results of more than 4000 h of high temperature testing in the 900-1000 °C range. We identify the major components of the high temperature wavelength drift and we propose mechanisms that could be causing them.
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http://dx.doi.org/10.3390/s21041454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922305PMC
February 2021

Ultrafast Laser Processing of Optical Fibers for Sensing Applications.

Sensors (Basel) 2021 Feb 19;21(4). Epub 2021 Feb 19.

National Research Council Canada, 100 Sussex Drive, Ottawa, ON K1A 0R6, Canada.

A review of recent progress in the use of infrared femtosecond lasers to fabricate optical fiber sensors that incorporate fiber Bragg gratings (FBG) and random fiber gratings (RFG) is presented. The important advancements in femtosecond laser writing based on the phase mask technique now allow through-the-coating (TTC) fabrication of Bragg gratings in ultra-thin fiber filaments, tilted fiber Bragg gratings, and 1000 °C-resistant fiber Bragg gratings with very strong cladding modes. As an example, through-the-coating femtosecond laser writing is used to manufacture distributed fiber Bragg grating sensor arrays for oil pipeline leak detection. The plane-by-plane femtosecond laser writing technique used for the inscription of random fiber gratings is also reviewed and novel applications of the resultant devices in distributed temperature sensing, fiber lasers and fiber laser sensors are discussed.
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http://dx.doi.org/10.3390/s21041447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922569PMC
February 2021

A continuous flow liquid propellant strand burner for high pressure monopropellant and bipropellant combustion studies.

Rev Sci Instrum 2021 Feb;92(2):025106

Montana Materials Science Program, Montana State University, Bozeman, Montana 59717, USA.

A combustion assembly capable of continuously burning monopropellant and bipropellant liquid fuels at pressures up to 80 bars (1145 psig) was designed and constructed. The assembly is based on a liquid propellant strand burner where a manifold maintains small positive differential pressures on the fuel to maintain a steady supply into the reaction vessel. Optical ports enable direct visualization of the flame and will allow for future spectroscopic and imaging studies of the flame. The strand burner design was tested using nitromethane with both air and inert environments in the reaction vessel. Continuous combustion was sustained for almost 8 min in air (34 bars/500 psig) and more than 6 min in N (70 bars/1000 psig). A unique outcome from the initial testing of this device is the ability to ignite liquid nitromethane in an inert environment without the use of a pilot flame started in air.
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http://dx.doi.org/10.1063/5.0022780DOI Listing
February 2021

The AUGIS Survival Predictor: Prediction of Long-term and Conditional Survival after Esophagectomy Using Random Survival Forests.

Ann Surg 2021 Feb 17. Epub 2021 Feb 17.

*School of Cancer Sciences, Faculty of Medicine, University of Southampton †Oxford University Hospitals NHS Trust ‡Sandwell and West Birmingham Hospitals NHS Trust §Velindre Cancer Centre, Cardiff ¶Clinical Effectiveness Unit, Royal College of Surgeons of England.

Objective:: To develop a predictive model for overall survival after esophagectomy using pre/postoperative clinical data and machine learning.

Summary Background Data:: For patients with esophageal cancer, accurately predicting long-term survival after esophagectomy is challenging. This study investigated survival prediction after esophagectomy using a Random Survival Forest (RSF) model derived from routine data from a large, well curated, national dataset.

Methods:: Patients diagnosed with esophageal adenocarcinoma or squamous cell carcinoma between 2012 and 2018 in England and Wales who underwent an esophagectomy were included. Prediction models for overall survival were developed using the RSF method and Cox regression from 41 patient and disease characteristics. Calibration and discrimination (time dependent AUC) were validated internally using bootstrap resampling.

Results:: The study analysed 6399 patients, with 2625 deaths during follow-up. Median follow-up was 41 months. Overall survival was 47.1% at 5 years. The final RSF model included 14 variables and had excellent discrimination with a 5-year tAUC of 83.9% (95%CI 82.6-84.9%), compared to 82.3% (95%CI 81.1-83.3%) for the Cox model. The most important variables were lymph node involvement, pT stage, CRM involvement (tumour at < 1 mm from cut edge) and age. There was a wide range of survival estimates even within TNM staging groups, with quintiles of prediction within Stage 3b ranging from 12.2-44.7% survival at 5 years.

Conclusions:: An RSF model for long-term survival after esophagectomy exhibited excellent discrimination and well calibrated predictions. At a patient level, it provides more accuracy than TNM staging alone and could help in the delivery of tailored treatment and follow-up.
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http://dx.doi.org/10.1097/SLA.0000000000004794DOI Listing
February 2021

Metformin doses to ensure efficacy and safety in patients with reduced kidney function.

PLoS One 2021 18;16(2):e0246247. Epub 2021 Feb 18.

School of Pharmacy, University of Otago, Dunedin, New Zealand.

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246247PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891741PMC
July 2021

Wheat Can Access Phosphorus From Algal Biomass as Quickly and Continuously as From Mineral Fertilizer.

Front Plant Sci 2021 28;12:631314. Epub 2021 Jan 28.

School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia.

Algae can efficiently take up excess nutrients from waterways, making them a valuable resource potentially capable of replacing synthesized and mined fertilizers for agriculture. The capacity of algae to fertilize crops has been quantified, but it is not known how the algae-derived nutrients become available to plants. We aimed to address this question: what are the temporal dynamics of plant growth responses to algal biomass? to better propose mechanisms by which plants acquire nutrients from algal biomass and thereby study and promote those processes in future agricultural applications. Data from various sources were transformed and used to reconstruct the nutrient release from the algae and subsequent uptake by wheat ( L.) (as reported in Schreiber et al., 2018). Plants had received 0.1x or 1x dried algae or wet algae, or zero, 0.1x or 1x mineral fertilizer calculated from agricultural practices for P application and grown to 55 days in three soils. Contents of P and other nutrients acquired from algae were as high as from mineral fertilizer, but varied based on moisture content and amount of algae applied to soils (by 55 days after sowing plants with 1x mineral fertilizer and 1x dried algae had 5.6 mg P g DW; 2.2-fold more than those with 0 or 0.1x mineral fertilizer, 0.1x dried algae and wet algae, and 1x wet algae). Absolute and relative leaf area growth and estimated P uptake rates showed similar dynamics, indicating that wheat acquires P from algae quickly. A model proposes that algal fertilizer promotes wheat growth after rapid transformation in soil to inorganic nutrients. We conclude theoretically that phosphorus from algal biomass is available to wheat seedlings upon its application and is released gradually over time with minor differences related to moisture content on application. The growth and P uptake kinetics hint at nutrient forms, including N, and biomass stimulation worthy of research to further exploit algae in sustainable agriculture practices. Temporal resolved phenotype analyses in combination with a mass-balance approach is helpful for understanding resource uptake from recycled and biofertilizer sources by plants.
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http://dx.doi.org/10.3389/fpls.2021.631314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879783PMC
January 2021
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