Publications by authors named "Andrew Jones"

1,207 Publications

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Skeletal Muscle Nitrate as a Regulator of Systemic Nitric Oxide Homeostasis.

Exerc Sport Sci Rev 2021 Oct 16. Epub 2021 Oct 16.

Molecular Medicine Branch, NIDDK, National Institutes of Health,Bethesda, MD 20892, U.S. Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK.

Abstract: Non-enzymatic nitric oxide (NO) generation via the reduction of nitrate and nitrite ions, along with remarkably high levels of nitrate ions in skeletal muscle, have been recently described. Skeletal muscle nitrate storage may be critical for maintenance of NO homeostasis in healthy ageing and nitrate supplementation may be useful for treatment of specific pathophysiologies as well as enhancing normal functions.
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http://dx.doi.org/10.1249/JES.0000000000000272DOI Listing
October 2021

Food biodiversity and total and cause-specific mortality in 9 European countries: An analysis of a prospective cohort study.

PLoS Med 2021 Oct 18;18(10):e1003834. Epub 2021 Oct 18.

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

Background: Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population.

Methods And Findings: We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10-P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out.

Conclusions: In this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.
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http://dx.doi.org/10.1371/journal.pmed.1003834DOI Listing
October 2021

Management of Urological Malignancy in Heart and Lung Transplant Recipients: An Irish National Cohort Study.

Exp Clin Transplant 2021 Oct;19(10):1069-1075

>From the Department of Urology, Mater Misericordiae University Hospital, Dublin, Ireland.

Objectives: Following the first hearttransplantin Ireland in 1985, there have been almost 700 deceased donor heart and lung transplants carried out in Ireland at a single institution. In this retrospective study, our aim was to assess the incidence and management of urological malignancies arising in this national cohort.

Materials And Methods: Our retrospective analysis included all heart and lung transplant recipients identified as having a urological malignancy. Primary outcome variables included incidence, management, and clinical outcomes following cancer diagnosis.

Results: A total of 28 patients (4.1%) had radiologically or histologically confirmed urological malignancies. Fourteen patientswere diagnosedwith prostate cancer, with 13 who underwent radical treatment. Eight renal cell carcinomas were diagnosed in heart transplant recipients, with 5 who underwent nephrectomies. Two bladder cancers and 1 uppertract urothelial carcinoma were diagnosed and managed with endoscopic resection, radiotherapy, and nephroureterectomy, respectively. Two patients were diagnosed with penile squamous cell carcinoma and managed with radical surgery and lymph node dissection/sampling, with 1 patient receiving adjuvant chemoradiotherapy.

Conclusions: Urological malignancies are not common in heart and lung transplant recipients; however, standard management options can be safely used, including radical surgery. Prospective monitoring of these patients and potential considerations for screening should be maintained.
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http://dx.doi.org/10.6002/ect.2021.0206DOI Listing
October 2021

Interaction of exercise bioenergetics with pacing behavior predicts track distance running performance.

J Appl Physiol (1985) 2021 Oct 7. Epub 2021 Oct 7.

Sport and Health Sciences, College of Life and Environmental Sciences, St. Luke's Campus, University of Exeter, Exeter, United Kingdom.

The best possible finishing time for a runner competing in distance track events can be estimated from their critical speed (CS) and the finite amount of energy that can be expended above CS (D'). During tactical races with variable pacing, the runner with the 'best' combination of CS and D' and, therefore, the fastest estimated finishing time prior to the race, does not always win. We hypothesized that final race finishing positions depend on the relationships between the pacing strategy employed, the athletes' initial CS, and their instantaneous D' (i.e., D' balance) as the race unfolds. Using publicly available data from the 2017 IAAF World Championships men's 5,000 m and 10,000 m races, race speed, CS, and D' balance were calculated. The correlation between D' balance and actual finishing positions was non-significant utilizing start-line values but improved to R > 0.90 as both races progressed. The D' balance with 400 m remaining was strongly associated with both final 400 m split time and proximity to the winner. Athletes who exhausted their D' were unable to hold pace with the leaders, whereas a high D´ remaining enabled a fast final 400 m and a high finishing position. The D' balance model was able to accurately predict finishing positions in both a 'slow' 5,000 m and a 'fast' 10,000 m race. These results indicate that while CS and D' can characterize an athlete's performance capabilities prior to the start, the pacing strategy that optimizes D' utilization significantly impacts final race outcome.
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http://dx.doi.org/10.1152/japplphysiol.00223.2021DOI Listing
October 2021

The Impact of Elevated Body Core Temperature on Critical Power as Determined by a 3-min All-Out Test.

J Appl Physiol (1985) 2021 Oct 7. Epub 2021 Oct 7.

Department of Human Physiology, University of Oregon, Eugene, OR, United States.

Critical power (CP) delineates the heavy and severe exercise intensity domains, and sustained work rates above CP result in an inexorable progression of oxygen uptake to a maximal value and, subsequently, the limit of exercise tolerance. The finite work capacity above CP, W', is defined by the curvature constant of the power-duration relationship. Heavy or severe exercise in a hot environment generates additional challenges related to the rise in body core temperature (T) that may impact CP and W'. The purpose of this study was to determine the effect of elevated T on CP and W'. CP and W' were estimated by end-test power (EP; mean of final 30s) and work above end-test power (WEP), respectively, from 3-min "all-out" tests performed on a cycle ergometer. Volunteers (n = 8, 4 female) performed the 3-min tests during a familiarization visit and two experimental visits (Thermoneutral vs Hot, randomized crossover design). Before experimental 3-min tests, subjects were immersed in water (Thermoneutral: 36°C for 30 min; Hot: 40.5°C until T was ≥ 38.5°C). Mean T was significantly greater in Hot compared to Thermoneutral (38.5±0.0°C vs. 37.4±0.2°C; mean±SD, P<0.01). All 3-min tests were performed in an environmental chamber (Thermoneutral: 18°C, 45% RH; Hot: 38°C, 40% RH). EP was similar between Thermoneutral (239 ± 57W) and Hot (234 ± 66W; P = 0.55). WEP was similar between Thermoneutral (10.9 ± 3.0 kJ) and Hot (9.3 ± 3.6; P = 0.19). These results suggest that elevated T has no significant impact on EP or WEP.
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http://dx.doi.org/10.1152/japplphysiol.00253.2021DOI Listing
October 2021

Homebrewed psilocybin: can new routes for pharmaceutical psilocybin production enable recreational use?

Bioengineered 2021 Dec;12(1):8863-8871

Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, OH, USA.

Psilocybin, a drug most commonly recognized as a recreational psychedelic, is quickly gaining attention as a promising therapy for an expanding range of neurological conditions, including depression, anxiety, and addiction. This growing interest has led to many recent advancements in psilocybin synthesis strategies, including multiple fermentation-based approaches catalyzed by recombinant microorganisms. In this work, we show that psilocybin can be produced in biologically relevant quantities using a recombinant strain in a homebrew style environment. In less than 2 days, we successfully produced approximately 300 mg/L of psilocybin under simple conditions with easily sourced equipment and supplies. This finding raises the question of how this new technology should be regulated as to not facilitate clandestine biosynthesis efforts, while still enabling advancements in psilocybin synthesis technology for pharmaceutical applications. Here, we present our homebrew results, and suggestions on how to address the regulatory concerns accompanying this new technology.
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http://dx.doi.org/10.1080/21655979.2021.1987090DOI Listing
December 2021

A systematic review and meta-analysis of longitudinal cohort studies comparing mental health before versus during the COVID-19 pandemic in 2020.

J Affect Disord 2021 Oct 1;296:567-576. Epub 2021 Oct 1.

Department of Psychology, University of Liverpool, Eleanor Rathbone Building, Liverpool L69 7ZA, UK.

Background: Increases in mental health problems have been observed during the COVID-19 pandemic. The objectives were to examine the extent to which mental health symptoms changed during the pandemic in 2020, whether changes were persistent or short lived, and if changes were symptom specific.

Methods: Systematic review and meta-analysis of longitudinal cohort studies examining changes in mental health among the same group of participants before vs. during the pandemic in 2020.

Results: Sixty-five studies were included. Compared to pre-pandemic outbreak, there was an overall increase in mental health symptoms observed during March-April 2020 (SMC = .102 [95% CI: .026 to .192]) that significantly declined over time and became non-significant (May-July SMC = .067 [95% CI: -.022 to .157]. Compared to measures of anxiety (SMC = 0.13, p = 0.02) and general mental health (SMC = -.03, p = 0.65), increases in depression and mood disorder symptoms tended to be larger and remained significantly elevated in May-July [0.20, 95% CI: .099 to .302]. In primary analyses increases were most pronounced among samples with physical health conditions and there was no evidence of any change in symptoms among samples with a pre-existing mental health condition.

Limitations: There was a high degree of unexplained heterogeneity observed (Is > 90%), indicating that change in mental health was highly variable across samples.

Conclusions: There was a small increase in mental health symptoms soon after the outbreak of the COVID-19 pandemic that decreased and was comparable to pre-pandemic levels by mid-2020 among most population sub-groups and symptom types.
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http://dx.doi.org/10.1016/j.jad.2021.09.098DOI Listing
October 2021

Discharge Documentation and Follow-Up of Critically Ill Patients With Acute Kidney Injury Treated With Kidney Replacement Therapy: A Retrospective Cohort Study.

Front Med (Lausanne) 2021 14;8:710228. Epub 2021 Sep 14.

Department of Critical Care, King's College London, Guy's and St Thomas' Hospital National Health Service Foundation Trust, London, United Kingdom.

Leading organisations recommend follow-up of acute kidney injury (AKI) survivors, as these patients are at risk of long-term complications and increased mortality. Information transfer between specialties and from tertiary to primary care is essential to ensure timely and appropriate follow-up. Our aim was to examine the association between completeness of discharge documentation and subsequent follow-up of AKI survivors who received kidney replacement therapy (KRT) in the Intensive Care Unit (ICU). We retrospectively analysed the data of 433 patients who had KRT for AKI during ICU admission in a tertiary care centre in the UK between June 2017 and May 2018 and identified patients who were discharged from hospital alive. Patients with pre-existing end-stage kidney disease and patients who were transferred from hospitals outside the catchment area were excluded. The primary objective was to assess the completeness of discharge documentation from critical care and hospital; secondary objectives were to determine cardiovascular medications reconciliation after AKI, and to investigate kidney care and outcomes at 1 year. The development of AKI and the need for KRT were mentioned in 85 and 82% of critical care discharge letters, respectively. Monitoring of kidney function post-discharge was recommended in 51.6% of critical care and 36.3% of hospital discharge summaries. Among 35 patients who were prescribed renin-angiotensin-aldosterone system inhibitors before hospitalisation, 15 (42.9%) were not re-started before discharge from hospital. At 3 months, creatinine and urine protein were measured in 88.2 and 11.8% of survivors, respectively. The prevalence of chronic kidney disease stage III or worse increased from 27.2% pre-hospitalisation to 54.9% at 1 year ( < 0.001). Our data demonstrate that discharge summaries of patients with AKI who received KRT lacked essential information. Furthermore, even in patients with appropriate documentation, renal follow-up was poor suggesting the need for more education and streamlined care pathways.
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http://dx.doi.org/10.3389/fmed.2021.710228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476795PMC
September 2021

Nitrate-rich beetroot juice ingestion reduces skeletal muscle O uptake and blood flow during exercise in sedentary men.

J Physiol 2021 Sep 29. Epub 2021 Sep 29.

Department of Nutrition, Exercise and Sports, Integrative Physiology Section, Cardiovascular Physiology, University of Copenhagen, Copenhagen, Denmark.

Dietary nitrate supplementation has been shown to reduce pulmonary O uptake during submaximal exercise and enhance exercise performance. However, the effects of nitrate supplementation on local metabolic and haemodynamic regulation in contracting human skeletal muscle remain unclear. To address this, eight healthy young male sedentary subjects were assigned in a randomized, double-blind, crossover design to receive nitrate-rich beetroot juice (NO3, 9 mmol) and placebo (PLA) 2.5 h prior to the completion of a double-step knee-extensor exercise protocol that included a transition from unloaded to moderate-intensity exercise (MOD) followed immediately by a transition to intense exercise (HIGH). Compared with PLA, NO3 increased plasma levels of nitrate and nitrite. During MOD, leg and leg blood flow (LBF) were reduced to a similar extent (∼9%-15%) in NO3. During HIGH, leg was reduced by ∼6%-10% and LBF by ∼5%-9% (did not reach significance) in NO3. Leg kinetics was markedly faster in the transition from passive to MOD compared with the transition from MOD to HIGH both in NO3 and PLA with no difference between PLA and NO3. In NO3, a reduction in nitrate and nitrite concentration was detected between arterial and venous samples. No difference in the time to exhaustion was observed between conditions. In conclusion, elevation of plasma nitrate and nitrate reduces leg skeletal muscle and blood flow during exercise. However, nitrate supplementation does not enhance muscle kinetics during exercise, nor does it improve time to exhaustion when exercising with a small muscle mass. KEY POINTS: Dietary nitrate supplementation has been shown to reduce systemic O uptake during exercise and improve exercise performance. The effects of nitrate supplementation on local metabolism and blood flow regulation in contracting human skeletal muscle remain unclear. By using leg exercise engaging a small muscle mass, we show that O uptake and blood flow are similarly reduced in contracting skeletal muscle of humans during exercise. Despite slower kinetics in the transition from moderate to intense exercise, no effects of nitrate supplementation were observed for kinetics and time to exhaustion. Nitrate and nitrite concentrations are reduced across the exercising leg, suggesting that these ions are extracted from the arterial blood by contracting skeletal muscle.
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http://dx.doi.org/10.1113/JP281995DOI Listing
September 2021

Cryopreservation of 13 Commercial Genotypes Using In Vitro Nodal Explants.

Plants (Basel) 2021 Aug 28;10(9). Epub 2021 Aug 28.

Gosling Research Institute for Plant Preservation, Department of Plant Agriculture, University of Guelph, Guelph, ON N1G 2W1, Canada.

Cannabis has developed into a multi-billion-dollar industry that relies on clonal propagation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of . The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: nodes were cultured for 17 h in a pre-culture solution (PCS), followed by a 20-min treatment in a loading solution (LS), and a 60 min incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40 °C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3-80%) and regrowth of shoots (26.7-66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.
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http://dx.doi.org/10.3390/plants10091794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470898PMC
August 2021

Functional Characteristics of the Lepidopteran Ionotropic GABA Receptor 8916 Subunit Interacting with the LCCH3 or the RDL Subunit.

J Agric Food Chem 2021 Oct 23;69(39):11582-11591. Epub 2021 Sep 23.

College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, P. R. China.

The ionotropic γ-aminobutyric acid (iGABA) receptor is commonly considered as a fast inhibitory channel and is an important insecticide target. Since 1990, RDL, LCCH3, and GRD have been successively isolated and found to be potential subunits of the insect iGABA receptor. More recently, one orphan gene named 8916 was found and considered to be another potential iGABA receptor subunit according to its amino acid sequence. However, little information about 8916 has been reported. Here, the 8916 subunit from was studied to determine whether it can form part of a functional iGABA receptor by co-expressing this subunit with CsRDL1 or CsLCCH3 in the system. Cs8916 or CsLCCH3 did not form functional ion channels when expressed alone. However, Cs8916 was able to form heteromeric ion channels when expressed with either CsLCCH3 or CsRDL1. The recombinant heteromeric Cs8916/LCCH3 channel was a cation-selective channel, which was sensitive to GABA or β-alanine. The current of the Cs8916/LCCH3 channel was inhibited by dieldrin, endosulfan, fipronil, or ethiprole. In contrast, fluralaner, broflanilide, and avermectin showed little effect on the Cs8916/LCCH3 channel (ICs > 10 000 nM). The Cs8916/RDL1 channel was sensitive to GABA, but was significantly different in EC and for GABA to those of homomeric CsRDL1. Fluralaner, fipronil, or dieldrin showed antagonistic actions on Cs8916/RDL1. In conclusion, Cs8916 is a potential iGABA receptor subunit, which can interact with CsLCCH3 to generate a cation-selective channel that is sensitive to several insecticides. Also, as Cs8916/RDL1 has a higher EC than homomeric CsRDL1, Cs8916 may affect the physiological functions of CsRDL1 and therefore play a role in fine-tuning GABAergic signaling.
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http://dx.doi.org/10.1021/acs.jafc.1c00385DOI Listing
October 2021

Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential.

Nat Commun 2021 09 21;12(1):5553. Epub 2021 Sep 21.

Centre for Proteome Research, Department of Biochemistry & Systems Biology, Institute of Systems, Molecular & Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool, L69 7ZB, UK.

SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigens S and N: the main targets for vaccine and antibody testing efforts. We discover significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We show that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, show a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19.
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http://dx.doi.org/10.1038/s41467-021-25796-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455558PMC
September 2021

Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy.

Nature 2021 Sep 21. Epub 2021 Sep 21.

Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA.

Monoclonal antibodies (mAbs) with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefit in cases of mild to moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease. Treatment generally requires the administration of high doses of these mAbs with limited efficacy in preventing disease complications or mortality among hospitalized COVID-19 patients. Here we report the development and evaluation of Fc-optimized anti-SARS-CoV-2 mAbs with superior potency to prevent or treat COVID-19 disease. In several animal models of COVID-19 disease, we demonstrate that selective engagement of activating FcγRs results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection upon SARS-CoV-2 challenge and treatment of pre-infected animals. Our results highlight the importance of FcγR pathways in driving antibody-mediated antiviral immunity, while excluding any pathogenic or disease-enhancing effects of FcγR engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered mAbs with optimal Fc effector function and improved clinical efficacy against COVID-19 disease.
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http://dx.doi.org/10.1038/s41586-021-04017-wDOI Listing
September 2021

Crop diversity is associated with higher child diet diversity in Ethiopia, particularly among low-income households, but not in Vietnam.

Public Health Nutr 2021 Sep 16:1-12. Epub 2021 Sep 16.

Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.

Objectives: To examine associations of household crop diversity with school-aged child dietary diversity in Vietnam and Ethiopia and mechanisms underlying these associations.

Design: We created a child diet diversity score (DDS) using data on seven food groups consumed in the last 24 h. Generalised estimating equations were used to model associations of household-level crop diversity, measured as a count of crop species richness (CSR) and of plant crop nutritional functional richness (CNFR), with DDS. We examined effect modification by household wealth and subsistence orientation, and mediation by the farm's market orientation.

Setting: Two survey years of longitudinal data from the Young Lives cohort.

Participants: Children (aged 5 years in 2006 and 8 years in 2009) from rural farming households in Ethiopia (n 1012) and Vietnam (n 1083).

Results: There was a small, positive association between household CNFR and DDS in Ethiopia (CNFR-DDS, β = 0·13; (95 % CI 0·07, 0·19)), but not in Vietnam. Associations of crop diversity and child diet diversity were strongest among poor households in Ethiopia and among subsistence-oriented households in Vietnam. Agricultural earnings positively mediated the crop diversity-diet diversity association in Ethiopia.

Discussion: Children from households that are poorer and those that rely more on their own agricultural production for food may benefit most from increased crop diversity.
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http://dx.doi.org/10.1017/S1368980021003281DOI Listing
September 2021

Risk of anaemia among women engaged in biomass-based fish smoking as their primary livelihood in the central region of Ghana: a comparative cross-sectional study.

BMC Nutr 2021 Sep 6;7(1):50. Epub 2021 Sep 6.

School of Public Health, University of Michigan, Ann Arbor, MI, 48109-2029, USA.

Background: Fish smoking using biomass fuel is an important livelihood for women living in the coastal regions of Ghana and may contribute to anaemia risk. We assessed whether women who smoke fish as their primary livelihood are at increased risk of anaemia compared to women in other livelihoods in the Central Region of Ghana.

Methods: We conducted a comparative cross-sectional study of 330 randomly selected adult women (18-49 years) whose primary livelihood was either fish smoking (FSL) involving the burning of biomass fuel (n = 175) or other livelihoods (OL) not involving burning of firewood (n = 155). Data on participants' recent diet were collected from a single, quantitative 24-h dietary recall and qualitative 7-day food frequency questionnaire of animal-source food (ASF) consumption. We further assessed participants' haemoglobin concentration using the Urit 12 Hemocue system. We compared total iron intakes, the proportion of dietary iron from animal and plant sources, mean haemoglobin concentrations, and anaemia prevalence between FSL and OL women.

Results: Fish was the most frequently consumed ASF by both groups of women. Although OL women consumed more diverse ASFs in the past week compared with the FSL women (3.4 ± 1.2 vs. 2.7 ± 1.3; p < 0.001), the contribution of ASFs to total iron intake in the past day was greater for the FSL women (49.5% vs. 44.0%; p = 0.030). Estimated total dietary iron intake in the past day was generally low (5.2 ± 4.7 mg) and did not differ by group. The unadjusted prevalence of anaemia was 32 and 27.1% among the FSL and OL women, respectively (p = 0.33). After covariates adjustment, the FSL women had statistically higher anaemia prevalence (36.4% vs. 20.5%; p = 0.032) and 80% greater risk of being anemic (RR: 1.8; 95% CI: 1.1, 3.0) than the OL women.

Conclusion: Women who use biomass fuel to smoke fish as their primary livelihood had an increased risk of anaemia. Furthermore, the average 24-h dietary iron intake among both the FSL and OL women was below their daily iron requirement. Interventions to enhance women's dietary iron intake and reduce their livelihood related biomass smoke exposure may be warranted in this population.
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http://dx.doi.org/10.1186/s40795-021-00456-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420040PMC
September 2021

Interoception and obesity: a systematic review and meta-analysis of the relationship between interoception and BMI.

Int J Obes (Lond) 2021 Sep 3. Epub 2021 Sep 3.

Institute of Population Health Sciences, University of Liverpool, Liverpool, UK.

Background: Interoception refers to the processes by which we sense, interpret and integrate signals originating from within the body. Deficits in interoception have been linked to higher BMI and may contribute to weight gain. However, there have been conflicting findings and it is not clear how higher BMI is associated with different facets of interoception, such as interoceptive accuracy (the ability to detect internal signals) and sensibility (the tendency to attend to internal signals).

Methods: We conducted a systematic review and meta-analysis of studies that measured interoception and BMI. We examined relationships between interoception and BMI in children and adults separately and as a function of interoceptive facet and measure. In sensitivity analyses, we tested for evidence of publication bias and whether the results were consistent when studies with a high risk of bias were excluded.

Results: A total of 87 articles were eligible for inclusion. In adults (121 effects, 10,425 participants), there was cross-sectional evidence of higher BMI being associated with overall deficits in interoception (r = -0.054, 95% CI: -0.084 to -0.025) and this was consistent across sensitivity analyses. There was no statistically significant evidence of moderation by interoceptive facet or measure, although there was some variability in effect size estimates based on interoceptive facet and measures. A smaller meta-analysis limited to studies that compared participants with normal weight vs. overweight/obesity indicated poorer interoception in participants with overweight/obesity (SMD = -0.39, 95% CI -0.60 to -0.18).

Conclusions: In cross-sectional studies, deficits in interoception are associated with higher BMI. However, it remains unclear whether deficits in interoception contribute to or are a consequence of weight gain and obesity.
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http://dx.doi.org/10.1038/s41366-021-00950-yDOI Listing
September 2021

Feral equids' varied effects on ecosystems.

Science 2021 08;373(6558):973

Arizona Game and Fish Department, Phoenix, AZ 85086, USA.

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http://dx.doi.org/10.1126/science.abl5863DOI Listing
August 2021

Neither Beetroot Juice Supplementation nor Increased Carbohydrate Oxidation Enhance Economy of Prolonged Exercise in Elite Race Walkers.

Nutrients 2021 Aug 12;13(8). Epub 2021 Aug 12.

Australian Institute of Sport, Bruce, Canberra, ACT 2616, Australia.

Given the importance of exercise economy to endurance performance, we implemented two strategies purported to reduce the oxygen cost of exercise within a 4 week training camp in 21 elite male race walkers. Fourteen athletes undertook a crossover investigation with beetroot juice (BRJ) or placebo (PLA) [2 d preload, 2 h pre-exercise + 35 min during exercise] during a 26 km race walking at speeds simulating competitive events. Separately, 19 athletes undertook a parallel group investigation of a multi-pronged strategy (MAX; = 9) involving chronic (2 w high carbohydrate [CHO] diet + gut training) and acute (CHO loading + 90 g/h CHO during exercise) strategies to promote endogenous and exogenous CHO availability, compared with strategies reflecting lower ranges of current guidelines (CON; = 10). There were no differences between BRJ and PLA trials for rates of CHO ( = 0.203) or fat ( = 0.818) oxidation or oxygen consumption ( = 0.090). Compared with CON, MAX was associated with higher rates of CHO oxidation during exercise, with increased exogenous CHO use (CON; peak = ~0.45 g/min; MAX: peak = ~1.45 g/min, < 0.001). High rates of exogenous CHO use were achieved prior to gut training, without further improvement, suggesting that elite athletes already optimise intestinal CHO absorption via habitual practices. No differences in exercise economy were detected despite small differences in substrate use. Future studies should investigate the impact of these strategies on sub-elite athletes' economy as well as the performance effects in elite groups.
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http://dx.doi.org/10.3390/nu13082767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398364PMC
August 2021

Preparation of Rat Skeletal Muscle Homogenates for Nitrate and Nitrite Measurements.

J Vis Exp 2021 07 29(173). Epub 2021 Jul 29.

Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health;

Nitrate ions (NO3) were once thought to be inert end products of nitric oxide (NO) metabolism. However, previous studies demonstrated that nitrate ions can be converted back to NO in mammals through a two-step reduction mechanism: nitrate being reduced to nitrite (NO2) mostly by oral commensal bacteria, then nitrite being reduced to NO by several mechanisms including via heme- or molybdenum-containing proteins. This reductive nitrate pathway contributes to enhancing NO-mediated signaling pathways, particularly in the cardiovascular system and during muscular exercise. The levels of nitrate in the body before such utilization are determined by two different sources: endogenous NO oxidation and dietary nitrate intake, principally from plants. To elucidate the complex NO cycle in physiological circumstances, we have examined further the dynamics of its metabolites, nitrate and nitrite ions, which are relatively stable compared to NO. In previous studies skeletal muscle was identified as a major storage organ for nitrate ions in mammals, as well as a direct source of NO during exercise. Therefore, establishing a reliable methodology to measure nitrate and nitrite levels in skeletal muscle is important and should be helpful in extending its application to other tissue samples. This paper explains in detail the preparation of skeletal muscle samples, using three different homogenization methods, for nitrate and nitrite measurements and discusses important issues related to homogenization processes, including the size of the samples. Nitrate and nitrite concentrations have also been compared across four different muscle groups.
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http://dx.doi.org/10.3791/62427DOI Listing
July 2021

Recalcitrance of Cannabis sativa to de novo regeneration; a multi-genotype replication study.

PLoS One 2021 13;16(8):e0235525. Epub 2021 Aug 13.

Department of Plant Agriculture, University of Guelph, Guelph, ON, Canada.

Cannabis sativa is relatively recalcitrant to de novo regeneration, but several studies have reported shoot organogenesis or somatic embryogenesis from non-meristematic tissues. Most report infrequent regeneration rates from these tissues, but a landmark publication from 2010 achieved regeneration from leaf explants with a 96% response rate, producing an average of 12.3 shoots per explant in a single drug-type accession. Despite the importance regeneration plays in plant biotechnology and the renewed interest in this crop the aforementioned protocol has not been used in subsequent papers in the decade since it was published, raising concerns over its reproducibility. Here we attempted to replicate this important Cannabis regeneration study and expand the original scope of the study by testing it across 10 drug-type C. sativa genotypes to assess genotypic variation. In our study, callus was induced in all 10 genotypes but callus growth and appearance substantially differed among cultivars, with the most responsive genotype producing 6-fold more callus than the least responsive. The shoot induction medium failed to induce shoot organogenesis in any of the 10 cultivars tested, instead resulting in necrosis of the calli. The findings of this replication study raise concerns about the replicability of existing methods. However, some details of the protocol could not be replicated due to missing details in the original paper and regulatory issues, which could have impacted the outcome. These results highlight the importance of using multiple genotypes in such studies and providing detailed methods to facilitate replication.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235525PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363012PMC
August 2021

Steady-state [Formula: see text] above MLSS: evidence that critical speed better represents maximal metabolic steady state in well-trained runners.

Eur J Appl Physiol 2021 Nov 5;121(11):3133-3144. Epub 2021 Aug 5.

Sport and Health Sciences, University of Exeter, St. Luke's Campus, Heavitree Road, Exeter, EX12LU, UK.

The metabolic boundary separating the heavy-intensity and severe-intensity exercise domains is of scientific and practical interest but there is controversy concerning whether the maximal lactate steady state (MLSS) or critical power (synonymous with critical speed, CS) better represents this boundary. We measured the running speeds at MLSS and CS and investigated their ability to discriminate speeds at which [Formula: see text] was stable over time from speeds at which a steady-state [Formula: see text] could not be established. Ten well-trained male distance runners completed 9-12 constant-speed treadmill tests, including 3-5 runs of up to 30-min duration for the assessment of MLSS and at least 4 runs performed to the limit of tolerance for assessment of CS. The running speeds at CS and MLSS were significantly different (16.4 ± 1.3 vs. 15.2 ± 0.9 km/h, respectively; P < 0.001). Blood lactate concentration was higher and increased with time at a speed 0.5 km/h higher than MLSS compared to MLSS (P < 0.01); however, pulmonary [Formula: see text] did not change significantly between 10 and 30 min at either MLSS or MLSS + 0.5 km/h. In contrast, [Formula: see text] increased significantly over time and reached [Formula: see text] at end-exercise at a speed ~ 0.4 km/h above CS (P < 0.05) but remained stable at a speed ~ 0.5 km/h below CS. The stability of [Formula: see text] at a speed exceeding MLSS suggests that MLSS underestimates the maximal metabolic steady state. These results indicate that CS more closely represents the maximal metabolic steady state when the latter is appropriately defined according to the ability to stabilise pulmonary [Formula: see text].
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http://dx.doi.org/10.1007/s00421-021-04780-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505327PMC
November 2021

A Ball-Milling-Enabled Cross-Electrophile Coupling.

Org Lett 2021 08 3;23(16):6337-6341. Epub 2021 Aug 3.

Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, 29-39 Brunswick Square, Bloomsbury, London, WC1N 1AX, United Kingdom.

The nickel-catalyzed cross-electrophile coupling of aryl halides and alkyl halides enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive C-C bond formation was achieved in the absence of bulk solvent and air/moisture sensitive setups, in reaction times of 2 h. The mechanical action provided by ball milling permits the use of a range of zinc sources to turnover the nickel catalytic cycle, enabling the synthesis of 28 cross-electrophile coupled products.
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http://dx.doi.org/10.1021/acs.orglett.1c02096DOI Listing
August 2021

Longitudinal associations with alcohol consumption during the first COVID-19 lockdown: Associations with mood, drinking motives, context of drinking, and mental health.

Drug Alcohol Depend 2021 09 21;226:108913. Epub 2021 Jul 21.

Department of Psychology, Institute of Population Health, University of Liverpool, United Kingdom; Liverpool Centre for Alcohol Research, United Kingdom.

Background: Coronavirus (COVID-19) resulted in lockdown measures in the UK, which has impacted alcohol use. Alcohol is often used as a coping mechanism and there are public health concerns regarding excessive consumption due to the pandemic. We aimed to longitudinally assess drinking behaviors, and associated factors, during the first UK government-mandated lockdown.

Methods: An online survey was distributed through social media (8 April 2020, onwards). Fortnightly follow up surveys were emailed to participants. The primary outcome measure was 'weekly unit consumption' and data was collected on a range of potentially related factors: demographics, factors relating to COVID-19 (e.g., health, work status), drinking motives, context of drinking, drinking intentions, mood, depression and anxiety.

Findings: A total of 539 self-selected participants completed the baseline survey, with 186 completing at least 3 follow up surveys for multilevel modelling analysis. Personal coping motives, anxiety, drinking at home alone, and drinking at home with others were positively associated with alcohol consumption during lockdown. The following baseline measures also predicted increased consumption: male gender, lower education, and higher AUDIT scores (based on behavior prior to lockdown). Findings were consistent when utilizing an inverse probability weight to account for predictors of attrition (female, younger age, higher baseline AUDIT scores).

Conclusions: Those already drinking at hazardous levels were more likely to increase their consumption, as were those who were drinking to cope. As we recover from the pandemic, there is a need for widespread alcohol support, and certain groups may need targeted support.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108913DOI Listing
September 2021

Longitudinal assessment of lung clearance index to monitor disease progression in children and adults with cystic fibrosis.

Thorax 2021 Jul 22. Epub 2021 Jul 22.

Academic Department of Child Health, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK.

Background: Lung clearance index (LCI) is a valuable research tool in cystic fibrosis (CF) but clinical application has been limited by technical challenges and uncertainty about how to interpret longitudinal change. In order to help inform clinical practice, this study aimed to assess feasibility, repeatability and longitudinal LCI change in children and adults with CF with predominantly mild baseline disease.

Methods: Prospective, 3-year, multicentre, observational study of repeated LCI measurement at time of clinical review in patients with CF >5 years, delivered using a rapid wash-in system.

Results: 112 patients completed at least one LCI assessment and 98 (90%) were still under follow-up at study end. The median (IQR) age was 14.7 (8.6-22.2) years and the mean (SD) FEV z-score was -1.2 (1.3). Of 81 subjects with normal FEV (>-2 z-scores), 63% had raised LCI (indicating worse lung function). For repeat stable measurements within 6 months, the mean (limits of agreement) change in LCI was 0.9% (-18.8% to 20.7%). A latent class growth model analysis identified four discrete clusters with high accuracy, differentiated by baseline LCI and FEV. Baseline LCI was the strongest factor associated with longitudinal change. The median total test time was under 19 min.

Conclusions: Most patients with CF with well-preserved lung function show stable LCI over time. Cluster behaviours can be identified and baseline LCI is a risk factor for future progression. These results support the use of LCI in clinical practice in identifying patients at risk of lung function decline.
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http://dx.doi.org/10.1136/thoraxjnl-2021-216928DOI Listing
July 2021

Do socioeconomic health gradients persist over time and beyond income? A distributional analysis using UK biomarker data.

Econ Hum Biol 2021 Jul 10;43:101036. Epub 2021 Jul 10.

School of Population Health, University of New South Wales, Sydney, Australia. Electronic address:

This paper analyses the relationship between health and socioeconomic disadvantage by adopting a dynamic approach accounting for spatial and temporal changes across ten domains including social isolation, environment, financial hardship and security. As a first step we develop a measure of overall multidimensional deprivation and undertake a decomposition analysis to explore the role of breadth and duration of deprivation on shaping the deprivation gradient in health. Subsequently, we employ unconditional quantile regression to conduct a distributional analysis of the gradient to understand how the gradient evolves for people with vulnerability in health. In contrast to the majority of existing studies, we capture health status using a range of nurse measured biomarkers, rather than self reported health measures, taken from the UKHLS and BHPS databases. The first main finding is that the socioeconomic gradient in most of our health measures is not solely attributed to income as it accounts for only 3.8% of total deprivation and thus it is important to account for other domains through a multidimensional deprivation measure in health gradient analysis. Our second finding is the existence of a systematic deprivation gradient for BMI, waist circumference, heart rate, C-reactive protein and HbA1c where evolution over time is an important factor particularly for individuals with greater burden of illness lying at the right tail of the biomarker distribution. Thus cost effective health policy would need to adopt targeted interventions prioritising people experiencing persistent deprivation in dimensions such as housing conditions and social isolation.
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http://dx.doi.org/10.1016/j.ehb.2021.101036DOI Listing
July 2021

The TOR-dependent phosphoproteome and regulation of cellular protein synthesis.

EMBO J 2021 Aug 23;40(16):e107911. Epub 2021 Jul 23.

Cell Cycle Laboratory, The Francis Crick Institute, London, UK.

Cell growth is orchestrated by a number of interlinking cellular processes. Components of the TOR pathway have been proposed as potential regulators of cell growth, but little is known about their immediate effects on protein synthesis in response to TOR-dependent growth inhibition. Here, we present a resource providing an in-depth characterisation of Schizosaccharomyces pombe phosphoproteome in relation to changes observed in global cellular protein synthesis upon TOR inhibition. We find that after TOR inhibition, the rate of protein synthesis is rapidly reduced and that notable phosphorylation changes are observed in proteins involved in a range of cellular processes. We show that this reduction in protein synthesis rates upon TOR inhibition is not dependent on S6K activity, but is partially dependent on the S. pombe homologue of eIF4G, Tif471. Our study demonstrates the impact of TOR-dependent phospho-regulation on the rate of protein synthesis and establishes a foundational resource for further investigation of additional TOR-regulated targets both in fission yeast and other eukaryotes.
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http://dx.doi.org/10.15252/embj.2021107911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365262PMC
August 2021

Incidence, associated risk factors, and the ideal mode of delivery following preterm labour between 24 to 28 weeks of gestation in a low resource setting.

PLoS One 2021 22;16(7):e0254801. Epub 2021 Jul 22.

University of Manchester, Manchester, United Kingdom.

Background: Preterm labour, between 24 to 28 weeks of gestation, remains prevalent in low resource settings. There is evidence of improved survival after 24 weeks though the ideal mode of delivery remains unclear. There are no clear management protocols to guide patient management. We sought to determine the incidence of preterm labour occurring between 24 to 28 weeks, its associated risk factors and the preferred mode of delivery in a low resource setting with the aim of streamlining patient care.

Methods: Between February 2020 and September 2020, we prospectively followed 392 women with preterm labour between 24 to 28 weeks of gestation and their newborns from admission to discharge at Kawempe National Referral hospital in Kampala, Uganda. The primary outcome was perinatal mortality associated with the different modes of delivery. Secondary outcomes included neonatal and maternal infections, admission to the Neonatal Special Care Unit (SCU), need for neonatal resuscitation, preterm birth and maternal death. Chi-square test was used to assess the association between perinatal mortality and categorical variables such as parity, mode of delivery, employment status, age, antepartum hemorrhage, digital vaginal examination, and admission to Special Care unit. Multivariate logistic regression was used to assess the association between comparative outcomes of the different modes of delivery and maternal and neonatal risk factors.

Results: The incidence of preterm labour among women who delivered preterm babies between 24 to 28 weeks was 68.9% 95% CI 64.2-73.4). Preterm deliveries between 24 to 28 weeks contributed 20% of the all preterm deliveries and 2.5% of the total hospital deliveries. Preterm labour was independently associated with gravidity (p-value = 0.038), whether labour was medically induced (p-value <0.001), number of digital examinations (p-value <0.001), history of vaginal bleeding prior to onset of labour (p-value < 0.001), whether tocolytics were given (p-value < 0.001), whether an obstetric ultrasound scan was done (p-value <0.001 and number of babies carried (p-value < 0.001). At multivariate analysis; multiple pregnancy OR 15.45 (2.00-119.53), p-value < 0.001, presence of fever prior to admission OR 4.03 (95% CI .23-13.23), p-value = 0.002 and duration of drainage of liquor OR 0.16 (0.03-0.87), p-value = 0.034 were independently associated with preterm labour. The perinatal mortality rate in our study was 778 per 1000 live births. Of the 392 participants, 359 (91.5%), had vaginal delivery, 29 (7.3%) underwent Caesarean delivery and 4 (1%) had assisted vaginal delivery. Caesarean delivery was protective against perinatal mortality compared to vaginal delivery OR = 0.36, 95% CI 0.14-0.82, p-value = 0.017). The other protective factors included receiving antenatal corticosteroids OR = 0.57, 95% CI 0.33-0.98, p-value = 0.040, Doing 3-4 digital exams per day, OR = 0.41, 95% 0.18-0.91, p-value = 0.028) and hospital stay of > 7 days, p value = 0.001. Vaginal delivery was associated with maternal infections, postpartum hemorrhage, and admission to the Special Care Unit.

Conclusion: Caesarean delivery is the preferred mode of delivery for preterm deliveries between 24 to 28 weeks of gestation especially when labour is not established in low resource settings. It is associated with lesser adverse pregnancy outcomes when compared to vaginal delivery for remote gestation ages.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254801PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297859PMC
July 2021

Assessing the Effects of Healthy and Neuropathological Aging on Personality with the Iowa Scales of Personality Change.

Dev Neuropsychol 2021 Aug 20;46(5):393-408. Epub 2021 Jul 20.

Departments of Neurology and Psychological and Brain Sciences, University of Iowa, Iowa City, United States.

Personality changes in older adults with brain disease may be confounded by effects of normal aging. In this cross-sectional study, ratings with the Iowa Scales of Personality Change for 62 healthy older adults (OA-H, aged 60+) were compared to matched older adults with brain diseases (OA-BD). OA-H did not show any significant personality changes from middle age to older adulthood. However, between 10% and 20% of OA-H developed a disturbance in , and . Otherwise, the pattern of findings suggesting normal aging effects on personality disturbances in clinical groups are generally minimal.
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http://dx.doi.org/10.1080/87565641.2021.1956500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463441PMC
August 2021
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