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Article ; Online: Epistasis Between HLA-DRB1*16:02:01 and SLC16A11 T-C-G-T-T Reduces Odds for Type 2 Diabetes in Southwest American Indians.

Williams, Robert C / Hanson, Robert L / Peters, Bjoern / Kearns, Kendall / Knowler, William C / Bogardus, Clifton / Baier, Leslie J

Diabetes

2024

Abstract: ... test. We define the risk-protection haplotype of SLC16A11, T-C-G-T-T, as allele "2" of a di-allelic ...

Abstract	We sought to identify genetic/immunologic contributors of type 2 diabetes in an indigenous American community by genotyping all study participants for both high resolution HLA-DRB1 alleles and SLC16A11 to test their risk and/or protection for T2D. These genes were selected based on independent reports that HLA-DRB116:02:01 is protective for T2D and that SLC16A11 associates with T2D in individuals with BMI<35kg/m2, and here test the interaction of the two loci with a more complete dataset and perform a BMI sensitivity test. We define the risk-protection haplotype of SLC16A11, T-C-G-T-T, as allele "2" of a di-allelic genetic model with three genotypes, SLC16A1111, 12, and 22, where allele "1" is the wildtype. Both earlier findings were confirmed. Together in the same logistic model with BMI≥35, DRB116:02:01 remains protective, 0.73, while SLC16A11 switches from risk to protection OR = 0.57 (22) and 0.78 (12), respectively; an added interaction term was statistically significant (OR = 0.49 with 12). Bootstrapped (b=10,000) statistical power of interaction, 0.4801, yielded mean OR = 0.43. Sensitivity analysis demonstrated the interaction significant in BMI range 30-41. To investigate the epistasis we used the primary function of the HLA-DRB1 molecule, peptide binding and presentation, to search the entire array of 15mer peptides for both the wildtype and ancient human SLC16A11 molecules for a pattern of strong binding that was associated with risk and protection for T2D. Applying computer binding algorithms suggests the core peptide at SLC16A11 D127G, FSAFASGLL, might be key for moderating risk for T2D with potential implications for T1D.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db23-0925
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Article ; Online: G protein-coupled estrogen receptor-1 enhances excitatory synaptic responses in the entorhinal cortex.

Batallán Burrowes, Ariel A / Sundarakrishnan, Adithi / Bouhour, Camille / Chapman, Clifton Andrew

Hippocampus

2021 Volume 31, Issue 11, Page(s) 1191–1201

Abstract: ... However, the application of the G protein-coupled estrogen receptor-1 (GPER1) agonist G1 (100 nM) induced a reversible ...

Abstract	Activation of estrogen receptors is thought to modulate cognitive function in the hippocampus, prefrontal cortex, and striatum by affecting both excitatory and inhibitory synaptic transmission. The entorhinal cortex is a major source of cortical sensory and associational input to the hippocampus, but it is unclear whether either estrogens or progestogens may modulate cognitive function through effects on synaptic transmission in the entorhinal cortex. This study assessed the effects of the brief application of either 17-β estradiol (E2) or progesterone on excitatory glutamatergic synaptic transmission in the female rat entorhinal cortex in vitro. Rats were ovariectomized on postnatal day (PD) 63 and also received subdermal E2 implants to maintain constant low levels of circulating E2 on par with estrus. Electrophysiological recordings from brain slices were obtained between PD70 and PD86, and field excitatory postsynaptic potentials (fEPSPs) reflecting the activation of the superficial layers of the entorhinal cortex were evoked by the stimulation of layer I afferents. The application of E2 (10 nM) for 20 min resulted in a small increase in the amplitude of fEPSPs that reversed during the 30-min washout period. The application of the ERα agonist propylpyrazoletriol (PPT) (100 nM) or the β agonist DPN (1 μM) did not significantly affect synaptic responses. However, the application of the G protein-coupled estrogen receptor-1 (GPER1) agonist G1 (100 nM) induced a reversible increase in fEPSP amplitude similar to that induced by E2. Furthermore, the potentiation of responses induced by G1 was blocked by the GPER1 antagonist G15 (1 μM). Application of progesterone (100 nM) or its metabolite allopregnanolone (1 μM) did not significantly affect synaptic responses. The potentiation of synaptic transmission in the entorhinal cortex induced by the activation of GPER1 receptors may contribute to the modulation of cognitive function in female rats.
MeSH term(s)	Animals ; Electric Stimulation ; Entorhinal Cortex/physiology ; Excitatory Postsynaptic Potentials/physiology ; Female ; GTP-Binding Proteins/pharmacology ; Rats ; Receptors, Estrogen ; Receptors, G-Protein-Coupled ; Synaptic Transmission/physiology
Chemical Substances	Gper1 protein, rat ; Receptors, Estrogen ; Receptors, G-Protein-Coupled ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1074352-2
ISSN	1098-1063 ; 1050-9631
ISSN (online)	1098-1063
ISSN	1050-9631
DOI	10.1002/hipo.23383
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Article: Use of the g-index for assessment of citation-based scholarly activity of United States radiation oncology residents and subsequent choice of academic versus private practice career.

McClelland Iii, Shearwood / Mitin, Timur / Nabavizadeh, Nima / Fuller, Clifton David / Thomas, Charles R / Jaboin, Jerry J

Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology

2019 Volume 24, Issue 3, Page(s) 294–297

Abstract: ... citations. The g-index addresses this limitation by assessing the largest number of manuscripts (g ... by an author cited at least (g × g) times, but has yet to be applied to radiation oncology resident ... database was searched to collect and calculate g-index data for each resident.: Results: The mean g ...

Abstract	Introduction: The Hirsch index (h-index) evaluates citation-based scholarly activity, but has limited ability to acknowledge those publishing a smaller number of manuscripts with exceedingly high citations. The g-index addresses this limitation by assessing the largest number of manuscripts (g) by an author cited at least (g × g) times, but has yet to be applied to radiation oncology resident productivity. Methods: A list of recent radiation oncology resident graduates (comprising 86% of the 2016 graduating class) and their post-residency career choice was compiled. The Scopus bibliometric citation database was searched to collect and calculate g-index data for each resident. Results: The mean g-index score for all resident graduates was 7.16. Residents with a PhD had significantly higher g-index scores (11.97 versus 5.80; Conclusion: Radiation oncology resident graduates published on average a minimum of seven manuscripts cited at least 49 times. PhD-degree graduates had significantly higher g-index scores, as did residents choosing academic over private practice careers. There was no significant gender-related difference in g-index score regardless of career choice. The majority of academic careers are produced from programs graduating at least three residents.
Language	English
Publishing date	2019-04-30
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2188087-6
ISSN	1507-1367
ISSN	1507-1367
DOI	10.1016/j.rpor.2019.03.005
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Zs.A 6108: Show issues

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Article ; Online: A reduction of 3 g/day from a usual 9 g/day salt diet improves endothelial function and decreases endothelin-1 in a randomised cross_over study in normotensive overweight and obese subjects.

Dickinson, Kacie M / Clifton, Peter M / Keogh, Jennifer B

Atherosclerosis

2014 Volume 233, Issue 1, Page(s) 32–38

Abstract: ... effects on vascular function. The aim was to compare the effects of 9 g salt/day with 6 g salt/day intake ... weeks each on a reduced salt (RS) (6 g/day) and usual salt diet (US) (9 g/day). Flow-mediated-dilatation ... Conclusions: A small reduction in dietary salt intake of 3 g/day improves endothelial function ...

Abstract	Background and aim: It is unclear if a modest reduction in dietary salt intake has beneficial effects on vascular function. The aim was to compare the effects of 9 g salt/day with 6 g salt/day intake on measures of vascular function and explore mechanisms of effect in overweight and obese adults. Methods: Twenty-five overweight/obese subjects (BMI 27-40 kg/m(2)) completed a randomised cross-over study of 6 weeks each on a reduced salt (RS) (6 g/day) and usual salt diet (US) (9 g/day). Flow-mediated-dilatation (FMD), 24 h blood pressure (BP), augmentation index (AIx), pulse wave velocity (PWV), plasma and urinary nitrate/nitrite, asymmetric dimethylarginine (ADMA), renin, aldosterone and endothelin-1 and vascular adhesion molecules were measured after 2 days and 6 weeks. Adherence to the diets was determined from two 24 h urine collections. Results: Urinary sodium excretion was 155 ± 58 mmol/24 h US vs 113 ± 45 mmol/24 h RS (p = 0.002). Following the RS diet there was a significant improvement in FMD from 3.5 ± 2.8% to 5.6 ± 2.8% (P < 0.001) and decrease in serum endothelin-1 from 1.45 ± 0.38 pg/ml to 1.25 ± 0.39 pg/ml (P < 0.05). Endothelium-independent vasodilatation was also significantly different between treatments (P < 0.05). AIx, PWV, serum ADMA and plasma and urinary nitrate/nitrite concentrations were not different between treatments. Change in FMD was related to the urinary sodium: creatinine ratio (r = -0.47, P < 0.05) and was independent of blood pressure. Aldosterone and renin were unchanged. Conclusions: A small reduction in dietary salt intake of 3 g/day improves endothelial function in normotensive overweight and obese subjects. This response may be mediated by serum endothelin-1. This small reduction in salt had no effect on aldosterone and renin concentrations. This trial was registered with the Australian and New Zealand Clinical Trials Registry Unique Identifier: ACTRN12609000321246 http://www.anzctr.org.au/ACTRN12609000321246.aspx.
MeSH term(s)	Adult ; Cross-Over Studies ; Diet, Sodium-Restricted ; Endothelin-1/blood ; Endothelium, Vascular/physiology ; Female ; Humans ; Male ; Sulfonamides/pharmacology ; Vasodilation
Chemical Substances	Endothelin-1 ; Sulfonamides ; bosentan (Q326023R30)
Language	English
Publishing date	2014-03
Publishing country	Ireland
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2013.11.078
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Zs.A 226: Show issues

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Article ; Online: Achieving the salt intake target of 6 g/day in the current food supply in free-living adults using two dietary education strategies.

Ireland, Dani-Maree / Clifton, Peter M / Keogh, Jennifer B

Journal of the American Dietetic Association

2010 Volume 110, Issue 5, Page(s) 763–767

Abstract: There are national targets for salt intake of 6 g salt/day in Australia and the United States ... or by the Food Standards Australia and New Zealand's low-salt guideline of 120 mg sodium/100 g food ... to 6.4+/-2.8 g salt/24 hours) in the Tick group and from 132+/-44 to 98+/-50 mmol/24 hours (7.9+/-2.6 ...

Abstract	There are national targets for salt intake of 6 g salt/day in Australia and the United States. Despite this, there is limited knowledge about the effectiveness of dietary education in reducing salt intake to this level. The objective of this study was to investigate whether dietary education enabled a reduction in salt consumption. In an 8-week parallel study, 49 healthy free-living adults were recruited from the Adelaide community by newspaper advertisement. In a randomized parallel design, participants received dietary education to choose foods identified by either Australia's National Heart Foundation Tick symbol or by the Food Standards Australia and New Zealand's low-salt guideline of 120 mg sodium/100 g food. Sodium excretion was assessed by 24-hour urinary sodium collections at baseline and weeks 4 and 8. Participants' experiences of following the education strategies were recorded by self-administered questionnaire. These data were collected between August and October 2008. Forty-three participants completed the study. After 8 weeks, urinary sodium excretion decreased from 121+/-50 to 106+/-47 mmol/24 hours (7.3+/-3.0 to 6.4+/-2.8 g salt/24 hours) in the Tick group and from 132+/-44 to 98+/-50 mmol/24 hours (7.9+/-2.6 to 6.0+/-3.0 g salt/24 hours) in the Food Standards Australia New Zealand group (P<0.05, with no between-group difference). Barriers to salt reduction were limited variety and food choice, difficulty when eating out, and increased time associated with identifying foods. In conclusion, dietary sodium reduction is possible among free-living individuals who received dietary advice.
MeSH term(s)	Diet, Sodium-Restricted ; Female ; Food Analysis ; Food Supply ; Health Behavior ; Health Education/methods ; Humans ; Hypertension/prevention & control ; Male ; Mental Recall ; Middle Aged ; Nutrition Policy ; Nutritional Sciences/education ; Sodium/urine ; Sodium Chloride, Dietary/administration & dosage ; Sodium Chloride, Dietary/adverse effects ; Sodium Chloride, Dietary/urine ; Sodium, Dietary/administration & dosage ; Sodium, Dietary/adverse effects ; Surveys and Questionnaires
Chemical Substances	Sodium Chloride, Dietary ; Sodium, Dietary ; Sodium (9NEZ333N27)
Language	English
Publishing date	2010-05
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	390806-9
ISSN	1878-3570 ; 0002-8223
ISSN (online)	1878-3570
ISSN	0002-8223
DOI	10.1016/j.jada.2010.02.006
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Zs.A 21: Show issues

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Article: Alcohol use disorder treatment delivered outside hepatology clinic.

Winder, Gerald Scott / Clifton, Erin G

Clinical liver disease

2023 Volume 21, Issue 5, Page(s) 134–137

Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2657644-2
ISSN	2046-2484
ISSN	2046-2484
DOI	10.1097/CLD.0000000000000018
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Article ; Online: International symposium on pheochromocytoma: an event of dedicated healthcare professionals and researchers striving for better patient outcomes.

Pacak, Karel / Clifton-Bligh, Roderick

Endocrine-related cancer

2023 Volume 30, Issue 5

Abstract: ... reference limits to assess the likelihood of having a PPGL (e.g. patients at high and low risk) including ...

Abstract	Pheochromocytomas and paragangliomas (PPGLs) are defined as neuroendocrine tumors that produce catecholamines. Many recent advances in their management, localization, treatment, as well as surveillance have significantly improved outcomes for patients with PPGLs or carriers of pathogenic genetic variants linked to the development of these tumors. At present, those advances mainly include the molecular stratification of PPGLs into seven clusters, the 2017 WHO revised definition of these tumors, the presence of specific clinical features pointing toward PPGL, the use of plasma metanephrines and 3-methoxytyramine with specific reference limits to assess the likelihood of having a PPGL (e.g. patients at high and low risk) including age-specific reference limits, nuclear medicine guidelines outlining cluster- and metastatic disease-specific functional (here mainly positron emission tomography and metaiodobenzylguanidine scintigraphy) imaging in the precise diagnostic localization of PPGLs, the guidelines for using radio- vs chemotherapy for patients with metastatic disease, and the international consensus on initial screening and follow-up of asymptomatic germline SDHx pathogenic variant carriers. Furthermore, new collaborative efforts particularly based on multi-institutional and worldwide initiatives are now considered key forces in improving our understanding and knowledge about these tumors and future successful treatments or even preventative interventions.
MeSH term(s)	Humans ; Pheochromocytoma/diagnosis ; Pheochromocytoma/genetics ; Pheochromocytoma/therapy ; Paraganglioma/genetics ; Adrenal Gland Neoplasms/diagnosis ; Adrenal Gland Neoplasms/genetics ; Adrenal Gland Neoplasms/therapy ; Positron-Emission Tomography ; Metanephrine ; Delivery of Health Care
Chemical Substances	Metanephrine (5001-33-2)
Language	English
Publishing date	2023-04-13
Publishing country	England
Document type	Editorial ; Research Support, N.I.H., Intramural
ZDB-ID	1218450-0
ISSN	1479-6821 ; 1351-0088
ISSN (online)	1479-6821
ISSN	1351-0088
DOI	10.1530/ERC-23-0030
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Zs.A 4192: Show issues

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Article: Achieving the Salt Intake Target of 6 g/Day in the Current Food Supply in Free-Living Adults Using Two Dietary Education Strategies

Ireland, Dani-Maree / Clifton, Peter M / Keogh, Jennifer B

Journal of the American Dietetic Association. 2010 May, v. 110, no. 5

2010

Abstract: There are national targets for salt intake of 6 g salt/day in Australia and the United States ... or by the Food Standards Australia and New Zealand's low-salt guideline of 120 mg sodium/100 g food ... 8 g salt/24 hours) in the Tick group and from 132±44 to 98±50 mmol/24 hours (7.9±2.6 to 6.0±3.0 g ...

Abstract	There are national targets for salt intake of 6 g salt/day in Australia and the United States. Despite this, there is limited knowledge about the effectiveness of dietary education in reducing salt intake to this level. The objective of this study was to investigate whether dietary education enabled a reduction in salt consumption. In an 8-week parallel study, 49 healthy free-living adults were recruited from the Adelaide community by newspaper advertisement. In a randomized parallel design, participants received dietary education to choose foods identified by either Australia's National Heart Foundation Tick symbol or by the Food Standards Australia and New Zealand's low-salt guideline of 120 mg sodium/100 g food. Sodium excretion was assessed by 24-hour urinary sodium collections at baseline and weeks 4 and 8. Participants' experiences of following the education strategies were recorded by self-administered questionnaire. These data were collected between August and October 2008. Forty-three participants completed the study. After 8 weeks, urinary sodium excretion decreased from 121±50 to 106±47 mmol/24 hours (7.3±3.0 to 6.4±2.8 g salt/24 hours) in the Tick group and from 132±44 to 98±50 mmol/24 hours (7.9±2.6 to 6.0±3.0 g salt/24 hours) in the Food Standards Australia New Zealand group (P<0.05, with no between-group difference). Barriers to salt reduction were limited variety and food choice, difficulty when eating out, and increased time associated with identifying foods. In conclusion, dietary sodium reduction is possible among free-living individuals who received dietary advice.
Keywords	elderly nutrition ; elderly ; dietary minerals ; sodium ; salts ; low sodium diet ; nutrition education ; food supply ; food choices ; Reference Daily Intakes ; eating habits ; New Zealand ; Australia
Language	English
Dates of publication	2010-05
Size	p. 763-767.
Document type	Article
ZDB-ID	390806-9
ISSN	1878-3570 ; 0002-8223
ISSN (online)	1878-3570
ISSN	0002-8223
DOI	10.1016/j.jada.2010.02.006
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Metabolic Syndrome-Role of Dietary Fat Type and Quantity.

Clifton, Peter

Nutrients

2019 Volume 11, Issue 7

Abstract: ... to polyunsaturated fat (PUFA) for fasting insulin and glucose lowering. The addition of 3-4 g of N3 fats will lower TG ...

Abstract	Background: Metabolic syndrome increases the risk of cardiovascular disease (CVD) over and above that related to type 2 diabetes. The optimal diet for the treatment of metabolic syndrome is not clear. Materials and methods: A review of dietary interventions in volunteers with metabolic syndrome as well as studies examining the impact of dietary fat on the separate components of metabolic syndrome was undertaken using only recent meta-analyses, if available. Results: Most of the data suggest that replacing carbohydrates with any fat, but particularly polyunsaturated fat, will lower triglyceride(TG), increase high density lipoprotein (HDL) cholesterol, and lower blood pressure, but have no effects on fasting glucose in normal volunteers or insulin sensitivity, as assessed by euglycemic hyperinsulinemic clamps. Fasting insulin may be lowered by fat. Monounsaturated fat (MUFA) is preferable to polyunsaturated fat (PUFA) for fasting insulin and glucose lowering. The addition of 3-4 g of N3 fats will lower TG and blood pressure (BP) and reduce the proportion of subjects with metabolic syndrome. Dairy fat (50% saturated fat) is also related to a lower incidence of metabolic syndrome in cohort studies.
MeSH term(s)	Biomarkers/blood ; Blood Glucose/metabolism ; Blood Pressure ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/prevention & control ; Cholesterol, HDL/blood ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/diet therapy ; Diabetes Mellitus, Type 2/epidemiology ; Diet, Carbohydrate-Restricted/adverse effects ; Dietary Fats/administration & dosage ; Dietary Fats/adverse effects ; Humans ; Incidence ; Insulin/blood ; Insulin Resistance ; Meta-Analysis as Topic ; Metabolic Syndrome/blood ; Metabolic Syndrome/diet therapy ; Metabolic Syndrome/epidemiology ; Nutritive Value ; Treatment Outcome ; Triglycerides/blood
Chemical Substances	Biomarkers ; Blood Glucose ; Cholesterol, HDL ; Dietary Fats ; Insulin ; Triglycerides
Language	English
Publishing date	2019-06-26
Publishing country	Switzerland
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu11071438
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Article: Association of -3826 G variant in uncoupling protein-1 with increased BMI in overweight Australian women.

Heilbronn, L K / Kind, K L / Pancewicz, E / Morris, A M / Noakes, M / Clifton, P M

Diabetologia

2000 Volume 43, Issue 2, Page(s) 242–244

Abstract: ... overweight/obese women (mean body mass index 34.1 kg/m2, range 25.0 to 47.5 kg/m2) for the -3826 A-->G ... for glucose and lipid measurements.: Results: The -3826 G allele was found with a frequency of 0.23 and was ... this significance (p = 0.06). The -3826 G variant was associated with increased fasting glucose (p = 0.01). This was ...

Abstract	Aims/hypothesis: To determine whether genetic variation in uncoupling protein-1 (UCP-1) is associated with obesity or obesity-related risk factors in overweight women. Methods: We genotyped 526 overweight/obese women (mean body mass index 34.1 kg/m2, range 25.0 to 47.5 kg/m2) for the -3826 A-->G uncoupling protein-1 polymorphism. Of the 526 women genotyped 144 had fasting blood samples analysed for glucose and lipid measurements. Results: The -3826 G allele was found with a frequency of 0.23 and was associated with higher BMI (p = 0.02). A higher frequency of this polymorphism (0.33) was found in subjects with Type II (non-insulin-dependent) diabetes mellitus (p = 0.02), though adjustment for BMI weakened this significance (p = 0.06). The -3826 G variant was associated with increased fasting glucose (p = 0.01). This was, however, a result of a greater proportion of women with Type II diabetes also having the G variant (p = 0.10, adjusted for Type II diabetes). The -3826 G variant of uncoupling protein-1 did not have an effect on other metabolic variables associated with obesity. Conclusion/interpretation: In overweight Australian women the -3826 G variant of UCP-1 increased the susceptibility to obesity indicating that UCP-1 could be involved in weight regulation.
MeSH term(s)	Alleles ; Australia ; Body Mass Index ; Carrier Proteins/genetics ; Diabetes Mellitus/genetics ; Diabetes Mellitus/physiopathology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/physiopathology ; European Continental Ancestry Group/genetics ; Female ; Genetic Variation ; Humans ; Ion Channels ; Membrane Proteins/genetics ; Middle Aged ; Mitochondrial Proteins ; Obesity/genetics ; Obesity/physiopathology ; Polymorphism, Genetic ; Uncoupling Protein 1
Chemical Substances	Carrier Proteins ; Ion Channels ; Membrane Proteins ; Mitochondrial Proteins ; UCP1 protein, human ; Uncoupling Protein 1
Language	English
Publishing date	2000-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s001250050036
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