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Article ; Online: Intracellular detection of singlet oxygen using fluorescent nanosensors.

Nath, Peuli / Hamadna, Sameer Sayel / Karamchand, Leshern / Foster, John / Kopelman, Raoul / Amar, Jacques G / Ray, Aniruddha

The Analyst

2021 Volume 146, Issue 12, Page(s) 3933–3941

Abstract: Detection of singlet oxygen is of great importance for a range of therapeutic applications, particularly photodynamic therapy, plasma therapy and also during photo-endosomolytic activity. Here we present a novel method of intracellular detection of ... ...

Abstract	Detection of singlet oxygen is of great importance for a range of therapeutic applications, particularly photodynamic therapy, plasma therapy and also during photo-endosomolytic activity. Here we present a novel method of intracellular detection of singlet oxygen using biocompatible polymeric nanosensors, encapsulating the organic fluorescent dye, Singlet Oxygen Sensor Green (SOSG) within its hydrophobic core. The singlet oxygen detection efficiency of the nanosensors was quantified experimentally by treating them with a plasma source and these results were further validated by using Monte Carlo simulations. The change in fluorescence intensity of the nanosensors serves as a metric to detect singlet oxygen in the local micro-environment inside mammalian cancer cells. We used these nanosensors for monitoring singlet oxygen inside endosomes and lysosomes of cancer cells, during cold plasma therapy, using a room-temperature Helium plasma jet.
MeSH term(s)	Animals ; Fluorescent Dyes ; Oxygen ; Photochemotherapy ; Photosensitizing Agents ; Singlet Oxygen
Chemical Substances	Fluorescent Dyes ; Photosensitizing Agents ; Singlet Oxygen (17778-80-2) ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-05-11
Publishing country	England
Document type	Journal Article
ZDB-ID	210747-8
ISSN	1364-5528 ; 0003-2654
ISSN (online)	1364-5528
ISSN	0003-2654
DOI	10.1039/d1an00456e
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Article: The effects of weight loss treatments on upper and lower body fat.

Kopelman, P G

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity

2004 Volume 21, Issue 8, Page(s) 619–625

Abstract: The intra-abdominal visceral deposition of adipose tissue, which characterises upper body obesity, is a major contributor to the development of hypertension, glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body obesity may ... ...

Abstract	The intra-abdominal visceral deposition of adipose tissue, which characterises upper body obesity, is a major contributor to the development of hypertension, glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body obesity may have comparable amounts of adipose tissue but remain relatively free from the metabolic consequences of obesity. This raises an obvious question-are there particular weight reducing treatments which specifically target intra-abdominal fat? In theory, surgical removal of upper body fat should be effective. In reality, neither liposuction nor apronectomy ('tummy tuck') have any beneficial metabolic effects, they simply remove subcutaneous adipose tissue which is often rapidly replaced. Vertical banded gastroplasty and gastric bypass operations may be dramatically effective in improving blood pressure, insulin sensitivity and glucose tolerance. However, these benefits result from a parallel reduction in visceral and total body fat. Studies of body fat distribution in postmenopausal women confirm that the marked decrease in adiposity, following a programme of very low calorie diet and exercise, reflects a comparable reduction in visceral and thigh fat. The reduction in waist circumference after a low fat/exercise programme suggests a similar situation in men. Exercise has an important role in treatment but, once again, the fat loss is generalised. Nevertheless, the improved metabolic parameters seen in exercising obese subjects, independent of weight loss, suggest other beneficial actions. Growth hormone (GH) has a marked lipolytic action. GH replacement treatment for GH deficient adults with pronounced abdominal fat deposition, has been shown to reduce intra-abdominal fat by 47% compared to 27% decrease in abdominal subcutaneous fat. Similar beneficial actions on abdominal fat have been reported following treatment with testosterone in obese men. The potential hazards of such treatments make them unsuitable therapy for obesity. Dexfenfluramine is effective in reducing total body fat but the results from a six month randomised controlled trial indicates that it does not specifically influence changes in waist circumference associated with weight loss. In conclusion, any treatment which reduces total body fat will, by its nature, reduce intra-abdominal visceral fat. There are presently no specific treatments which can be recommended for intra-abdominal fat but increasing knowledge of the biochemical aberrations associated with visceral adiposity may lead to more specific therapies for the future.
MeSH term(s)	Abdomen ; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Adult ; Body Composition ; Diet, Reducing ; Exercise Therapy ; Female ; Growth Hormone/deficiency ; Growth Hormone/therapeutic use ; Humans ; Insulin/metabolism ; Male ; Middle Aged ; Obesity/diet therapy ; Obesity/pathology ; Obesity/therapy
Chemical Substances	Insulin ; Growth Hormone (9002-72-6)
Language	English
Publishing date	2004-09-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1103255-8
ISSN	0307-0565
ISSN	0307-0565
DOI	10.1038/sj.ijo.0800458
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Article: Hemoglobin A1c as a Substitute for Oral Glucose Testing in Early Pregnancy Screening

Crimmins, Sarah D. / Martin, Lucille M. / Myers, Madalyn / Elsamadicy, Emad / Quebedeaux, Tabitha M. / Desai, Andrea N. / Kopelman, Jerome N.

American Journal of Perinatology

2023

Abstract: ... missing delivery information. The diagnosis of GDM was made by a 3-hour 100-g glucose tolerance test ... a specificity of 83.3%, and a false positive rate of 16.7% ( p < 0.001). The area under the ROC curve ...

Abstract	Objective: Current recommendations for individuals with risk factors for gestational diabetes mellitus (GDM) call for screening in early pregnancy. However, there is currently no clear consensus on a specific screening modality. This study evaluates whether a hemoglobin A1c (HbA1c) screening in individuals with risk factors for gestational diabetes (GDM) could be used instead of an early 1-hour glucose challenge test (GCT). We hypothesized that the HbA1c could replace 1-hour GCT in early pregnancy evaluation Study Design: This is a prospective observational trial at a single tertiary referral center of women with at least one risk factor for GDM who were screened at <16 weeks of gestation with both 1-hour GCT or HbA1c. Exclusion criteria include: previous diagnosis of diabetes mellitus, multiple gestation, miscarriage, or missing delivery information. The diagnosis of GDM was made by a 3-hour 100-g glucose tolerance test, using the Carpenter–Coustan criteria (at least two results >94, 179, 154, and 139 mg/dL for fasting, 1-, 2-, and 3-hour values, respectively), 1-hour GCT > 200 mg/dL, or HbA1c > 6.5%. Results: A total of 758 patients met inclusion criteria. A total of 566 completed a 1-hour GCT and 729 had an HbA1c collected. The median gestational age at testing was 9 1/7 weeks (range: 4 0/7 –15 6/7 weeks]. Twenty-one participants were diagnosed with GDM at <16 weeks' GA. The receiver operating characteristic (ROC) curves identified the optimal valves for a positive screen for an HbA1c > 5.6%. The HbA1c had a sensitivity of 84.2%, a specificity of 83.3%, and a false positive rate of 16.7% ( p < 0.001). The area under the ROC curve for the HbA1c was 0.898. Gestational age of delivery was slightly earlier with individuals with an elevated HbA1c but no other changes in delivery or neonatal outcomes. Contingent screening improved specificity (97.7%) and decreased false positive rate to 4.4%. Conclusion: HbA1c may be a good assessment in early pregnancy for gestational diabetes. Key Points: HbA1c is a rational assessment in early pregnancy. An HbA1c > 5.6% is associated with gestational diabetes. Contingent screening limits the need for additional testing.
Keywords	early pregnancy screening ; diabetes in pregnancy ; hemoglobin A1c ; oral glucose testing
Language	English
Publishing date	2023-06-12
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	605671-4
ISSN	1098-8785 ; 0735-1631
ISSN (online)	1098-8785
ISSN	0735-1631
DOI	10.1055/s-0043-1769796
Database	Thieme publisher's database

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Zs.A 1929: Show issues

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Article ; Online: Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

Kopelman, Zachary A / Tian, Chunqiao / Tumas, Jordyn / Phippen, Neil T / Tarney, Christopher M / Hope, Erica R / Winkler, Stuart S / Jokajtys, Suzanne / Kucera, Calen W / Chan, John K / Richardson, Michael T / Kapp, Daniel S / Hamilton, Chad A / Leath, Charles A / Jones, Nathaniel L / Rocconi, Rodney P / Farley, John H / Secord, Angeles Alvarez / Cosgrove, Casey M /

Powell, Matthew A / Klopp, Ann / Walker, Joan L / Fleming, Gini F / Bateman, Nicholas W / Conrads, Thomas P / Maxwell, G Larry / Darcy, Kathleen M

Gynecologic oncology

2024 Volume 183, Page(s) 103–114

Abstract: Objective: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).: Methods: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant ... ...

Abstract	Objective: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). Methods: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. Results: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. Conclusions: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2024.03.026
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Zs.A 885: Show issues

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Article ; Online: Parent Ratings of Generalized and Indirect Effects of Functional Communication Training for Children with Autism Spectrum Disorder.

O'Brien, Matthew J / Pelzel, Kelly E / Hendrix, Nicole M / Schieltz, Kelly M / Miller, Kenzie / Call, Nathan A / Tsami, Loukia / Lerman, Dorothea C / Berg, Wendy K / Kopelman, Todd G / Wacker, David P / Lindgren, Scott D

Behavior modification

2021 Volume 46, Issue 5, Page(s) 971–1001

Abstract: Functional communication training (FCT) is a behavioral treatment that has been shown to reduce problem behavior and increase appropriate communication in young children with autism spectrum disorder (ASD). In this study, we assessed the effects of FCT ... ...

Abstract	Functional communication training (FCT) is a behavioral treatment that has been shown to reduce problem behavior and increase appropriate communication in young children with autism spectrum disorder (ASD). In this study, we assessed the effects of FCT on targeted and nontargeted problem behaviors outside of the training context, as well as parent stress, for 30 young children with ASD and their parents. Indirect measures of generalization treatment effects were administered prior to and following FCT treatment delivered via telehealth. Children demonstrated significant improvement on both targeted (measured via observation) and nontargeted (measured via checklist) problem behaviors, both within and outside of the training context, and parent stress was significantly reduced following treatment. These results suggest that the impact of FCT may extend beyond the training context for both the children being treated and the parents delivering treatment, even when generalization is not specifically programmed for during treatment.
MeSH term(s)	Autism Spectrum Disorder/therapy ; Behavior Therapy/methods ; Child ; Child, Preschool ; Communication ; Humans ; Parents/education ; Problem Behavior
Language	English
Publishing date	2021-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	432229-0
ISSN	1552-4167 ; 0145-4455
ISSN (online)	1552-4167
ISSN	0145-4455
DOI	10.1177/01454455211018815
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Article: Obesity as a medical problem.

Kopelman, P G

Nature

2000 Volume 404, Issue 6778, Page(s) 635–643

Abstract: Obesity is now so common within the world's population that it is beginning to replace undernutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart ... ...

Abstract	Obesity is now so common within the world's population that it is beginning to replace undernutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart disease, certain forms of cancer, and sleep-breathing disorders. Obesity is defined by a body-mass index (weight divided by square of the height) of 30 kg m(-2) or greater, but this does not take into account the morbidity and mortality associated with more modest degrees of overweight, nor the detrimental effect of intra-abdominal fat. The global epidemic of obesity results from a combination of genetic susceptibility, increased availability of high-energy foods and decreased requirement for physical activity in modern society. Obesity should no longer be regarded simply as a cosmetic problem affecting certain individuals, but an epidemic that threatens global well being.
MeSH term(s)	Forecasting ; Humans ; Obesity/complications ; Obesity/epidemiology ; Obesity/etiology ; Obesity/physiopathology
Language	English
Publishing date	2000-04-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/35007508
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Article: Physiopathology of prolactin secretion in obesity.

Kopelman, P G

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity

2000 Volume 24 Suppl 2, Page(s) S104–8

Abstract: In many species prolactin is of biological importance and has a major role in determining the deposition and mobilization of fat. In human physiology, outside pregnancy, prolactin secretion is altered by increasing body weight in both children and adults. ...

Abstract	In many species prolactin is of biological importance and has a major role in determining the deposition and mobilization of fat. In human physiology, outside pregnancy, prolactin secretion is altered by increasing body weight in both children and adults. Prolactin in this circumstance appears to be marker of hypothalamic-pituitary function: the prolactin response to insulin-hypoglycaemia, thyrotrophin releasing hormone stimulation and other stimulatory factors may be diminished. In addition, obesity alters the 24h spontaneous release of prolactin with a generalised dampening of release. A number of explanations have been given as possible causes for these alterations, but it seems likely that they reflect obesity per se and are associated with hyperinsulinaemia. Weight reduction, with accompanying decrease in plasma insulin levels, leads to a normalization of prolactin responses in most, but not all, circumstances. To date, no molecular basis has been identified which links prolactin with increasing body fatness, weight and appetite: new data suggests a possible link in obese men between fasting plasma prolactin and leptin concentrations.
MeSH term(s)	Adrenal Glands/physiopathology ; Body Weight ; Humans ; Hypothalamus/physiopathology ; Leptin/physiology ; Obesity/physiopathology ; Pituitary Gland/physiopathology ; Prolactin/metabolism ; Thyrotropin-Releasing Hormone
Chemical Substances	Leptin ; Thyrotropin-Releasing Hormone (5Y5F15120W) ; Prolactin (9002-62-4)
Language	English
Publishing date	2000-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1103255-8
ISSN	0307-0565
ISSN	0307-0565
DOI	10.1038/sj.ijo.0801291
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Article: Is the hypothalamic-pituitary-adrenal axis really hyperactivated in visceral obesity?

Kopelman, P G

Journal of endocrinological investigation

1999 Volume 22, Issue 1, Page(s) 76–79

MeSH term(s)	Abdomen ; Adipocytes/physiology ; Adrenal Glands/physiopathology ; Glucocorticoids/physiology ; Humans ; Hypothalamus/physiopathology ; Obesity/physiopathology ; Pituitary Gland/physiopathology
Chemical Substances	Glucocorticoids
Language	English
Publishing date	1999-01
Publishing country	Italy
Document type	Comment ; Journal Article ; Review
ZDB-ID	432272-1
ISSN	1720-8386 ; 0391-4097 ; 1121-1369
ISSN (online)	1720-8386
ISSN	0391-4097 ; 1121-1369
DOI	10.1007/BF03345483
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Article: Clinical treatment of obesity: are drugs and surgery the answer?

Kopelman, P.G

Proceedings of the Nutrition Society. 2005 Feb., v. 64, no. 1

2005

Abstract: Obesity treatment remains a 'Cinderella' of all clinical management programmes, but generally without a happy ending. The great expectation for new therapeutic agents has not been fulfilled in clinical practice, whilst the restriction of eating through ... ...

Abstract	Obesity treatment remains a 'Cinderella' of all clinical management programmes, but generally without a happy ending. The great expectation for new therapeutic agents has not been fulfilled in clinical practice, whilst the restriction of eating through surgical division of the upper bowel seems strange in an age of advanced and sophisticated technology. The better understanding of the neuro-regulation of appetite, and its application as part of evidence-based clinical interventions, could lead to a more coherent approach to obesity treatment. Nevertheless, investigation of potential neuroendocrine targets for appetite suppression suggests redundancy in the systems, which make development of effective agents against single receptors impractical. Importantly, the progressive rise in the prevalence of obesity will inevitably mean that only a small proportion of afflicted patients will actually be treated by long-term drugs and surgery. Drugs and surgery are not currently the answer for the majority of obese individuals. What is required is a better way of identifying patients who may particularly benefit from such approaches. However, the major emphasis must be the development of effective population-wide interventions that halt the increase in fatness and ensure that future generations maintain and enjoy a healthy body weight.
Keywords	obesity ; drug therapy ; surgery ; appetite suppressants ; human diseases ; disease prevalence ; complications ; pathogenesis ; food intake ; appetite ; human physiology ; neurosecretory system ; pharmacology ; lifestyle
Language	English
Dates of publication	2005-02
Size	p. 65-71.
Document type	Article
Note	Lecture presented at the symposium on the "Treatment of obesity," July 5-8, 2004, Dublin, Republic of Ireland.
ZDB-ID	391142-1
ISSN	1475-2719 ; 0029-6651
ISSN (online)	1475-2719
ISSN	0029-6651
Database	NAL-Catalogue (AGRICOLA)

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Article: Emerging management strategies for obesity.

Kopelman, P G

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity

1998 Volume 22 Suppl 1, Page(s) S7–11; discussion S12, S42

Abstract: Management strategies for obesity, which include drug therapy, are emerging as a consequence of the increasing recognition of the medical seriousness of obesity. Obesity requires appropriate and effective management by suitably trained members of a ... ...

Abstract	Management strategies for obesity, which include drug therapy, are emerging as a consequence of the increasing recognition of the medical seriousness of obesity. Obesity requires appropriate and effective management by suitably trained members of a multidisciplinary team, with treatment programmes putting equal importance on weight reduction and its maintenance. Such programmes must also take into account the reduction in risk from co-morbid conditions after modest weight loss (5-10% of initial body weight). The use of an anti-obesity drug may be justified for patients at risk from obesity where dietary methods, including exercise and behaviour modification, have failed to achieve a 10% reduction in initial body weight after at least three months from the start of the episode of managed care. Anti-obesity drugs must be prescribed in an appropriate setting, with patients being reviewed on a regular basis. Essential elements for managed weight loss include, a printed management programme, appropriate equipment, specified and realistic weight-loss goals, documentation of individual patient's health risks, and clearly defined follow-up procedures with explicit guidelines for the use of drugs and notification of other doctors involved in the patient's care. The process of drug treatment necessitates a system of regular medical audit. Many health-care professionals and lay persons remain sceptical about the scientific value of anti-obesity drugs. The emergence of increasingly specific and effective agents underlines the importance of ensuring appropriate use for patients at risk from obesity.
MeSH term(s)	Humans ; Obesity/drug therapy ; Obesity/therapy ; Weight Loss
Language	English
Publishing date	1998-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1103255-8
ISSN	0307-0565
ISSN	0307-0565
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