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Article ; Online: No Influence of Low-, Medium-, or High-Dose Tyrosine on Exercise in a Warm Environment.

Tumilty, Les / Gregory, Nicholas / Beckmann, Manfred / Thatcher, Rhys

Medicine and science in sports and exercise

2019 Volume 52, Issue 6, Page(s) 1404–1413

Abstract: Purpose: Tyrosine administration may counter exercise fatigue in a warm environment, but the typical dose is inconclusive, with little known about higher doses. We explored how three tyrosine doses influenced the circulating ratio of tyrosine/amino ... ...

Abstract	Purpose: Tyrosine administration may counter exercise fatigue in a warm environment, but the typical dose is inconclusive, with little known about higher doses. We explored how three tyrosine doses influenced the circulating ratio of tyrosine/amino acids competing for brain uptake and hypothesized that a medium and high dose would enhance exercise performance in a warm environment. Methods: Eight recreationally trained, non-heat-acclimated male individuals (mean ± SD age, 23 ± 4 yr; stature, 181 ± 7 cm; body mass, 76.1 ± 5.9 kg; peak oxygen uptake, 4.1 ± 0.5 L·min) performed a peak oxygen uptake test, two familiarization trials, then four experimental trials in a randomized order separated by 7 d. Before exercise, subjects drank 2 × 300 mL sugar-free drinks delivering 0 (PLA), 150 (LOW), 300 (MED), or 400 (HIGH) mg·kg body mass tyrosine in a double-blind fashion. Subjects performed a 60-min constant intensity cycling then a simulated time trial in 30°C and 60% relative humidity. Results: Time trial performance (P = 0.579) was not influenced by tyrosine ingestion. The plasma ratio of tyrosine/∑(free-tryptophan, leucine, isoleucine, valine, phenylalanine, methionine), a key determinant of brain tyrosine influx, increased relative to PLA (P < 0.001). The increase was similar (P > 0.05) in MED (7.7-fold) and HIGH (8.2-fold), and greater than that in LOW (5.3-fold; P < 0.05). No differences existed between trials in core and skin temperature, heart rate, RPE, or thermal sensation (P > 0.05). Conclusion: Exercise performance in a warm environment was not influenced by tyrosine availability in recreationally trained male individuals. The results provide novel data informing future studies, on the tyrosine dose maximizing the circulating ratio of tyrosine/amino acids competing for brain uptake.
MeSH term(s)	Adult ; Amino Acids/blood ; Blood Glucose/metabolism ; Body Mass Index ; Body Temperature Regulation ; Brain/metabolism ; Double-Blind Method ; Exercise/physiology ; Fatigue/prevention & control ; Heart Rate ; Hot Temperature ; Humans ; Lactic Acid/blood ; Perception/physiology ; Physical Endurance/physiology ; Plasma Volume ; Skin Temperature ; Tyrosine/administration & dosage ; Tyrosine/blood ; Young Adult
Chemical Substances	Amino Acids ; Blood Glucose ; Lactic Acid (33X04XA5AT) ; Tyrosine (42HK56048U)
Language	English
Publishing date	2019-12-12
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	603994-7
ISSN	1530-0315 ; 0195-9131 ; 0025-7990
ISSN (online)	1530-0315
ISSN	0195-9131 ; 0025-7990
DOI	10.1249/MSS.0000000000002245
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Article ; Online: First- and second-line treatment of advanced metastatic non-small-cell lung cancer: a global view.

Thatcher, Nicholas

BMC proceedings

2008 Volume 2 Suppl 2, Page(s) S3

Abstract: Treatment of non-small-cell lung cancer is dependent on disease stage. For patients with metastasis or locally advanced disease, the importance of finding therapeutic schemes that may benefit this population is important. This review discusses ... ...

Abstract	Treatment of non-small-cell lung cancer is dependent on disease stage. For patients with metastasis or locally advanced disease, the importance of finding therapeutic schemes that may benefit this population is important. This review discusses therapeutic options for first- and second-line treatment in patients with advanced non-small-cell lung cancer. According to current data, the combination of two cytotoxic agents is the optimum first-line treatment for patients with non-small-cell lung cancer and performance status of 0-1. Addition of bevacizumab has shown to provide an even longer survival and to increase response rate. Within the first-line setting, erlotinib appears to be effective in the treatment of elderly patients who would not derive a benefit from standard chemotherapy or those refusing standard chemotherapy. The administration of erlotinib as first-line maintenance therapy is being assessed. There are currently three drugs approved for second-line treatment of patients with advanced non-small-cell lung cancer after failure of first-line chemotherapy. These drugs have proven to be effective in phase III trials. In the phase III trial BR.21 study, the response rate was 8.9% in the erlonitib group, and less than 1% in placebo; median response duration was 7.9 months and 3.7 months, respectively; and the median survival was 6.7 months and 4.7 with erlotinib and placebo, respectively. One-year survival was 31% and 21% with erlotinib and placebo, respectively. In addition, the BR.21 trial revealed that significantly greater improvements in overall quality of life and in both physical and emotional functioning were observed in the erlotinib arm as compared with the placebo arm. Erlotinib is not significantly associated with hematologic adverse effects. Erlotinib is administered orally, and does not require concomitant administration of other drugs, thus causing patients less inconvenience. Analysis of data from different subgroups included in the BR.21 trial show that overall survival is similar among women and men, among patients with adenocarcinoma and epidermoid carcinoma or Asian patients compared with other ethnicities. Combination of erlotinib and bevacizumab in the second-line treatment of patients with advanced disease has been evaluated as anti-angiogenic properties. This combination therapy has provided promising results which should be confirmed in future studies.
Language	English
Publishing date	2008-09-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2411867-9
ISSN	1753-6561 ; 1753-6561
ISSN (online)	1753-6561
ISSN	1753-6561
DOI	10.1186/1753-6561-2-s2-s3
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Article ; Online: Brief lifestyle interventions for prediabetes in primary care: a service evaluation.

Thatcher, Rhys / Gregory, Nicholas / Cheung, Wai Yee / Dunseath, Gareth J / Parsons, Sharon N / Goodwin, Mark / Luzio, Stephen D

BMC primary care

2022 Volume 23, Issue 1, Page(s) 45

Abstract: Background: The increasing number of cases of prediabetes in the UK is concerning, particularly in Wales where there is no standard programme of support. The aim of the current service evaluation was to examine the effectiveness of brief lifestyle ... ...

Abstract	Background: The increasing number of cases of prediabetes in the UK is concerning, particularly in Wales where there is no standard programme of support. The aim of the current service evaluation was to examine the effectiveness of brief lifestyle interventions on glucose tolerance in people at risk of developing type 2 diabetes. Methods: In this pragmatic service evaluation clinical data on people deemed at risk of developing type 2 diabetes were evaluated from two GP clusters. Patients (n = 1207) received a single 15 to 30-min, face-to-face, consultation with a health care practitioner. Interventions were assessed by changes in HbA1c and distribution across the HbA1c ranges 12 months following intervention. Statistical significance of reversion to normoglycaemia and development of diabetes were assessed through comparison with expected rates without intervention. Results: Between baseline and 12-month follow-up HbA1c fell from 43.85 ± 1.57 mmol/mol (6.16 ± 0.14%) to 41.63 ± 3.84 mmol/mol (5.96 ± 0.35%), a decrease of 2.22 mmol/mol (0.20%) (95% CI 2.01 (0.18%), 2.42 (0.22%); p < 0.0001). The proportion of people with normal glucose tolerance at 12 months (0.50 95%CI 0.47, 0.52) was significantly larger than the lower (0.06 (p < 0.0001) and the upper (0.19 (p < 0.0001)) estimates based on no intervention. Conclusion: Results indicate significant improvement in glucose tolerance across GP clusters. The brief intervention has the potential to offer a robust and effective option to support people at risk of developing type 2 diabetes. Further research in the form of a randomised trial is needed to confirm this and identify those likely to benefit most from this intervention.
MeSH term(s)	Crisis Intervention ; Diabetes Mellitus, Type 2/epidemiology ; Glucose ; Glycated Hemoglobin A/analysis ; Humans ; Life Style ; Prediabetic State/therapy ; Primary Health Care
Chemical Substances	Glycated Hemoglobin A ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-03-14
Publishing country	England
Document type	Journal Article
ISSN	2731-4553
ISSN (online)	2731-4553
DOI	10.1186/s12875-022-01658-2
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Article ; Online: Biosimilars: what the oncologist should know.

Thill, Marc / Thatcher, Nicholas / Hanes, Vladimir / Lyman, Gary H

Future oncology (London, England)

2019 Volume 15, Issue 10, Page(s) 1147–1165

Abstract: As originator biologic medicines lose patent protection, some biopharmaceutical companies are focusing on developing similar versions of these costly and complex therapies with a goal of providing more affordable treatment options. Many of these ... ...

Abstract	As originator biologic medicines lose patent protection, some biopharmaceutical companies are focusing on developing similar versions of these costly and complex therapies with a goal of providing more affordable treatment options. Many of these molecules, known as biosimilars, are now approved worldwide and several more are expected to be introduced in the near future. As more biosimilars become available, it is important for clinicians to become familiar with this new category of products and understand how biosimilars are developed, how their development differs from that of originator biologics and how they differ from generics. This review aims to provide the practicing clinician with the knowledge needed to understand biosimilars, along with some guidance on their use in treating oncologic diseases.
MeSH term(s)	Biosimilar Pharmaceuticals/pharmacokinetics ; Biosimilar Pharmaceuticals/therapeutic use ; Drug Approval ; Humans ; Neoplasms/drug therapy ; Oncologists ; Practice Guidelines as Topic/standards ; Therapeutic Equivalency ; Tissue Distribution
Chemical Substances	Biosimilar Pharmaceuticals
Language	English
Publishing date	2019-02-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2018-0728
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Article: The place of targeted therapy in the patient management of non-small cell lung cancer.

Thatcher, Nicholas

Lung cancer (Amsterdam, Netherlands)

2007 Volume 57 Suppl 2, Page(s) S18–23

Abstract: There is much interest in the use of targeted therapies for the management of non-small cell lung cancer (NSCLC). To date, four targeted therapies - bevacizumab, cetuximab, erlotinib and gefitinib - have been investigated in randomised trials, in the ... ...

Abstract	There is much interest in the use of targeted therapies for the management of non-small cell lung cancer (NSCLC). To date, four targeted therapies - bevacizumab, cetuximab, erlotinib and gefitinib - have been investigated in randomised trials, in the treatment of advanced NSCLC. In the first-line setting, bevacizumab has been shown to significantly prolong survival when added to carboplatin/paclitaxel, as demonstrated in a large phase III study. However, issues of toxicity limit this treatment regimen to selected patients. The addition of bevacizumab to gemcitabine/cisplatin will be reported at ASCO 2007. The addition of cetuximab to cisplatin/vinorelbine has also been shown to improve survival in a randomised phase II study. Erlotinib has been investigated as monotherapy in first-line chemo-naïve patients and has demonstrated objective response rates of 10-23%. However, in a study comparing erlotinib versus chemotherapy, the outcome was less favourable for patients who had received erlotinib. Erlotinib monotherapy has also been investigated in recurrent disease, and has been shown to improve overall survival over that achieved with placebo. The greatest benefit was observed in never-smokers with epidermal growth factor receptor-positive tumours. In a further phase II randomised study, the effect of combining two targeted therapies has been investigated. This study compared erlotinib/bevacizumab versus bevacizumab/chemotherapy versus chemotherapy alone. Both regimens including targeted therapy were comparable and superior to chemotherapy alone. However, these are preliminary data and further research is required to clarify the role of targeted therapies in the management of advanced NSCLC.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Cetuximab ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms/drug therapy ; Quinazolines/therapeutic use
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Quinazolines ; Bevacizumab (2S9ZZM9Q9V) ; Erlotinib Hydrochloride (DA87705X9K) ; Cetuximab (PQX0D8J21J) ; gefitinib (S65743JHBS)
Language	English
Publishing date	2007-08
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632771-0
ISSN	0169-5002
ISSN	0169-5002
DOI	10.1016/S0169-5002(07)70423-3
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: First- and second-line treatment of advanced metastatic non-small-cell lung cancer

Thatcher Nicholas

BMC Proceedings, Vol 2, Iss Suppl 2, p S

a global view

2008 Volume 3

Abstract: Abstract Treatment of non-small-cell lung cancer is dependent on disease stage. For patients with metastasis or locally advanced disease, the importance of finding therapeutic schemes that may benefit this population is important. This review discusses ... ...

Abstract	Abstract Treatment of non-small-cell lung cancer is dependent on disease stage. For patients with metastasis or locally advanced disease, the importance of finding therapeutic schemes that may benefit this population is important. This review discusses therapeutic options for first- and second-line treatment in patients with advanced non-small-cell lung cancer. According to current data, the combination of two cytotoxic agents is the optimum first-line treatment for patients with non-small-cell lung cancer and performance status of 0–1. Addition of bevacizumab has shown to provide an even longer survival and to increase response rate. Within the first-line setting, erlotinib appears to be effective in the treatment of elderly patients who would not derive a benefit from standard chemotherapy or those refusing standard chemotherapy. The administration of erlotinib as first-line maintenance therapy is being assessed. There are currently three drugs approved for second-line treatment of patients with advanced non-small-cell lung cancer after failure of first-line chemotherapy. These drugs have proven to be effective in phase III trials. In the phase III trial BR.21 study, the response rate was 8.9% in the erlonitib group, and less than 1% in placebo; median response duration was 7.9 months and 3.7 months, respectively; and the median survival was 6.7 months and 4.7 with erlotinib and placebo, respectively. One-year survival was 31% and 21% with erlotinib and placebo, respectively. In addition, the BR.21 trial revealed that significantly greater improvements in overall quality of life and in both physical and emotional functioning were observed in the erlotinib arm as compared with the placebo arm. Erlotinib is not significantly associated with hematologic adverse effects. Erlotinib is administered orally, and does not require concomitant administration of other drugs, thus causing patients less inconvenience. Analysis of data from different subgroups included in the BR.21 trial show that overall survival is similar among women and men, among patients with adenocarcinoma and epidermoid carcinoma or Asian patients compared with other ethnicities. Combination of erlotinib and bevacizumab in the second-line treatment of patients with advanced disease has been evaluated as anti-angiogenic properties. This combination therapy has provided promising results which should be confirmed in future studies.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2008-09-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Conference proceedings: Second Heidelberg Thoracic Oncology Symposium on the Diagnosis and Treatment of Pleural Mesothelioma--introduction.

Thatcher, Nicholas

Lung cancer (Amsterdam, Netherlands)

2004 Volume 45 Suppl 1, Page(s) S1–2

MeSH term(s)	Combined Modality Therapy ; Humans ; Mesothelioma/diagnosis ; Mesothelioma/therapy ; Pleural Neoplasms/diagnosis ; Pleural Neoplasms/therapy ; Prognosis
Language	English
Publishing date	2004-08
Publishing country	Ireland
Document type	Congresses ; Editorial
ZDB-ID	632771-0
ISSN	0169-5002
ISSN	0169-5002
DOI	10.1016/j.lungcan.2004.04.003
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Article ; Online: Synthesis, Optimization, and Structure-Activity Relationships of Nicotinamide Phosphoribosyltransferase (NAMPT) Positive Allosteric Modulators (N-PAMs).

Shen, Zhengnan / Ratia, Kiira / Krider, Isabella / Ackerman-Berrier, Martha / Penton, Christopher / Musku, Soumya Reddy / Gordon-Blake, Jesse M / Laham, Megan S / Christie, Nicholas / Ma, Nina / Fu, Jiqiang / Xiong, Rui / Courey, Jenna M / Velma, Ganga Reddy / Thatcher, Gregory R J

Journal of medicinal chemistry

2023 Volume 66, Issue 24, Page(s) 16704–16727

Abstract: Depletion of nicotinamide adenine dinucleotide ( ... ...

Abstract	Depletion of nicotinamide adenine dinucleotide (NAD
MeSH term(s)	Nicotinamide Phosphoribosyltransferase/chemistry ; Nicotinamide Phosphoribosyltransferase/metabolism ; NAD/metabolism ; Niacinamide/pharmacology ; Cell Line, Tumor ; Cytokines/metabolism ; Structure-Activity Relationship
Chemical Substances	Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; NAD (0U46U6E8UK) ; Niacinamide (25X51I8RD4) ; Cytokines
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c01406
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Article ; Online: Mechanism of Allosteric Modulation of Nicotinamide Phosphoribosyltransferase to Elevate Cellular NAD

Ratia, Kiira M / Shen, Zhengnan / Gordon-Blake, Jesse / Lee, Hyun / Laham, Megan S / Krider, Isabella S / Christie, Nicholas / Ackerman-Berrier, Martha / Penton, Christopher / Knowles, Natalie G / Musku, Soumya Reddy / Fu, Jiqiang / Velma, Ganga Reddy / Xiong, Rui / Thatcher, Gregory R J

Biochemistry

2023 Volume 62, Issue 4, Page(s) 923–933

Abstract: In aging and disease, cellular nicotinamide adenine dinucleotide ( ... ...

Abstract	In aging and disease, cellular nicotinamide adenine dinucleotide (NAD
MeSH term(s)	Humans ; Cytokines/metabolism ; Longevity ; NAD/metabolism ; Niacinamide/pharmacology ; Niacinamide/metabolism ; Nicotinamide Phosphoribosyltransferase/chemistry ; Nicotinamide Phosphoribosyltransferase/metabolism ; Allosteric Site
Chemical Substances	Cytokines ; NAD (0U46U6E8UK) ; Niacinamide (25X51I8RD4) ; Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12)
Language	English
Publishing date	2023-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/acs.biochem.2c00655
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Article: Computer-Facilitated Screening and Brief Intervention for Alcohol Use Risk in Adolescent Patients of Pediatric Primary Care Offices: Protocol for a Cluster Randomized Controlled Trial.

Shrier, Lydia A / O'Connell, Madison M / Torres, Alessandra / Shone, Laura P / Fiks, Alexander G / Plumb, Julia A / Maturo, Jessica L / McCaskill, Nicholas H / Harris, Donna / Burke, Pamela J / Felt, Thatcher / Murphy, Marie Lynd / Sherritt, Lon / Harris, Sion Kim

JMIR research protocols

2024 Volume 13, Page(s) e55039

Abstract: Background: Alcohol and other substance use disorders usually begin with substance use in adolescence. Pediatric primary care offices, where most adolescents receive health care, are a promising venue for early identification of substance use and for ... ...

Abstract	Background: Alcohol and other substance use disorders usually begin with substance use in adolescence. Pediatric primary care offices, where most adolescents receive health care, are a promising venue for early identification of substance use and for brief intervention to prevent associated problems and the development of substance use disorder. Objective: This study tests the effects of a computer-facilitated screening and brief intervention (cSBI) system (the CRAFFT [Car, Relax, Alone, Forget, Family/Friends, Trouble] Interactive System [CRAFFT-IS]) on heavy episodic drinking, riding with a driver who is substance impaired, or driving while substance impaired among adolescents aged 14 to 17 years presenting for a well visit at pediatric primary care practices. Methods: We are conducting a cluster randomized controlled trial of the CRAFFT-IS versus usual care and recruiting up to 40 primary care clinicians at up to 20 pediatric primary care practices within the American Academy of Pediatrics (AAP) Pediatric Research in Office Settings network. Clinicians are randomized 1:1 within each practice to implement the CRAFFT-IS or usual care with a target sample size of 1300 adolescent patients aged 14 to 17 years. At study start, intervention clinicians complete web-based modules, trainer-led live sessions, and mock sessions to establish baseline competency with intervention counseling. Adolescents receive mailed recruitment materials that invite adolescents to complete an eligibility survey. Eligible and interested adolescents provide informed assent (parental permission requirement has been waived). Before their visit, enrolled adolescents seeing intervention clinicians complete a self-administered web-based CRAFFT screening questionnaire and view brief psychoeducational content illustrating substance use-associated health risks. During the visit, intervention clinicians access a computerized summary of the patient's screening results and a tailored counseling script to deliver a motivational interviewing-based brief intervention. All participants complete previsit, postvisit, and 12-month follow-up study assessments. Primary outcomes include past 90-day heavy episodic drinking and riding with a driver who is substance impaired at 3-, 6-, 9-, and 12-month follow-ups. Multiple logistic regression modeling with generalized estimating equations and mixed effects modeling will be used in outcomes analyses. Exploratory aims include examining other substance use outcomes (eg, cannabis and nicotine vaping), potential mediators of intervention effect (eg, self-efficacy not to drink), and effect moderation by baseline risk level and sociodemographic characteristics. Results: The AAP Institutional Review Board approved this study. The first practice and clinicians were enrolled in August 2022; as of July 2023, a total of 6 practices (23 clinicians) had enrolled. Recruitment is expected to continue until late 2024 or early 2025. Data collection will be completed in 2025 or 2026. Conclusions: Findings from this study will inform the promotion of high-quality screening and brief intervention efforts in pediatric primary care with the aim of reducing alcohol-related morbidity and mortality during adolescence and beyond. Trial registration: ClinicalTrials.gov NCT04450966; https://www.clinicaltrials.gov/study/NCT04450966. International registered report identifier (irrid): DERR1-10.2196/55039.
Language	English
Publishing date	2024-03-26
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2719222-2
ISSN	1929-0748
ISSN	1929-0748
DOI	10.2196/55039
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