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Article ; Online: Systemic artery to pulmonary artery aneurysm malformations associated with variants at MCF2L.

Mitchell, S E / Martin, R P / Terry, P / Drant, S E / Valle, D / Dietz, H / Sobreira, N

American journal of medical genetics. Part A

2023 Volume 191, Issue 5, Page(s) 1250–1260

Abstract: Arteriovenous malformations (AVM) are characterized by abnormal vessels connecting arteries and veins resulting in a disruption of normal blood flow. Hereditary hemorrhagic telangiectasia (HHT) is the most common cause of pulmonary AVM characterized by a ...

Abstract	Arteriovenous malformations (AVM) are characterized by abnormal vessels connecting arteries and veins resulting in a disruption of normal blood flow. Hereditary hemorrhagic telangiectasia (HHT) is the most common cause of pulmonary AVM characterized by a right to left shunt. Here we describe a distinct malformation where the flow of blood was from a systemic artery to the pulmonary artery (PA) resulting in a left to right shunt instead of the right to left shunt seen in individuals with HHT. This distinct malformation was identified in seven probands, one from a multiplex family containing 10 affected individuals from five generations. To identify the molecular basis of this distinct malformation, we performed exome sequencing (ES) on the seven probands and the affected paternal female cousin from the multiplex family. PhenoDB was used to prioritize candidate causative variants along with burden analysis. We describe the clinical and radiological details of the new systemic artery to PA malformation with or without pulmonary artery aneurysm (SA-PA(A)) and recommend distinct treatment techniques. Moreover, ES analysis revealed possible causative variants identified in three families with variants in a novel candidate disease gene, MCF2L. Further functional studies will be necessary to better understand the molecular mechanisms involved on SA-PA(A) malformation, however our findings suggest that MCF2L is a novel disease gene associated with SA-PA(A).
MeSH term(s)	Humans ; Female ; Pulmonary Artery/diagnostic imaging ; Pulmonary Artery/abnormalities ; Vascular Malformations/genetics ; Arteriovenous Malformations ; Telangiectasia, Hereditary Hemorrhagic/diagnostic imaging ; Telangiectasia, Hereditary Hemorrhagic/genetics ; Aneurysm/diagnostic imaging ; Aneurysm/genetics ; Rho Guanine Nucleotide Exchange Factors
Chemical Substances	MCF2L protein, human ; Rho Guanine Nucleotide Exchange Factors
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.63141
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Article: RT-PCR Method for Detecting Cowpea Mottle Carmovirus in Vigna Germ Plasm.

Gillaspie, A G / Mitchell, S E / Stuart, G W / Bozarth, R F

Plant disease

2019 Volume 83, Issue 7, Page(s) 639–643

Abstract: A highly sensitive reverse transcription-polymerase chain reaction (RT-PCR) method was developed to detect cowpea mottle carmovirus (CPMoV) in newly acquired germ plasm of Vigna spp. It detected virus in tissues diluted up to ... ...

Abstract	A highly sensitive reverse transcription-polymerase chain reaction (RT-PCR) method was developed to detect cowpea mottle carmovirus (CPMoV) in newly acquired germ plasm of Vigna spp. It detected virus in tissues diluted up to 10
Language	English
Publishing date	2019-03-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	754182-x
ISSN	0191-2917
ISSN	0191-2917
DOI	10.1094/PDIS.1999.83.7.639
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Article ; Online: Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone.

Speakman, J R / Mitchell, S E / Mazidi, M

Experimental gerontology

2016 Volume 86, Page(s) 28–38

Abstract: Almost exactly 100years ago Osborne and colleagues demonstrated that restricting the food intake of a small number of female rats extended their lifespan. In the 1930s experiments on the impact of diet on lifespan were extended by Slonaker, and ... ...

Abstract	Almost exactly 100years ago Osborne and colleagues demonstrated that restricting the food intake of a small number of female rats extended their lifespan. In the 1930s experiments on the impact of diet on lifespan were extended by Slonaker, and subsequently McCay. Slonaker concluded that there was a strong impact of protein intake on lifespan, while McCay concluded that calories are the main factor causing differences in lifespan when animals are restricted (Calorie restriction or CR). Hence from the very beginning the question of whether food restriction acts on lifespan via reduced calorie intake or reduced protein intake was disputed. Subsequent work supported the idea that calories were the dominant factor. More recently, however, this role has again been questioned, particularly in studies of insects. Here we review the data regarding previous studies of protein and calorie restriction in rodents. We show that increasing CR (with simultaneous protein restriction: PR) increases lifespan, and that CR with no PR generates an identical effect. None of the residual variation in the impact of CR (with PR) on lifespan could be traced to variation in macronutrient content of the diet. Other studies show that low protein content in the diet does increase median lifespan, but the effect is smaller than the CR effect. We conclude that CR is a valid phenomenon in rodents that cannot be explained by changes in protein intake, but that there is a separate phenomenon linking protein intake to lifespan, which acts over a different range of protein intakes than is typical in CR studies. This suggests there may be a fundamental difference in the responses of insects and rodents to CR. This may be traced to differences in the physiology of these groups, or reflect a major methodological difference between 'restriction' studies performed on rodents and insects. We suggest that studies where the diet is supplied ad libitum, but diluted with inert components, should perhaps be called dietary or caloric dilution, rather than dietary or caloric restriction, to distinguish these potentially important methodological differences.
MeSH term(s)	Animals ; Caloric Restriction ; Diet, Protein-Restricted ; Energy Intake/physiology ; Female ; Longevity/physiology ; Male ; Mice ; Rats
Language	English
Publishing date	2016-03-19
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	390992-x
ISSN	1873-6815 ; 0531-5565
ISSN (online)	1873-6815
ISSN	0531-5565
DOI	10.1016/j.exger.2016.03.011
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Article ; Online: Estimating Costs in A Cost-Effectiveness Analysis: Adherence to HTA Guidance.

Mauskopf, J A / Mitchell, S E / Samuel, M

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

2014 Volume 17, Issue 7, Page(s) A548

Language	English
Publishing date	2014-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1471745-1
ISSN	1524-4733 ; 1098-3015
ISSN (online)	1524-4733
ISSN	1098-3015
DOI	10.1016/j.jval.2014.08.1782
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Article ; Online: Factors influencing individual variability in high fat diet-induced weight gain in out-bred MF1 mice.

Vaanholt, L M / Sinclair, R E / Mitchell, S E / Speakman, J R

Physiology & behavior

2015 Volume 144, Page(s) 146–155

Abstract: Easy access to high-energy palatable foods has been suggested to have contributed to the world-wide obesity epidemic. However, within these 'obesogenic' environments many people manage to remain lean. Mice also show variability in their weight gain ... ...

Abstract	Easy access to high-energy palatable foods has been suggested to have contributed to the world-wide obesity epidemic. However, within these 'obesogenic' environments many people manage to remain lean. Mice also show variability in their weight gain responses to high-fat diet (HFD) feeding and their weight loss responses to calorically restricted (CR) feeding. In this study we investigated which factors contribute to determining susceptibility to HFD-induced obesity in mice, and whether the responses in weight gain on HFD are correlated with the responses to CR. One-hundred twenty four mice were exposed to 30% CR for 28days followed by a 14day recovery period, and subsequent exposure to 60% HFD for 28days. Responses in various metabolic factors were measured before and after each exposure (body mass; BM, body composition, food intake; FI, resting metabolic rate; RMR, physical activity, body temperature and glucose tolerance; GT). Weight changes on HFD ranged from -1 to 26%, equivalent to -0.2g to 10.5g in absolute mass. Multiple regression models showed that fat free mass (FFM) of the mice before exposure to HFD predicted 12% of the variability in weight gain on HFD (p<0.001). Also, FI during the first week of HFD feeding predicted 20% of the variability in BM and fat mass (FM) gain 4weeks later. These data may point to a role for the reward system in driving individual differences in FI and weight gain. Weight gain on the HFD was significantly negatively correlated to weight loss on CR, indicating that animals that are poor at defending against weight gain on HFD, were also poor at defending against CR-induced weight loss. Changes in FM and FFM in response to HFD or CR were not correlated however.
MeSH term(s)	Animals ; Basal Metabolism ; Body Composition ; Body Temperature/physiology ; Body Weight/physiology ; Caloric Restriction ; Diet, High-Fat/adverse effects ; Eating/physiology ; Female ; Food Preferences ; Glucose Tolerance Test ; Linear Models ; Male ; Mice ; Motor Activity ; Obesity/etiology ; Obesity/metabolism ; Rest ; Statistics, Nonparametric
Language	English
Publishing date	2015-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2015.03.029
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Article ; Online: Implementation and adaptation of the Re-Engineered Discharge (RED) in five California hospitals: a qualitative research study.

Mitchell, S E / Weigel, G M / Laurens, V / Martin, J / Jack, B W

BMC health services research

2017 Volume 17, Issue 1, Page(s) 291

Abstract: Background: Project Re-Engineered Discharge (RED) is an evidence-based strategy to reduce readmissions disseminated and adapted by various health systems across the country. To date, little is known about how adapting Project RED from its original ... ...

Abstract	Background: Project Re-Engineered Discharge (RED) is an evidence-based strategy to reduce readmissions disseminated and adapted by various health systems across the country. To date, little is known about how adapting Project RED from its original protocol impacts RED implementation and/or sustainability. The goal of this study was to identify and characterize contextual factors influencing how five California hospitals adapted and implemented RED and the subsequent impact on RED program sustainability. Methods: Participant observation and key informant and focus group interviews with 64 individuals at five California hospitals implementing RED in 2012 and 2013 were conducted. These involved hospital leadership, personnel responsible for Project RED implementation, hospital staff, and clinicians. Interview transcripts were coded and analyzed using a modified grounded theory approach and constant comparative analysis. Results: Both internal and external contextual factors were identified that influenced hospitals' decisions on RED adaptation and implementation. These also impacted RED sustainability. External factors included: impending federal penalties for hospitals with high readmission rates targeting specific diagnoses, and access to external funding and technical support to help hospitals implement RED. Internal or organizational level contextual factors included: committed leadership prioritizing Project RED; RED adaptations; depth, accountability and influence of the implementation team; sustainability planning; and hospital culture. Only three of the five hospitals continued Project RED beyond the implementation period. Conclusions: The sustainability of RED in participating hospitals was only possible when hospitals approached RED implementation as a transformational process rather than a patient safety project, maintained a high level of fidelity to the RED protocol, and had leadership and an implementation team who embraced change and failure in the pursuit of better patient care and outcomes. Hospitals who were unsuccessful in implementing a sustainable RED process lacked all or most of these components in their approach.
MeSH term(s)	California ; Focus Groups ; Hospitals ; Humans ; Leadership ; Organizational Innovation ; Patient Discharge ; Patient Safety ; Personnel, Hospital ; Program Development ; Qualitative Research
Language	English
Publishing date	2017-04-19
Publishing country	England
Document type	Journal Article
ISSN	1472-6963
ISSN (online)	1472-6963
DOI	10.1186/s12913-017-2242-z
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Article ; Online: The treatment of open femoral fractures with bone loss.

Mitchell, S E / Keating, J F / Robinson, C M

The Journal of bone and joint surgery. British volume

2010 Volume 92, Issue 12, Page(s) 1678–1684

Abstract: The results of the treatment of 31 open femoral fractures (29 patients) with significant bone loss in a single trauma unit were reviewed. A protocol of early soft-tissue and bony debridement was followed by skeletal stabilisation using a locked ... ...

Abstract	The results of the treatment of 31 open femoral fractures (29 patients) with significant bone loss in a single trauma unit were reviewed. A protocol of early soft-tissue and bony debridement was followed by skeletal stabilisation using a locked intramedullary nail or a dynamic condylar plate for diaphyseal and metaphyseal fractures respectively. Soft-tissue closure was obtained within 48 hours then followed, if required, by elective bone grafting with or without exchange nailing. The mean time to union was 51 weeks (20 to 156). The time to union and functional outcome were largely dependent upon the location and extent of the bone loss. It was achieved more rapidly in fractures with wedge defects than in those with segmental bone loss. Fractures with metaphyseal defects healed more rapidly than those of comparable size in the diaphysis. Complications were more common in fractures with greater bone loss, and included stiffness of the knee, malunion and limb-length discrepancy. Based on our findings, we have produced an algorithm for the treatment of these injuries. We conclude that satisfactory results can be achieved in most femoral fractures with bone loss using initial debridement and skeletal stabilisation to maintain length, with further procedures as required.
MeSH term(s)	Adolescent ; Adult ; Aged ; Algorithms ; Bone Plates ; Bone Transplantation/methods ; Debridement/methods ; Female ; Femoral Fractures/diagnostic imaging ; Femoral Fractures/surgery ; Follow-Up Studies ; Fracture Fixation, Internal/methods ; Fracture Fixation, Intramedullary ; Fracture Healing ; Fractures, Open/diagnostic imaging ; Fractures, Open/surgery ; Humans ; Male ; Middle Aged ; Prognosis ; Radiography ; Soft Tissue Injuries/surgery ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2010-12
Publishing country	England
Document type	Journal Article
ZDB-ID	220626-2
ISSN	2044-5377 ; 0301-620X ; 0447-9076
ISSN (online)	2044-5377
ISSN	0301-620X ; 0447-9076
DOI	10.1302/0301-620X.92B12.25190
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Article ; Online: Targeted Literature Review Of Unmet Need In The Hyperlipidaemia Population With High Risk Of Cardiovascular Disease.

Mitchell, S E / Roso, S / Samuel, M / Woods, M S / Pladevall-Vila, M

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

2014 Volume 17, Issue 7, Page(s) A476

Language	English
Publishing date	2014-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1471745-1
ISSN	1524-4733 ; 1098-3015
ISSN (online)	1524-4733
ISSN	1098-3015
DOI	10.1016/j.jval.2014.08.1363
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Article ; Online: Making a long story short: noncoding RNAs and chromosome change.

Brown, J D / Mitchell, S E / O'Neill, R J

Heredity

2011 Volume 108, Issue 1, Page(s) 42–49

Abstract: As important as the events that influence selection for specific chromosome types in the derivation of novel karyotypes, are the events that initiate the changes in chromosome number and structure between species, and likewise polymorphisms, variants and ...

Abstract	As important as the events that influence selection for specific chromosome types in the derivation of novel karyotypes, are the events that initiate the changes in chromosome number and structure between species, and likewise polymorphisms, variants and disease states within species. Although once thought of as transcriptional 'noise', noncoding RNAs (ncRNAs) are now recognized as important mediators of epigenetic regulation and chromosome stability. Here we highlight recent work that illustrates the influence short and long ncRNAs have as participants in the function and stability of chromosome regions such as centromeres, telomeres, evolutionary breakpoints and fragile sites. We summarize recent evidence that ncRNAs can facilitate chromosome change and present mechanisms by which ncRNAs create DNA breaks. Finally, we present hypotheses on how they may create novel karyotypes and thus affect chromosome evolution.
MeSH term(s)	Animals ; Chromosomal Instability ; Chromosome Breakpoints ; Chromosome Fragile Sites ; Chromosomes/genetics ; Chromosomes/metabolism ; Evolution, Molecular ; Humans ; Karyotype ; RNA, Untranslated/genetics
Chemical Substances	RNA, Untranslated
Language	English
Publishing date	2011-11-09
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2423-5
ISSN	1365-2540 ; 0018-067X
ISSN (online)	1365-2540
ISSN	0018-067X
DOI	10.1038/hdy.2011.104
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Article ; Online: Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets.

Vaanholt, L M / Milne, A / Zheng, Y / Hambly, C / Mitchell, S E / Valencak, T G / Allison, D B / Speakman, J R

Physiology & behavior

2016 Volume 154, Page(s) 1–7

Abstract: Lactation is one of the most energetically expensive behaviours, and trade-offs may exist between the energy devoted to it and somatic maintenance, including protection against oxidative damage. However, conflicting data exist for the effects of ... ...

Abstract	Lactation is one of the most energetically expensive behaviours, and trade-offs may exist between the energy devoted to it and somatic maintenance, including protection against oxidative damage. However, conflicting data exist for the effects of reproduction on oxidative stress. In the wild, a positive relationship is often observed, but in laboratory studies oxidative damage is often lower in lactating than in non-breeding animals. We hypothesised that this discrepancy may exist because during lactation food intake increases many-fold resulting in a large increase in the intake of dietary antioxidants which are typically high in laboratory rodent chow where they are added as a preservative. We supplied lactating and non-breeding control mice with either a standard or low antioxidant diet and studied how this affected the activity of endogenous antioxidants (catalase, superoxide dismutase; SOD, and glutathione peroxidise; GPx) and oxidative damage to proteins (protein carbonyls, PC) in liver and brain tissue. The low antioxidant diet did not significantly affect activities of antioxidant enzymes in brain or liver, and generally did not result in increased protein damage, except in livers of control mice on low antioxidant diet. Catalase activity, but not GPx or SOD, was decreased in both control and lactating mice on the low antioxidant diet. Lactating mice had significantly reduced oxidative damage to both liver and brain compared to control mice, independent of the diet they were given. In conclusion, antioxidant content of the diet did not affect oxidative stress in control or reproductive mice, and cannot explain the previously observed reduction in oxidative stress in lactating mammals studied in the laboratory. The reduced oxidative stress in the livers of lactating mice even under low antioxidant diet treatment was consistent with the 'shielding' hypothesis.
MeSH term(s)	Administration, Oral ; Analysis of Variance ; Animals ; Antioxidants/administration & dosage ; Body Mass Index ; Brain/drug effects ; Brain/metabolism ; Female ; Glutathione/metabolism ; Glutathione Peroxidase/metabolism ; Lactation/drug effects ; Liver/drug effects ; Liver/metabolism ; Male ; Mice ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Protein Carbonylation/drug effects ; Reproduction/drug effects ; Reproduction/physiology ; Superoxide Dismutase/metabolism ; Time Factors
Chemical Substances	Antioxidants ; Glutathione Peroxidase (EC 1.11.1.9) ; Superoxide Dismutase (EC 1.15.1.1) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2016-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2015.11.009
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