ABSTRACT
OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has proven to be a significant hardship for the entire world. Health care systems and their workers have been stretched to their limits. Research regarding whether this increased strain has affected patient safety has not been sufficient, especially in emergency medical services. The aim of this study was to determine if there has been an increased rate of adverse events in ground and helicopter emergency medical services since the onset of the COVID-19 pandemic. METHODS: A 2-year retrospective review was performed at a Midwest regional critical care transport service. The rate of adverse events for 1-year periods before and after March 13, 2020, was the primary outcome. All adverse events that generated a quality improvement incident report form (QIRF) were included, except those generated for non-clinical-related incidents. Additionally, a smaller time frame between May 1st and August 31st of both years was included containing all flagged adverse events from peer reviewers; not all of these generated a QIRF. RESULTS: In the time period between March 13, 2019, and March 12, 2020, 5 of 3,154 (0.16%) calls generated a QIRF versus 21 of 3,185 (0.66%) calls between March 13, 2020, and March 12, 2021. There was a significant relationship showing an adverse event was more likely to happen after the onset of COVID-19 compared with before (χ21 [N = 6,339] = 8.643, P ≤ .001). Additionally, from May 1st to August 31st, the total adverse event rates were 16.86% (143/848 calls) and 24.46% (387/1,582 calls) for 2019 and 2020, respectively. Similarly, statistical significance existed for adverse events occurring after onset of the pandemic versus before (χ21 [N = 2,430] = 18.253, P ≤ .001). CONCLUSION: A higher rate of adverse events for the year after the onset of COVID-19 existed. Additional studies looking at the causes of adverse events and patient outcomes should be undertaken to further understand this increase.
Subject(s)
Air Ambulances , COVID-19 , Emergency Medical Services , Humans , Retrospective Studies , COVID-19/epidemiology , Air Ambulances/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Pandemics , Patient Safety , SARS-CoV-2 , Quality ImprovementABSTRACT
Intracellular actin networks assemble through the addition of ATP-actin subunits at the growing barbed ends of actin filaments. This is followed by "aging" of the filament via ATP hydrolysis and subsequent phosphate release. Aged ADP-actin subunits thus "treadmill" through the filament before being released back into the cytoplasmic monomer pool as a result of depolymerization at filament pointed ends. The necessity for aging before filament disassembly is reinforced by preferential binding of cofilin to aged ADP-actin subunits over newly-assembled ADP-Pi actin subunits in the filament. Consequently, investigations into how cofilin influences pointed-end depolymerization have, thus far, focused exclusively on aged ADP-actin filaments. Using microfluidics-assisted Total Internal Reflection Fluorescence (mf-TIRF) microscopy, we reveal that, similar to their effects on ADP filaments, cofilin and cyclase-associated protein (CAP) also promote pointed-end depolymerization of ADP-Pi filaments. Interestingly, the maximal rates of ADP-Pi filament depolymerization by CAP and cofilin together remain approximately 20-40 times lower than for ADP filaments. Further, we find that the promotion of ADP-Pi pointed-end depolymerization is conserved for all three mammalian cofilin isoforms. Taken together, the mechanisms presented here open the possibility of newly-assembled actin filaments being directly disassembled from their pointed-ends, thus bypassing the slow step of Pi release in the aging process.
Subject(s)
Actin Cytoskeleton , Actins , Actin Cytoskeleton/metabolism , Animals , Actins/metabolism , Actin Depolymerizing Factors/metabolism , Adenosine Diphosphate/metabolism , Rabbits , Mice , Polymerization , Cofilin 1/metabolismABSTRACT
Intracellular actin networks assemble through the addition of ATP-actin subunits at the growing barbed ends of actin filaments. This is followed by "aging" of the filament via ATP hydrolysis and subsequent phosphate release. Aged ADP-actin subunits thus "treadmill" through the filament before being released back into the cytoplasmic monomer pool as a result of depolymerization at filament pointed ends. The necessity for aging before filament disassembly is reinforced by preferential binding of cofilin to aged ADP-actin subunits over newly-assembled ADP-Pi actin subunits in the filament. Consequently, investigations into how cofilin influences pointed-end depolymerization have, thus far, focused exclusively on aged ADP-actin filaments. Using microfluidics-assisted Total Internal Reflection Fluorescence (mf-TIRF) microscopy, we reveal that, similar to their effects on ADP filaments, cofilin and cyclase-associated protein (CAP) also promote pointed-end depolymerization of ADP-Pi filaments. Interestingly, the maximal rates of ADP-Pi filament depolymerization by CAP and cofilin together remain approximately 20-40 times lower than for ADP filaments. Further, we find that the promotion of ADP-Pi pointed-end depolymerization is conserved for all three mammalian cofilin isoforms. Taken together, the mechanisms presented here open the possibility of newly-assembled actin filaments being directly disassembled from their pointed-ends, thus bypassing the slow step of Pi release in the aging process.
ABSTRACT
OBJECTIVE: Intubation is a vital skill performed by flight nurses and paramedics. Before flight training, nurses do not routinely intubate and must be trained in proper techniques. Flight paramedics universally train in intubation before flight training and are the primary managers of in-flight airways. The aim of this study was to determine if a difference exists in intubation attempts and success rates between flight nurses and flight paramedics. METHODS: A 5-year retrospective chart review was performed from a regional helicopter emergency medical service. Intubation attempts and the success of flight nurses compared with flight paramedics were the primary outcomes. RESULTS: Three hundred three of 322 cases in which intubation was attempted were successful. Three hundred forty-four total intubation attempts were made. Two hundred seventy-one (88.9%) patients were intubated by paramedics, and 32 (10.5%) were intubated by nurses. Of the 19 unsuccessfully intubated patients, 14 (73.7%) were attempted by a paramedic and 5 (26.3%) by a nurse. Two hundred seventy-seven intubations were successful on the first attempt, 250 (90.3%) of which were performed by a paramedic and 27 (9.7%) by a nurse. CONCLUSION: Flight paramedics performed more intubations with greater success than flight nurses.
Subject(s)
Emergency Medical Services , Emergency Medical Technicians , Humans , Paramedics , Retrospective Studies , Intubation, Intratracheal/methods , Emergency Medical Services/methods , Emergency Medical Technicians/education , AircraftABSTRACT
OBJECTIVES: Helicopter emergency services (HEMS) serve a crucial role in the triage and transport of critically ill patients. Rapid transport to definitive care has become the goal of all prehospital EMS as shorter scene intervals have been associated with decreased mortality. Over the past several years, we have seen a rise in physicians trained in emergency medicine and EMS responding in the prehospital setting in our HEMS region. Our goal is to determine if the presence of EMS physicians on scene calls with HEMS delays time to hospital for patients. METHODS: This retrospective chart review collected on-scene time data from January 2016 to November 2020. Data were collected from our regional HEMS provider database via EMSCharts. We compared the HEMS scene intervals between calls which were serviced by HEMS crews alone, versus those where EMS physicians were present. The Wilcoxon rank-sum test was used to compare these two distributions, and a p-value <0.05 was used to determine statistical significance. RESULTS: We analyzed 1106 scene calls, four of which were excluded as they should have been designated as inter-facility transfers. Our analysis included 1079 scene calls with HEMS crews alone, and 23 scene calls with EMS physicians, with median HEMS scene intervals of 18 min and 19 min, respectively. A Wilcoxon rank-sum test comparing both distributions had a p-value of 0.30 (z= -1.04). CONCLUSION: There was no significant difference between HEMS scene intervals at calls serviced by HEMS crews alone versus those where EMS physicians were present. EMS physician presence was not associated with prolonged HEMS scene intervals.
ABSTRACT
BACKGROUND: Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. RESULTS: To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other factors that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF). CONCLUSIONS: Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.
Subject(s)
Drosophila Proteins , Infertility , Female , Animals , Drosophila , Drosophila melanogaster/genetics , Histones/genetics , Chromatin Assembly and Disassembly/genetics , Computational Biology , Drosophila Proteins/genetics , Transcription Factors/genetics , Homeodomain Proteins/genetics , Protein Serine-Threonine KinasesABSTRACT
INTRODUCTION: Repair of multiple lower extremity long bone fractures with intramedullary nail (IMN) fixation is associated with significant cardiopulmonary burden and may result in mortality. These patients are at an increased risk for fat embolism syndrome, pulmonary embolism, Acute Respiratory Distress Syndrome (ARDS), and pneumonia. No standardized guidelines exist to guide treatment of these patients. Further, there is a paucity of data regarding the risk of simultaneous versus staged fixation of multiple long bone fractures that includes both tibial and femoral injuries, as patients with multiple concomitant fractures are often excluded from relevant analyses. Our level one trauma center aimed to identify whether simultaneous fixation, defined by definitive fixation of multiple lower extremity long bone fractures during one operative event, led to increased cardiopulmonary complications as compared to a staged approach, defined as multiple operations to reach definitive fixation. PATIENTS AND METHODS: The Michigan Trauma Quality Improvement Program (MTQIP) database from 35 Level I and II trauma centers was queried to identify patients from January 2016 - December 2019. The primary outcome was incidence of cardiopulmonary complications for staged and simultaneous IMN fixation. RESULTS: We identified 11,427 patients with tibial and/or femoral fractures during the study period. 146 patients met the inclusion criteria of two or more fractures treated with IMN fixation. 118 patients underwent simultaneous IMN fixation, and 28 patients received staged IMN fixation. There were no significant differences in injury severity score (ISS), demographics, pre-existing conditions, and cardiopulmonary complications between the two groups. There was a statistically significant difference in hospital length of stay (LOS) (p = 0.0012). The median hospital LOS for simultaneous fixation was 8.3 days versus 15.8 days for the staged cohort, a difference of 7.5 days. CONCLUSION: This is the largest retrospective study to date examining simultaneous versus staged IMN fixation in patients with multiple long bone lower extremity fractures. In contrast to previous studies, we found no difference in cardiopulmonary complications. Given these findings, patients with multiple long bone lower extremity fractures should be considered for simultaneous IMN, an approach which may decrease hospital LOS.
Subject(s)
Femoral Fractures , Fracture Fixation, Intramedullary , Tibial Fractures , Humans , Fracture Fixation, Intramedullary/adverse effects , Retrospective Studies , Femoral Fractures/diagnostic imaging , Femoral Fractures/surgery , Femoral Fractures/complications , Femur , Lower Extremity , Treatment Outcome , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery , Tibial Fractures/complicationsABSTRACT
Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets and 27 factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax, Abdominal-A and Abdominal-B, suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other transcription factors that target the histone gene array: JIL-1, Hr78, the long isoform of fs(1)h as well as the generalized transcription factors TAF-1, TFIIB, and TFIIF. Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.
ABSTRACT
ABSTRACT: Traditional preventive management of patients suffering from a minor ischemic stroke and/or transient ischemic attack indicated dual antiplatelet agents for 90 days. Newer clinical trial data suggest that therapeutic effectiveness is reached much sooner than previous guideline recommendations. Continued use of dual antiplatelet therapy beyond newly studied durations of efficacy has shown an increased risk in hemorrhagic complications with little to no additional preventive benefit. This article highlights newer trial data and recognizes a significant change in therapeutic management for patients suffering a minor ischemic stroke and/or transient ischemic attack.
Subject(s)
Ischemic Attack, Transient , Ischemic Stroke , Humans , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/chemically induced , Platelet Aggregation Inhibitors/therapeutic use , Clinical Trials as TopicABSTRACT
Low-protein diets promote metabolic health in rodents and humans, and the benefits of low-protein diets are recapitulated by specifically reducing dietary levels of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. Here, we demonstrate that each BCAA has distinct metabolic effects. A low isoleucine diet reprograms liver and adipose metabolism, increasing hepatic insulin sensitivity and ketogenesis and increasing energy expenditure, activating the FGF21-UCP1 axis. Reducing valine induces similar but more modest metabolic effects, whereas these effects are absent with low leucine. Reducing isoleucine or valine rapidly restores metabolic health to diet-induced obese mice. Finally, we demonstrate that variation in dietary isoleucine levels helps explain body mass index differences in humans. Our results reveal isoleucine as a key regulator of metabolic health and the adverse metabolic response to dietary BCAAs and suggest reducing dietary isoleucine as a new approach to treating and preventing obesity and diabetes.
Subject(s)
Amino Acids, Branched-Chain/metabolism , Diet , Isoleucine/metabolism , Valine/metabolism , Adipose Tissue, White/metabolism , Animals , Body Mass Index , Diet/veterinary , Energy Metabolism , Fibroblast Growth Factors/deficiency , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Humans , Liver/metabolism , Male , Mechanistic Target of Rapamycin Complex 1/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Obesity/metabolism , Obesity/pathology , Protein Serine-Threonine Kinases/metabolism , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolismABSTRACT
S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate epigenetic states and subsequent gene expression. This metabolism-epigenome link sensitizes chromatin methylation to altered SAM abundance, yet the mechanisms that allow organisms to adapt and protect epigenetic information during life-experienced fluctuations in SAM availability are unknown. We identified a robust response to SAM depletion that is highlighted by preferential cytoplasmic and nuclear mono-methylation of H3 Lys 9 (H3K9) at the expense of broad losses in histone di- and tri-methylation. Under SAM-depleted conditions, H3K9 mono-methylation preserves heterochromatin stability and supports global epigenetic persistence upon metabolic recovery. This unique chromatin response was robust across the mouse lifespan and correlated with improved metabolic health, supporting a significant role for epigenetic adaptation to SAM depletion in vivo. Together, these studies provide evidence for an adaptive response that enables epigenetic persistence to metabolic stress.
Subject(s)
DNA Methylation/genetics , Heterochromatin/genetics , Metabolome/genetics , S-Adenosylmethionine/metabolism , Animals , Cell Nucleus/genetics , Cell Nucleus/metabolism , Chromatin/genetics , Cytoplasm/genetics , Cytoplasm/metabolism , Epigenesis, Genetic/genetics , Gene Expression Regulation/genetics , HCT116 Cells , Heterochromatin/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histones/genetics , Humans , Methionine/genetics , Mice , Protein Processing, Post-Translational/genetics , Proteomics/methodsABSTRACT
Calorie restriction (CR) extends the healthspan and lifespan of diverse species. In mammals, a broadly conserved metabolic effect of CR is improved insulin sensitivity, which may mediate the beneficial effects of a CR diet. This model has been challenged by the identification of interventions that extend lifespan and healthspan yet promote insulin resistance. These include rapamycin, which extends mouse lifespan yet induces insulin resistance by disrupting mTORC2 (mechanistic target of rapamycin complex 2). Here, we induce insulin resistance by genetically disrupting adipose mTORC2 via tissue-specific deletion of the mTORC2 component Rictor (AQ-RKO). Loss of adipose mTORC2 blunts the metabolic adaptation to CR and prevents whole-body sensitization to insulin. Despite this, AQ-RKO mice subject to CR experience the same increase in fitness and lifespan on a CR diet as wild-type mice. We conclude that the CR-induced improvement in insulin sensitivity is dispensable for the effects of CR on fitness and longevity.
Subject(s)
Adiposity/physiology , Insulin Resistance/physiology , Insulin/metabolism , Mechanistic Target of Rapamycin Complex 2/metabolism , Adiposity/drug effects , Animals , Caloric Restriction/methods , Energy Intake/drug effects , Energy Intake/physiology , Humans , Longevity/drug effects , Longevity/physiology , Mice , Mice, Inbred C57BL , Signal Transduction/drug effects , Signal Transduction/physiology , Sirolimus/pharmacologyABSTRACT
The wide applications of lithium intercalating complex metal oxides in energy storage devices call for a better understanding of their environmental impact at the end of their life cycle. In this study, we examine the biological impact of a panel of nanoscale lithium nickel manganese cobalt oxides (Li x Ni y Mn z Co1-y-z O2, 0 < x, y, z < 1, abbreviated to NMCs) to a model Gram-positive bacterium, Bacillus subtilis, in terms of cellular respiration and growth. A highly sensitive single-cell gel electrophoresis method is also applied for the first time to understand the genotoxicity of these nanomaterials to bacterial cells. Results from these assays indicate that the free Ni and Co ions released from the incongruent dissolution of the NMC material in B. subtilis growth medium induced both hindered growth and cellular respiration. More remarkably, the DNA damage induced by the combination of the two ions in solution is comparable to that induced by the NMC material, which suggests that the free Ni and Co ions are responsible for the toxicity observed. A material redesign by enriching Mn is also presented. The combined approaches of evaluating their impact on bacterial growth, respiration, and DNA damage at a single-cell level, as well as other phenotypical changes allows us to probe the nanomaterials and bacterial cells from a mechanistic prospective, and provides a useful means to an understanding of bacterial response to new potential environmental stressors.
ABSTRACT
Queen conch (Lobatus gigas) is a marine gastropod endemic to the Caribbean. This species is a cultural symbol, being a significant local food source and the second largest commercial fishery in the region. However, over-exploitation and natural habitat degradation have exerted high survival pressure on this species. This work aims to provide novel proteomic data to highlight the metabolism of the species and to provide an important tool for the understanding of queen conch biology and physiology. Herein, we profiled the whole proteome from 3 organs (gills, digestive gland and muscle) of L. gigas combining gel-free and gel-based techniques. Overall 420 clusters of proteins were identified corresponding to the minimum identification requirement of protein sequence redundancy. Gene ontology and KEGG analysis highlighted 59 metabolic pathways between identified proteins. The most relevant routes according to the number of sequences found per pathway were purine and thiamine metabolism, closely related to nucleotide and carbohydrate metabolism. We also emphasize the high number of proteins associated to the biosynthesis of antibiotics (93 proteins and a total of 28 enzymes), which were among the top-twenty pathways identified by KEGG analysis. The proteomics approach allowed the identification and description of putative markers of oxidative stress, xenobiotic metabolism, heat shock response and respiratory chain for the first time in the species, which could be extremely useful in future investigations for diagnosing and monitoring L. gigas population health.
Subject(s)
Gastropoda/metabolism , Proteome , Animals , Databases, Protein , Proteomics/methodsABSTRACT
Early diagnosis of endometritis in dairy cattle is currently requires invasive techniques and specialist expertise. The goal of this study is to utilize a gel-free mass-spectrometry based proteomics approach to compare the plasma proteome of dairy cattle with cytological endometritis to those without. Blood samples were collected from cows (Nâ¯=â¯112) seven days postpartum (DPP). Plasma samples from a cohort of 20 animals with cytological endometritis (nâ¯=â¯10) and without (nâ¯=â¯10) as classified 21 DPP were selected for proteomic analysis. Differential abundances of proteins between the two animal groups were determined using both fold change (≥1.5 fold change) and statistical significance threshold (pâ¯<â¯.05). A total of 181 non-redundant proteins were quantified, and 25 proteins were found with differential abundance. These include 4 binding protein alpha and mannose binding lectin 2 involved in immune responses. Differentially abundant proteins between the animals were then processed using PANTHER for gene ontology. Gene ontology included associations with innate immune processes, acute phase responses and immune regulation. A potential marker for disease identified here is the "uncharacterized protein G5E513," a protein previously defined by RNA-transcripts. These proteins may form the basis for endometritis prognosis, the development of which is proceeded by systemic changes in immune function. SIGNIFICANCE: Endometritis is a costly reproductive disease of lactating dairy cows that warrants timely diagnosis. We utilized a gel-free mass-spectrometry based proteomics approach to compare the plasma proteome of dairy cattle with cytological endometritis to those without, for the characterization of changes in the proteomic profile associated with uterine disease postpartum. Furthermore, we compared the plasma proteome of healthy and affected cows in the same physiological status of production to better understand the relationship between changes in expression of circulating proteins and to unravel essential biological mechanisms involved in bovine cytological endometritis.
Subject(s)
Blood Proteins/metabolism , Cattle Diseases/blood , Endometritis/blood , Lactation/metabolism , Proteome/metabolism , Animals , Biomarkers/analysis , Biomarkers/blood , Blood Proteins/analysis , Cattle , Cattle Diseases/metabolism , Cattle Diseases/pathology , Cell Biology , Dairying , Endometritis/metabolism , Endometritis/pathology , Female , Postpartum Period , Proteome/analysis , Puerperal Disorders/blood , Puerperal Disorders/metabolism , Puerperal Disorders/pathology , Puerperal Disorders/veterinaryABSTRACT
Seasonal weight loss (SWL) is a primary constraint for farmers in the Mediterranean and tropics. One cost-effective solution to SWL is utilizing breeds like the Damara sheep that have adapted to deal with nutritional stress. Previous studies concluded that one of the adaptation mechanisms of SWL is a specialized fatty acid metabolism. Accordingly, hepatic-mitochondrial proteomes were compared across two different breeds (24 sheep total, Merino, n = 12 and Damara, n = 12) and two different diets (restricted vs unrestricted diet, 6 per breed, per diet, 24 total). Mitochondrial-proteins were isolated and relatively quantified using Blue native PAGE / 2D-electrophoresis and then analyzed via mass spectrometry. The tool ReviGO summarized the proteomes' gene-ontology terms. A total of 50 proteins were identified with 7 changing significantly in abundance (ANOVA p-value<0.05). Specific abundance patterns of corticosteroid and inflammatory response-associated proteins such as annexin and glutamate dehydrogenase suggests that the Damara has an unusual inflammation response when subjected to SWL in addition to its unique metabolism. All significant proteins warrant further study; Annexin in particular shows promise as a potentially useful biomarker.
Subject(s)
Mitochondria, Liver/metabolism , Mitochondrial Proteins/metabolism , Sheep/physiology , Animals , Breeding , Mitochondria, Liver/chemistry , Mitochondrial Proteins/analysis , Proteome/analysis , Proteome/metabolism , Seasons , Weight LossABSTRACT
The effect of feed restriction on the liver protein profiles of two different breeds of sheep was studied. We compared Merino with the Damara, breeds with respectively low and high tolerance to nutritional stress. Each breed was grouped into two nutritional treatments: restricted (12-14% loss of live weight) and control (maintenance). The trial lasted 42â¯days. Animals were sacrificed and liver samples subjected to label free shotgun proteomics. The resultant proteins had both their fold change and statistical significance in an unpaired t-test calculated to identify differential protein abundance. The tool WebGestalt was utilized to perform an Overrepresentation Enrichment Analysis (ORA) for gene ontology terms associated with the significant proteins. We further validated shotgun proteomics findings using a selected reaction monitoring (SRM)-based targeted proteomics approach, where similar trends in regulation were obtained for a subset of relevant proteins across an independent cohort of animals. Results confirm that Damara has adapted to nutritional stress by mobilizing stored fatty acids within adipose tissue and converting them to energy more efficiently than Merino. Finally, Merino had an overabundance pattern primarily directed to protein synthesis pathways. Regulated proteins identified may be used as a basis for marker selection towards tolerance to nutritional stress. BIOLOGICAL SIGNIFICANCE: Sheep are one of the most important livestock animals. They remain however poorly understudied and described. Seasonal weight loss (SWL) due to pasture scarcity during the dry season is one of the most limiting conditions to ruminant production in the tropics. To counter SWL, farmers may use supplementation, expensive or difficult to implement. A more suitable long-term solution would be to use breeds that are naturally adapted to nutritional stress. This work contrasts two breeds with different levels of tolerance to SWL, the Damara and the Merino, respectively well and poorly adapted. Comparison is conducted at the level of the hepatic tissue and using label free proteomics. This work identifies a series of pathways in the liver of the Damara via label free proteomics that suggest a unique fatty acid metabolic process within this breed. Proteins that have increased abundance in the Damara in association with fatty acid metabolism may be used as potential markers of tolerance to nutritional stress. This research will pave the way for more viable, long-term solutions for farmers facing annual production problems due to drought in the tropics and the Mediterranean region.
Subject(s)
Liver/chemistry , Proteome/metabolism , Seasons , Weight Loss , Adaptation, Physiological , Animals , Biomarkers/analysis , Fatty Acids/metabolism , Nutrients/deficiency , Proteomics/methods , Sheep, Domestic , Species Specificity , Stress, PhysiologicalABSTRACT
Obesity and diabetes are major challenges to global health, and there is an urgent need for interventions that promote weight loss. Dietary restriction of methionine promotes leanness and improves metabolic health in mice and humans. However, poor long-term adherence to this diet limits its translational potential. In this study, we develop a short-term methionine deprivation (MD) regimen that preferentially reduces fat mass, restoring normal body weight and glycemic control to diet-induced obese mice of both sexes. The benefits of MD do not accrue from calorie restriction, but instead result from increased energy expenditure. MD promotes increased energy expenditure in a sex-specific manner, inducing the fibroblast growth factor (Fgf)-21-uncoupling protein (Ucp)-1 axis only in males. Methionine is an agonist of the protein kinase mechanistic target of rapamycin complex (mTORC)-1, which has been proposed to play a key role in the metabolic response to amino acid-restricted diets. In our study, we used a mouse model of constitutive hepatic mTORC1 activity and demonstrate that suppression of hepatic mTORC1 signaling is not required for the metabolic effects of MD. Our study sheds new light on the mechanisms by which dietary methionine regulates metabolic health and demonstrates the translational potential of MD for the treatment of obesity and type 2 diabetes.-Yu, D., Yang, S. E., Miller, B. R., Wisinski, J. A., Sherman, D. S., Brinkman, J. A., Tomasiewicz, J. L., Cummings, N. E., Kimple, M. E., Cryns, V. L., Lamming, D. W. Short-term methionine deprivation improves metabolic health via sexually dimorphic, mTORC1-independent mechanisms.
Subject(s)
Energy Metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Methionine/deficiency , Obesity/metabolism , Sex Characteristics , Animals , Caloric Restriction , Female , Fibroblast Growth Factors/metabolism , Male , Mice , Obesity/diet therapy , Obesity/pathology , Uncoupling Protein 1/metabolismABSTRACT
The purpose of this study was to compare the clinical outcome, union rate, and complications of a consecutive series of Scaphoid excision and limited wrist arthrodesis performed by a single surgeon using distal radius bone graft and K-wires or circular plate fixation. A sequential series of ten patients(11 wrists) who were stabilized with temporary K-wires were compared to 11 patients (11 wrists) who were stabilized with a circular plate. Minimum follow-up was 1 year. One patient in the K-wire group was converted to a wrist fusion. Six of the remaining ten patients in the K-wire fixation group and 8 of the 11 patients in the circular plate fixation group returned for the following blinded evaluations: Quick DASH, analog pain scale, range of motion, grip and pinch strength, plain x-ray, and multi-detector computed tomography evaluation. One non-union occurred in the K-wire group. There were no non-unions in the circular plate fixation group. There was no difference in any of remaining measures or rate of complications. This study shows that equivalent results can be obtained using circular plate fixation compared to K-wires when equivalent bone graft source and fusion technique are used. If K-wire removal requires a return to the OR, circular plate fixation is more cost-effective.
ABSTRACT
PURPOSE: The goal was to register physical training volume and to measure changes in physical fitness in soldiers during a peacekeeping mission. The relationship between these factors and motivation for physical training was also investigated. METHODS: Physical training volume was registered and maximal oxygen uptake, 3-km run time, sit-ups, push-ups, and chin-ups were tested before and after 1 year of service for 71 Norwegian soldiers in the international Kosovo Force. Self-determined motivation was measured at the end of the service. RESULTS: Physical training volume was 117 +/- 77 minutes/week. The average maximal oxygen uptake decreased by 2.5 +/- 0.8% (p < 0.01). Intrinsic motivation positively predicted physical training volume (p < 0.01). CONCLUSIONS: A large variation in training volume was found, and only one-third of the soldiers improved physical fitness and maintained body weight. Fostering intrinsic motivation toward physical training is key to increasing training volume. However, obligatory training could ensure a minimum of physical training among the soldiers who were least motivated for physical training.