Discordant skeletal muscle gene and protein responses to exercise.

The ability of skeletal muscle to adapt to repeated contractile stimuli is one of the most intriguing aspects of physiology. The molecular bases underpinning these adaptations involve increased protein activity and/or expression, mediated by an array of pre- and post-transcriptional processes, as well as translational and post-translational control. A longstanding dogma assumes a direct relationship between exercise-induced increases in mRNA levels and subsequent changes in the abundance of the proteins they encode. Drawing on the results of recent studies, we dissect and question the common assumption of a direct relationship between changes in the skeletal muscle transcriptome and proteome induced by repeated muscle contractions (e.g., exercise).

Resistance-only and concurrent exercise induce similar myofibrillar protein synthesis rates and associated molecular responses in moderately active men before and after training.

Aerobic and resistance exercise (RE) induce distinct molecular responses. One hypothesis is that these responses are antagonistic and unfavorable for the anabolic response to RE when concurrent exercise is performed. This thesis may also depend on the participants' training status and concurrent exercise order. We measured free-living myofibrillar protein synthesis (MyoPS) rates and associated molecular responses to resistance-only and concurrent exercise (with different exercise orders), before and after training. Moderately active men completed one of three exercise interventions (matched for age, baseline strength, body composition, and aerobic capacity): resistance-only exercise (RE, n = 8), RE plus high-intensity interval exercise (RE+HIIE, n = 8), or HIIE+RE (n = 9). Participants trained 3 days/week for 10 weeks; concurrent sessions were separated by 3 h. On the first day of Weeks 1 and 10, muscle was sampled immediately before and after, and 3 h after each exercise mode and analyzed for molecular markers of MyoPS and muscle glycogen. Additional muscle, sampled pre- and post-training, was used to determine MyoPS using orally administered deuterium oxide (D2 O). In both weeks, MyoPS rates were comparable between groups. Post-exercise changes in proteins reflective of protein synthesis were also similar between groups, though MuRF1 and MAFbx mRNA exhibited some exercise order-dependent responses. In Week 10, exercise-induced changes in MyoPS and some genes (PGC-1ɑ and MuRF1) were dampened from Week 1. Concurrent exercise (in either order) did not compromise the anabolic response to resistance-only exercise, before or after training. MyoPS rates and some molecular responses to exercise are diminished after training.

Small peptides: could they have a big role in metabolism and the response to exercise?

Exercise is a powerful non-pharmacological intervention for the treatment and prevention of numerous chronic diseases. Contracting skeletal muscles provoke widespread perturbations in numerous cells, tissues and organs, which stimulate multiple integrated adaptations that ultimately contribute to the many health benefits associated with regular exercise. Despite much research, the molecular mechanisms driving such changes are not completely resolved. Technological advancements beginning in the early 1960s have opened new avenues to explore the mechanisms responsible for the many beneficial adaptations to exercise. This has led to increased research into the role of small peptides (<100 amino acids) and mitochondrially derived peptides in metabolism and disease, including those coded within small open reading frames (sORFs; coding sequences that encode small peptides). Recently, it has been hypothesized that sORF-encoded mitochondrially derived peptides and other small peptides play significant roles as exercise-sensitive peptides in exercise-induced physiological adaptation. In this review, we highlight the discovery of mitochondrially derived peptides and newly discovered small peptides involved in metabolism, with a specific emphasis on their functions in exercise-induced adaptations and the prevention of metabolic diseases. In light of the few studies available, we also present data on how both single exercise sessions and exercise training affect expression of sORF-encoded mitochondrially derived peptides. Finally, we outline numerous research questions that await investigation regarding the roles of mitochondrially derived peptides in metabolism and prevention of various diseases, in addition to their roles in exercise-induced physiological adaptations, for future studies.

Structural maturation of myofilaments in engineered 3D cardiac microtissues characterized using small angle x-ray scattering.

Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, and designing therapies. Here we use a method not commonly applied to biological materials, small angle x-ray scattering, to characterize the structural development of hiPSC-CMs within three-dimensional engineered tissues during their preliminary stages of maturation. An x-ray scattering experimental method enables the reliable characterization of the cardiomyocyte myofilament spacing with maturation time. The myofilament lattice spacing monotonically decreases as the tissue matures from its initial post-seeding state over the span of 10 days. Visualization of the spacing at a grid of positions in the tissue provides an approach to characterizing the maturation and organization of cardiomyocyte myofilaments and has the potential to help elucidate mechanisms of pathophysiology, and disease progression, thereby stimulating new biological hypotheses in stem cell engineering.

The effect of sleep restriction, with or without high-intensity interval exercise, on behavioural alertness and mood state in young healthy males.

Mood state and alertness are negatively affected by sleep loss, and can be positively influenced by exercise. However, the potential mitigating effects of exercise on sleep-loss-induced changes in mood state and alertness have not been studied comprehensively. Twenty-four healthy young males were matched into one of three, 5-night sleep interventions: normal sleep (NS; total sleep time (TST) per night = 449 ± 22 min), sleep restriction (SR; TST = 230 ± 5 min), or sleep restriction and exercise (SR + EX; TST = 235 ± 5 min, plus three sessions of high-intensity interval exercise (HIIE)). Mood state was assessed using the profile of mood states (POMS) and a daily well-being questionnaire. Alertness was assessed using psychomotor vigilance testing (PVT). Following the intervention, POMS total mood disturbance scores significantly increased for both the SR and SR + EX groups, and were greater than the NS group (SR vs NS; 31.0 ± 10.7 A.U., [4.4-57.7 A.U.], p = 0.020; SR + EX vs NS; 38.6 ± 14.9 A.U., [11.1-66.1 A.U.], p = 0.004). The PVT reaction times increased in the SR (p = 0.049) and SR + EX groups (p = 0.033) and the daily well-being questionnaire revealed increased levels of fatigue in both groups (SR; p = 0.041, SR + EX; p = 0.026) during the intervention. Despite previously demonstrated physiological benefits of performing three sessions of HIIE during five nights of sleep restriction, the detriments to mood, wellness, and alertness were not mitigated by exercise in this study. Whether alternatively timed exercise sessions or other exercise protocols could promote more positive outcomes on these factors during sleep restriction requires further research.

Immunolabelling perturbs the endogenous and antibody-conjugated elemental concentrations during immuno-mass spectrometry imaging.

Immuno-mass spectrometry imaging uses lanthanide-conjugated antibodies to spatially quantify biomolecules via laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The multi-element capabilities allow for highly multiplexed analyses that may include both conjugated antibodies and endogenous metals to reveal relationships between disease and chemical composition. Sample handling is known to perturb the composition of the endogenous elements, but there has been little investigation into the effects of immunolabelling and coverslipping. Here, we used cryofixed muscle sections to examine the impact of immunolabelling steps on the concentrations of a Gd-conjugated anti-dystrophin primary antibody, and the endogenous metals Cu and Zn. Primary antibody incubation resulted in a decrease in Zn, and an increase in Cu. Zn was removed from the cytoplasm where it was hypothesised to be more labile, whereas concentrated locations of Zn remained in the cell membrane in all samples that underwent the immunostaining process. Cu increased in concentration and was found mostly in the cell membrane. The concentration of the Gd-conjugated antibody when compared to the standard air-dried sample was not significantly different when coverslipped using an organic mounting medium, whereas use of an aqueous mounting medium significantly reduced the concentration of Gd. These results build on the knowledge of how certain sample handling techniques change elemental concentrations and distributions in tissue sections. Immunolabelling steps impact the concentration of endogenous elements, and separate histological sections are required for the quantitative analysis of endogenous elements and biomolecules. Additionally, coverslipping tissue sections for complementary immunohistochemical/immunofluorescent imaging may compromise the integrity of the elemental label, and organic mounting media are recommended over aqueous mounting media.

Method of Anesthesia and Perioperative Risk Factors, Maternal Anesthesia Complications, and Neonatal Mortality Following Cesarean Delivery in Africa: A Substudy of a 7-Day Prospective Observational Cohort Study.

BACKGROUND: The African Surgical Outcomes Study (ASOS) found that maternal mortality following cesarean delivery in Africa is 50 times higher than in high-income countries, and associated with obstetric hemorrhage and anesthesia complications. Mothers who died were more likely to receive general anesthesia (GA). The associations between GA versus spinal anesthesia (SA) and preoperative risk factors, maternal anesthesia complications, and neonatal outcomes following cesarean delivery in Africa are unknown. METHODS: This is a secondary explanatory analysis of 3792 patients undergoing cesarean delivery in ASOS, a prospective observational cohort study, across 22 African countries. The primary aim was to estimate the association between preoperative risk factors and the outcome of the method of anesthesia delivered. Secondary aims were to estimate the association between the method of anesthesia and the outcomes (1) maternal intraoperative hypotension, (2) severe maternal anesthesia complications, and (3) neonatal mortality. Generalized linear mixed models adjusting for obstetric gravidity and gestation, American Society of Anesthesiologists (ASA) category, urgency of surgery, maternal comorbidities, fetal distress, and level of anesthesia provider were used. RESULTS: Of 3709 patients, SA was performed in 2968 (80%) and GA in 741 (20%). Preoperative factors independently associated with GA for cesarean delivery were gestational age (adjusted odds ratio [aOR], 1.093; 95% confidence interval [CI], 1.052-1.135), ASA categories III (aOR, 11.84; 95% CI, 2.93-46.31) and IV (aOR, 11.48; 95% CI, 2.93-44.93), eclampsia (aOR, 3.92; 95% CI, 2.18-7.06), placental abruption (aOR, 6.23; 95% CI, 3.36-11.54), and ruptured uterus (aOR, 3.61; 95% CI, 1.36-9.63). SA was administered to 48 of 94 (51.1%) patients with eclampsia, 12 of 28 (42.9%) with cardiac disease, 14 of 19 (73.7%) with preoperative sepsis, 48 of 76 (63.2%) with antepartum hemorrhage, 30 of 55 (54.5%) with placenta previa, 33 of 78 (42.3%) with placental abruption, and 12 of 29 (41.4%) with a ruptured uterus. The composite maternal outcome "all anesthesia complications" was more frequent in GA than SA (9/741 [1.2%] vs 3/2968 [0.1%], P < .001). The unadjusted neonatal mortality was higher with GA than SA (65/662 [9.8%] vs 73/2669 [2.7%], P < .001). The adjusted analyses demonstrated no association between method of anesthesia and (1) intraoperative maternal hypotension and (2) neonatal mortality. CONCLUSIONS: Analysis of patients undergoing anesthesia for cesarean delivery in Africa indicated patients more likely to receive GA. Anesthesia complications and neonatal mortality were more frequent following GA. SA was often administered to high-risk patients, including those with eclampsia or obstetric hemorrhage. Training in the principles of selection of method of anesthesia, and the skills of safe GA and neonatal resuscitation, is recommended.

Analysis of a 5-year, evidenced-based, rational blood utilisation project in a South African regional hospital.

BACKGROUND: Blood products are a lifesaving but limited resource, particularly in resource-limited settings. Evidence-based transfusion criteria tailored to local hospitals have shown great promise in reducing costs, minimising shortages, and ameliorating the morbidity and mortality associated with liberal blood product usage. We implemented the "Saving Blood, Saving Lives" project to: promote responsible blood product use and reduce blood product ordering inefficiencies and expenditure. METHODS: A comprehensive change management programme, preceded by 3 months of clinical department consultation and training, was implemented. A new evidence-based protocol for blood product utilisation was developed, together with an accountability form. This form was used in monthly audit meetings to refine policies, identify new problems, improve communication, and to drive hospital staff accountability and training. The primary measure of the programme's success was the change in the number of red cell concentrate units ordered. RESULTS: Project implementation required minimal time and no additional budget or staff. Annual red cell concentrate usage reduced from 7211 units in year one to 4077 units in year 5 (p < 0.001). Similar reductions were seen in freeze-dried plasma and platelet usage, as well as administrative costs. Total project saving, adjusted to baseline admission numbers, amounted to over R46 million ($2.5 million). CONCLUSIONS: As a change management programme centred the "Saving Blood, Saving Lives" project, was able to significantly reduce blood product-related administration and expenditure by implementing evidence-based transfusion criteria. The programme is simple, replicable and cost effective, making it ideally suited for use in resource-constrained environments.

Autophagy and Exercise: Current Insights and Future Research Directions.

Autophagy is a cellular process by which proteins and organelles are degraded inside the lysosome. Exercise is known to influence the regulation of autophagy in skeletal muscle. However, as gold standard techniques to assess autophagy flux in vivo are restricted to animal research, important gaps remain in our understanding of how exercise influences autophagy activity in humans. Using available datasets, we show how the gene expression profile of autophagy receptors and ATG8 family members differ between human and mouse skeletal muscle, providing a potential explanation for their differing exercise-induced autophagy responses. Furthermore, we provide a comprehensive view of autophagy regulation following exercise in humans by summarizing human transcriptomic and phosphoproteomic datasets that provide novel targets of potential relevance. These newly identified phosphorylation sites may provide an explanation as to why both endurance and resistance exercise lead to an exercise-induced reduction in LC3B-II, while possibly divergently regulating autophagy receptors, and, potentially, autophagy flux. We also provide recommendations to use ex vivo autophagy flux assays to better understand the influence of exercise, and other stimuli, on autophagy regulation in humans. This review provides a critical overview of the field and directs researchers towards novel research areas that will improve our understanding of autophagy regulation following exercise in humans.

Lipid Spectrum Generator: A Simple Script for the Generation of Accurate In Silico Lipid Fragmentation Spectra.

Due to the complexity of lipids in nature, the use of in silico generated spectral libraries to identify lipid species from mass spectral data has become an integral part of many lipidomic workflows. However, many in silico libraries are either limited in usability or their capacity to represent lipid species. Here, we introduce Lipid Spectrum Generator, an open-source in silico spectral library generator specifically designed to aid in the identification of lipids in liquid chromatography-tandem mass spectrometry analysis.

Investigation of product-derived lymphoma following infusion of piggyBac-modified CD19 chimeric antigen receptor T cells.

We performed a phase 1 clinical trial to evaluate outcomes in patients receiving donor-derived CD19-specific chimeric antigen receptor (CAR) T cells for B-cell malignancy that relapsed or persisted after matched related allogeneic hemopoietic stem cell transplant. To overcome the cost and transgene-capacity limitations of traditional viral vectors, CAR T cells were produced using the piggyBac transposon system of genetic modification. Following CAR T-cell infusion, 1 patient developed a gradually enlarging retroperitoneal tumor due to a CAR-expressing CD4+ T-cell lymphoma. Screening of other patients led to the detection, in an asymptomatic patient, of a second CAR T-cell tumor in thoracic para-aortic lymph nodes. Analysis of the first lymphoma showed a high transgene copy number, but no insertion into typical oncogenes. There were also structural changes such as altered genomic copy number and point mutations unrelated to the insertion sites. Transcriptome analysis showed transgene promoter-driven upregulation of transcription of surrounding regions despite insulator sequences surrounding the transgene. However, marked global changes in transcription predominantly correlated with gene copy number rather than insertion sites. In both patients, the CAR T-cell-derived lymphoma progressed and 1 patient died. We describe the first 2 cases of malignant lymphoma derived from CAR gene-modified T cells. Although CAR T cells have an enviable record of safety to date, our results emphasize the need for caution and regular follow-up of CAR T recipients, especially when novel methods of gene transfer are used to create genetically modified immune therapies. This trial was registered at www.anzctr.org.au as ACTRN12617001579381.

A Comprehensive Phylogenomic Platform for Exploring the Angiosperm Tree of Life.

The tree of life is the fundamental biological roadmap for navigating the evolution and properties of life on Earth, and yet remains largely unknown. Even angiosperms (flowering plants) are fraught with data gaps, despite their critical role in sustaining terrestrial life. Today, high-throughput sequencing promises to significantly deepen our understanding of evolutionary relationships. Here, we describe a comprehensive phylogenomic platform for exploring the angiosperm tree of life, comprising a set of open tools and data based on the 353 nuclear genes targeted by the universal Angiosperms353 sequence capture probes. The primary goals of this article are to (i) document our methods, (ii) describe our first data release, and (iii) present a novel open data portal, the Kew Tree of Life Explorer (https://treeoflife.kew.org). We aim to generate novel target sequence capture data for all genera of flowering plants, exploiting natural history collections such as herbarium specimens, and augment it with mined public data. Our first data release, described here, is the most extensive nuclear phylogenomic data set for angiosperms to date, comprising 3099 samples validated by DNA barcode and phylogenetic tests, representing all 64 orders, 404 families (96$\%$) and 2333 genera (17$\%$). A "first pass" angiosperm tree of life was inferred from the data, which totaled 824,878 sequences, 489,086,049 base pairs, and 532,260 alignment columns, for interactive presentation in the Kew Tree of Life Explorer. This species tree was generated using methods that were rigorous, yet tractable at our scale of operation. Despite limitations pertaining to taxon and gene sampling, gene recovery, models of sequence evolution and paralogy, the tree strongly supports existing taxonomy, while challenging numerous hypothesized relationships among orders and placing many genera for the first time. The validated data set, species tree and all intermediates are openly accessible via the Kew Tree of Life Explorer and will be updated as further data become available. This major milestone toward a complete tree of life for all flowering plant species opens doors to a highly integrated future for angiosperm phylogenomics through the systematic sequencing of standardized nuclear markers. Our approach has the potential to serve as a much-needed bridge between the growing movement to sequence the genomes of all life on Earth and the vast phylogenomic potential of the world's natural history collections. [Angiosperms; Angiosperms353; genomics; herbariomics; museomics; nuclear phylogenomics; open access; target sequence capture; tree of life.].

Tranexamic acid at cesarean delivery: drug-error deaths.

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.

Combining CD34+ stem cell selection with prophylactic pathogen and leukemia directed T-cell immunotherapy to simultaneously reduce graft versus host disease, infection, and leukemia recurrence after allogeneic stem cell transplant.

We designed a trial to simultaneously address the problems of graft versus host disease (GVHD), infection, and recurrence of malignancy after allogeneic stem cell transplantation. CD34+ stem cell isolation was used to minimize the development of acute and chronic GVHD. Two prophylactic infusions, one combining donor-derived cytomegalovirus, Epstein-Barr virus, and Aspergillus fumigatus specific T-cells and the other comprising donor-derived CD19 directed chimeric antigen receptor (CAR) bearing T-cells, were given 21-28 days after transplant. Two patients were transplanted for acute lymphoblastic leukemia from HLA identical siblings using standard doses of cyclophosphamide and total body irradiation without antilymphocyte globulin. Patients received no post-transplant immune suppression and were given no pre-CAR T-cell lymphodepletion. Neutrophil and platelet engraftment was prompt. Following adoptive T-cell infusions, there was rapid appearance of antigen-experienced CD8+ and to a lesser extent CD4+ T-cells. Tetramer-positive T-cells targeting CMV and EBV appeared rapidly after T-cell infusion and persisted for at least 1 year. CAR T-cell expansion occurred and persisted for up to 3 months. T-cell receptor tracking confirmed the presence of product-derived T-cell clones in blood targeting all three pathogens. Both patients are alive over 3 years post-transplant without evidence of GVHD or disease recurrence. Combining robust donor T-cell depletion with directed T-cell adoptive immunotherapy targeting infectious and malignant antigens permits independent modulation of GVHD, infection, and disease recurrence. The combination may separate GVHD from the graft versus tumor effect, accelerate immune reconstitution, and improve transplant tolerability.

Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging in Biology.

Elemental imaging gives insight into the fundamental chemical makeup of living organisms. Every cell on Earth is comprised of a complex and dynamic mixture of the chemical elements that define structure and function. Many disease states feature a disturbance in elemental homeostasis, and understanding how, and most importantly where, has driven the development of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) as the principal elemental imaging technique for biologists. This review provides an outline of ICP-MS technology, laser ablation cell designs, imaging workflows, and methods of quantification. Detailed examples of imaging applications including analyses of cancers, elemental uptake and accumulation, plant bioimaging, nanomaterials in the environment, and exposure science and neuroscience are presented and discussed. Recent incorporation of immunohistochemical workflows for imaging biomolecules, complementary and multimodal imaging techniques, and image processing methods is also reviewed.

Tranexamic acid at cesarean delivery: drug-error deaths.

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.

The effect of caffeine on exercise performance is not influenced by ADORA2A genotypes, alone or pooled with CYP1A2 genotypes, in adolescent athletes.

PURPOSE: This study investigated the influence of the different genotypes of ADORA2A (1976 C > T, rs 5751876), alone or pooled with CYP1A2 (163 C > A rs 762551) genotypes, on the ergogenic effects of caffeine (CAF) on various aspects of physical performance in male adolescent athletes. METHODS: Ninety male adolescent athletes (age = 15.5 ± 2 years) were classified according to their genotypes for 1976 C > T ADORA2A (TT homozygous or CADORA2A allele carriers) and 163 C > A CYP1A2 (AA homozygous or CCYP1A2 allele carriers). Participants were further divided in four groups (1-TTADORA2A + AACYP1A2; 2-TTADORA2A + AC/CCCYP1A2; 3-AACYP1A2 + CT/CCADORA2A;4-AC/CCCYP1A2 + CT/CCADORA2A). Using a randomized, crossover, counterbalanced, and double-blind design, participants ingested CAF (6 mg kg-1) or a placebo (PLA, 300 mg of cellulose) one hour before performing a sequence of physical tests: handgrip strength, agility test, countermovement jump (CMJ), Spike Jump (SJ), sit-ups, push-ups, and the Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). RESULTS: CAF enhanced handgrip strength (CAF: 35.0 ± 9.2 kg force; PLA: 33.5 ± 8.9 kg force; p = 0.050), CMJ height (CAF: 49.6 ± 12.3 cm; PLA: 48.3 ± 13.6 cm; p = 0.013), SJ height (CAF: 54.7 ± 13.3 cm; PLA: 53.1 ± 14.8 cm; p = 0.013), number of sit-ups (CAF: 37 ± 8; PLA: 35 ± 8; p = 0.001), and distance covered on the Yoyo IR1 test (CAF: 991.6 ± 371.0 m; PLA: 896.0 ± 311.0 m; p = 0.001), This CAF-induced improvement on exercise performance was, however, independent of genotypes groups (all p > 0.05). CAF had no effect on agility (CAF: 15.8 ± 1.2 s; PLA: 15.9 ± 1.3 s; p = 0.070) and push-up (CAF: 26.6 ± 12.0; PLA: 25.0 ± 11.0; p = 0.280) tests. CONCLUSION: The acute caffeine intake of 6.0 mg.kg-1 improves several aspects of physical performance, which seems to be independent of ADORA2A genotypes, alone or in combination with CYP1A2 genotypes.

Optimization of chromatographic buffer conditions for the simultaneous analysis of phosphatidylinositol and phosphatidylinositol phosphate species in canola.

The phosphatidylinositols and phosphatidylinositol phosphates are a set of closely related lipids known to influence various cellular functions. Irregular distributions of these molecules have been correlated with the development and progression of multiple diseases, including Alzheimer's, bipolar disorder, and various cancers. As a result, there is continued interest regarding the speciation of these compounds, with specific consideration on how their distribution may differ between healthy and diseased tissue. The comprehensive analysis of these compounds is challenging due to their varied and unique chemical characteristics, and current generalized lipidomics methods have proven unsuitable for phosphatidylinositol analysis and remain incapable of phosphatidylinositol phosphate analysis. Here we improved upon current methods by enabling the sensitive and simultaneous analysis of phosphatidylinositol and phosphatidylinositol phosphate species, whilst enhancing their characterization through chromatographic resolution between isomeric species. A 1 mM ammonium bicarbonate and ammonia buffer was determined optimal for this goal, enabling the identification of 148 phosphatidylinositide species, including 23 lyso-phosphatidylinositols, 51 phosphatidylinositols, 59 oxidized-phosphatidylinositols, and 15 phosphatidylinositol phosphates. As a result of this analysis, four distinct canola cultivars were differentiated based exclusively on their unique phosphatidylinositide-lipidome, indicating analyses of this type may be of use when considering the development and progression of the disease through lipidomic profiles.

Oral diseases are associated with cognitive function in adults over 60 years old.

OBJECTIVE: To investigate the bidirectional association between oral diseases and cognitive function comprehensively. SUBJECTS AND METHODS: This cross sectional study utilized data from the National Health and Nutrition Examination Survey. Oral diseases include periodontitis, dental caries, and tooth loss (end point of oral disease resulting in tooth extraction). Cognitive function included three domains: memory, processing speed, and executive function. A global cognitive score was then derived from sum of the three cognitive domains. Oral cognition associations were examined using various statistical models: (1) Regress oral disease on cognitive function; (2) Regress cognitive function on oral disease; and (3) Structural equation modelling treating cognition and oral disease as latent variables. RESULTS: There were 2508 participants aged 60+ who had both oral and cognitive information. Associations between various oral disease and global cognitive score were observed (Odds ratio ORcog->periodontitis 0.95, 95% Confidence Interval [0.92, 0.99]; ßcog->caries -0.13, [-0.23, -0.04]; ßcog->tooth loss -0.03 [-0.04, -0.01]; ßtooth loss->cog -0.04 [-0.06, -0.02]; ßcaries->cog -0.03 [-0.06, -0.01]; ßperiodontitis->cog -0.39 [-0.69, -0.10]). Significant correlation was also found between these oral disease and cognitive function using structural equation model (r -0.22, [-0.34, -0.10]). CONCLUSIONS: This study found robust bidirectional associations between oral disease and cognitive function using various modelling approaches among the aging population.