SELENBP1 overexpression in the prefrontal cortex underlies negative symptoms of schizophrenia.

The selenium-binding protein 1 (SELENBP1) has been reported to be up-regulated in the prefrontal cortex (PFC) of schizophrenia patients in postmortem reports. However, no causative link between SELENBP1 and schizophrenia has yet been established. Here, we provide evidence linking the upregulation of SELENBP1 in the PFC of mice with the negative symptoms of schizophrenia. We verified the levels of SELENBP1 transcripts in postmortem PFC brain tissues from patients with schizophrenia and matched healthy controls. We also generated transgenic mice expressing human SELENBP1 (hSELENBP1 Tg) and examined their neuropathological features, intrinsic firing properties of PFC 2/3-layer pyramidal neurons, and frontal cortex (FC) electroencephalographic (EEG) responses to auditory stimuli. Schizophrenia-like behaviors in hSELENBP1 Tg mice and mice expressing Selenbp1 in the FC were assessed. SELENBP1 transcript levels were higher in the brains of patients with schizophrenia than in those of matched healthy controls. The hSELENBP1 Tg mice displayed negative endophenotype behaviors, including heterotopias- and ectopias-like anatomical deformities in upper-layer cortical neurons and social withdrawal, deficits in nesting, and anhedonia-like behavior. Additionally, hSELENBP1 Tg mice exhibited reduced excitabilities of PFC 2/3-layer pyramidal neurons and abnormalities in EEG biomarkers observed in schizophrenia. Furthermore, mice overexpressing Selenbp1 in FC showed deficits in sociability. These results suggest that upregulation of SELENBP1 in the PFC causes asociality, a negative symptom of schizophrenia.

Dimethyloxalylglycine Suppresses SREBP1c and Lipogenic Gene Expressions in Hepatocytes Independently of HIF1A.

Dimethyloxalylglycine (DMOG) is a representative inhibitor of the prolyl hydroxylase domain (PHD), which mediates the degradation of hypoxia-inducible factor-1-alpha (HIF1A). DMOG exerts its pharmacological effects via the canonical pathway that involves PHD inhibition; however, it remains unclear whether DMOG affects lipogenic gene expression in hepatocytes. We aimed to elucidate the effects of DMOG on sterol regulatory element-binding protein-1c (SREBP1c), a master regulator of fatty acid synthesis in hepatocytes. DMOG treatment inhibited SREBP1c mRNA and protein expression in HepG2 and AML12 hepatocytes and reduced the transcript levels of SREBP1c-regulated lipogenic genes. A luciferase reporter assay revealed that DMOG inhibited the transcriptional activity of SREBP1c. Moreover, DMOG suppressed SREBP1c expression in mice liver. Mechanistically, treatment with DMOG enhanced the expression of HIF1A and insulin-induced gene 2 (INSIG2), which inhibits the activation of SREBP1c. However, HIF1A or INSIG2 knockdown failed to reverse the inhibitory effect of DMOG on SREBP1c expression, suggesting a redundant role of HIF1A and INSIG2 in terms of repressing SREBP1c. DMOG did not function through the canonical pathway involving inhibition of SREBP1c by PHD, highlighting the presence of non-canonical pathways that mediate its anti-lipogenic effect.

Insidious onset of spontaneous spinal epidural hematoma in immune thrombocytopenic purpura: a case-based review.

INTRODUCTION: Spontaneous spinal epidural hematoma (SSEH) can result from various etiologies with a variable degree of neurological deficits. Here, we describe a rare case of SEH secondary to immune thrombocytopenic purpura (ITP) in a child and review the literature of SSEH caused by ITP. CASE REPORT: A 9-year-old female who presented with rapid neurological decline, including bowel and bladder incontinence and paraparesis. A SSEH was observed extending from C2 to T6, causing a mass effect on the spinal cord. Her platelet count was only 7000/µL. Multidisciplinary care was established with neurosurgery, pediatric hematology, and pediatric surgery. The patient was managed emergently with splenectomy and surgical evacuation, with multilevel laminectomy and laminoplasty for evacuation of the hematoma. After a short course of rehabilitation, the patient regained all neurological function. CONCLUSION: We report the first case of cervicothoracic SSEH secondary to ITP in a child managed with emergent splenectomy and surgical evacuation with multilevel lamoplasty. We also described the methods of timely diagnosis, urgent management, and overall prognosis of patients with this condition.

Overexpression of Interleukin-8 Promotes the Progression of Fatty Liver to Nonalcoholic Steatohepatitis in Mice.

Nonalcoholic steatohepatitis (NASH) is an advanced stage of fatty liver disease characterized by liver damage, inflammation, and fibrosis. Although neutrophil infiltration is consistently observed in the livers of patients with NASH, the precise role of neutrophil-recruiting chemokines and infiltrating neutrophils in NASH pathogenesis remains poorly understood. Here, we aimed to elucidate the role of neutrophil infiltration in the transition from fatty liver to NASH by examining hepatic overexpression of interleukin-8 (IL8), a major chemokine responsible for neutrophil recruitment in humans. Mice fed a high-fat diet (HFD) for 3 months developed fatty liver without concurrent liver damage, inflammation, and fibrosis. Subsequent infection with an adenovirus overexpressing human IL8 for an additional 2 weeks increased IL8 levels, neutrophil infiltration, and liver injury in mice. Mechanistically, IL8-induced liver injury was associated with the upregulation of components of the NADPH oxidase 2 complex, which participate in neutrophil oxidative burst. IL8-driven neutrophil infiltration promoted macrophage aggregate formation and upregulated the expression of chemokines and inflammatory cytokines. Notably, IL8 overexpression amplified factors associated with fibrosis, including collagen deposition and hepatic stellate cell activation, in HFD-fed mice. Collectively, hepatic overexpression of human IL8 promotes neutrophil infiltration and fatty liver progression to NASH in HFD-fed mice.

Results From South Korean 2022 Para Report Card on Physical Activity for Children and Adolescents With Disabilities.

South Korea has developed its first Para Report Card on physical activity (PA) for children and adolescents with disabilities. Five national surveillance databases were used to evaluate PA indicators based on the benchmarks and grading rubric provided by Active Healthy Kids Global Alliance. Report card evaluation committees were invited to grade and assess the results using strengths, weaknesses, opportunities, and threats analysis. Five indicators (overall PA, D+; organized sports and PA, D-; active transportation, D-; physical fitness, D+; and government, A+) and one additional indicator (sleep, C-) were assigned a letter grade. The other five indicators were graded as incomplete. The Para Report Card revealed a significant gap between the behavioral-indicator grades (D- to D+) and the policy-indicator grade (A+), suggesting that government strategies and investment have not yet been translated into behavioral PA among children and adolescents with disabilities.

Corrigendum to "Physical activity in the era of climate change and COVID-19 pandemic: Results from the South Korea's 2022 Report Card on physical activity for children and adolescents" [J Exercise Sci Fitness 21(1) (2023) 26-33].

[This corrects the article DOI: 10.1016/j.jesf.2022.10.014.].

Physical activity in the era of climate change and COVID-19 pandemic: Results from the South Korea's 2022 Report Card on physical activity for children and adolescents.

Background: With intensifying air pollutant levels and the COVID-19 pandemic, physical inactivity of South Korean children and adolescents may be threatened. Therefore, monitoring and surveillance of physical activity (PA) and relevant indicators are important for policy making pertaining to health promotion. Report Card is a third comprehensive evaluation of PA-related behaviors among and the sources of influence for South Korean children and adolescents. Purpose: To provide the outcome of the South Korea's 2022 Report Card on PA for children and adolescents. Methods: Based on a variety of sources including national surveys collected pre- and during-COVID-19 and information collected from government webpages, 11 indicators were graded by a committee of experts informed by the best available evidence. Data from during-COVID-19 were available for Overall PA, Sedentary Behavior, and Sleep and considered together in generating the overall grades. Results: Grades were assigned to behavioral indicators (Overall PA: D-; Active Transportation: B+; Sedentary Behavior: D; Sleep: F) and sources of Influence (Family and Peers: C-; School: A; Community and Environment: B-; Government: A). Organized Sport and PA, Active Play, and Physical Fitness could not be graded due to the lack of data. The results largely indicated that children and adolescents show unfavorable behavioral grades even with favorable grades observed for the sources of influence indicators. Trivial differences were observed pre- and during-pandemic for Overall PA (≥60 min of MVPA for ≥4 d/wk: 20.8% vs 19.9%) and Sleep (met age-specific recommendation: 14.1% vs 15.0%); however, a marked increase in Sedentary Behavior was observed (≤2 h/d screen time: 28.8% vs 20.1%). A stark weekday vs weekend difference was observed in sleep duration. In terms of PA related sources of influence, high accessibility to PA facilities (81.1%) and high satisfaction of neighborhood public transit (74.6%) and safety (80.7%) were well reflected in our Active Transportation grade (B+). Nonetheless, perception of green environments including outdoor air quality (44.0%), noise (39.6%) and green space (56.5%) showed lower scores, suggesting that new barriers to active lifestyles are emerging for South Korean children and adolescents. Gender differences were also observed for overall PA (≥60 min of MVPA for ≥4 d/wk: 29.1% for boys vs 11.3% for girls) and sleep (met age-specific recommendations: 17.3% for boys vs 11.4% for girls), but not for sedentary behavior (≤2 h/d screen time: 26.4% for boys and 24.9% for girls). Conclusions: Government and school policies/programs and the built environment are, in general, conducive to physically active lifestyles for South Korean children and adolescents; however, behavioural indicators received poor grades except for Active Transportation. A thorough evaluation of policies/programs at government, local, and school levels is needed to ensure that the efforts to have PA-enhancing infrastructure and systems are actually being translated into the behavior of children and adolescents in South Korea. Furthermore, improving PA surveillance, monitoring, and advocacy to ultimately establish healthy lifestyle patterns among children and adolescents is a top priority.

Global analysis of protein homomerization in Saccharomyces cerevisiae.

In vivo analyses of the occurrence, subcellular localization, and dynamics of protein-protein interactions (PPIs) are important issues in functional proteomic studies. The bimolecular fluorescence complementation (BiFC) assay has many advantages in that it provides a reliable way to detect PPIs in living cells with minimal perturbation of the structure and function of the target proteins. Previously, to facilitate the application of the BiFC assay to genome-wide analysis of PPIs, we generated a collection of yeast strains expressing full-length proteins tagged with the N-terminal fragment of Venus (VN), a yellow fluorescent protein variant, from their own native promoters. In the present study, we constructed a VC (the C-terminal fragment of Venus) fusion library consisting of 5671 MATα strains expressing C-terminally VC-tagged proteins (representing ∼91% of the yeast proteome). For genome-wide analysis of protein homomer formation, we mated each strain in the VC fusion library with its cognate strain in the VN fusion library and performed the BiFC assay. From this analysis, we identified 186 homomer candidates. We further investigated the functional relevance of the homomerization of Pln1, a yeast perilipin. Our data set provides a useful resource for understanding the physiological roles of protein homomerization. Furthermore, the VC fusion library together with the VN fusion library will provide a valuable platform to systematically analyze PPIs in the natural cellular context.

Body Composition Impacts Hematopoietic Stem Cell Transplant Outcomes in Both Autologous and Allogeneic Transplants: A Systematic Review.

According to World Health Organization, over 50,000 hematopoietic stem cell transplants (HSCTs) are performed annually worldwide. Though HSCT can extend life-expectancy and improve disease-related health burdens, it is not without risks. Post-transplant overall survival is improving; therefore, it is imperative that factors contributing to or impeding further improvements are well understood. The purpose of this systematic review is to explore current data on body composition (specifically weight loss, BMI, obesity and sarcopenia) and the relation to HSCT outcomes. A literature search was conducted via PubMed and Web of Science databases. Key words included "body composition," "sarcopenia," "hematopoietic stem cell transplant," "malnutrition," "body mass index," and "obesity." Results indicated that 16 out of 18 analyzed studies found a statistically significant relationship between body composition, in particular higher BMI and weight loss, and at least one survival-related outcome variable (eg., non-relapse mortality, overall survival and/or relapse). Based on the findings of this review, body composition, whether evaluated before or during HSCT, can impact a wide variety of post-transplant outcomes. This speaks to the importance of evaluating patients pre-transplant, identifying potential risk factors for worsened outcomes, and providing immediate interventions in order to optimize transplant outcomes.

Traction Performance Evaluation of the Electric All-Wheel-Drive Tractor.

This study aims to design, develop, and evaluate the traction performance of an electric all-wheel-drive (AWD) tractor based on the power transmission and electric systems. The power transmission system includes the electric motor, helical gear reducer, planetary gear reducer, and tires. The electric system consists of a battery pack and charging system. An engine-generator and charger are installed to supply electric energy in emergency situations. The load measurement system consists of analog (current) and digital (battery voltage and rotational speed of the electric motor) components using a controller area network (CAN) bus. A traction test of the electric AWD tractor was performed towing a test vehicle. The output torques of the tractor motors during the traction test were calculated using the current and torque curves provided by the motor manufacturer. The agricultural work performance is verified by comparing the torque and rpm (T-N) curve of the motor with the reduction ratio applied. The traction is calculated using torque and specifications of the wheel, and traction performance is evaluated using tractive efficiency (TE) and dynamic ratio (DR). The results suggest a direction for the improvement of the electric drive system in agricultural research by comparison with the conventional tractor through the analysis of the agricultural performance and traction performance of the electric AWD tractor.

Analysis of the Effect of Tillage Depth on the Working Performance of Tractor-Moldboard Plow System under Various Field Environments.

The purpose of this study was to analyze the tillage depth effect on the tractor-moldboard plow systems in various soil environments and tillage depths using a field load measurement system. A field load measurement system can measure the engine load, draft force, travel speed, wheel axle load, and tillage depth in real-time. In addition, measurement tests of soil properties in the soil layer were preceded to analyze the effect of field environments. The presented results show that moldboard plow at the same tillage depth had a wide range of influences on the tractor's working load and performance under various environments. As the draft force due to soil-tool interaction occurred in the range of 5.6-17.7 kN depending on the field environment, the overall mean engine torque and rear axle torque were up to 2.14 times and 1.67 times higher in hard and clayey soil, respectively, than in soft soil environments. In addition, the results showed tractive efficiency of 0.56-0.73 and were analyzed to have a lugging ability of 67.8% with a 44% maximum torque rise. The engine power requirement in hardpan was similar within 3.6-9.6%, but the power demand of the rear axle differed by up to 18.4%.

Targeting mutant KRAS with CRISPR-Cas9 controls tumor growth.

KRAS is the most frequently mutated oncogene in human tumors, and its activating mutations represent important therapeutic targets. The combination of Cas9 and guide RNA from the CRISPR-Cas system recognizes a specific DNA sequence and makes a double-strand break, which enables editing of the relevant genes. Here, we harnessed CRISPR to specifically target mutant KRAS alleles in cancer cells. We screened guide RNAs using a reporter system and validated them in cancer cells after lentiviral delivery of Cas9 and guide RNA. The survival, proliferation, and tumorigenicity of cancer cells in vitro and the growth of tumors in vivo were determined after delivery of Cas9 and guide RNA. We identified guide RNAs that efficiently target mutant KRAS without significant alterations of the wild-type allele. Doxycycline-inducible expression of this guide RNA in KRAS-mutant cancer cells transduced with a lentiviral vector encoding Cas9 disrupted the mutant KRAS gene, leading to inhibition of cancer cell proliferation both in vitro and in vivo. Intra-tumoral injection of lentivirus and adeno-associated virus expressing Cas9 and sgRNA suppressed tumor growth in vivo, albeit incompletely, in immunodeficient mice. Expression of Cas9 and the guide RNA in cells containing wild-type KRAS did not alter cell survival or proliferation either in vitro and in vivo. Our study provides a proof-of-concept that CRISPR can be utilized to target driver mutations of cancers in vitro and in vivo.

Clinical Feasibility of High-Resolution Contrast-Enhanced Dynamic T1-Weighted Magnetic Resonance Imaging of the Upper Abdomen Using Compressed Sensing.

OBJECTIVE: The objective of this study was to evaluate the clinical feasibility of high-resolution contrast-enhanced dynamic T1-weighted imaging (T1WI) using compressed sensing (CS) in magnetic resonance imaging. METHODS: This study retrospectively included 35 patients who underwent dynamic T1WI using volumetric interpolated breath-hold examination (VIBE) with CS reconstruction (CS-VIBE) and 35 patients with conventional VIBE for comparison. Two observers assessed the liver and pancreas edges, hepatic artery, motion artifacts, and overall image quality. Quantitative analysis was performed by measuring signal intensity and image noise. RESULTS: The results showed that CS-VIBE achieved significantly better anatomic delineation of the liver and pancreas edges and hepatic artery clarity than VIBE (P < 0.001). There were no significant differences in motion artifacts in dynamic phases and overall image quality. The signal intensities and INs of CS-VIBE were higher than VIBE. CONCLUSIONS: High-resolution dynamic T1WI using CS provides better anatomic delineation with comparable or better overall image quality than conventional VIBE.

Estimation of Axle Torque for an Agricultural Tractor Using an Artificial Neural Network.

The objective of this study was to develop a model to estimate the axle torque (AT) of a tractor using an artificial neural network (ANN) based on a relatively low-cost sensor. ANN has proven to be useful in the case of nonlinear analysis, and it can be applied to consider nonlinear variables such as soil characteristics, unlike studies that only consider tractor major parameters, thus model performance and its implementation can be extended to a wider range. In this study, ANN-based models were compared with multiple linear regression (MLR)-based models for performance verification. The main input data were tractor engine parameters, major tractor parameters, and soil physical properties. Data of soil physical properties (i.e., soil moisture content and cone index) and major tractor parameters (i.e., engine torque, engine speed, specific fuel consumption, travel speed, tillage depth, and slip ratio) were collected during a tractor field experiment in four Korean paddy fields. The collected soil physical properties and major tractor parameter data were used to estimate the AT of the tractor by the MLR- and ANN-based models: 250 data points were used for developing and training the model were used, the 50 remaining data points were used to test the model estimation. The AT estimated with the developed MLR- and ANN-based models showed agreement with actual measured AT, with the R2 value ranging from 0.825 to 0.851 and from 0.857 to 0.904, respectively. These results suggest that the developed models are reliable in estimating tractor AT, while the ANN-based model showed better performance than the MLR-based model. This study can provide useful results as a simple method using ANNs based on relatively inexpensive sensors that can replace the existing complex tractor AT measurement method is emphasized.

Analysis of Tillage Depth and Gear Selection for Mechanical Load and Fuel Efficiency of an Agricultural Tractor Using an Agricultural Field Measuring System.

This study was conducted to analyze the effects of tillage depth and gear selection on the mechanical load and fuel efficiency of an agricultural tractor during plow tillage. In order to analyze these effects, we developed an agricultural field measuring system consisting of a load measurement part (wheel torque meter, proximity sensor, and real-time kinematic (RTK) global positioning system (GPS)) and a tillage depth measurement part (linear potentiometer and inclinometer). Field tests were carried out using moldboard plows with a maximum tillage depth of 20 cm and three gear selections (M2H, M3L, and M3H) in a rice stubble paddy field for plow tillage. The average travel speed and slip ratio had the lowest M2H and the highest M3L. M3H had the highest theoretical speed, but the travel speed was 0.13 km/h lower than M3L due to the reduction in the axle rotational speed at deep tillage depth. Regarding engine load, the higher the gear, the greater the torque and the lower the axle rotation speed. The front axle load was not significantly affected by the tillage depth as compared to other mechanical parts, except for the M3H gear. The rear axle load generated about twice the torque of the front wheel and overall, it tended to show a higher average rear axle torque at higher gear selection. The rear axle load and fuel rate were found to be most affected by the combination of the tillage depth and gear selection combination. Overall, field test results show that the M3H had the highest fuel efficiency and a high working speed while overcoming high loads at the same tillage depth. In conclusion, M3H is the most suitable gear stage for plow cultivation, and the higher the gear stage and the deeper the tillage depth during plowing, the higher the fuel efficiency. The results of this study will be useful for analyzing mechanical load and fuel efficiency during farm operations. In a future study, we will conduct load analysis studies in other farming operations that consider various soil mechanics factors as well as tillage depths and gear selections.

Development of a Real-Time Tillage Depth Measurement System for Agricultural Tractors: Application to the Effect Analysis of Tillage Depth on Draft Force during Plow Tillage.

The objectives of this study were to develop a real-time tillage depth measurement system for agricultural tractor performance analysis and then to validate these configured systems through soil non-penetration tests and field experiment during plow tillage. The real-time tillage depth measurement system was developed by using a sensor fusion method, consisting of a linear potentiometer, inclinometer, and optical distance sensor to measure the vertical penetration depth of the attached implement. In addition, a draft force measurement system was developed using six-component load cells, and an accuracy of 98.9% was verified through a static load test. As a result of the soil non-penetration tests, it was confirmed that sensor fusion type A, consisting of a linear potentiometer and inclinometer, was 6.34-11.76% more accurate than sensor fusion type B, consisting of an optical distance sensor and inclinometer. Therefore, sensor fusion type A was used during field testing as it was found to be more suitable for use in severe working environments. To verify the accuracy of the real-time tillage depth measurement system, a linear regression analysis was performed between the measured draft and the predicted values calculated using the American Society of Agricultural and Biological Engineers (ASABE) standards-based equation. Experimental data such as traveling speed and draft force showed that it was significantly affected by tillage depth, and the coefficient of determination value at M3-Low was 0.847, which is relatively higher than M3-High. In addition, the regression analysis of the integrated data showed an R-square value of 0.715, which is an improvement compared to the accuracy of the ASABE standard prediction formula. In conclusion, the effect of tillage depth on draft force of agricultural tractors during plow tillage was analyzed by the simultaneous operation of the proposed real-time tillage depth measurement system and draft force measurement system. In addition, system accuracy is higher than the predicted accuracy of ±40% based on the ASABE standard equation, which is considered to be useful for various agricultural machinery research fields. In future studies, real-time tillage depth measurement systems can be used in tractor power train design and to ensure component reliability, in accordance with agricultural working conditions, by predicting draft force and axle loads depending on the tillage depth during tillage operations.

Simulation of Design Factors of a Clutch Pack for Power-Shift Transmission for an Agricultural Tractor.

The objective of this study is the simulation of the most affected design factors and variables of the clutch pack for the power-shift transmission (PST) of a tractor based measured data. The simulation model, the mathematical model of sliding velocity, a moment of inertia, and clutch engagement pressure of clutch pack were developed using the powertrain and configurations of the real PST tractor. In this study, the sensor fusion method was used to precisely measure the proportional valve pressure by test bench, which was applied to the simulation model. The clutch engagement times were found 1.20 s at all temperatures for determined factors. The engagement pressures have a significant difference at various temperatures (25 to 100 °C) of the hydraulic oils after the 1.20 s but the most affected factors were satisfied with the simulation conditions that ensure the clutch engagement on time. Finally, this sensor fusion method is believed to be helpful in realizing precision agriculture through minimization of power loss and maximum energy efficiency of tractors.

Medial septal GABAergic projection neurons promote object exploration behavior and type 2 theta rhythm.

Exploratory drive is one of the most fundamental emotions, of all organisms, that are evoked by novelty stimulation. Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. Diverse exploratory behaviors have been described, although their heterogeneity is not certain because of the lack of solid experimental evidence for their distinction. Here we present results demonstrating that different neural mechanisms underlie different exploratory behaviors. Localized Cav3.1 knockdown in the medial septum (MS) selectively enhanced object exploration, whereas the null mutant (KO) mice showed enhanced-object exploration as well as open-field exploration. In MS knockdown mice, only type 2 hippocampal theta rhythm was enhanced, whereas both type 1 and type 2 theta rhythm were enhanced in KO mice. This selective effect was accompanied by markedly increased excitability of septo-hippocampal GABAergic projection neurons in the MS lacking T-type Ca(2+) channels. Furthermore, optogenetic activation of the septo-hippocampal GABAergic pathway in WT mice also selectively enhanced object exploration behavior and type 2 theta rhythm, whereas inhibition of the same pathway decreased the behavior and the rhythm. These findings define object exploration distinguished from open-field exploration and reveal a critical role of T-type Ca(2+) channels in the medial septal GABAergic projection neurons in this behavior.

The effects of caffeine on marksmanship accuracy and reaction time: a systematic review.

Military and law enforcement personnel are required to maintain optimal marksman accuracy and reaction time during extended duty hours amidst environmental stressors. Although caffeine is commonly used to mitigate the consequences of fatigue, the effects of caffeine on marksmanship accuracy are inconclusive. The purpose of this review was to determine the effect of caffeine on marksman accuracy and reaction time. A literature search was conducted and 17 articles were selected for review based on relevance and methodological quality. Caffeine consistently improved marksman reaction time but did not improve marksmanship accuracy. However, there is some evidence that caffeine attenuates performance decrements in marksman accuracy caused by stress and fatigue if optimal dosing strategies are employed. Dosing strategies timed according to hours of wakefulness and time before testing could prevent performance deterioration. Doses of 100-200 mg every 2 hours may effectively improve accuracy during extended duty; however, further research is needed. Practitioner Summary: The purpose of this review was to determine the effect of caffeine on marksman accuracy and reaction time. A literature search was conducted and 17 articles were selected for review based on relevance and methodological quality. Caffeine consistently improved marksman reaction time but did not improve marksmanship accuracy.

Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca2+ ) concentration. High Ca2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca2+ environment in transforming growth factors ß1 (TGFß1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca2+ -induced differentiated keratinocytes. Knockdown of TGFß1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFß1 further induced growth inhibition of keratinocyte in high extracellular Ca2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFß1/SMAD pathway. Taken together, we found that MSCs-derived TGFß1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602.