Metabolic Expenditure Research Articles

Human femur morphology and histology variation with ancestry and behaviour in an ancient sample from Vietnam

BackgroundThere is a genetic component to the minimum effective strain (MES)—a threshold which determines when bone will adapt to function—which suggests ancestry should play a role in bone (re)modelling. Further elucidating this is difficult in living human populations because of the high global genetic admixture. We examined femora from an anthropological skeletal assemblage (Mán Bạc, Vietnam) representing distinct ancestral groups. We tested whether femur morphological and histological markers of modelling and remodelling differed between ancestries despite their similar lifestyles. MethodsStatic histomorphometry data collected from subperiosteal cortical bone of the femoral midshaft, and gross morphometric measures of femur robusticity, were studied in 17 individuals from the Mán Bạc collection dated to 1906–1523 cal. BC. This assemblage represents agricultural migrants with affinity to East Asian groups, who integrated with the local hunter-gatherers with affinity to Australo-Papuan groups during the mid-Holocene. Femur robusticity and histology data were compared between groups of ‘Migrant’ (n = 8), ‘Admixed’ (n = 4), and ‘Local’ (n = 5). ResultsLocal individuals had more robust femoral diaphyses with greater secondary osteon densities, and relatively large secondary osteon and Haversian canal parameters than the migrants. The Migrant group showed gracile femoral shafts with the least dense bone made up of small secondary osteons and Haversian canals. The Admixed individuals fell between the Migrant and Local categories in terms of their femoral data. However, we also found that measures of how densely bone is remodelled per unit area were in a tight range across all three ancestries. ConclusionsBone modelling and remodelling markers varied with ancestral histories in our sample. This suggests that there is an ancestry related predisposition to bone optimising its metabolic expenditure likely in relation to the MES. Our results stress the need to incorporate population genetic history into hierarchical bone analyses. Understanding ancestry effects on bone morphology has implications for interpreting biomechanical loading history in past and modern human populations.

Astragalus polysaccharide prevents heart failure-induced cachexia by alleviating excessive adipose expenditure in white and brown adipose tissue

BackgroundAstragalus polysaccharide (APS) is a key active ingredient isolated from Astragalus membranaceus that has been reported to be a potential treatment for obesity and diabetes by regulating lipid metabolism and adipogenesis, alleviating inflammation, and improving insulin resistance. However, whether APS regulates lipid metabolism in the context of cachexia remains unclear. Therefore, this study analysed the effects of APS on lipid metabolism and adipose expenditure in a heart failure (HF)-induced cardiac cachexia rat model. MethodsA salt-sensitive hypertension-induced cardiac cachexia rat model was used in the present study. Cardiac function was detected by echocardiography. The histological features and fat droplets in fat tissue and liver were observed by H&E staining and Oil O Red staining. Immunohistochemical staining, Western blotting and RT‒qPCR were used to detect markers of lipolysis and adipose browning in white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT). Additionally, sympathetic nerve activity and inflammation in adipose tissue were detected.ResultsRats with HF exhibited decreased cardiac function and reduced adipose accumulation as well as adipocyte atrophy. In contrast, administration of APS not only improved cardiac function and increased adipose weight but also prevented adipose atrophy and FFA efflux in HF-induced cachexia. Moreover, APS inhibited HF-induced lipolysis and browning of white adipocytes since the expression levels of lipid droplet enzymes, including HSL and perilipin, and beige adipocyte markers, including UCP-1, Cd137 and Zic-1, were suppressed after administration of APS. In BAT, treatment with APS inhibited PKA-p38 MAPK signalling, and these effects were accompanied by decreased thermogenesis reflected by decreased expression of UCP-1, PPAR-γ and PGC-1α and reduced FFA β-oxidation in mitochondria reflected by decreased Cd36, Fatp-1 and Cpt1. Moreover, sympathetic nerve activity and interleukin-6 levels were abnormally elevated in HF rats, and astragalus polysaccharide could inhibit their activity.ConclusionAPS prevented lipolysis and adipose browning in WAT and decreased BAT thermogenesis. These effects may be related to suppressed sympathetic activity and inflammation. This study provides a potential approach to treat HF-induced cardiac cachexia.

Effectiveness Dose of injection acetaminophen for Control of Shivering after general Anesthesia in inguinal hernia Surgery

Inguinal hernia is the most common type of abdominal hernia which is 7 times more common in men than women. Surgical treatment is performed under general anesthesia. about 40 to 60 percent of patients of post-surgery are experiencing tremor. these patients after anesthesia, shivering is very undesirable and from the physiological aspect is very stressful, mild tremor increases the oxygen consumption like a light physical activity and judder increases the metabolic rate and oxygen consumption up to 600%. injection acetaminophen is a safe drug, in recent study determines of Effectiveness dose for control of shivering after anesthesia in surgeries. Aim: The aim of this study was to determine the effect of injection acetaminophen on the quality and timing of the Shivering after on the inguinal herniation surgery. Materials and Methods: This is a randomized double-blind study, that the statistical population was patients that were candidates for general surgery, that were referred to hospitals of Qazvin University of Medical Sciences for treatment. The patient’s undergone surgery with general anesthesia with number 1 and 2 anesthetic Class based on anesthesiologist detection. From 80 patients that were randomly selected, 40 people were selected for experimenting group with injection acetaminophen with IM injection of 0.5 mg/kg and 40 people were selected for the placebo control group (routine order) Results: The shivering in the experimenting group was decreased than the control group and was statistically significant. Tremor intensity in the experimental group was lower than the control group in all three measures (1, 2) which was also significant for comparing the linear regression, relative risk (RR) was 8in two groups according to the normal distribution of the data, in the age group between 20to 40 years the minimum range of tremor was observed and in the age group that were younger than 20 years range of tremor was observed. Conclusion: injection acetaminophen (IM) after general anesthesia can reduce the amount and severity of shivering at post-surgery and can be an effective choice drug in the post-surgery in patients with inguinal herniation surgery.

Can caffeine activate your brown fat? Effects of caffeine, ephedrine, and norepinephrine on nonshivering thermogenesis in congenic lean and obese LA/Ntul//-cp rats

To determine the effects of norepinephrine (NE) or of caffeine (CAF) alone or in combination with ephedrine (EPH) were determined in groups of lean and obese LA/Ntul//-cp Rats, Body weights of obese were >> lean littermates (p=<0.01) and measures of RMR of lean > Obese (p=<0.05). The effects of caffeine, ephedrine, a caffeine+ephedrine combo, and the β- agonist epinephrine was examined. Caffeine (CAF) resulted in a 33% increase in VO2, ‘nonephedrine’ (EPH) a 48% increase, the combination CAF+EPH a 53% increase, and the NE a 33% increase in VO2. In obese rats, the increases in VO2 were of a similar percentage (21 vs 48 vs 47 % vs 31% for CAF, EPH, CAF+EPH and NE respectively although the peak responses attained in the obese tended to be of a significantly lesser absolute magnitude than were observed in the lean phenotype. The time to peak thermogenic response was similar in lean and obese phenotypes for each of the 4 treatment regimens, but the duration of the peak responses to each treatment differed between lean and obese phenotypes (Obese > lean) for CAF, EPH and the CAF+EPH combination but duration of the VO2 response was similar in both phenotypes for the NE treatment. Thus, these observations are consistent with a significant CAF-stimulated thermogenic response that was qualitatively similar to that of NE in both lean and obese phenotypes of the congenic LA/Ntul//-cp rat and which thermogenic responses were further augmented with EPH alone or in combination with CAF. Although the mechanisms of action of the pharmacologic and physiologic mechanisms elicited may differ among the three agents studied the results indicate that they are complimentary in nature in bringing about increases in parameters of nonshivering thermogenesis and thus increasing metabolic energy expenditure in both lean and obese rats. In conclusion, while caffeine as monotherapy may bring about limited weight loss, the combination of caffeine plus ephedrine was more effective in the lean and obese phenotypes of the congenic, non-diabetic LA/Ntul//-cp (Corpulent) rat.

Effects of modern military footwear on the oxygen costs of walking in US Army personnel

Warfighters complete strenuous physical activity on their feet throughout their military careers. While greater physiologic costs of walking have been demonstrated with older models of military combat boots versus running shoes, these quantitative differences may not be applicable for contemporary military footwear. The purpose of this study was to quantify and compare physiological responses to walking when wearing modern military combat boots versus running shoes. In this randomized, counterbalanced crossover experiment, 34 active military personnel (29 men and 5 women; age, 26 ± 7 years; height, 1.74 ± 0.08 m; body mass, 77.9 ± 15.1 kg) completed an incremental walking test (4.18–7.08 km.h−1) on separate visits in running shoes (mass, 0.6 ± 0.1 kg) and military combat boots (mass, 1.2 ± 0.3 kg). Oxygen uptake (V̇O2), carbon dioxide production (V̇CO2), heart rate (HR), respiration rate (RR), and metabolic energy expenditure (Ṁ) measurements were collected and averaged over the final minute of each walking speed. The oxygen costs of walking were 6–9% higher when wearing combat boots versus running shoes (p < 0.01 for each comparison). Other cardiorespiratory indicators of exercise intensity, specifically V̇CO2, Ṁ, HR, and RR, increased by 2.7–9.9% (p < 0.02 for each indicator). Walking in modern military combat boots incurs noticeably increased metabolic and cardiorespiratory strain as compared to walking in running shoes. These physiological consequences emphasize the trade-off between the intended versatility and protective characteristics of military footwear and the economy of traditional running shoes. This strain must be considered when selecting footwear to maximize warfighter health and performance during military exercise interventions.

Effectiveness Dose of Injection Acetaminophen for Control of Shivering After General Anesthesia in Inguinal Hernia Surgery

Introduction: Inguinal hernia is the most common type of abdominal hernia which is 7 times more common in men than women. Surgical treatment is performed under general anesthesia. about 40 to 60 percent of patients of post-surgery are experiencing tremor. these patients after anesthesia, shivering is very undesirable and from the physiological aspect is very stressful, mild tremor increases the oxygen consumption like a light physical activity and judder increases the metabolic rate and oxygen consumption up to 600%. injection acetaminophen is a safe drug, in recent study determines of Effectiveness dose for control of shivering after anesthesia in surgeries. Aim: The aim of this study was to determine the effect of injection acetaminophen on the quality and timing of the Shivering after on the inguinal herniation surgery. Materials and Methods: This is a randomized double-blind study, that the statistical population was patients that were candidates for general surgery, that were referred to hospitals of Qazvin University of Medical Sciences for treatment. The patient’s undergone surgery with general anesthesia with number 1 and 2 anesthetic Class based on anesthesiologist detection. From 80 patients that were randomly selected, 40 people were selected for experimenting group with injection acetaminophen with IM injection of 0.5 mg/kg and 40 people were selected for the placebo control group (routine order). Results: The shivering in the experimenting group was decreased than the control group and was statistically significant. Tremor intensity in the experimental group was lower than the control group in all three measures [1, 2] which was also significant for comparing the linear regression, relative risk (RR) was 8in two groups according to the normal distribution of the data, in the age group between 20to 40 years the minimum range of tremor was observed and in the age group that were younger than 20 years range of tremor was observed. Conclusion: injection acetaminophen (IM) after general anesthesia can reduce the amount and severity of shivering at post-surgery and can be an effective choice drug in the post-surgery in patients with inguinal herniation surgery.

Relationship Between Weight Status And Basal Metabolism In Schoolchildren

There is currently a scientific trend to study the association between energy balance and its impact on health from the earliest stages of life. The aim of this study was to examine whether diet quality and physical activity moderate the association between weight status and basal metabolism in a sample of Murcian primary school children aged 8-12 years. Basal metabolism was calculated according to height, sex, and weight, with fixed coefficients following validated formulae. Physical activity was measured with the Krece-Plus test; the KIDMED questionnaire was used to quantify diet quality and nutritional status was assessed by body mass index (BMI; kg/m2) adjusted for sex and age. The results obtained indicate that overweight schoolchildren have a higher basal metabolism than their normal-weight peers considering their diet quality and physical activity level (p&amp;lt;.001, for both). Also, the effects of weight status on basal metabolism may be moderated by diet quality (p&amp;lt;.05) but not by physical activity (p&amp;gt;.05). These results may be of particular interest to educational and health personnel since generating strategies to improve school children’s eating habits, especially towards higher diet quality, could be vital as a method to increase basal metabolic energy expenditure and their overall health.

Evaluation of a machine-learning-driven active-passive upper-limb exoskeleton robot: Experimental human-in-the-loop study.

Evaluating exoskeleton actuation methods and designing an effective controller for these exoskeletons are both challenging and time-consuming tasks. This is largely due to the complicated human-robot interactions, the selection of sensors and actuators, electrical/command connection issues, and communication delays. In this research, a test framework for evaluating a new active-passive shoulder exoskeleton was developed, and a surface electromyography (sEMG)-based human-robot cooperative control method was created to execute the wearer's movement intentions. The hierarchical control used sEMG-based intention estimation, mid-level strength regulation, and low-level actuator control. It was then applied to shoulder joint elevation experiments to verify the exoskeleton controller's effectiveness. The active-passive assistance was compared with fully passive and fully active exoskeleton control using the following criteria: (1) post-test survey, (2) load tolerance duration, and (3) computed human torque, power, and metabolic energy expenditure using sEMG signals and inverse dynamic simulation. The experimental outcomes showed that active-passive exoskeletons required less muscular activation torque (50%) from the user and reduced fatigue duration indicators by a factor of 3, compared to fully passive ones.

The Impact of Training Load on Running Gait Variability: A Pilot Study

Purpose: Running gait variability appears to be a new metric related to fatigue in long-distance runners. However, no study has verified the changes in gait variability over a longitudinal study involving well-experienced runners. Therefore, the aim of this study was to investigate the changes in gait variability in distance runner before and after a 9-week endurance training program. Methods: A male runner (age 23 years; body mass 58 kg; stature 1.70 m, BMI 20 kg·m−2) completed two critical speed (CS) test and six trial at different speeds (calculated by CS) with 9-week of training in-between. At the same time heart rate (HR) was continuously recorded and normalized as a percentage of the maximal heart rate (220 - age) %HRmax, serving as a proxy for metabolic expenditure. Additionally, kinematic (contact time (CT), flight time (FT), step length (SL), step rate (SR)) and kinetic measurements (leg (kvert) and vertical (kleg) stiffness), were recorded. While the running gait variability was calculated as phase coordination index (PCI). Results: CS and HR were 16.40/18.00 km·h-1 and 93.19±1.23/93.81±2.38 %HRmax in baseline and after the training, respectively. The kinematic and kinetic variables studied at different speeds (13.80-14.40-15.00-15.70-16.40-17.10 km·h-1) showed a significative training effect vs baseline conditions for CT (P= .010), FT (P= .010), SL (P= .002), SR (P= .002), kvert (P=.003), kleg (P= .0001). At the same way the metabolic demand and PCI changed significantly after the training compared to the baseline condition for average/maximum HR (P= .009 – 0.024, respectively) and PCI (P= .009). Conclusions: These results suggest that gait variability is one mechanical determinant that demonstrates the adaptation of training load when neuromuscular output related to physiological efforts is under stress conditions, such as running training. Therefore, PCI could be a useful tool for monitoring the impact of running training load on bilateral running coordination. Keywords: human locomotion; footstep pattern coordination; running performance; endurance runners.

Relationship between Body Mass Index (BMI) and Foot Posture Index (FPI) Among Healthy Adults Aged 20-30 Years - An Observational Cross-Sectional Study

Background and Objective Obesity is the new epidemic globally. Obesity has also been linked to increased leg swing velocity higher metabolic expenditure and poorer postural stability all of which might affect foot function. Therefore this study was planned to determine the relationship between body mass index and foot posture index among healthy adults in the age group of 20-30 years studying at a medical university.Methods The study was conducted in the outpatient department of orthopaedics and physiotherapy SDM College of Medical Sciences and Hospital Dharwad India. This study was an observational cross-sectional study which included 50 healthy adult participants in the age group of 20-30 years based on the eligibility criteria. BMI was calculated using the Quelets index and foot posture scoring was done to determine the foot mass index. Descriptive analysis was done and presented as mean and standard deviation. Pearson correlation was done to determine the correlation between BMI and foot posture index. P less than 0.05 was considered significant.Results Increased body mass index was positively correlated with right and left foot posture indices. Conclusion Increased BMI leads to pronation of the feet. This can further cause the individual to walk slightly on the outside of the foot instead of the feet flat on the ground.

Integration of High-Throughput Imaging and Multiparametric Metabolic Profiling Reveals a Mitochondrial Mechanism of Tenofovir Toxicity.

Nephrotoxicity is a major cause of kidney disease and failure in drug development, but understanding of cellular mechanisms is limited, highlighting the need for better experimental models and methodological approaches. Most nephrotoxins damage the proximal tubule (PT), causing functional impairment of solute reabsorption and systemic metabolic complications. The antiviral drug tenofovir disoproxil fumarate (TDF) is an archetypal nephrotoxin, inducing mitochondrial abnormalities and urinary solute wasting, for reasons that were previously unclear. Here, we developed an automated, high-throughput imaging pipeline to screen the effects of TDF on solute transport and mitochondrial morphology in human-derived RPTEC/TERT1 cells, and leveraged this to generate realistic models of functional toxicity. By applying multiparametric metabolic profiling-including oxygen consumption measurements, metabolomics, and transcriptomics-we elucidated a highly robust molecular fingerprint of TDF exposure. Crucially, we identified that the active metabolite inhibits complex V (ATP synthase), and that TDF treatment causes rapid, dose-dependent loss of complex V activity and expression. Moreover, we found evidence of complex V suppression in kidney biopsies from humans with TDF toxicity. Thus, we demonstrate an effective and convenient experimental approach to screen for disease relevant functional defects in kidney cells in vitro, and reveal a new paradigm for understanding the pathogenesis of a substantial cause of nephrotoxicity.

Effect of Exercise Using an Exoskeletal Hip-Assist Robot on Physical Function and Walking Efficiency in Older Adults.

Robotic technology has developed rapidly in recent years, and several robotic devices have been applied to improve physical, sensory, intellectual, psychological, and social functioning in the elderly and people with disabilities. In this study, we investigated the effects of EX1-assisted exercise in various environments on physical function, muscle strength, and walking efficiency in older adults. We designated four experimental conditions and randomly assigned participants to one of four groups: A (overground walking without an EX1), B (overground walking using the resistance mode of EX1), C (stair ascent using the assistance mode of EX1), and Group D (inclined treadmill walking using the assistance mode of EX1). A total of 60 community-dwelling elderly persons participated in 10 exercise intervention sessions for 4 weeks, and all participants were assessed before and after the exercise intervention. Physical function was measured by the 10-meter walk test for self-selected velocity (10MWT-SSV), short physical performance battery (SPPB), Berg balance scale (BBS), timed up and go (TUG), functional reach test (FRT), geriatric depression scale-short form (GDS-SF), and muscle strength of trunk and lower extremity. Cardiopulmonary metabolic energy efficiency was measured using a portable telemetric gas analyzer system. A significant increase in the 10MWT-SSV and TUG test was observed in groups B, C, and D. A statistically significant improvement in the SPPB and FRT was seen only in group D, and GDS-SF scores decreased significantly after exercise with an EX1 in groups B and D. Trunk and lower limb muscle strength increased more in the groups that exercised with EX1 assistance than those without an EX1, particularly in group B. The net metabolic energy costs and energy expenditure measurement during walking significantly improved in exercise groups C and D. The findings in this study support the application of the EX1 to physical activity and exercise to improve age-related changes in physical function, muscle strength, and walking efficiency among older adults. In addition, personalized exercise programs using different modes and training environments with an EX1 can enhance physical performance and walking efficiency in the elderly.

Heart Rate Does Not Accurately Predict Metabolic Intensity During Variable-Intensity Roller Skiing or Cycling.

To critically appraise the utility of heart rate (HR) and power output (PO) to predict metabolic rate (MR) and oxygen consumption (V˙O2) during variable-intensity roller skiing and cycling. National-level cyclists (n = 8) and cross-country skiers (n = 9) completed a preliminary session to determine V˙O2max, and a variable-intensity protocol with 3 high-intensity stages at 90% V˙O2max for 3minutes interspersed with 3 moderate-intensity stages at 70% V˙O2max for 6minutes. Cardiorespiratory measures were recorded throughout. Linear HR-MR, HR-V˙O2, PO-MR, and PO-V˙O2 regressions were computed from the preliminary session, individually, for all athletes and used to predict MR and V˙O2 from both HR and PO, separately, during the variable-intensity protocol. Mean differences with 95% limits of agreement (LOA) between measured and predicted MR and V˙O2 were calculated. MR and V˙O2 estimated from HR displayed a mean bias close to zero but wide LOA. HR overestimated MR and V˙O2 during moderate intensity but underestimated MR and V˙O2 during high intensity, for both roller skiing and cycling. MR and V˙O2 estimated from PO were more consistent across the experimental trial, displaying a mean bias farther from zero but with tighter LOA. This study has demonstrated that HR has limited utility to predict metabolic intensity during variable-intensity roller skiing and cycling because of wide LOA. On the other hand, metabolic intensity predicted from PO had tighter LOA, suggesting better consistency. PO might provide a better prediction of metabolic intensity compared with HR, particularly when longer-duration steps are performed during preliminary testing.

Calcification of Indocyanine Green Laden Dendritic Mesoporous Manganese‐Silicon Nanocomposite for Multiple Oxygen Compensation Enhanced Phototherapy

AbstractIncreasing oxygen (O2) content and down‐regulating the concentration of glutathione (GSH) in tumor microenvironment (TME) by multiple approaches remain critical factors for the promotion of phototherapeutic effect, especially for photodynamic therapy (PDT). Herein, indocyanine green (ICG) laden dendritic mesoporous manganese‐silicon nanocomposite (NC) is designed and subsequently managed with calcification through in situ growth of calcium phosphate (IDMMS@CaP NC). As specific response behavior of the mildly acidic and GSH overexpressed TME, the IDMMS@CaP NC can rapidly collapse when accumulated at the tumor site, liberate Mn2+, Ca2+, and ICG, simultaneously reduce the concentration of GSH. Mn2+ can catalyze endogenous hydrogen peroxide to produce O2. Overloaded Ca2+ induces mitochondrial injury, and reduces cellular metabolism and O2 consumption. The photothermal effect from ICG with 808 nm laser irradiation can not only cause tumor cells necrosis but also accelerate blood flow to further improve the O2 content at the tumor site. Consequently, owing to effective GSH depletion and multiple O2 compensation, the PDT efficiency of ICG can be significantly increased. As proof of concept, the designed multifunctional nanocomposite will provide a general strategy for enhancing the role of phototherapy in cancer therapeutic area.

Thermoregulation and subjective thermal perception of N95 respirator users: Influence of significant workloads

Working under a significant metabolic rate while wearing an N95 mask increased the heat stress that users of protective clothing experienced. This study investigated in a climatic chamber preset at 25 °C and a relative humidity of 65% the changes in thermoregulation and thermal perception of 13 men and 12 women when performing exercises involving different metabolic consumption for 60 min first without wearing an N95 mask for 30 min and then donning a mask. The physiological parameters include the metabolic rate, tympanic temperature, heart rate, skin temperature, skin moisture, and transepidermal water loss (TEWL). Thermal perceptions, including thermal sensation, humidity sensation, thermal comfort, and thermal acceptance were surveyed. The results show that both N95 mask use and exercising contributed to vigorous thermoregulation, particularly in women. The tympanic temperature was between 35.5 °C and 36.5 °C during the experiment for both sexes. Skin temperature during the exercise with or without donning a mask was not influenced by the change in workload, indicating a balance in heat exchange between the body and ambient air. Skin moisture increased by 58.91% and 49.99% when the users of masks performed exercises involving moderate and very high metabolic rates, respectively, compared to levels when a mask was not worn. The TEWL of women and men when wearing a mask and jogging increased by 16.35% and 14.89%, respectively, compared to when not wearing the mask. These results suggests a potential thermal stress from using N95 masks and working in a warm environment when the users are not acclimatized.

Variations in 24-Hour Heart Rate, Physical Activity, Sleep, Autonomic Nervous Activity, and Motor Performance Measured Using a Multifunctional Wireless Holter Recorde in Early Childhood

The study aimed to implement motor performance measurements to clarify the physiological characteristics of aging, as well as the relationship between aging and motor performance. This study, we used a multifunctional wireless holter recorder to continuously measure the 24-hour heart rate, physical activity, sleep, and autonomic nervous system activity of early childhood aged 3–6 years. Results showed that average heart rate, average awake heart rate, average heart rate during sleep, and number of turns during sleep decreased with age. Basal metabolism and total energy expenditure varied significantly by age and sex. Motor performance increased significantly with age, and correlations were found between physical characteristics, physical activity, and mean heart rate during sleep. However, autonomic nervous system activity did not differ significantly with age and sex. Our results show the need for specific programs for each age group.

The effect of ketamine versus tramadol on prophylactic post-spinal shivering in those patients undergoing orthopedic surgery: a prospective cohort study design, 2020

BackgroundPost-spinal shivering is a common complication after spinal anesthesia with a high incidence among orthopedic patients. Untreated shivering may predispose to exacerbation of wound pain, increased metabolic demand, oxygen consumption, and hemostatic dysfunction. Various studies have been done on the effectiveness of preventing post-spinal shivering using ketamine and other drugs. However, little information on better prophylactic agents in terms of effectiveness and availability. Therefore, this study was intended to compare 0.25 mg/kg of Ketamine (K) versus 0.5 mg/kg of Tramadol (T) for the prevention of post-spinal shivering.MethodA prospective cohort study design was employed on 516 patients undergoing orthopedic surgery under spinal anesthesia, and they were selected by a consecutive sampling technique. Patients were divided into two groups based on the anesthetist in charge. Patients who received an intravenous prophylactic dose of Ketamine before spinal anesthesia are called Ketamine groups and patients who received Tramadol are called Tramadol groups (control). The severity and incidence of shivering, blood pressure, heart rate, and axillary body temperature were measured and recorded for one hour at 10-min intervals during the intraoperative period. Descriptive statistics, chi-square, independent t-test, and multivariable logistic regression were used. Significance was declared at a p-value lower than 0.05.ResultsThe overall incidence of post-spinal shivering was 187 (36.2%), of which it was 74 (28.7%) on ketamine and 113 (43.8%) on tramadol with a p-value of 0.001. The incidence of nausea and vomiting was 157 (60.9%) on tramadol and 8 (3.1%) on ketamine, with a p-value of 0.001. Patients aged 18–35 years (AOR 0.08 (0.02, 0.27), 36–55 years (AOR 0.24, 0.07, 0.81), and those patients with a prolonged duration of surgery (AOR 1.47 (1.37–1.58)) were more likely to experience post-spinal shivering. And Low-dose ketamine has a protective effect against developing post-spinal shivering with an AOR of 0.427 (0.28–0.63).ConclusionLow-dose ketamine is more effective in reducing the incidence and severity of shivering after spinal anesthesia. Therefore, we recommend using low-dose ketamine to be effective as a prophylactic for post-spinal shivering in those patients undergoing orthopedic surgery under spinal anesthesia.

Hepatic Acat2 overexpression promotes systemic cholesterol metabolism and adipose lipid metabolism in mice

Aims/hypothesisAcetyl coenzyme A acetyltransferase (ACAT), also known as acetoacetyl-CoA thiolase, catalyses the formation of acetoacetyl-CoA from acetyl-CoA and forms part of the isoprenoid biosynthesis pathway. Thus, ACAT plays a central role in cholesterol metabolism in a variety of cells. Here, we aimed to assess the effect of hepatic Acat2 overexpression on cholesterol metabolism and systemic energy metabolism.MethodsWe generated liver-targeted adeno-associated virus 9 (AAV9) to achieve hepatic Acat2 overexpression in mice. Mice were injected with AAV9 through the tail vein and subjected to morphological, physiological (body composition, indirect calorimetry, treadmill, GTT, blood biochemistry, cardiac ultrasonography and ECG), histochemical, gene expression and metabolomic analysis under normal diet or feeding with high-fat diet to investigate the role of ACAT2 in the liver.ResultsHepatic Acat2 overexpression reduced body weight and total fat mass, elevated the metabolic rate, improved glucose tolerance and lowered the serum cholesterol level of mice. In addition, the overexpression of Acat2 inhibited fatty acid, glucose and ketone metabolic pathways but promoted cholesterol metabolism and changed the bile acid pool and composition of the liver. Hepatic Acat2 overexpression also decreased the size of white adipocytes and promoted lipid metabolism in white adipose tissue. Furthermore, hepatic Acat2 overexpression protected mice from high-fat-diet-induced weight gain and metabolic defectsConclusions/interpretationOur study identifies an essential role for ACAT2 in cholesterol metabolism and systemic energy expenditure and provides key insights into the metabolic benefits of hepatic Acat2 overexpression. Thus, adenoviral Acat2 overexpression in the liver may be a potential therapeutic tool in the treatment of obesity and hypercholesterolaemia.Graphical abstract

TMET-19. DEFINING A NOVEL ROLE FOR CD97 IN REGULATING GBM GLYCOLYTIC METABOLISM

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Despite multimodal therapy, disease recurrence is inevitable. To identify novel vulnerabilities of GBM, we performed an arrayed CRISPR/Cas9 screen against select adhesion G protein-coupled receptors (aGPCRs), many of which we found to be de novo expressed in GBM. Knockout of CD97, previously implicated in GBM cell migration, produced the most striking proliferative disadvantage in patient-derived GBM cultures (PDGC) among aGPCRs tested. We found high CD97 surface expression in all our PDGCs, while levels remained nearly undetectable in non-neoplastic brain cells, confirming that CD97 is de novo expressed in GBM. Upon shRNA-mediated knockdown of CD97 in PDGCs from all three TCGA transcriptional subtypes, we observed reduced proliferation, as measured by cell cycle analysis. Notably, CD97 knockdown also significantly reduced tumorsphere formation capacity as measured by limiting dilution assays; an effect that was partially rescued upon CD97 overexpression. To elucidate mechanisms of action of CD97, we performed RNA-sequencing and GO pathway enrichment analysis from PDGCs following CD97 knockdown. The top downregulated pathways involved glycolytic metabolism, specifically involving many genes relevant for glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) processing. Indeed, when we measured metabolite levels under both steady-state and flux conditions using mass spectrometry, we observed an accumulation of G6P and a depletion of most downstream glycolytic and Krebs cycle metabolites upon CD97 knockdown. Furthermore, Seahorse metabolic assays revealed deficits in both glycolytic metabolism and oxygen consumption. We aim to interrogate the activity of specific glycolytic enzymes involved in processing G6P and F6P, pinpointing how these are influenced by CD97 signaling pathways (MAPK or Akt). Overall; our studies suggest a novel role of CD97 in regulating GBM metabolism (Warburg effect), and provide a strong scientific rationale for developing biologics to target CD97 which appears to be universally and de novo expressed in GBM.

The metabolomics approach revealed a distinctive metabolomics pattern associated with hyperthyroidism treatment

Hyperthyroidism is characterized by increased thyroid hormone production, which impacts various processes, including metabolism and energy expenditure. Yet, the underlying mechanism and subsequent influence of these changes are unknown. Metabolomics is a broad analytical method that enables qualitative and quantitative examination of metabolite level changes in biological systems in response to various stimuli, pathologies, or treatments. This study uses untargeted metabolomics to explore the potential pathways and metabolic patterns associated with hyperthyroidism treatment. The study consisted of 20 patients newly diagnosed with hyperthyroidism who were assessed at baseline and followed up after starting antithyroid treatment. Two blood samples were taken from each patient, pre (hyperthyroid state) and post-treatment (euthyroid state). Hyperthyroid and euthyroid states were identified based on thyroxine and thyroid-stimulating hormone levels. The metabolic alteration associated with antithyroid therapy was investigated using liquid chromatography- high-resolution mass spectrometry. The untargeted metabolomics data was analyzed using both univariate and multivariate analyses using MetaboAnalyst v5.0. The significant metabolic pattern was identified using the lab standard pipeline, which included molecular annotation in the Human Metabolome Database, LipidMap, LipidBlast, and METLIN. The identified metabolites were examined using pathway and network analyses and linked to cellular metabolism. The results revealed a strong group separation between the pre- and post-hyperthyroidism treatment (Q2 = 0.573, R2 = 0.995), indicating significant differences in the plasma metabolome after treatment. Eighty-three mass ions were significantly dysregulated, of which 53 and 30 characteristics were up and down-regulated in the post-treatment compared to the pre-treatment group, respectively. The medium-chain acylcarnitines, octanoylcarnitine, and decanoylcarnitine, previously found to rise in hyperthyroid patients, were among the down-regulated metabolites, suggesting that their reduction could be a possible biomarker for monitoring euthyroid restoration. Kynurenine is a downregulated tryptophan metabolite, indicating that the enzyme kynurenine 3-hydroxylase, inhibited in hyperthyroidism, is back functioning. L-cystine, a cysteine dimer produced from cysteine oxidation, was among the down-regulated metabolites, and its accumulation is considered a sign of oxidative stress, which was reported to accompany hyperthyroidism; L-cystine levels dropped, this suggests that the plasma level of L-cystine can be used to monitor the progress of euthyroid state restoration. The plasma metabolome of patients with hyperthyroidism before and after treatments revealed differences in the abundance of several small metabolites. Our findings add to our understanding of hyperthyroidism's altered metabolome and associated metabolic processes and shed light on acylcarnitines as a new biomarker for treatment monitoring in conjunction with thyroxine and thyroid-stimulating hormone.