BACKGROUND: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain.
METHODS: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions.
RESULTS: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (-59%), and adenosine monophosphate (-39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers.
CONCLUSIONS: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers.

GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B0 and B1+-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml. Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B0 and B1+-inhomogeneities within the range of [-0.3, +0.3] ppm and [40 %, 250 %], respectively. Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus). Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B1+/B1--inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio. Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012). Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18-27 min (GABA+) and 9-18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.

Perioperative acid-base disturbance could be informative regarding the possible slow graft function (SGF) or delayed graft function (DGF) development. There is a lack of data regarding the relationship between perioperative acid-base parameters and graft dysfunction in kidney transplant (KT) recipients. We aim to determine the incidence of graft dysfunction types and the association between them and acid-base parameters. We performed a prospective, cohort study on 54 adults, KT recipients, between 1st of January 2019 and 31st of December 2019. Graft function was defined and classified in three categories: immediate graft function (IGF) (serum creatinine < 3 mg/dL at day 5 after KT), SGF (serum creatinine ≥ 3mg/dL at day 5 or ≥ 2.5mg dL at day 7 after KT) and DGF (the need for at least one dialysis treatment in the first week after kidney transplantation). Among the 54 KT recipients, the incidence of SGF and DGF was 13% and 11.1%, respectively. SGF was significantly associated with lower intraoperative pH (7.26± 0.05 vs 7.35± 0.06, p= 0.004), preoperative and intraoperative base excess (BE) [-7.0 (-10.0 ߝ -6.0) vs -3.4 (-7.8 ߝ - 2.1) mmol/L, p= 0.04 and -10.3 (-11.0 ߝ -9.1) vs -4.0 (-6.3 ߝ - 3.0) mmol/L, p= 0.002, respectively] and serum bicarbonate (HCO3-) (16.0± 2.7 vs 19.3± 3.4 mmol/L, p= 0.01 and 14.1± 1.9 vs 18.8± 3.2 mmol/L, p= 0.002 respectively), compared to IGF. DGF was significantly associated with lower intraoperative values of pH (7.27± 0.05 vs 7.35± 0.06, p= 0.003), BE [-7.1 (-10.9 ߝ -6.1) vs -4.0 (-6.3 ߝ - 3.0) mmol/L, p= 0.02] and HCO3- (15.9± 2.4 vs 18.8± 3.2 mmol/L, p=0.02) compared to IGF. No differences were observed between SGF and DGF patients in any of the perioperative acid-base parameters. In conclusion we found that kidney graft dysfunction types are associated with perioperative acid-base parameters and perioperative metabolic acidosis could provide important information to predict SGF or DGF occurrence.

暂无摘要。

OBJECTIVE: Weight loss has multiple beneficial effects on body composition and metabolism, but whether these depend on the rate at which body weight is lost is not clear. We analyzed data from studies in which the same amount of weight loss was induced rapidly or gradually.
RESULTS: Thirteen studies were included in which the same percentage weight loss was achieved at slow or fast rates (range: 0.2 to 3.2 kg/week) by means of dietary calorie restriction, exercise, and bariatric surgery. Faster rates of weight loss may result in more fat-free mass and less fat mass being lost during the dynamic phase of weight reduction compared with slower rates of weight loss, in conjunction with greater declines in resting energy expenditure. However, these differences are attenuated after 2-4 weeks of stabilization at the new, lower body weight, and do not affect the rate and amount of weight regain 9-33 months later (nor the tissue composition of regained weight). Differences in waist circumference, visceral and liver fat contents, resting blood pressure, fasting blood lipid profile, and insulin and adipokine concentrations in response to different rates of weight loss are trivial. The decline in fasting glucose concentration and the improvement in insulin sensitivity after 6-11% weight loss are both greater with rapid than gradual weight loss, but not different after 18-20% weight loss. Changes in body composition and metabolism after losing the same amount of body weight at different rates are largely similar, and occasional differences are likely not meaningful clinically for the long-term management of obesity and cardiometabolic diseases.

Life-history theory predicts that animals should develop adaptive trade-offs between survival and reproduction to maximize their fitness. This results in a continuum of life-history strategies among species, ranging from slow to fast paces-of-life. The optimal pace-of-life has been shown to vary within environmental gradients, with a commonly observed pattern of a slow-to-fast continuum from the tropics to the poles. Within species, pace-of-life variability has however received much less attention. In this study, we investigated whether or not the pace-of-life of populations within a species follows the expected slow-fast continuum associated with latitude. We analysed the variability of life-history strategies among populations of the European roller Coracias garrulus, a long-distance migratory species, comparing breeding parameters and adult survival between populations across a latitudinal gradient. The findings showed a negative correlation between survival and clutch size in roller populations, with a slower pace-of-life in the northern populations and a faster pace-of-life in the southern populations: a reverse gradient to what might be expected from inter-specific studies. These results suggest that northern populations would benefit from measures enhancing adult survival probability, such as reduction in harvesting rates, while southern populations would respond better to actions favouring reproductive success, such as nesting site provisioning. This study highlights that life-history traits can vary substantially between populations of a single species with a large latitudinal breeding range, and pinpoint how knowledge about this variability may be key in anticipating different populations\' responses to threats as well as to conservation strategies.

The plague has been wreaking havoc on people in Madagascar with the COVID-19 pandemic. Madagascar\'s healthcare sector is striving to respond to COVID-19 in the face of a plague outbreak that has created a new strain on the country\'s public health system. The goal and activities of the gradual epidemic of plague in Madagascar during COVID-19 are described in this research. In order to contain the plague and the COVID-19 pandemic in this country, we have suggested long-term recommendations that can help to contain the outbreak so that it may spread to non-endemic areas.

Pulses are recommended for healthy eating due to their high content of nutrients and bioactive compounds that can undergo changes during cooking. This study investigated the effects of four cooking methods (boiling, pressure, microwave, slow) and three heating solutions (water, salt, sugar) on the phenolic acids and antioxidant properties of three pulses (faba beans, lentils, peas). The composition of phenolic acids differed among the three pulses with p-coumaric and ferulic being the dominant acids. Cooking increased free phenolic acids and lessened bound phenolic acids in faba beans and peas, while decreased both free and bound phenolic acids in lentils. Cooking resulted in reductions in total phenol content (TPC) in faba bean methanol and bound extracts. Pressure and microwave cooking increased TPC in lentil methanol extracts, while pot boiling and slow cooking reduced TPC. Microwave cooking resulted in increases in TPC in bound phenolic extracts from lentils. For peas, cooking increased TPC in both methanol and bound phenolic extracts. Significant changes were also observed in the antioxidant capacity of cooked pulses based on the scavenging ability of DPPH, ABTS and peroxyl radicals subject to the type of pulse, polyphenol and antioxidant assay. Despite the significant reduction in antioxidants, high amounts of phenolics with potent antioxidant activities are still found in cooked pulses.

Skeletal muscle function is essential for health, and it depends on the proper activity of myofibers and their innervating motor neurons. Each adult muscle is composed of different types of myofibers with distinct contractile and metabolic characteristics. The proper balance of myofiber types is disrupted in most muscle degenerative disorders, representing another factor compromising muscle function. One promising therapeutic approach for the treatment of these diseases is cell replacement based on the targeted differentiation of pluripotent stem cells (PSCs) towards the myogenic lineage. We have previously shown that transient induction of Pax3 or Pax7 in PSCs allows for the generation of skeletal myogenic progenitors endowed with myogenic regenerative potential, but whether they contribute to different fiber types remains unknown.
Here, we investigate the fiber type composition of mouse PSC-derived myofibers upon their transplantation into dystrophic and non-dystrophic mice. Our data reveal that PSC-derived myofibers express slow and oxidative myosin heavy-chain isoforms, along with developmental myosins, regardless of the recipient background. Furthermore, transplantation of the mononuclear cell fraction re-isolated from primary grafts into secondary recipients results in myofibers that maintain preferential expression of slow and oxidative myosin heavy-chain isoforms but no longer express developmental myosins, thus indicating postnatal composition.
Considering oxidative fibers are commonly spared in the context of dystrophic pathogenesis, this feature of PSC-derived myofibers could be advantageous for therapeutic applications.

Control of respiration provides a powerful voluntary portal to entrain and modulate central autonomic networks. Slowing and deepening breathing as a relaxation technique has shown promise in a variety of cardiorespiratory and stress-related disorders, but few studies have investigated the physiological mechanisms conferring its benefits. Recent evidence suggests that breathing at a frequency near 0.1 Hz (6 breaths per minute) promotes behavioral relaxation and baroreflex resonance effects that maximize heart rate variability. Breathing around this frequency appears to elicit resonant and coherent features in neuro-mechanical interactions that optimize physiological function. Here we explore the neurophysiology of slow, deep breathing and propose that coincident features of respiratory and baroreceptor afferent activity cycling at 0.1 Hz entrain central autonomic networks. An important role is assigned to the preferential recruitment of slowly-adapting pulmonary afferents (SARs) during prolonged inhalations. These afferents project to discrete areas in the brainstem within the nucleus of the solitary tract (NTS) and initiate inhibitory actions on downstream targets. Conversely, deep exhalations terminate SAR activity and activate arterial baroreceptors via increases in blood pressure to stimulate, through NTS projections, parasympathetic outflow to the heart. Reciprocal SAR and baroreceptor afferent-evoked actions combine to enhance sympathetic activity during inhalation and parasympathetic activity during exhalation, respectively. This leads to pronounced heart rate variability in phase with the respiratory cycle (respiratory sinus arrhythmia) and improved ventilation-perfusion matching. NTS relay neurons project extensively to areas of the central autonomic network to encode important features of the breathing pattern that may modulate anxiety, arousal, and attention. In our model, pronounced respiratory rhythms during slow, deep breathing also support expression of slow cortical rhythms to induce a functional state of alert relaxation, and, via nasal respiration-based actions on olfactory signaling, recruit hippocampal pathways to boost memory consolidation. Collectively, we assert that the neurophysiological processes recruited during slow, deep breathing enhance the cognitive and behavioral therapeutic outcomes obtained through various mind-body practices. Future studies are required to better understand the physio-behavioral processes involved, including in animal models that control for confounding factors such as expectancy biases.