Cyclic changes in cortisol across the estrous cycle in parous and nulliparous Asian elephants

 In the context of reproduction, glucocorticoids (GCs) are generally considered to have negative effects. However, in well-studied model species, GCs fluctuate predictability across the estrous cycles, and short-term increases promote healthy ovarian function. Reproductive challenges have plagued captive elephant populations, which are not currently self-sustaining. Efforts to understand reproductive dysfunction in elephants have focused on the suppressive effects of cortisol, but the potential permissive or stimulatory effects of cortisol are unknown. In this study, we provide a detailed examination of cortisol patterns across the estrous cycle in Asian elephants (Elephas maximus). Time series analysis was used to analyze cortisol and progesterone data for a total of 73 cycles from eight females. We also compared cortisol profiles between females that successfully conceived and females that failed to conceive despite repeated mating attempts. Our results revealed that cortisol fluctuates predictably across the estrous cycle, with a peak during the second half of the follicular phase followed by low levels throughout the luteal phase. Furthermore, this pattern was significantly altered in nulliparous females; cortisol concentrations did not decline during the luteal phase to the same extent as in parous females. This study highlights the complexity of cortisol signaling and suggests future directions for understanding the role of cortisol in reproductive dysfunction.

Enhanced lithium storage in ZnFe2O4-C nanocomposite produced by a low-energy ball milling

Preparation of novel nanocomposite structure of ZnFe2O4-C is achieved by combining a sol-gel and a low energy ball milling method. The crucial feature of the composite's structure is that sol-gel synthesised ZnFe2O4 nanoparticles are dispersed and attached uniformly along the chains of Super P Li™ carbon black matrix by adopting a low energy ball milling. The composite ZnFe2O4-C electrodes are capable of delivering a very stable reversible capacity of 681 mAh g-1 (96% retention of the calculated theoretical capacity of ∼710 mAh g-1) at 0.1 C after 100 cycles with a remarkable Coulombic efficiency (82%) improvement in the first cycle. The rate capability of the composite is significantly improved and obtained capacity was as high as 702 at 0.1, 648 at 0.5, 582 at 1, 547 at 2 and 469 mAh g-1 at 4 C (2.85 A g-1), respectively. When cell is returned to 0.1 C, the capacity recovery was still ∼98%. Overall, the electrochemical performance (in terms of cycling stability, high rate capability, and capacity retention) is outstanding and much better than those of the related reported works. Therefore, our smart electrode design enables ZnFe2O4-C sample to be a high quality anode material for lithium-ion batteries.

The neuro-immune pathophysiology of central and peripheral fatigue in systemic immune-inflammatory and neuro-immune diseases

Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

The putative role of viruses, bacteria, and chronic fungal biotoxin exposure in the genesis of intractable fatigue accompanied by cognitive and physical disability

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

Fatigue is a major issue for children and adolescents with physical disabilities

AIM: This study aimed to investigate fatigue, and its correlates, in children and adolescents with physical disabilities. METHOD: Sixty-five young people aged 8 to 17 years (35 males, 30 females; mean age 13y 2mo, SD 2y 8mo) with mild to moderate physical disabilities (Gillette Functional Assessment Questionnaire levels 7-10) were recruited. Self-reported fatigue was measured using the PedsQL Multidimensional Fatigue Scale. Physical activity was measured using 7-day hip-worn accelerometer. Associations between fatigue, physical activity, and socio-demographic characteristics were examined using analysis of covariance, with significance (α) set at 0.05. Results were compared with normative data from other paediatric populations. RESULTS: Among children with physical disabilities, fatigue was associated with being physically inactive (F-statistic=4.42, p=0.040), female (F=4.37, p=0.042), and of low socio-economic status (F=3.94, p=0.050). Fatigue was not associated with age, weight status, or functional impairment. Young people with physical disabilities experienced high levels of fatigue compared with other paediatric health populations, and comparable to the paediatric cancer population. INTERPRETATION: Fatigue is an important issue for young people with physical disabilities. Clinicians and researchers working with this group should be mindful that fatigue is likely to impact on an individual's ability to undertake new treatment regimens or interventions. Interventions aimed at reducing fatigue are warranted. Increasing physical activity might play a role in reducing fatigue.

Inter-cycle variability of ignition delay in an ethanol fumigated common rail diesel engine

An experimental study has been performed to investigate the ignition delay of a modern heavy-duty common-rail diesel engine run with fumigated ethanol substitutions up to 40% on an energy basis. The ignition delay was determined through the use of statistical modelling in a Bayesian framework this framework allows for the accurate determination of the start of combustion from single consecutive cycles and does not require any differentiation of the in-cylinder pressure signal. At full load the ignition delay has been shown to decrease with increasing ethanol substitutions and evidence of combustion with high ethanol substitutions prior to diesel injection have also been shown experimentally and by modelling. Whereas, at half load increasing ethanol substitutions have increased the ignition delay. A threshold absolute air to fuel ratio (mole basis) of above ~110 for consistent operation has been determined from the inter-cycle variability of the ignition delay, a result that agrees well with previous research of other in-cylinder parameters and further highlights the correlation between the air to fuel ratio and inter-cycle variability. Numerical modelling to investigate the sensitivity of ethanol combustion has also been performed. It has been shown that ethanol combustion is sensitive to the initial air temperature around the feasible operating conditions of the engine. Moreover, a negative temperature coefficient region of approximately 900{1050 K (the approximate temperature at fuel injection) has been shown with for n-heptane and n-heptane/ethanol blends in the numerical modelling. A consequence of this is that the dominate effect influencing the ignition delay under increasing ethanol substitutions may rather be from an increase in chemical reactions and not from in-cylinder temperature. Further investigation revealed that the chemical reactions at low ethanol substitutions are different compared to the high (> 20%) ethanol substitutions.

Temporal dynamics of the circadian heart rate following low and high volume exercise training in sedentary male subjects

Purpose: Increased risk of arrhythmic events occurs at certain times during the circadian cycle with the highest risk being in the second and fourth quarter of the day. Exercise improves treatment outcome in individuals with cardiovascular disease. How different exercise protocols affect the circadian rhythm and the associated decrease in adverse cardiovascular risk over the circadian cycle has not been shown. Methods: Fifty sedentary male participants were randomized into an 8-week high volume and moderate volume training and a control group. Heart rate was recorded using Polar Electronics and investigated with Cosinor analysis and by Poincaré plot derived features of SD1, SD2 and the complex correlation measure (CCM) at 1-h intervals over the 24-h period. Results: Moderate exercise significantly increased vagal modulation and the temporal dynamics of the heart rate in the second quarter of the circadian cycle (p = 0.004 and p = 0.007 respectively). High volume exercise had a similar effect on vagal output (p = 0.003) and temporal dynamics (p = 0.003). Cosinor analysis confirms that the circadian heart rate displays a shift in the acrophage following moderate and high volume exercise from before waking (1st quarter) to after waking (2nd quarter of day). Conclusions: Our results suggest that exercise shifts vagal influence and increases temporal dynamics of the heart rate to the 2nd quarter of the day and suggest that this may be the underlying physiological change leading to a decrease in adverse arrhythmic events during this otherwise high-risk period.

Effect of an acute bout of plyometric exercise on neuromuscular fatigue and recovery in recreational athletes

Although plyometric training is widely used by sports coaches as a method of improving explosive power in athletes, many prescribe volumes in excess of the National Strength and Conditioning Association recommendations. The purpose of this study was to assess voluntary and evoked muscle characteristics to assess the neuromuscular impact of a high-volume bout of plyometric exercise that was non-exhaustive. Ten athletes who did not have plyometric training experience and were in their competitive season for club-level sport volunteered for the study. After at least 2 days without high-intensity activity, subjects were assessed on maximal twitch torque, time to peak torque, rate of twitch torque development, twitch half-relaxation time, rate of twitch relaxation, and voluntary activation by the interpolated twitch technique before, immediately after, and 2 hours after a high-volume plyometric training program (212 ground contacts). Data were analyzed by repeated-measures analysis of variance and described as mean +/- SD and Cohen d. Statistically significant decrements appeared immediately after the training protocol in the total torque generated by maximal voluntary contractions (p < 0.05, d = -0.51) and twitch (p < 0.01, d = -0.92), rate of twitch torque development (p < 0.01, d = -0.77), and rate of relaxation (p < 0.01, d = -0.73). However, we did not observe any differences that remained statistically different after 2 hours. There were no significant differences observed at any time point in time to peak twitch, half-relaxation time, or voluntary activation. We conclude that high-volume plyometric training results primarily in peripheral fatigue that substantially impairs force and rate of force development. We recommend that coaches carefully monitor the volume of plyometric training sessions to avoid neuromuscular impairments that can result in suboptimal training.

Bimodal grain size distributions in UFG materials produced by SPD - their evolution and effect on the fatigue and monotonic strength properties

In ultrafine-grained (UFG) materials produced by severe plastic deformation (SPD) techniques such as ECAP (equal channel angular pressing), bimodal grain size distributions have been observed under different circumstances, for example shortly after ECAP, after rest or anneal and/or after mild cyclic deformation at rather low homologous temperature. It has been shown that the mechanical monotonic and fatigue properties of some UFG materials can be modified (sometimes enhanced) by introducing a bimodal grain size distribution by a mild annealing treatment which leads, in some cases, to a good combination of strength and ductility. Here, the conditions under which bimodal grain size distributions evolve by (adiabatic) heating during ECAP and during subsequent annealing or cyclic deformation will be explored, and the effects on the mechanical properties, as studied by the authors and as reported so far in the literature, will be reviewed and discussed. In particular, the role of temperature rise during ECAP will be considered in some detail.

Temozolomide in pediatric low-grade glioma

BACKGROUND: We describe a retrospective series of children with low-grade glioma who received temozolomide. PROCEDURE: Eligible patients had had a diagnosis of low-grade glioma with or without histological confirmation. Temozolomide was administered at a dose of 200 mg/m(2) daily for 5 days, in a 4-week cycle. Therapy was stopped on completion of the targeted 12 cycles of chemotherapy or on evidence of tumor progression. RESULTS: Thirteen eligible patients were identified, eight male and five female. Median age at diagnosis was 5.5 years (range 2.6-15.0 years) and at commencement of temozolomide treatment was 9.0 years (range 3.8-15.2 years). Nine patients had a histological diagnosis of pilocytic astrocytoma. Twelve patients had received carboplatin prior to temozolomide, including three in combination with vincristine. A total of 111 cycles of therapy have been administered. Hematological toxicity and nausea were the most common adverse effects. Median time to progression was 6.7 months (range 1.5-41.8 months). Event-free survival rate at 3 years was 57%. Twelve of 13 patients remain alive at the time of report. Eleven have stable disease (SD). CONCLUSION: Temozolomide appears to be active in pediatric low-grade glioma, with the advantage of oral administration and excellent tolerability.

Influence of fuel-borne oxygen on European stationary cycle: diesel engine performance and emissions with a special emphasis on particulate and NO emissions

Exploration of sustainable fuels and their influence on reductions in diesel emissions are nowadays a challenge for the engine and fuel researchers. This study investigates the role of fuel-borne oxygen on engine performance and exhaust emissions with a special emphasis on diesel particulate and nitric oxide (NO) emissions. A number of oxygenated-blends were prepared with waste cooking biodiesel as a base oxygenated fuel. Triacetin, a derivative from transesterified biodiesel was chosen for its high oxygen content and superior fuel properties. The experimental campaign was conducted with a 6-cylinder, common rail turbocharged diesel engine equipped with highly precise instruments for nano and other size particles and other emissions. All experiments were performed in accordance with European Stationary Cycle (ESC 13-mode). A commercial diesel was chosen as a reference fuel with 0% oxygen and five other oxygenated blends having a range of 6.02–14.2% oxygen were prepared. The experimental results revealed that the oxygenated blends having higher a percentage of fuel-borne oxygen reduced particulate matter (PM), particle number (PN), unburned hydrocarbon (UBHC) and carbon monoxide (CO) emissions to a significantly low level with a slight penalty of NO emissions. The main target of this study was to effectively utilise triacetin as an additive for waste cooking biodiesel and suppress emissions without deteriorating engine performance. The key finding of this investigation is the significant reductions in both particle mass and number emissions simultaneously without worsening engine performance with triacetin-biodiesel blends. Reductions in both particle mass and number emissions with a cost-effective additive would be a new dimension for the fuel and engine researchers to effectively use triacetin as an emission suppressor in the future.