Impacts of different triathlon races on systemic cytokine profile and metabolic parameters in healthy individuals: a systematic review.

The present systematic review aimed to discuss the impacts of different triathlon protocols on the level of pro and anti-inflammatory cytokines, as well as biomarkers related to the performance of healthy individuals. Four databases [PubMed (28 articles), Scopus (24 articles), Science Direct (200 articles), and SPORT Discus (1101 articles) were assessed. The eligibility criteria were applied, and the selected articles were used in the peer review, independently, as they were identified by March 2022. Of the 1359 articles found, 10 were included in this systematic review. Despite the difference in triathlon protocols, it was observed an increase in pro and anti-inflammatory cytokines including IL-4 and IL-10, and chemokines, such as IL-8 and MCP-1. Moreover, the anti-inflammatory serum levels increase after triathlon. Overall, the studies also reported enhancement in the serum levels of cortisol, creatine kinase, C reactive protein, Endothelial Growth Factor, Vascular Endothelial Growth Factor, Myostatin, Lactate dehydrogenase, free fatty acids, and lactate dehydrogenase in triathlon athletes. This systematic review indicates that different triathlon race promotes an acute elevation of circulating cytokines and chemokines levels which return to standard levels after triathlon races. The findings of this systematic review demonstrate that the modulation of inflammatory parameters may be associated with an increase in metabolic indicators (CK, Cortisol, and LDH) after the end of different types of triathlon races.

Precision neuromodulation: Promises and challenges of spinal stimulation for multi-modal rehabilitation.

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar presentations when developing spinal stimulation-based therapies. We also motivate advancement of multi-modal rehabilitation paradigms, which leverage the dense interconnectivity of sensorimotor spinal networks and the unique ability of electrical stimulation to modulate these networks to facilitate and guide simultaneous rehabilitation across domains.

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury.

Electrical stimulation of spinal networks below a spinal cord injury (SCI) is a promising approach to restore functions compromised by inadequate excitatory neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared motor pathways and spinal motor networks rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by SCI. Debilitating spasms, spasticity, and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. But whereas spasms and spasticity can often be managed pharmacologically, SCI-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from etiologies other than SCI, and it has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for motor rehabilitation. Thus, we reasoned that spinal stimulation intended to increase transmission in motor pathways may simultaneously reduce transmission in spinal pain pathways. Using a well-validated pre-clinical model of SCI that results in severe bilateral motor impairments and SCI-related neuropathic pain, we show that the responsiveness of neurons integral to the development and persistence of the neuropathic pain state can be enduringly reduced by motor-targeted spinal stimulation while preserving spinal responses to non-pain-related sensory feedback. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with SCI.

Spinal stimulation for motor rehabilitation immediately modulates nociceptive transmission.

Objective. Spinal cord injury (SCI) often results in debilitating movement impairments and neuropathic pain. Electrical stimulation of spinal neurons holds considerable promise both for enhancing neural transmission in weakened motor pathways and for reducing neural transmission in overactive nociceptive pathways. However, spinal stimulation paradigms currently under development for individuals living with SCI continue overwhelmingly to be developed in the context of motor rehabilitation alone. The objective of this study is to test the hypothesis that motor-targeted spinal stimulation simultaneously modulates spinal nociceptive transmission.Approach. We characterized the neuromodulatory actions of motor-targeted intraspinal microstimulation (ISMS) on the firing dynamics of large populations of discrete nociceptive specific and wide dynamic range (WDR) neurons. Neurons were accessed via dense microelectrode arrays implantedin vivointo lumbar enlargement of rats. Nociceptive and non-nociceptive cutaneous transmission was induced before, during, and after ISMS by mechanically probing the L5 dermatome.Main results. Our primary findings are that (a) sub-motor threshold ISMS delivered to spinal motor pools immediately modulates concurrent nociceptive transmission; (b) the magnitude of anti-nociceptive effects increases with longer durations of ISMS, including robust carryover effects; (c) the majority of all identified nociceptive-specific and WDR neurons exhibit firing rate reductions after only 10 min of ISMS; and (d) ISMS does not increase spinal responsiveness to non-nociceptive cutaneous transmission. These results lead to the conclusion that ISMS parameterized to enhance motor output results in an overall net decrease n spinal nociceptive transmission.Significance. These results suggest that ISMS may hold translational potential for neuropathic pain-related applications and that it may be uniquely suited to delivering multi-modal therapeutic benefits for individuals living with SCI.

Spontaneous Multimodal Neural Transmission Suggests That Adult Spinal Networks Maintain an Intrinsic State of Readiness to Execute Sensorimotor Behaviors.

Spontaneous action potential discharge (spAP) is both ubiquitous and functionally relevant during neural development. spAP remains a prominent feature of supraspinal networks in maturity, even during unconsciousness. Evidence suggests that spAP persists in mature spinal networks during wakefulness, and one function of spAP in this context could be maintenance of a "ready state" to execute behaviors. The extent to which spAP persists in mature spinal networks during unconsciousness remains unclear, and its function(s), if any, are likewise unresolved. Here, we attempt to reconcile some of the questions and contradictions that emerge from the disintegrated picture of adult spinal spAP currently available. We recorded simultaneously from large populations of spinal interneurons in vivo in male rats, characterizing the spatial distribution of spAP in the lumbar enlargement and identifying subgroups of spontaneously active neurons. We find (1) concurrent spAP throughout the dorsoventral extent of the gray matter, with a diverse yet strikingly consistent mixture of neuron types across laminae; (2) the proportion of neurons exhibiting spAP in deeper, sensorimotor integrative regions is comparable to that in more superficial, sensory-dominant regions; (3) firing rate, but not spike train variability, varies systematically with region; and (4) spAP includes multimodal neural transmission consistent with executing a spinally-mediated behavior. These findings suggest that adult spAP may continue to support a state of readiness to execute sensorimotor behaviors even during unconsciousness. Such functionality has implications for our understanding of how perception is translated into action, of experience-dependent modification of behavior, and (mal)adaptative responses to injury or disease.SIGNIFICANCE STATEMENT Neurons often discharge action potentials (APs) seemingly spontaneously, that is, in the absence of ongoing behaviors or overt stimuli. This phenomenon is particularly evident during neural development, where spontaneous AP discharge (spAP) is ubiquitous in the central nervous system and is crucial to establishing connectivity among functionally related groups of neurons. The function(s) of spAP in adult spinal networks, if any, have remained enigmatic, especially during unconsciousness. Here, we report evidence that one such function could be to support an intrinsic state of readiness to execute sensorimotor behaviors. This finding has implications for our understanding of how perception is translated into action, of experience-dependent modification of behavior, and (mal)adaptative responses to injury or disease.

Light therapy for the treatment of delayed sleep-wake phase disorder in adults: a systematic review.

Delayed sleep-wake phase disorder (DSWPD) is characterized by sleep onset times, beyond the usual schedules and social conveniences, which potentially impacts on health as well as on school and professional performance. The most common treatment for DSWPD is the light administration (light therapy), through light devices, with or without behavioral instructions. Since there is no consensus in the literature about its efficacy and how it should be processed, this study aims to evaluate the light therapy effectiveness in the delayed sleep-wake phase disorder therapeutics. A systematic review was conducted using the MEDLINE/PubMed, Virtual Health Library Brazil, PsycINFO, Web of Science and Scopus databases along with a hand search until September 2020. The included studies presented participants diagnosed with insomnia or DSWPD, over 18-years old, treated only with morning light therapy, mentioning the light intensity (lux) used, and investigations with a control group. Studies reporting individuals with neurological or psychiatric disorders, shift-workers, or evaluating other sleep disorders were excluded. Among the 411 studies identified, five were selected for this review, resulting in a total sample of 140 individuals. Only two studies produced long-term results, showing that the benefits did not persist. In most studies, there were no statistically significant differences in the variables when comparing the intervention group and the control group. However, there were substantial clinical and laboratory advances in the sleep phase using light therapy when comparing phase advances for the same group concerning baseline values of sleep variables.

Autonomous control of ventilation through closed-loop adaptive respiratory pacing.

Mechanical ventilation is the standard treatment when volitional breathing is insufficient, but drawbacks include muscle atrophy, alveolar damage, and reduced mobility. Respiratory pacing is an alternative approach using electrical stimulation-induced diaphragm contraction to ventilate the lung. Oxygenation and acid-base homeostasis are maintained by matching ventilation to metabolic needs; however, current pacing technology requires manual tuning and does not respond to dynamic user-specific metabolic demand, thus requiring re-tuning of stimulation parameters as physiological changes occur. Here, we describe respiratory pacing using a closed-loop adaptive controller that can self-adjust in real-time to meet metabolic needs. The controller uses an adaptive Pattern Generator Pattern Shaper (PG/PS) architecture that autonomously generates a desired ventilatory pattern in response to dynamic changes in arterial CO2 levels and, based on a learning algorithm, modulates stimulation intensity and respiratory cycle duration to evoke this ventilatory pattern. In vivo experiments in rats with respiratory depression and in those with a paralyzed hemidiaphragm confirmed that the controller can adapt and control ventilation to ameliorate hypoventilation and restore normocapnia regardless of the cause of respiratory dysfunction. This novel closed-loop bioelectronic controller advances the state-of-art in respiratory pacing by demonstrating the ability to automatically personalize stimulation patterns and adapt to achieve adequate ventilation.

Restoring Ventilatory Control Using an Adaptive Bioelectronic System.

Ventilatory pacing by electrical stimulation of the phrenic nerve or of the diaphragm has been shown to enhance quality of life compared to mechanical ventilation. However, commercially available ventilatory pacing devices require initial manual specification of stimulation parameters and frequent adjustment to achieve and maintain suitable ventilation over long periods of time. Here, we have developed an adaptive, closed-loop, neuromorphic, pattern-shaping controller capable of automatically determining a suitable stimulation pattern and adapting it to maintain a desired breath-volume profile on a breath-by-breath basis. The system adapts the pattern of stimulation parameters based on the error between the measured volume sampled every 40 ms and a desired breath volume profile. In vivo studies in anesthetized male Sprague-Dawley rats without and with spinal cord injury by spinal hemisection at C2 indicated that the controller was capable of automatically adapting stimulation parameters to attain a desired volume profile. Despite diaphragm hemiparesis, the controller was able to achieve a desired volume in the injured animals that did not differ from the tidal volume observed before injury (p = 0.39). Closed-loop adaptive pacing partially mitigated hypoventilation as indicated by reduction of end-tidal CO2 values during pacing. The closed-loop controller was developed and parametrized in a computational testbed before in vivo assessment. This bioelectronic technology could serve as an individualized and autonomous respiratory pacing approach for support or recovery from ventilatory deficiency.

Inhibition of salt appetite in sodium-depleted rats by carvacrol: Involvement of noradrenergic and serotonergic pathways.

Carvacrol, a monoterpene phenol present in the essential oil of oregano, possesses several biological properties, such as antioxidant, anti-inflammatory, anxiolytic, anticonvulsive and antinociceptive. In vitro studies have shown that carvacrol inhibits serotonin, noradrenaline and dopamine transporters and the enzymes monoamine oxidase-A and B. Different brain functions are controlled by monoamines, including cardiovascular control, thirst and sodium appetite. In the present study we investigated the effects of intracerebroventricular (i.c.v.) injection of carvacrol on sodium appetite, and the participation of brain serotonergic and noradrenergic pathways on carvacrol effects. Neuronal activation in homeostasis-related brain areas induced by i.c.v. injection of carvacrol was also evaluated. Carvacrol dose-dependently inhibited hypertonic saline intake (1.5%) in sodium-depleted rats, and this antinatriorexigenic effect was reduced by brain serotonergic depletion and by alpha-adrenergic blockade. Furthermore, i.c.v. injections of carvacrol significantly increased the neuronal activation in brain areas involved in the control of salt appetite, such as MnPO, OVLT, PVN, SON, CeA and MeA. Taken together, our data show that carvacrol presents antinatriorexigenic activity through serotonin and noradrenaline pathways within brain circuits involved in the modulation of the body fluid homeostasis.

Use of Mueller matrix polarimetry and optical coherence tomography in the characterization of cervical collagen anisotropy.

Preterm birth (PTB) presents a serious medical health concern throughout the world. There is a high incidence of PTB in both developed and developing countries ranging from 11% to 15%, respectively. Recent research has shown that cervical collagen orientation and distribution changes during pregnancy may be useful in predicting PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent materials, such as the cervix's extracellular matrix. Noninvasive, full-field Mueller matrix polarimetry (MMP) imaging methodologies, and optical coherence tomography (OCT) imaging were used to assess cervical collagen content and structure in nonpregnant porcine cervices. We demonstrate that the highly ordered structure of the nonpregnant porcine cervix can be observed with MMP. Furthermore, when utilized ex vivo, OCT and MMP yield very similar results with a mean error of 3.46% between the two modalities.

Microbiological and clinical outcomes of fixed complete-arch mandibular prostheses supported by immediate implants in individuals with history of chronic periodontitis.

OBJECTIVES: The aim of this study was to assess the microbiological and clinical outcomes of immediate implants placed in chronically infected sockets for rehabilitation with fixed full-arch mandibular prostheses. MATERIAL AND METHODS: Fourteen individuals (mean age 60.14 ± 7.69 years) were enrolled in this investigation and followed up until 8 months of function. Microbiological (microbial count and profile) and clinical (probing depth, clinical attachment level, bleeding on probing, and bone resorption) parameters were conducted before teeth extraction (T0 - baseline) and after 4 (T1 ) and 8 (T2 ) months of loading. Thirty-nine microbial species including periodontopathogenic species and Candida spp. were detected and quantified by DNA checkerboard analysis. RESULTS: Moderate to high levels of pathogenic and non-pathogenic species were found colonizing teeth and implant-related sites. No significant differences in total or individual microbial counts and microbial profile were found over time (P = 0.4929). Probing depth values from teeth (T0 : 3.05 ± 1.45) were significantly higher when compared with implants (T1 : 1.81 ± 0.56; T2 : 1.66 ± 0.53; P < 0.0001). High percentages of bleeding sites were found for both teeth and implants, with the highest values recorded for teeth (P < 0.05). No significant differences were detected comparing marginal bone resorption over time. CONCLUSIONS: Total and individual counts of target species did not differ between teeth and implants for 8 months of investigation. The mean proportions of pathogenic and non-pathogenic species remained unaltered, and no clinical complications were reported over time. Data obtained suggest that immediate loading of complete mandibular prostheses retained by implants placed immediately after extraction may be a viable treatment option for edentulous individuals with previous history of periodontal disease.

Role of the sarcolemmal adenosine triphosphate-sensitive potassium channel in hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility.

BACKGROUND: Hyperkalemic cardioplegia (Plegisol) has been shown to result in myocyte swelling and reduced contractility. We have demonstrated the elimination of these detrimental effects by the addition of an adenosine triphosphate-sensitive K+ (KATP) channel opener. To examine whether the mitochondrial or sarcolemmal KATP channel might be involved, volume and contractility in isolated myocytes from wild-type mice and mice lacking the sarcolemmal KATP channel (Kir6.2-/-) were evaluated. METHODS: Myocytes were perfused for 20 minutes each with control 37 degrees C Tyrode's solution, test solution, and then control solution. Test solutions were (n = 10 per group) either 9 degrees C Plegisol or 9 degrees C Plegisol with 100 micromol/L of diazoxide, a putative mitochondrial-specific KATP channel opener. Cell volume and contractility were measured by digital video microscopy at baseline and during the test solution and reexposure periods. RESULTS: Myocytes from wild-type mice, perfused with 9 degrees C Plegisol, demonstrated significant cell swelling (11.2% +/- 0.4%; p < 0.01) and diminished contractility (32.5% +/- 9.6% reduction in percent shortening, 47.2% +/- 10.1% reduction in peak velocity of shortening, and 52.0% +/- 8.8% reduction in peak velocity of relengthening; p < 0.05) versus baseline. Cell swelling and diminished contractility were significantly reduced by the addition of diazoxide. In Kir6.2-/- myocytes, Plegisol caused a greatly reduced level of cell swelling (3.2% +/- 0.1%; p < 0.01), and this was unaffected by diazoxide. Contractility was unchanged in Kir6.2-/- myocytes after Plegisol. CONCLUSIONS: The sarcolemmal KATP channel appears necessary for exaggerated cell swelling and reduced contractility to occur after hyperkalemic cardioplegia in mouse myocytes.

Transgenic overexpression of SUR1 in the heart suppresses sarcolemmal K(ATP).

The lack of pathological consequences of cardiac ATP-sensitive potassium channel (K(ATP)) channel gene manipulation is in stark contrast to the effect of similar perturbations in the pancreatic beta-cell. Because the pancreatic and cardiac channel share the same pore-forming subunit (Kir6.2), the different effects of genetic manipulation likely reflect, at least in part, the tissue-specific expression of the regulatory subunit (SUR1 in pancreas vs. SUR2A in heart) of the bipartite channel complex. To examine this, we have generated transgenic (TG) mice that overexpress epitope-tagged SUR1 or SUR2A under the transcriptional control of the alpha-myosin heavy chain promoter. Western blot and real time RT-PCR analysis confirm transgene expression in the heart, and variable levels of SUR1 RNA and protein, in 16 viable founder lines. Surprisingly, activation of channels by either pharmacological agents (diazoxide and pinacidil) or metabolic inhibitors (oligomycin and 2-deoxyglucose) reveals a suppression of total K(ATP) conductance in high expressing TG mice. Moreover, K(ATP) channel activity was significantly reduced in excised cardiac patches from TG myocytes that overexpress either SUR1 or SUR2A. Using a recombinant cell system, we show that overexpression of either SUR1 or Kir6.2 suppresses the functional expression of K(ATP) from optimized dimeric SUR1-Kir6.2. Thus, the graded effect of SUR1 expression in the intact heart appears to demonstrate an in vivo requirement for 1:1 expression ratio of Kir6.2 and SURx.