"1 The authors conducted a discriminant multivariate analysis to investigate the predictive variables influencing audiological outcomes in patients with idiopathic sudden sensorineural hearing loss ...(ISSNHL) treated with intra tympanic steroid (ITS) injections. ...considering the 81 % spontaneous recovery rate shown in the studies by Kitajiri et al8 and Bayoumy et al,9 it could be intriguing to evaluate the potential association between the severity of ISSNHL, the pretreatment compromised threshold, and the presence of irreversibly dead cochlear regions. The grade of hearing loss in our study offers a general categorization of the overall hearing loss, whereas the threshold provides detailed information about an individual's hearing abilities across various frequencies at a specific dB level.This has been the preferred selection in several studies.3 5 Regarding spontaneous recovery in the mentioned studies,6-7 ethical issues surrounding depriving patients diagnosed with idiopathic sudden sensorineural hearing loss (ISSNHL) of a potentially effective intratympanic steroid (ITS) or other management modalities and thus waiting for spontaneous recovery are multifaceted and require careful consideration of the principles of respecting a patient's autonomy, beneficence, nonmaleficence, justice, and the specific circumstances of the case.8-9 Quantifying this recovery would be especially useful if no method of steroid administration has proven to be better in individuals with ISSNHL who are not receiving treatment because the spontaneous hearing recovery rate in these patients is large. ...I appreciate The Journal of International Advanced Otology
Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the ...etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1β intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1β/ IL-1β R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies.
Meniere's disease (MD) represents a clinical syndrome characterized by episodes of spontaneous vertigo, associated with fluctuating, low to medium frequencies sensorineural hearing loss (SNHL), ...tinnitus, and aural fullness affecting one or both ears. To date, the cause of MD remains substantially unknown, despite increasing evidence suggesting that oxidative stress and neuroinflammation may be central to the development of endolymphatic hydrops and consequent otholitic degeneration and displacement in the reuniting duct, thus originating the otolithic crisis from vestibular otolithic organs utricle or saccule. As a starting point to withstand pathological consequences, cellular pathways conferring protection against oxidative stress, such as vitagenes, are also induced, but at a level not sufficient to prevent full neuroprotection, which can be reinforced by exogenous nutritional approaches. One emerging strategy is supplementation with mushrooms. Mushroom preparations, used in traditional medicine for thousands of years, are endowed with various biological actions, including antioxidant, immunostimulatory, hepatoprotective, anticancer, as well as antiviral effects. For example, therapeutic polysaccharopeptides obtained from
are commercially well established. In this study, we examined the hypothesis that neurotoxic insult represents a critical primary mediator operating in MD pathogenesis, reflected by quantitative increases of markers of oxidative stress and cellular stress response in the peripheral blood of MD patients. We evaluated systemic oxidative stress and cellular stress response in MD patients in the absence and in the presence of treatment with a biomass preparation from
. Systemic oxidative stress was estimated by measuring, in plasma, protein carbonyls, hydroxynonenals (HNE), and ultraweak luminescence, as well as by lipidomics analysis of active biolipids, such as lipoxin A4 and F2-isoprostanes, whereas in lymphocytes we determined heat shock proteins 70 (Hsp72), heme oxygenase-1 (HO-1), thioredoxin (Trx), and γ-GC liase to evaluate the systemic cellular stress response. Increased levels of carbonyls, HNE, luminescence, and F2-isoprostanes were found in MD patients with respect to the MD plus
-treated group. This was paralleled by a significant (
< 0.01) induction, after
treatment, of vitagenes such as HO-1, Hsp70, Trx, sirtuin-1, and γ-GC liase in lymphocyte and by a significant (
< 0.05) increase in the plasma ratio-reduced glutathione (GSH) vs. oxidized glutathione (GSSG). In conclusion, patients affected by MD are under conditions of systemic oxidative stress, and the induction of vitagenes after mushroom supplementation indicates a maintained response to counteract intracellular pro-oxidant status. The present study also highlights the importance of investigating MD as a convenient model of cochlear neurodegenerative disease. Thus, searching innovative and more potent inducers of the vitagene system can allow the development of pharmacological strategies capable of enhancing the intrinsic reserve of vulnerable neurons, such as ganglion cells to maximize antidegenerative stress responses and thus providing neuroprotection.
We performed a systematic review on the early assessment of swallowing function after cerebrovascular stroke.
A systematic review of the English language literature of the past 20 years was performed ...regarding swallowing function and cerebrovascular stroke. All articles reporting swallowing evaluation through clinical examination validated scores, and diagnostic tools were included in the summary.
The systematic review of the literature identified 1,768 potentially relevant studies with 7 papers retrieved with a total of 589 stroke dysphagic patients. While at the clinical neurological assessment, The National Institutes of Health Stroke Scale was more frequently used as a clinical outcome predictor. The Bedside screening approach was carried out in 6 papers to assess patients with probable swallowing disorders. Among the diagnostic tools, seven studies performed the Flexible Fiberoptic Endoscopic evaluation assessing scoring validated system while two papers reported early swallowing outcomes Videofluoroscopic Swallow Study.
Our systematic review revealed the findings significantly associated with dysphagia in post-cerebrovascular patients. Endoscopic evaluation of swallowing proved to be the most used method in the literature, effective in identifying early predictors of dysphagia. Given the presence of different assessing scores employed and reduced study samples enrolled, further studies with large courts are necessary for a greater significance.
Modulation of endogenous cellular defense mechanisms via the vitagene system represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in ...neurodegeneration. The possibility of high-throughoutput screening using proteomic techniques, particularly redox proteomics, provide more comprehensive overview of the interaction of proteins, as well as the interplay among processes involved in neuroprotection. Here by introducing the hormetic dose response concept, the mechanistic foundations and applications to the field of neuroprotection, we discuss the emerging role of heat shock protein as prominent member of vitagene network in neuroprotection and redox proteomics as a tool for investigating redox modulation of stress responsive vitagenes. Hormetic mechanisms are reviewed as possibility of targeted therapeutic manipulation in a cell-, tissue- and/or pathway-specific manner at appropriate points in the neurodegenerative disease process.
There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. ...Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses.
Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding.
Conceivably, activation of LXA4 signaling and modulation of stress responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.
Obstructive Sleep Apnea (OSA) syndrome is a respiratory sleep disorder characterized by partial or complete episodes of upper airway collapse with reduction or complete cessation of airflow. Although ...the connection remains debated, several mechanisms such as intermittent hypoxemia, sleep deprivation, hypercapnia disruption of the hypothalamic-pituitary-adrenal axis have been associated with poor neurocognitive performance. Different treatments have been proposed to treat OSAS patients as continuous positive airway pressure (CPAP), mandibular advancement devices (MAD), surgery; however, the effect on neurocognitive functions is still debated. This article presents the effect of OSAS treatments on neurocognitive performance by reviewing the literature.
We performed a comprehensive review of the English language over the past 20 years using the following keywords: neurocognitive performance and sleep apnea, neurocognitive improvement and CPAP, OSAS, and cognitive dysfunction. We included in the analysis papers that correlated OSA treatment with neurocognitive performance improvement. All validated tests used to measure different neurocognitive performance improvements were considered.
Seventy papers reported neurocognitive Performance improvement in OSA patients after CPAP therapy. Eighty percent of studies found improved executive functions such as verbal fluency or working memory, with partial neural recovery at long-term follow-up. One article compared the effect of MAD, CPAP treatment on cognitive disorders, reporting better improvement of CPAP and MAD than placebo in cognitive function.
CPAP treatment seems to improve cognitive defects associated with OSA. Limited studies have evaluated the effects of the other therapies on cognitive function.
To evaluate the role of clinical scores assessing the risk of disease severity in patients with clinical suspicion of obstructive sleep apnea syndrome (OSA). The hypothesis was tested by applying ...artificial intelligence (AI) to demonstrate its effectiveness in distinguishing between mild-moderate OSA and severe OSA risk.
A support vector machine model (SVM) was developed from the samples included in the analysis (N = 498), and they were split into 75% for training (N = 373) with the remaining for testing (N = 125). Two diagnostic thresholds were selected for OSA severity: mild to moderate (apnea-hypopnea index (AHI) ≥ 5 events/h and AHI < 30 events/h) and severe (AHI ≥ 30 events/h). The algorithms were trained and tested to predict OSA patient severity.
The sensitivity and specificity for the SVM model were 0.93 and 0.80 with an accuracy of 0.86; instead, the logistic regression full mode reported a value of 0.74 and 0.63, respectively, with an accuracy of 0.68. After backward stepwise elimination for features selection, the reduced logistic regression model demonstrated a sensitivity and specificity of 0.79 and 0.56, respectively, and an accuracy of 0.67.
Artificial intelligence could be applied to patients with symptoms related to OSA to identify individuals with a severe OSA risk with clinical-based algorithms in the OSA framework.
•LOX (but not LOXL2) promotes breast cancer metastatic osteolytic lesions in vivo.•LOX (but not LOXL2) enhances RANKL-induced osteoclast differentiation in vitro.•LOX (but not LOXL2) induces a robust ...IL-6 production by tumor cells in vitro.
The primary function of the lysyl oxidase (LOX) family, including LOX and its paralogue LOX-like (LOXL)-2, is to catalyze the covalent crosslinking of collagen and elastin in the extracellular matrix. LOX and LOXL2 are also facilitating breast cancer invasion and metastatic spread to visceral organs (lungs, liver) in vivo. Conversely, the contribution of LOX and LOXL2 to breast cancer bone metastasis remains scant. Here, using gene overexpression or silencing strategies, we investigated the role of LOX and LOXL2 on the formation of metastatic osteolytic lesions in animal models of triple negative breast cancer. In vivo, the extent of radiographic metastatic osteolytic lesions in animals injected with LOX-overexpressing LOX(+) tumor cells was 3-fold higher than that observed in animals bearing tumors silenced for LOX LOX(−). By contrast, the extent of osteolytic lesions between LOXL2(+) and LOXL2(−) tumor-bearing animals did not differ, and was comparable to that observed with LOX(−) tumor-bearing animals. In situ, TRAP staining of bone tissue sections from the hind limbs of LOX(+) tumor-bearing animals was substantially increased compared to LOX(−), LOXL2(+) and LOXL2(−)-tumor-bearing animals, which was indicative of enhanced active-osteoclast resorption. In vitro, tumor-secreted LOX increased osteoclast differentiation induced by RANKL, whereas LOXL2 seemed to counteract LOX’s pro-osteoclastic activity. Furthermore, LOX (but not LOXL2) overexpression in tumor cells induced a robust production of IL-6, the latter being a pro-osteoclastic cytokine. Based on these findings, we propose a model in which LOX and IL-6 secreted from tumor cells act in concert to enhance osteoclast-mediated bone resorption that, in turn, promotes metastatic bone destruction in vivo.
PDF
