Middle Ear Welding Injury: Case Report and Literature Review.

Damage to the middle ear (ME) caused by penetrating welding sparks can lead to a variety of adverse outcomes. An exhaustive review of the literature is lacking, particularly with regard to clinical presentation, diagnostic-therapeutic work-up, and outcomes. Here we describe the clinical details of an injury caused by the largest welding foreign body ever reported in the ME.

COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT: Implications of inflammatory findings in cancer imaging.

We observed several patients presenting 2-[F]FDG uptake in the reactive axillary lymph node at PET/CT imaging, ipsilateral to the site of the COVID-19 vaccine injection. Analog finding was documented at [F]Choline PET/CT. The aim of our study was to describe this source of false positive cases.

NF-κB/c-Rel DNA-binding is reduced in substantia nigra and peripheral blood mononuclear cells of Parkinson's disease patients.

Although Parkinson's disease (PD) key neuropathological hallmarks are well known, the underlying pathogenic mechanisms of the disease still need to be elucidated to identify innovative disease-modifying drugs and specific biomarkers. NF-κB transcription factors are involved in regulating several processes associated with neurodegeneration, such as neuroinflammation and cell death, that could be related to PD pathology. NF-κB/c-Rel deficient (c-rel) mice develop a progressive PD-like phenotype.

Role of the TAp63 Isoform in Recurrent Nasal Polyps.

The pathogenic molecular mechanisms underlying the insurgence of nasal polyps has not been completely defined. In some patients, these lesions can have a recurrence after surgery removal, and the difference between recurrent and not recurrent patients is still unclear. To molecularly characterize and distinguish between these two classes, a cohort of patients affected by nasal polyposis was analysed.

Postural control abnormalities related to sleep deprivation in patients with Marfan Syndrome.

Background: Marfan syndrome (MFS) is a rare autosomal dominant connective tissue disorder affecting virtually every organ. Sleep disturbances, associated to high collapsibility in upper airways, are common in MFS; daytime sleepiness could lead to reduction in attention and motor coordination, with detrimental effects on balance.

Objective: To evaluate otoneurological function in MFS patients, compared to healthy subjects, and to investigate possible correlations with sleep deprivation extent.

I Uptake in Bronchiectasis Detected by Single Photon Emission Computed Tomography/Computed Tomography during Follow-up of Thyroid Cancer.

During follow-up of thyroid cancer, I whole-body scan showed intense tracer uptake in the right hemithorax of a patient previously submitted to thyroidectomy and radioiodine therapy for differentiated thyroid cancer. Thyroglobulin was undetectable at the time of the scan. Single-photon emission computed tomography/computed tomography (SPECT/CT) of the thorax correctly identified widespread bronchiectasis I-avid in the middle lobe of the right lung.

NF-κB/c-Rel deficiency causes Parkinson's disease-like prodromal symptoms and progressive pathology in mice.

Background: Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic nigrostriatal neuron loss and brain accumulation of Lewy bodies, protein aggregates mainly composed of α-synuclein. We reported that mice deficient for NF-κB/c-Rel (c-rel) develop a late-onset parkinsonism. At 18 months of age, c-rel mice showed nigrostriatal degeneration and accumulation of α-synuclein aggregates associated with a motor impairment responsive to L-DOPA administration.

Visual dependency and postural control on swing performance in golf players.

Individuals have to reweight the respective contribution of the different sources of sensorial information for regulating posture and balance, especially during fine task execution. Given the evidences indicating strategy during swing performance as associated with prioritization of task-relevant visuospatial information for skill execution, the aim of the present work is to assess differences in visual dependency (VD) and postural control in a population of expert (EXP) and non-expert (NEXP) golfers when compared with healthy subjects (HC) and to discover possible relationships between these outcomes and swing performance. Thus, 15 golfers (EXP = 7; NEXP = 8) and 32 matched HC underwent otoneurological testing including video Head Impulse Test, posturography and Rod and Disk Test (RDT).

A Polyphenol-Enriched Supplement Exerts Potent Epigenetic-Protective Activity in a Cell-Based Model of Brain Ischemia.

Bioactive components, due in part to their epigenetic properties, are beneficial for preventing several human diseases including cerebrovascular pathologies. However, no clear demonstration supports the idea that these molecules still conserve their epigenetic effects when acting at very low concentrations reproducing the brain levels achieved after oral administration of a micronutrient supplement. In the present study, we used a cellular model of brain ischemia to investigate the neuroprotective and epigenetic activities of a commercially available micronutrient mixture (polyphenol-enriched micronutrient mixture, PMM) enriched in polyphenols ((-)-epigallocatechin-3-gallate, quercetin, resveratrol), α-lipoic acid, vitamins, amino acids and other micronutrients.

Postural and vestibular changes related to CPAP treatment in moderate-to-severe OSA patients: a 12-month longitudinal study.

Purpose: To assess whether vestibulo-ocular reflex (VOR) gain, posturography parameters and related clinical outcomes can improve in OSA patients after 12 months of CPAP treatment, taking into consideration that a certain degree of vestibular dysfunction has been identified in these subjects.

Methods: Vestibular, postural, clinical, and polygraphic parameters were assessed in 32 OSA patients before and after beneficial CPAP treatment by means of video head impulse test (vHIT), static posturography (SP), Dizziness Handicap Inventory (DHI), Epworth Sleepiness Scale (ESS), and Apnea-Hypopnea Index (AHI), respectively, and were compared by means of a "within-subject" ANOVA model and Spearman's rank correlation.

Results: After the 12-month period of treatment, OSA patients demonstrated a significant reduction in AHI values, in both opened and closed eyes conditions of surface and length as well as in power spectra recorded in low, middle, and high frequency interval.

Synergistic Association of Valproate and Resveratrol Reduces Brain Injury in Ischemic Stroke.

Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275), respectively, an activator of the AMP-activated kinase (AMPK)-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs), synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker.

Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation.

CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer's disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis.

PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia.

The combination of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines, and the flavonoid luteolin has been found to exert neuroprotective activities in a variety of mouse models of neurological disorders, including brain ischemia. Indirect findings suggest that the two molecules can reduce the activation of mastocytes in brain ischemia, thus modulating crucial cells that trigger the inflammatory cascade. Though, no evidence exists about a direct effect of PEA and luteolin on mast cells in experimental models of brain ischemia, either used separately or in combination.

NF-κB in Innate Neuroprotection and Age-Related Neurodegenerative Diseases.

NF-κB factors are cardinal transcriptional regulators of inflammation and apoptosis, involved in the brain programing of systemic aging and in brain damage. The composition of NF-κB active dimers and epigenetic mechanisms modulating histone acetylation, finely condition neuronal resilience to brain insults. In stroke models, the activation of NF-κB/c-Rel promotes neuroprotective effects by transcription of specific anti-apoptotic genes.

CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid.

Activation of microglia associated with neuroinflammation and loss of phagocytic activity is considered to play a prominent role in the pathogenesis of Alzheimer's disease (AD). CHF5074 (CSP-1103) has been shown to improve cognition and reduce brain inflammation in patients with mild cognitive impairment (MCI). CHF5074 was also found to reverse impairments in recognition memory and improve hippocampal long-term potentiation when administered to plaque-free Tg2576 mice (5-month-old) for 4 weeks.

Pharmacological targeting of the β-amyloid precursor protein intracellular domain.

Amyloid precursor protein (APP) intracellular domain (AICD) is a product of APP processing with transcriptional modulation activity, whose overexpression causes various Alzheimer's disease (AD)-related dysfunctions. Here we report that 1-(3',4'-dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid) (CHF5074), a compound that favorably affects neurodegeneration, neuroinflammation and memory deficit in transgenic mouse models of AD, interacts with the AICD and impairs its nuclear activity. In neuroglioma-APPswe cells, CHF5074 shifted APP cleavage from Aβ42 to the less toxic Aβ38 peptide without affecting APP-C-terminal fragment, nor APP levels.

Electrophysiological and metabolic effects of CHF5074 in the hippocampus: protection against in vitro ischemia.

CHF5074 is a non-steroidal anti-inflammatory derivative holding disease-modifying potential for the treatment of Alzheimer's disease. The aim of the present study was to characterize the electrophysiological and metabolic profile of CHF5074 in the hippocampus. Electrophysiological recordings show that CHF5074 inhibits in a dose-dependent manner the current-evoked repetitive firing discharge in CA1 pyramidal neurons.

Targeted acetylation of NF-kappaB/RelA and histones by epigenetic drugs reduces post-ischemic brain injury in mice with an extended therapeutic window.

Unlabelled: Nuclear factor-kappaB (NF-κB) p50/RelA is a key molecule with a dual effect in the progression of ischemic stroke. In harmful ischemia, but not in preconditioning insult, neurotoxic activation of p50/RelA is characterized by RelA-specific acetylation at Lys310 (K310) and deacetylation at other Lys residues. The derangement of RelA acetylation is associated with activation of Bim promoter.

1B/(-)IRE DMT1 expression during brain ischemia contributes to cell death mediated by NF-κB/RelA acetylation at Lys310.

The molecular mechanisms responsible for increasing iron and neurodegeneration in brain ischemia are an interesting area of research which could open new therapeutic approaches. Previous evidence has shown that activation of nuclear factor kappa B (NF-κB) through RelA acetylation on Lys310 is the prerequisite for p50/RelA-mediated apoptosis in cellular and animal models of brain ischemia. We hypothesized that the increase of iron through a NF-κB-regulated 1B isoform of the divalent metal transporter-1 (1B/DMT1) might contribute to post-ischemic neuronal damage.

NF-κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress.

Brain cells display an amazing ability to respond to several different types of environmental stimuli and integrate this response physiologically. Some of these responses can outlive the original stimulus by days, weeks or even longer. Long-lasting changes in both physiological and pathological conditions occurring in response to external stimuli are almost always mediated by changes in gene expression.

The γ-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice.

Abnormal amyloid-β (Aβ) production and deposition is believed to represent one of the main causes of Alzheimer's disease (AD). γ-Secretase is the enzymatic complex responsible for Aβ generation from its precursor protein. Inhibition or modulation of γ-secretase represents an attractive therapeutic approach.

The γ-secretase modulator CHF5074 reduces the accumulation of native hyperphosphorylated tau in a transgenic mouse model of Alzheimer's disease.

The relationship between β-amyloid (Aβ) and tau is not fully understood, though it is proposed that in the pathogenesis of Alzheimer's disease (AD) Aβ accumulation precedes and promotes tau hyperphosphorylation via activation of glycogen synthase kinase-3beta (GSK-3β). Both events contribute to learning and memory impairments. Modulation of γ-secretase activity has proved to reduce the Aβ burden and cognitive deficits in mouse models of AD, but its ability in reducing the tau pathology remains elusive.

The acetylation of RelA in Lys310 dictates the NF-κB-dependent response in post-ischemic injury.

The activation of nuclear factor kappa B (NF-κB) p50/RelA is a key event in ischemic neuronal injury, as well as in brain ischemic tolerance. We tested whether epigenetic mechanisms affecting the acetylation state of RelA might discriminate between neuroprotective and neurotoxic activation of NF-κB during ischemia. NF-κB activation and RelA acetylation were investigated in cortices of mice subjected to preconditioning brain ischemia or lethal middle cerebral artery occlusion (MCAO) and primary cortical neurons exposed to preconditioning or lethal oxygen-glucose deprivation (OGD).

Glutamatergic reinnervation and assembly of glutamatergic synapses in adult rat skeletal muscle occurs at cholinergic endplates.

After denervation of adult rat abdominal muscles, the postsynaptic apparatus of neuromuscular junctions (NMJs) retains its original architecture and clustering of acetylcholine receptors (AChRs). When descending fibers of the spinal cord are surgically diverted to this muscle by a nerve grafting procedure, supraspinal glutamatergic neurons can innervate muscle fibers and restore motor function; the newly formed NMJs switch from a cholinergic to a glutamatergic-type synapse. We show here that regenerating nerve endings contact the fibers in an area occupied by cholinergic endplates.