Cortical Activation during Swallowing Exercise Tasks: an fNIRS Pilot Study.

This pilot study used functional near-infrared spectroscopy (fNIRS) to examine brain activity in selected regions of the left motor and sensory cortex while doing swallowing-related tasks. Specifically, differences in cortical activation during normal saliva swallows, effortful swallows, and tongue pressing were investigated. Nine healthy, right-handed adults (5 female, 4 male; Age: 22-30 years) were recruited. The tasks included were (1) normal saliva swallowing, (2) effortful saliva swallowing, and (3) lingual pressing against the palate. Each task was completed three times in a block, for a total of five blocks. Blocks were randomized and presented with set time intervals using PsychoPy. Motor activity was highest during effortful swallows, followed by normal swallows, and lingual presses. Activation in the sensory region was not significantly different across tasks; however, effortful swallows elicited the highest mean peak activation. Our findings suggest that fNIRS can be a viable imaging method used to examine differences in cortical activity in the context of swallowing. Its applicability in future dysphagia research should be explored.

Multi-glycomic analysis of spheroid glycocalyx differentiates 2- and 3-dimensional cell models.

A multi-glycomic method for characterizing the glycocalyx was employed to identify the difference between 2-dimensional (2D) and 3-dimensional (3D) culture models with two human colorectal cancer cell lines, HCT116 and HT29. 3D cell cultures are considered more representative of cancer due to their ability to mimic the microenvironment found in tumors. For this reason, they have become an important tool in cancer research. Cell-cell interactions increase in 3D models compared to 2D, indeed significant glycomic changes were observed for each cell line. Analyses included the N-glycome, O-glycome, glycolipidome, glycoproteome, and proteome providing the most extensive characterization of the glycocalyx between 3D and 2D thus far. The different glycoconjugates were affected in different ways. In the N-glycome, the 3D cells increased in high-mannose glycosylation and in core fucosylation. Glycolipids increased in sialylation. Specific glycoproteins were found to increase in the 3D cell, elucidating the pathways that are affected between the two models. The results show large structural and biological changes between the 2 models suggesting that the 2 are indeed very different potentially affecting individual outcomes in the study of diseases.

Clinical, dermoscopic, and pathologic features of onychopapilloma: A review of 47 cases.

BACKGROUND: Onychopapilloma is a benign neoplasm of the nail bed and the distal matrix. Although not uncommon in our experience, only up to 32 cases of this tumor have been reported in the literature. OBJECTIVE: We sought to review the clinical, dermoscopic, and pathologic features of onychopapilloma. METHODS: We retrospectively analyzed the clinical features of 47 patients with pathologically confirmed onychopapilloma diagnosed within the last 5 years, and reviewed the published literature. RESULTS: The most common clinical presentation was longitudinal erythronychia (n = 25); followed by longitudinal leukonychia (n = 7); longitudinal melanonychia (n = 4); long splinter hemorrhages without erythronychia, leukonychia, or melanonychia (n = 8); and short splinter hemorrhages without erythronychia, leukonychia, or melanonychia (n = 3), with subungual mass (n = 47) and distal fissuring (n = 11). Pathology was consistent with acanthosis of the nail bed and distal matrix, with matrix metaplasia underlying distal subungual hyperkeratosis. LIMITATIONS: This was a retrospective analysis. CONCLUSION: To our knowledge, our series of onychopapilloma is the largest so far. Among various clinical presentations, longitudinal erythronychia is the most common. Dermoscopy of the free edge of the nail plate showing a small subungual keratotic mass where the band reaches the nail plate margin provides a clue for the diagnosis.

Prognostic value of power doppler ultrasonography for equine superficial digital flexor tendon injury in thoroughbred racehorses.

The potential value of hypervascularity detected with power Doppler ultrasonography (PDU) within equine superficial digital flexor tendon (SDFT) as a prognostic factor of SDFT injury is not clear. The purpose of this study was to test the hypothesis that hypervascularity within SDFT is one of the risk factors for subsequent severe SDFT injury and to evaluate the prognostic value. A prospective cohort study of 97 Thoroughbred racehorses without any clinical signs of SDFT injury was conducted. Six variables of age, body weight, sex, the cross-sectional area of SDFT, PDU signal within SDFT and experience of steeplechase were assessed for the possibility of risk factors of subsequent SDFT injury in follow-up period of 1 year. Multivariable logistic regression analyses were used for assessment of the odds ratios (ORs) and 95 % confidence intervals (CIs) of SDFT injury. Multivariable logistic regression analysis revealed that the PDU signal within SDFT was a risk factor for the development of SDFT injury in follow-up period (P = 0.017). The adjusted OR of SDFT injury was significantly higher in PDU positive group than in PDU negative group (OR 3.17, 95 % CIs 1.20-8.35). Although further studies are required, these results would be useful for early detection and/or prevention of development for clinical severe SDFT injury.

Effects of oropharyngeal exercises on the swallowing mechanism of older adults: A systematic review.

PURPOSE: Age-related changes to the swallowing mechanism, or presbyphagia, may put older adults at a higher risk for developing diseases and dysphagia. Maintaining swallowing functions could help prevent frailty and facilitate healthy ageing. This review summarises and appraises the effects of oropharyngeal exercises on the swallowing functions of healthy older adults without dysphagia. It is hypothesised that these exercises will strengthen and improve the structures and functions of the normal ageing swallow. METHOD: This review was reported according to the PRISMA 2020 guidelines. Five electronic databases (Medline, Embase, Cochrane Library, Web of Science, CINAHL) and Google Scholar were searched in June 2021. A rerun was done in January 2023. Study selection, data extraction, and quality assessment were done by two independent raters. RESULT: A total of 23 studies were reviewed. Meta-analysis was not conducted due to the heterogenous training protocols and outcomes. Majority (n = 21) had fair quality due to incomplete reporting. Exercises targeting oral structures were implemented the most (n = 15), followed by variations of the head lift (n = 4), and effortful swallow exercise (n = 1). Others implemented combined or multiapproach exercise studies (n = 3). Apart from surface electromyography findings, statistically significant improvements in oral and pharyngeal phase swallowing outcomes such as increased lingual isometric and swallowing pressures, bite force, muscle thickness, hyolaryngeal excursion, and upper oesophageal sphincter opening diameter were reported in 95% of the studies (n = 22). CONCLUSION: Collective evidence suggests that strength training for swallowing-related structures leads to increases in structural strength, endurance, and muscle mass. The effects of exercises on overall swallowing efficiency and safety remain unclear. Results should be interpreted with caution due to methodological limitations. Further research should examine the long-term effects of these exercises in preventing frailty and reducing the burden of dysphagia in older adults.

Pilot Study Using Neurofeedback as a Tool to Reduce Surgical Resident Burnout.

BACKGROUND: Burnout is prevalent among surgical residents. Neurofeedback is a technique to train the brain in self-regulation skills. We aimed to assess the impact of neurofeedback on the cognitive workload and personal growth areas of surgery residents with burnout and depression. STUDY DESIGN: Fifteen surgical residents with burnout (Maslach Burnout Inventory [MBI] score > 27) and depression (Patient Health Questionnaire-9 Depression Screen [PHQ-9] score >10), from 1 academic institution, were enrolled and participated in this institutional review board-approved prospective study. Ten residents with more severe burnout and depression scores were assigned to receive 8 weeks of neurofeedback treatments, and 5 others with less severe symptoms were treated as controls. Each participant's cognitive workload (or mental effort) was assessed initially, and again after treatment via electroencephalogram (EEG) while the subjects performed n-back working memory tasks. Analysis of variance (ANOVA) tested for significance between the degree of change in the treatment and control groups. Each subject was also asked to rate changes in growth areas, such as sleep and stress. RESULTS: Both groups showed high cognitive workload in the pre-assessment. After the neurofeedback intervention, the treatment group showed a significant (p < 0.01) improvement in cognitive workload via EEG during the working memory task. These differences were not noted in the control group. There was significant correlation between time (NFB sessions) and average improvement in all growth areas (r = 0.98) CONCLUSIONS: Residents demonstrated high levels of burnout, correlating with EEG patterns indicative of post-traumatic stress disorder. There was a notable change in cognitive workload after the neurofeedback treatment, suggesting a return to a more efficient neural network.

Comparing the Efficacy, Safety, and Superiority of Calcitonin Gene-Related Peptide Monoclonal Antibodies and Botox in Preventing and Treating Migraines.

Both calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and OnabotulinumtoxinA (botox) are used in the prevention of chronic migraines. However, it is not clear which is more effective overall. This review will compare the efficacy, side effects, cost-effectiveness, and other factors between CGRP mAbs and botox. We searched Pubmed and Google Scholar using the keywords migraines, CGRP mAbs, botox, efficacy, side effects, aura. All articles, including case-control/cohort studies, case series, case reports, randomized control trials, traditional/systematic reviews, were analyzed. CGRP mAbs and botox both reduce the frequency of migraines in patients. Patients have reported they decreased migraines' frequency and intensity in several studies after being given each medication. While CGRP mAbs are more recent medications, botox has been studied for more than a decade as a migraine preventative. Both drugs have minor short-term side effects, but some CGRP mAbs may cause persistent constipation too. CGRP mAbs are self-injected every month, and botox is physician-injected every three months, making it easier to stay compliant. While both medications are expensive, botox has a lower cost over time. Botox is more effective prophylaxis of migraines based on the articles that were reviewed. While both CGRP mAbs and botox are efficacious and tolerable, botox has been studied longer, has fewer side effects, is more cost-effective, and is easier to comply with.

A Review of Pirfenidone as an Anti-Fibrotic in Idiopathic Pulmonary Fibrosis and Its Probable Role in Other Diseases.

Fibrosis is the result of chronic inflammation and is known to pathologically occur in many organs and systems. Pirfenidone (PFD) is an anti-fibrotic known for its use in idiopathic pulmonary fibrosis (IPF). In addition to being an anti-fibrotic, it acts as an anti-inflammatory and antioxidant as well. There have been studies on PFD in other diseases, some clinical and others preclinical. We have compiled and reviewed them to highlight just how widespread PFD use could be. Among many benefits of PFD in IPF, PFD has effectively improved patients' survival in those who had an acute exacerbation of IPF and has reduced respiratory-related hospitalization, among few others. PFD also has shown an improvement in vital capacity in patients with chronic hypersensitive pneumonitis. Also, it has demonstrated anti-fibrotic effects in systemic sclerosis-associated interstitial lung disease. In other diseases outside the lungs, PFD has reversed insulin resistance and proven to be effective in non-alcoholic steatohepatitis (NASH). It has prevented blindness post-alkali injury to the eye and has proven to decrease the proliferation of mesothelioma cells, just to name a few. This review encourages further research in connection with PFD and its use in other diseases and PFD pros in IPF.

Correction: Comparing the Efficacy, Safety, and Superiority of Calcitonin Gene-Related Peptide Monoclonal Antibodies and Botox in Preventing and Treating Migraines.

[This corrects the article DOI: 10.7759/cureus.13002.].

Can Pioglitazone Safeguard Patients of Lichen Planus Against Homocysteine Induced Accelerated Cardiovascular Aging and Reduced Myocardial Performance: A Systematic Review.

Lichen planus (L.P.) is a long-standing mucocutaneous inflammatory condition. A less familiar but essential illness association is increased arterial stiffness, endothelial dysfunction, and advanced atherosclerosis. Enhanced cardiac reconditioning and reduced performance of the heart have been suggested. Thiazolidinediones were commenced to manage hyperglycemia in diabetes mellitus. Recently, the class attained popularity after its action on vascular physiology was discovered. With this review, we attempted to explore whether an antidiabetic drug, pioglitazone (PIO), a peroxisome proliferator­activated receptor γ (PPAR gamma) agonist, can defend patients of lichen planus against increased arterial stiffness and cardiac changes. We methodically screened numerous databases using focused words and phrases for relevant articles. After a comprehensive exploration, we applied the inclusion and exclusion criteria and performed a quality appraisal. Items retained were exhaustively studied. High homocysteine (HHcy) levels in lichen planus play a significant role in modifying the arteries and leading to their dysfunction. Not only does homocysteine affect the precursor cells, but it also increases the free radical damage. Arterial damage and upraised resistance encountered by the heart reduce its performance. After an exhaustive analysis, in our opinion, pioglitazone works in various miscellaneous ways to mitigate the homocysteine mediated changes. Early inclusion of the drug in managing patients with lichen planus seems promising in minimizing the harmful effects of high homocysteine. Evaluating the risk-benefit ratio, we believe that a trial of pioglitazone could be given to patients without underlying cardiac conditions.

The Relationship of Rapid Eye Movement Sleep Behavior Disorder and Freezing of Gait in Parkinson's Disease.

Rapid eye movement sleep behavior disorder (RBD) contributes to injury due to the alteration of the expected atonia during rapid eye movement (REM) sleep. It occurs before the overt signs of Parkinson's disease (PD). The co-expression of PD and RBD is characterized by non-tremor predominant subtype and higher incidence of freezing. Freezing of gait (FOG) is a debilitating symptom seen in PD patients that lead to falls. While this phenomenon is understood poorly, the involvement of the pedunculopontine nucleus (PPN) and the neural circuits that control locomotion and gait have been examined. This network has also the same control for REM sleep and arousal. The close relationship between PD and RBD and FOG's consequences has led us to explore the relationship between RBD and PD with FOG. This review provides an overview of the neural connections that control gait, locomotion, and REM sleep. The neural changes were seen in PD with FOG and RBD, and sensory and motor changes observed in these two diseases. The functional neuroanatomy that controls REM sleep, arousal, and locomotion overlap significantly with multiple neural circuits affected in RBD and PD with FOG. Visual perception dysfunction and motor symptoms that primarily affect gait initiation are common to both patients with RBD and FOG in PD, leading to freezing episodes. Prospective studies should be conducted to elucidate the relationship of RBD and PD with FOG subtype and find innovative treatment approaches and diagnostic tools for PD with FOG.

A retrospective cohort study investigating risk factors for the failure of Thoroughbred racehorses to return to racing after superficial digital flexor tendon injury.

A retrospective cohort study was conducted to investigate risk factors for the failure of Thoroughbred racehorses to return to racing after an injury of the superficial digital flexor tendon (SDFT). Successful return was defined as the completion of five or more races after SDFT injury. The official Japan Racing Association (JRA) medical records of racehorses with a core-type SDFT injury were reviewed for clinical variables related to the characteristics of the horse and the severity of SDFT injuries at the time of diagnosis. Data on racing outcomes were obtained from the official JRA racing database. Risk factors were screened using univariable logistic regression and subsequent multivariable model building. Forty-nine of 346 (14.2%) horses successfully returned to racing after SDFT injuries. Multivariable model building revealed that an increase in the total number of injured zones (defined as the total number of zones in which the injured hypoechoic area was observed at the time of ultrasonographic diagnosis of SDFT injury) was associated with an increased risk of failure to return to racing after SDFT injury. Horse characteristics, such as age, body mass and sex, were not associated with a successful return to racing. In the rehabilitation of cases with larger (longer) lesions, more effective and careful medical management may be needed for an improvement in the athletic outcomes.

Comparison of alfaxalone, ketamine and thiopental for anaesthetic induction and recovery in Thoroughbred horses premedicated with medetomidine and midazolam.

REASONS FOR PERFORMING STUDY: There is limited information on clinical use of the new injectable anaesthetic agent alfaxalone in Thoroughbred horses. OBJECTIVES: To compare anaesthetic induction and recovery characteristics and cardiopulmonary responses between alfaxalone, ketamine and thiopental in Thoroughbred horses premedicated with medetomidine and midazolam. STUDY DESIGN: Randomised blinded experimental cross-over study. METHODS: Six Thoroughbred horses were anaesthetised 3 times with alfaxalone 1 mg/kg bwt, ketamine 2.5 mg/kg bwt or thiopental 4 mg/kg bwt after premedication with medetomidine 6 µg/kg bwt and midazolam 20 µg/kg bwt. Qualities of anaesthetic induction and recovery were scored on a scale of 1 (poor) to 5 (excellent). Induction time and recovery time were recorded. Cardiopulmonary values (heart rate, respiratory rate, arterial blood pressures, and arterial blood gases) were recorded throughout anaesthesia. Data were analysed with nonparametric methods. RESULTS: The anaesthetic induction (P = 0.2) and recovery (P = 0.1) quality scores (median, range) were not different amongst protocols and were 4.0, 3-5; 5.0, 4-5; 4.5, 3-5; and 4.5, 3-5; 3.5, 2-5; 4.0, 2-5 for alfaxalone, ketamine and thiopental, respectively. Induction time for ketamine (67, 53-89 s) was significantly longer than that for alfaxalone (49, 40-51 s, P = 0.01) and thiopental (48, 43-50 s, P = 0.01). Time to standing for alfaxalone (44, 40-63 min, P = 0.01) and thiopental (39, 30-58 min, P = 0.01) was significantly longer than that for ketamine (25, 18-26 min). Cardiovascular values were maintained within the clinically acceptable level throughout anaesthesia. Respiratory rate significantly decreased during anaesthesia for all 3 drugs; however, spontaneous breathing did not disappear, and PaCO2 values were maintained at approximately 50 mmHg. CONCLUSIONS: All 3 drugs showed similar effects in relation to anaesthetic induction and recovery qualities and cardiopulmonary responses. However, alfaxalone and thiopental prolonged recovery time compared with ketamine.

Universality of S-matrix correlations for deterministic plus random Hamiltonians.

We study S-matrix correlations for random matrix ensembles with a Hamiltonian H=H(0)+straight phi, in which H0 is a deterministic NxN matrix and straight phi belongs to a Gaussian random matrix ensemble. Using Efetov's supersymmetry formalism, we show that in the limit N-->infinity correlation functions of S-matrix elements are universal on the scale of the local mean level spacing: the dependence of H0 enters into these correlation functions only through the average S matrix and the average level density. This statement applies to each of the three symmetry classes (unitary, orthogonal, and symplectic).

Identification of high-affinity anti-IL-1 alpha autoantibodies in normal human serum as an interfering substance in a sensitive enzyme-linked immunosorbent assay for IL-1 alpha.

A highly reproducible, sensitive, and specific sandwich enzyme-linked immunosorbent assay (ELISA) for recombinant human IL-1 alpha (rhIL-1 alpha) has been developed. Results from this ELISA have demonstrated that the concentration of rhIL-1 alpha added to normal human serum (NHS) decreased by 16.3% after 3 h and 24.9% after 6 h at room temperature. Molecular exclusion column chromatography with Sephacryl S-300 HR revealed that 125I-labeled IL-1 alpha added to normal human serum rapidly formed higher molecular weight complexes without indication of proteolytic degradation. The observed reduction in immunoreactivity was correlated with this protein complex formation and accounted for the apparent instability of rhIL-1 alpha in NHS. Immunoblot analysis indicated that the molecular weight of the binding protein was 150-160K, and the IL-1 alpha binding activity was removed and recovered from NHS by Protein-G affinity chromatography; indicating that the binding protein was IL-1 alpha-specific IgG. The binding of 125I-labeled IL-1 alpha to the serum binding proteins could be inhibited by unlabeled IL-1 alpha (IC50 = 7.4 x 10(-11) M) but not by unlabeled IL-1 beta. Kinetic analysis with 125I-labeled IL-1 alpha revealed that the average binding affinity of these IL-1 alpha-specific IgGs was 4.7 x 10(10) M-1. These results suggest that these autoantibodies may interfere with the detection of IL-1 alpha in human serum by various assay systems and also could be a regulator of circulating IL-1 alpha.

Production of virus-like particles by the transposable genetic element, copia, of Drosophila melanogaster.

Using the calcium-phosphate procedure the plasmid cDm2055, which carries the copia transposable element of Drosophila melanogaster, was co-transfected with the Neor-carrying plasmid pSVCneo-1 into the D. hydei cell line KUN-DH-33 which was free of copia. The Neor transfectants stably carried both plasmids as tandem oligomers integrated in the chromosome and virus-like particles (VLP) were produced specifically in the transfectants that received the copia plasmid. The particles were quite similar in various aspects such as size, morphology, density, RNA content and molecular weight of the major protein component, to retrovirus-like particles (RVLP) that spontaneously appear in cultured cells of D. melanogaster: the reverse transcriptase activity however seemed to be low compared to that of the D. melanogaster RVLP. This finding demonstrates that the retrovirus-like particles (RVLP) in Drosophila cultured cells are produced by the transposable genetic element copia resident in the host chromosomes.

Characterization of anti-IL-1 alpha autoantibodies in the sera from healthy humans.

Previously, we reported that pooled normal human serum contained anti-IL-1 alpha autoantibodies. Further characterization studies have been undertaken with sera from individual healthy humans. Molecular exclusion chromatography demonstrated that 9 of 38 test sera contained anti-IL-1 alpha autoantibodies that specifically bound 125I-IL-1 alpha. The autoantibodies formed immune complexes composed of either one IgG or two IgG molecules bound to one 125I-IL-1 alpha molecule. The data suggest that the autoantibodies recognize at least two separate antigenic sites on IL-1 alpha. The autoantibodies neutralized IL-1 alpha induced IL-2 secretion by mouse thymocytes (EL-4 NOB-1). Further, in an in vitro competitive receptor binding assay, the autoantibodies completely blocked 125I-IL-1 alpha binding to recombinant human IL-1 receptor expressed on CHO cells. Our previous studies have established a correlation between inhibition of 125I-IL-1 alpha binding to receptor bearing cells and neutralization of IL-1 bioactivity in vitro and in vivo. These data suggest that development of anti-IL-1 alpha autoantibodies may play a significant role in modulating the effects of high local or systemic concentrations of IL-1 alpha.