Rejected

Gradenigo syndrome is a clinical triad of abducens nerve palsy, retro-orbital pain (trigeminal ganglionitis), and chronic otorrhea (otitis media). The etiology of Gradenigo syndrome results from apical petrositis secondary to suppurative otitis media. Although apical petrositis has gradually become uncommon in modern society due to the widespread use of antibiotics, Gradenigo syndrome should be considered in the differential diagnosis of a child's diplopia.

Cutaneous allodynia (CA) is a pain in response to non-nociceptive stimulation and a marker of central sensitisation. Probable migraine (PM) is a migraine subtype that fulfils all but one criterion of migraine. Headache intensity and the disability of individuals with PM are similar or lower than individuals with migraine. This study compared CA prevalence and characteristics of PM and migraine using a nationally representative sample in Korea. The Allodynia Symptom Checklist-12 (ASC-12) was used to assess CA (ASC-12 score ≥ 3). PM and migraine prevalence were 11.6% and 5.0%, respectively. CA prevalence did not significantly differ between PM and migraine (14.5% vs. 16.0%, p = 0.701). Participants with PM with CA reported a higher monthly headache frequency (3.3 ± 4.3 vs. 1.8 ± 3.6, p = 0.044), more severe headache intensity (Visuals Analogue Scale, 6.0 [4.0-7.0] vs. 5.0 [3.0-6.0], p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, p < 0.001) than those without CA. Multiple regression analyses revealed that headache frequency and intensity, anxiety, and depression were significant factors for CA in participants with PM. In conclusion, CA prevalence among participants with PM and migraine were comparable. Anxiety, depression, and headache frequency and intensity were significant factors for CA in participants with PM.

Regulation of cellular excitability and oscillatory behavior of resting membrane potential in nerve cells are largely mediated by the low-voltage activated T-type calcium channels. This calcium channel family is constituted by three isoforms, namely, Ca3.1, Ca3.2, and Ca3.3, that are largely distributed in the nervous system and other parts of the body. Dysfunction of T-type calcium channels is associated with a wide range of pathophysiologies including epilepsy, neuropathic pain, cardiac problems, and major depressive disorders. Due to their pharmacological relevance, finding molecular agents able to modulate the channel's function may provide therapeutic means to ameliorate their related disorders. Here we used electrophysiological experiments to show that genistein, a canonical tyrosine kinase inhibitor, reduces the activity of the human Ca3.3 channel in a concentration-dependent manner. The inhibitory effect of genistein is independent of tyrosine kinase modulation and does not affect the voltage-dependent gating of the channel. Subsequently, we used computational methods to identify plausible molecular poses for the interaction of genistein and the Ca3.3 channel. Starting from different molecular poses, we carried out all-atom molecular dynamics (MD) simulations to identify the interacting determinants for the Ca3.3/genistein complex formation. Our extensive (microsecond-length) simulations suggest specific binding interactions that seem to stabilize the protein/inhibitor complex. Furthermore, our results from the unbiased MD simulations are in good agreement with the recently solved cryoelectron microscopy structure of the Ca3.1/Z944 complex in terms of both the location of the ligand binding site and the role of several equivalent amino acid residues. Proposed interacting complex loci were subsequently tested and corroborated by electrophysiological experiments using another naturally occurring isoflavone derivative, daidzein. Thus, by using a combination of and techniques, we have identified interacting determinants relevant to the Ca3.3/genistein complex formation and propose that genistein directly blocks the function of the human Ca3.3 channel as a result of such interaction. Specifically, we proposed that a combination of polar interactions involving the three hydroxyl groups of genistein and an aromatic interaction with the fused rings are the main binding interactions in the complex formation. Our results pave the way for the rational development of improved and novel low-voltage activated T-type calcium channel inhibitors.

Changes in headache characteristics in obstructive sleep apnea (OSA) patients following oral appliance treatment was investigated for the first time. Thirteen OSA patients with headaches treated with a mandibular advancement device were investigated. Level I polysomnography and Migraine Disability Assessment Questionnaire were completed before and after treatment. Various headache characteristics and concomitant conditions were analyzed. The patient was considered a headache responder when ≥ 30% reduction in headache frequency following treatment. Differences in headache and polysomnographic parameters were compared between headache responder groups. Eight patients (62%) were headache responders. Eleven patients (85%) before and 7 (54%) after treatment reported morning headaches. Significantly more patients had bilateral headache in the responder group before treatment (P = 0.035). The severest headache intensity (P = 0.018) at baseline showed a significant decrease in the headache responder group after treatment. The time spent in N2 (r = - 0.663, P = 0.014), REM sleep (r = 0.704, P = 0.007) and mean oxygen saturation (r = 0.566, P = 0.044) showed a significant correlation with post-treatment average headache intensity. Pre-treatment lower PLM index (r = - 0.632, P = 0.027) and higher mean oxygen saturation levels (r = 0.592, P = 0.043) were significantly correlated with higher post-treatment severest headache intensity. Treatment with an oral appliance is beneficial for many OSA patients with headaches. It should be considered as an alternative treatment in headache patients with mild to moderate OSA.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

To explore patient experience of chronic wound care across diverse models of outpatient wound care delivery.

The COVID-19 pandemic has resulted in an incomparable disease burden worldwide. One of the main contributors stems from the multisystem inflammatory syndrome associated with SARS-CoV-2 infection. The numbers of those affected continue to rise with the increasing number of confirmed COVID-19 cases. However, we are yet to fully comprehend the risk factors, disease progression and prognosis for individuals affected. We describe a case of a previously healthy 17-year-old boy who tested positive for the SARS-CoV-2 virus. He presented with a 5-day history of mild influenza-like symptoms, however, quickly required ventilatory support in the intensive care unit. Two months postdischarge, he developed an isolated petechial rash on his palms and soles. His cutaneous presentation was in association with a mixed sensorimotor peripheral neuropathy, debilitating neuropathic pain and intermittent respiratory distress. We postulate that cutaneous manifestations post-COVID-19 could be indicatory of the newly identified multisystem inflammatory syndrome.

Transforaminal full-endoscopic lumbar discectomy (TELD) can be performed under local anesthesia. However, there have been no reports on risk factors for a change in vital signs or the need for additional medications to maintain adequate analgesia during this procedure. The purpose of this study was to identify risk factors for additional intravenous medication during TELD under local anesthesia. The following factors were retrospectively evaluated in 113 consecutive patients who underwent TELD under local anesthesia at our institution: demographic characteristics, radiological features at the intervertebral disc level, distance between the superior articular process and the exiting nerve root, height of the intervertebral disc, height of the bulging disc, height of the intervertebral foramen, and distance from the insertion site to the spinous process on magnetic resonance imaging (MRI) and computed tomography (CT) scans of the lumbar spine. Logistic regression analysis was performed to determine factors associated with the need for additional drugs. In all, 23 cases (20.4%) required additional intraoperative medications because of hypertension, hypotension, bradycardia, or pain. Logistic regression analysis revealed that age (partial regression coefficient 0.05, p = 0.02) and bulging disc height (partial regression coefficient -0.7, p = 0.003) influenced the need for additional drugs. There were significant associations of need for additional intravenous medication with older age (>62 years) and a smaller bulging disc height (<8.2 mm). Patients with these factors require close monitoring for changes in vital signs or increasing pain when performing TELD under local anesthesia and may need additional intravenous medication.

Infection by human T-lymphotropic virus 1 (HTLV-1) is often seen as the cause of chronic infection or lymphoproliferative disorders, but many clinicians do not recognise its association with severe immunosuppression. We report the case of a woman in her 70s from the Caribbean who sought care at the emergency department for weakness, fatigue and weight loss. Further work-up showed atypical lymphocytosis with floral lymphocytes and smudge cells in the peripheral blood smear and hypercalcaemia. Chest CT demonstrated a moderate right pleural effusion. Results of HIV testing were negative, and screening and confirmatory tests for HTLV-1 were positive. Empiric antibiotic therapy was administered, and the patient was discharged home. Five days later, she was readmitted with shortness of breath and severe abdominal pain. A disseminated infection with was diagnosed. Despite aggressive intravenous antifungal therapy, the patient died on day 7 of hospitalisation.