Aim
Recently, with the second wave of COVID-19, the Indian subcontinent has witnessed a dramatic rise in mucormycosis infection in patients recovered from COVID-19. This association has been documented in various case reports/case series and institutional experiences, and the mortality associated with this fungal infection is emerging as a cause of concern. The aim of the present paper is to provide a scientific overview on the pathogenesis of mucormycosis in COVID-19 beyond the conventional understanding of the disease process, which may not otherwise explain the increased incidence of mucormycosis in SARS-CoV-2.
Methodology
This paper is structured as a narrative review of the published literature on the pathogenesis of COVID-19 which contributes to the development of mucormycosis. Apart from the acknowledged role of ketoacidosis, high blood sugar, and iron metabolism in the pathogenesis of mucormycosis, other factors involved in pathophysiology of COVID-19 which might alter or enhance the mucormycosis infection such as (1) the role of ferritin, (2) high serum iron, (3) free radical-induced endothelitis, (4) hepcidin activation, (5) upregulation of glucose receptor protein (GRP78) are discussed in the pathophysiology of COVID-19-associated mucormycosis.
Conclusion
A new proposal for the pathogenesis based on the ferritin, viral mimicry of hepcidin and GRP78–CotH3 interaction, which clearly explains the surge in mucormycosis in SARS-CoV-2 infection, has been explained.
BackgroundPost-transcriptional regulation
by heterogeneous ribonucleoproteins (hnRNPs) is an important regulatory paradigm in cancer development. Our proteomic analysis revealed hnRNPD overexpression in oral dysplasia as compared with normal mucosa; its role in oral carcinogenesis remains unknown. Here in we determined the hnRNPD associated protein networks and its clinical significance in oral squamous cell carcinoma (OSCC).MethodsImmunoprecipitation (IP) followed by tandem mass spectrometry was used to identify the binding partners of hnRNPD in oral cancer cell lines. Ingenuity pathway analysis (IPA) was carried out to unravel the protein interaction networks associated with hnRNPD and key interactions were confirmed by co-IP-western blotting. hnRNPD expression was analyzed in 183 OSCCs, 44 oral dysplasia and 106 normal tissues using immunohistochemistry (IHC) and correlated with clinico-pathological parameters and follow up data over a period of 91 months. Kaplan–Meier survival and Cox-multivariate-regression analyses were used to evaluate the prognostic significance of hnRNPD in OSCC.ResultsWe identified 345 binding partners of hnRNPD in oral cancer cells. IPA unraveled novel protein–protein interaction networks associated with hnRNPD and suggested its involvement in multiple cellular processes: DNA repair, replication, chromatin remodeling, cellular proliferation, RNA splicing and stability, thereby directing the fate of oral cancer cells. Protein–protein interactions of hnRNPD with 14-3-3ζ, hnRNPK and S100A9 were confirmed using co-IP-western blotting. IHC analysis showed significant overexpression of nuclear hnRNPD in oral dysplasia [p = 0.001, Odds ratio (OR) = 5.1, 95 % CI = 2.1–11.1) and OSCCs (p = 0.001, OR = 8.1, 95 % CI = 4.5–14.4) in comparison with normal mucosa. OSCC patients showing nuclear hnRNPD overexpression had significantly reduced recurrence free survival [p = 0.026, Hazard ratio = 1.95, 95 % CI = 1.0–3.5] by Kaplan–Meier survival and Cox-multivariate-regression analyses and has potential to define a high-risk subgroup among OSCC patients with nodal negative disease.ConclusionsOur findings suggest novel functions of hnRNPD in cellular proliferation and survival, besides RNA splicing and stability in oral cancer. Association of nuclear hnRNPD with poor prognosis in OSCC patients taken together with its associated protein networks in oral cancer warrant future studies designed to explore its potential as a plausible novel target for molecular therapeutics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0637-3) contains supplementary material, which is available to authorized users.
The aim of the study was to evaluate the effectiveness of greater occipital nerve decompression for the management of occipital neuralgia. Eleven patients of medical refractory occipital neuralgia were enrolled in the study. Local anaesthetic blocks were used for confirming diagnosis. All of them underwent surgical decompression of greater occipital nerve at the level of semispinalis capitis and trapezial tunnel. A pre and postoperative questionnaire was used to compare the severity of pain and number of pain episodes/month. Mean pain episodes reported by patients before surgery were 17.1 ± 5.63 episodes per month. This reduced to 4.1 ± 3.51 episodes per month (P < 0.0036) postsurgery. The mean intensity of pain also reduced from a preoperative 7.18 ± 1.33 to a postoperative of 1.73 ± 1.95 (P < 0.0033). Three patients reported complete elimination of pain after surgery while 6 patients reported significant relief of their symptoms. Only 2 patients failed to notice any significant improvement. The mean follow-up period was 12.45 ± 1.29 months. Surgical decompression of greater occipital nerve is a simple and viable treatment modality for the management of occipital neuralgia.
Migraine surgery has been recently reported as an alternative to medical management to provide long-term relief in migraine sufferers. A prospective study was designed wherein patients diagnosed with migraine were screened for surgery by injecting botulinum toxin type A at the primary trigger site. Surgery consisted of corrugator supercilii muscle resection to decompress supra-trochlear and supra-orbital nerves with avulsion of zygomaticotemporal branch of trigeminal nerve. Using pre and postsurgery questionnaires, information regarding the degree of reduction of migraines with regard to severity and frequency; and surgical site problems was acquired. Thirty patients volunteered for migraine surgery. Mean migraine headaches reduced from 15.2 ± 6.3 episodes per month to 1.9 ± 2.4 episodes per month (P < 0.0001) postsurgery. The mean intensity of migraine headache also reduced from a preoperative 7.3 ± 3.5 to a postoperative of 1.3 ± 1.4 (P < 0.0001). Fourteen (46.7%) patients reported complete elimination of migraine after surgery while an equal number reported significant relief of symptoms. Two (6.6%) patients failed to notice any significant improvement after surgery. The mean follow-up period was 11.1 ± 2 months with no major surgical complications. Results of the authors' study confirm prior published results that surgical treatment of migraine is a reality. Surgeons can easily incorporate this simple surgical procedure in their armamentarium to offer relief to numerous migraine patients.
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