Mucormycosis, New Causative Agents, and New Susceptible Populations: Review of Cases in a Tertiary Care Hospital in Iran (2007-2021).

Background: Mucormycosis is an aggressive opportunistic fungal infection that afflicts patients with severe underlying immunosuppression, uncontrolled hyperglycemia and/or ketoacidosis, iron overload, and occasionally healthy patients who are inoculated with fungal spores through traumatic injuries. The epidemiology of mucormycosis has changed after the COVID-19 pandemic, with mucormycosis becoming the most common and the fatal coinfection. Methods: In a retrospective, cross-sectional study, 82 hospitalized patients with a definite diagnosis of mucormycosis were reported from 2007 to 2021 in a referral, tertiary care center in Tehran, Iran. Results: The number of post-COVID cases increased 4.6 times per year, with 41.5% of patients admitted during the two years of the pandemic. Mucormycosis was more common in women (57.3%), and the most common underlying diseases were diabetes (43.7%), both COVID-19 and diabetes (23.2%), cancer (11%), rheumatic diseases (7.3%), COVID-19 without other underlying diseases (6.1%), and transplantation (4.9%). Rhino-orbito-cerebral Mucormycosis (54.9%) followed by Sino-orbital infection (23.2%) was the most common presentation. There was a significant relationship between the use of immunosuppressive agents and the development of Mucormycosis (P<0.005) The average mortality was 41.5%, but this ratio decreased to 35% during the pandemic era. Conclusion: The COVID-19 pandemic caused a 4.6-fold increase in the number of mucormycosis patients, and there was a significant relationship between hyperglycemia, corticosteroid use, and mucormycosis. The death rate during the COVID-19 pandemic has decreased by 6.5%, and during the COVID period, the interval between the arrival of a patient with mucormycosis and the start of the correct treatment was significantly decreased.

Hearing status in patients with overdose of illicit drugs.

Background: The overdose of illicit drugs is not always fatal but can lead to various complications. One of the unusual medical complications is a sensorineural hearing loss (SNHL). There are multiple case reports about this subject. Considering the importance of hearing loss on quality of life, we investigated hearing status in patients with overdose of illicit drugs. Methods: This cross-sectional study was performed in Loghman Hakim hospital in Shahid Beheshti University of Medical Sciences, Tehran, Iran, in 2016-2017. The hearing status of 95 patients with illicit drugs overdose and 44 healthy individuals were assessed using standard pure tone audiometry and distortion product otoacoustic emissions. The patient group was categorized based on hearing status and compared based on some variables. We applied 2 independent t tests, Mann-Whitney, Chi-square, and binary logistic regression tests. All analyses were conducted in Stata 12 (STATA Corp, USA) and significance level was set at less than 0.05. Results: We found higher percentage frequency of SNHL in the patient group than the control group (15.8% vs 2.3%; p=0.021). The frequency of hearing loss was 21.7% in opioid users, 5.3% in stimulant users, and 6.3% in concomitant use of both. There was a significant relationship between SNHL and overdose of illicit drugs (aOR = 14.48, 95% CI = 1.53-136.44; p=0.019) with adjusting age, sex, and smoking. Conclusion: Illicit drugs overdose can potentially affect the hearing system. Opioid drugs, especially methadone and tramadol, have been found to affect the hearing system. Therefore, it is important to conduct longitudinal studies to demonstrate the role of opioid drugs on the hearing system.

The contributory role of long non-coding RNAs (lncRNAs) in head and neck cancers: Possible biomarkers and therapeutic targets?

Along with the developments in techniques for genome study, our understanding of its sequences has completely changed. The non-coding sequences of the human genome are no longer considered as "junk" but are rather known to be the source of high-functioning molecules. Some of the most fascinating transcripts in this regard are long non-coding RNAs (lncRNAs) ___RNA molecules that exceed 200 nucleotides and are not transcribed from protein-coding regions of the genome. These transcripts are capable of gene regulation by various mechanisms, from epigenetic changes and chromosomal arrangements to post-transcription modulation of messenger RNAs. Furthermore, lncRNAs interact with other non-coding transcripts such as microRNAs that further affects gene expression. Considering the fact that cancer is a disease of deregulated expression, recent studies have identified lncRNAs acting as either oncogene or tumor suppressor in a wide range of human malignancies. Head and neck cancer (HNC), with a high incidence rate and unfavorable survival, is no exception in this matter and many investigations have introduced lncRNAs involved in its tumor progression and drug response, as well as those acting as promising diagnostic or prognostic markers. The present study reviews the vital regulatory roles of lncRNAs and further introduces their role in progression of HNC subtypes.

NUPR1- CHOP experssion, autophagosome formation and apoptosis in the postmortem striatum of chronic methamphetamine user.

Methamphetamine (Meth) is a neuro-stimulator substrate which might lead to neural cell death and the activation of several interconnected cellular pathways as well. However, the precise molecular mechanisms underlying Meth-induced neural cell death remained unclear yet. The current study aimed to assess the specific relationship between long-term Meth exposure and several endoplasmic reticulum stress, autophagy, and apoptosis associated markers including C/EBP homologous protein (CHOP), Tribbles homolog 3(Trib3), Nuclear protein 1(NUPR1), and Beclin-1 expression in postmortem human striatum. Therefore, the effects of long-term Meth exposure on autophagy and apoptosis in the striatum of postmortem users were evaluated and molecular, immunehistochemical, and histological examinations were performed on 10 control and 10 Meth-addicted brains. The level of CHOP, Trib3, NUPR1, and Beclin-1, Microtubule-associated proteins 1A/1B light chain 3B(LC3), Caspase 3, and Autophagy protein 5 (ATG5) were measured by using qPCR and immunohistochemistry. Stereological neural cell counting, Hematoxylin and Eosin, Nissl and Tunel staining were also performed. Based on our findings, the expression level of CHOP, Trib3, NUPR1, and Beclin-1 in the striatum of Meth group were significantly higher than the control group. Besides, the neuronal cell death was substantially increased in the striatum based on data obtained from the Tunel assay and the stereological analysis. Long-term presence of Meth in the brain can induce ER stress and overexpression of NUPR1 which is associated with the upregulation of CHOP, a pro-apoptotic transcription factor. Moreover, an increase in Trib3 expression is implicated in CHOP-dependent autophagic cell death during Meth-induced ER stress accompanied by an increase in neuronal cell death in the striatum of the postmortem human brains. Beclin 1 expression was also upregulated which may due to the activation of autophagic mechanisms upon prolonged Meth exposure.

Trans-nasal Trans-sphenoidal Endoscopic Resection of Spindle Cell Oncocytoma of Adenohypophysis: The First Case Report in a Child and a Review of Literature.

Spindle cell oncocytoma (SCO) is a rare tumor of adenohypophysis, arising from the sellar region. So far, about 35 cases of SCO in the sellar region have been reported. In this report, we present the first case of pediatric SCO and review the literature concerning the tumor origin, clinical presentations, radiological features, and treatment modalities. An 8-year-old male was referred to our clinic with progressive visual loss in the left eye and headache over the past 6 months. Cranial magnetic resonance imaging revealed a solid adenohypophysis mass with suprasellar extension, as well as compression and displacement of the optic chiasm. The patient underwent endoscopic trans-sphenoidal resection of the tumor. The tumor was diagnosed as SCO based on the histological study. He did not receive radiation therapy. The patient's condition remained stable, with no radiological recurrence in the past follow-up 2 years after the surgery.

Protective effect of Photobiomodulation Therapy and Bone Marrow Stromal Stem Cells Conditioned Media on Pheochromocytoma Cell Line 12 Against Oxidative Stress Induced by Hydrogen Peroxide.

Introduction: Bone marrow stromal stem cells (BMSCs), a type of adult stem cells, secrete bioactive molecules such as trophic factors, growth factors, chemokine and cytokines that may be effective against oxidative stress in neurodegenerative diseases. In this study, we examined the protective effect of BMSCs conditioned media (CM) and photobiomodulation therapy (PBMT) on PC12 cells exposed to H2O2 as an oxidative injury model. Methods: BMSCs were cultured and confirmed by flow cytometry analysis and underwent osteogenic and adipogenic differentiation. Then, PC12-H2O2 cells were co-treated with BMSCs-CM and PBMT. The effect of BMSCs-CM and PBMT (He-Ne laser, 632.8nm, 3mW, 1.2J/ cm2 , 378s) on Bax/Bcl2 expression, cell viability, was assessed by real-time PCR and MTT assay. The length of the Neurite and cell body areas were assessed by Cell A software. Results: Flowcytometry analysis, as well as osteogenic and adipogenic staining, confirmed the BMSCs. The length of the Neurite was the highest in the group which received CM+PBMT and cell body areas were significant in CM+PBMT compared to other groups. Based on our results, elevating H2O2 concentration increased cell death significantly and using concentrations of 250 µM resulted in a dramatic increase in the mortality compared to the other groups. Conclusion: Our result demonstrated that the combination of CM +PBMT has a protective effect on PC12 cells against oxidative stress.

Protective effect of [Pyr1]-apelin-13 on oxidative stress-induced apoptosis in hair cell-like cells derived from bone marrow mesenchymal stem cells.

Oxidative stress plays an important role in auditory dysfunction. Exogenous cell therapy has brought new hopes for repairing mammalian inner ear hair cells. However, poor cell viability of transplanted cells under oxidative stress conditions has limited their therapeutic potential. The adipocytokine apelin-13 was isolated from a bovine stomach. Apelin-13 might protect oxidative stress-induced hair cell damage was raised considering other oxidative stress-induced injury, including brain ischemia-induced cell death. Therefore, we evaluated the protective effects of apelin- 13 on the damage induced by hydrogen peroxide (H2O2) to the hair cells-derived from bone marrow mesenchymal stem cells (BMSCs) in vitro. Stem cells were differentiated into hair cell- like cells with B27, FGF, EGF and IGF-1. Expression of neuron specific markers including ß tubulin III, Nestin, MAP2, Neurofilament 68 and GFAP was tested by flow cytometry. As well, inner ear hair cell markers such as Myosin VIIA, Sox2 and TrkB expression were assayed by immunocytochemistry (ICC) method. We designed an in vitro model of oxidative stress by exposing hair cell- like cells to H2O2. Protein expression levels of caspase-3, Bax and Bcl-2 were detected by western blot. Apoptotic cells were also detected by acridin-orange staining and TUNEL assay. Protein expression of caspase-3 and Bax/Bcl-2 ratio was significantly lower in the apelin-13-pretreated group than only H2O2 treated group. In addition, apoptotic cells were significantly decreased in the apelin-13+H2O2 co-treated cells compared to the H2O2-treated group. Treating hair cells-like cells with apelin13 increases their survival against oxidative stress damage by inhibition of apoptosis signaling pathway.

A brief report of plexiform neurofibroma.

Plexiform neurofibroma (PNF) is a rare variant of neurofibromatosis type1 (NF-1), which histopathologically, is a subtype of benign nerve sheath tumors, neurofibromas (NF). It develops as a result of proliferation in all parts of peripheral nervous system and can cause the functional damage, deformities, pain, considerable mortality, and morbidity and even the increasing risk of malignant transformation in some critical cases. Currently, the surgical intervention is the treatment of choice for PNF patients, which due to the tumor invasion, massive growth, and the chance of postoperative regrowth is not possible. The diagnosis of isolated tumor is an uncommon event. Considering the rarity of this neoplasm, herein, we describe a case of isolated PNF, so the purpose of this presenting is the rarity of recording. We describe a case of isolated plexiform neurofibroma presented with 7-year history of a slowly growing postauricular soft subcutaneous mass in a 14-year-old boy, which caused the right auricular deformity. After initial evaluation by imaging studies, the patient underwent to surgical resection of the mass and the diagnosis of plexiform neurofibroma was confirmed by histopathologic examination. Surgical excision of the mass had been done before which concluded the satisfactory result and based on oncologist diagnosis, further intervention such as radiotherapy or chemotherapy was not needed. The patient left the hospital with a clinical stability and was suggested to continue the regular follow-up. In conclusion, considering neurofibroma (NF) as differential diagnosis for subcutaneous masses in head and neck area is critical for early diagnosis and treatment procedure.