Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

The effect of dopaminergic neuron transplantation and melatonin co-administration on oxidative stress-induced cell death in Parkinson's disease.

A gradual degeneration of the striatum and loss of nigral dopamine cells are characteristic of Parkinson's disease. Nowadays, combination therapy for neurodegenerative disease is considered. This study aimed to investigate the effects of melatonin and dopaminergic neurons derived from adipose tissue stem cells (ADSCs) in a rat model of Parkinson's disease. Parkinson's disease was induced in rats using neurotoxin 6-Hydroxydopamine. The treatment was performed using melatonin and dopaminergic neurons transplantation. Subsequently, behavioral tests, western blot analysis for Caspase-3 expression, GSH (Glutathione) content and stereology analysis for the volume and cell number of substantia nigra and striatum were performed. Treatment with melatonin and dopaminergic neuron transplantation increased the number of neurons in substantia nigra and striatum while the number of glial cell and the volume of substantia nigra and striatum did not show significant change between groups. Western blot analysis for caspase 3 indicated the significant differences between groups. The results also indicated the increased level of glutathione (GSH) content in treatment groups. this study showed that combination therapy with melatonin and dopaminergic neurons could greatly protect the neurons, reduce oxidative stress and improve the symptoms of PD.

Application of Mesenchymal Stem Cells and Exosome alone or Combination Therapy as a Treatment Strategy for Wound Healing.

The process of wound healing consists of multiple phases, and any disruptions in these phases can lead to the wound becoming chronic and impose heavy financial and psychological costs on the patient and a huge economic burden on the country's healthcare system. Various treatments such as drugs, matrix and scaffolds, blood products, cell therapy, and a combination of these treatments are used for wound healing. The use of mesenchymal stem cells (MSCs) is one of these methods that have produced appropriate responses in the healing of patients' wounds. MSCs by secreting growth factors, cytokines, chemokines, and RNAs elicit changes in cell proliferation, migration, growth, signaling, immunomodulation, and wound re-epithelialization process, and as a result, accelerate wound closure and wound healing. These cells can be isolated from different body sources with different cell characteristics and used directly on the wound site or by injection. In addition, MSCs-derived exosomes have attracted growing attention due to circumventing concerns relating to the direct use of MSCs. To increase the performance of MSCs, they can be used together with other compounds such as platelets, matrices, or scaffolds. This study examined the functions of MSCs in wound healing, as well as the vesicles they secrete, cellular and molecular mechanisms, and combined treatments with MSCs for wound healing.

Dental stem cells improve memory and reduce cell death in rat seizure model.

Epilepsy is a common neurological disorder that significantly affects the quality of life of patients. In this study, we aim to evaluate the effectiveness of dental pulp stem cell (DPSC) transplantation in decreasing inflammation and cell death in brain cells, thus reducing seizure damage. We induced seizures in rats using intraperitoneal injections of pentylenetetrazole (PTZ). In the PTZ + DPSC group, we conducted bilateral hippocampal transplantation of DPSCs in PTZ-lesioned rat models. After 1 month, we performed post-graft analysis and measured some behavioral factors, such as working memory and long-term memory, using a T-maze test and passive avoidance test, respectively. We investigated the immunohistopathology and distribution of astrocyte cells through light microscopy and Sholl analysis. Additionally, we employed the Voronoi tessellation method to estimate the spatial distribution of the cells in the hippocampus. Compared to the control group, we observed a reduction in astrogliosis, astrocyte process length, the number of branches, and intersections distal to the soma in the hippocampus of the PTZ + DPSC group. Further analysis indicated that the grafted DPSCs decreased the expression of caspase-3 in the hippocampus of rats with induced seizures. Moreover, the DPSCs transplant protected hippocampal pyramidal neurons against PTZ toxicity and improved the spatial distribution of the hippocampal neurons. Our findings suggest that DPSCs transplant can be an effective modifier of astrocyte reactivation and inflammatory responses.

The effect of Brucella abortus on glial activation and cell death in adult male rat's hippocampus.

A zoonotic disease called brucellosis can cause flu-like symptoms and heart inflammation. The bacteria responsible for this disease can also enter the brain, causing a condition called neurobrucellosis that can result in long-term neurological problems. In this study, researchers aimed to determine the changes in the hippocampal cells of rats infected with Brucella. For the study, 24 adult male albino rats were inoculated with 1 × 106 CFU Brucella abortus 544. The rats were then deeply anesthetized, and their hippocampus samples were taken for stereological, histological, and molecular studies. The results showed that the infected rats had increased microgliosis and astrogliosis. Furthermore, a high level of caspase-3 in their hippocampal tissue indicated their susceptibility to apoptosis. Additionally, there was a decrease in expression of Ki67, which further supported this. Sholl's analysis confirmed a significant failure in glial morphology. The study demonstrated that the pathogen has the ability to destroy the hippocampus and potentially affect its normal physiology. However, more research is needed to clarify various aspects of neurobrucellosis.

Lupus Anticoagulant Is Associated with Critical Cases and High Mortality in COVID-19: A Literature Review.

Background: In severe COVID-19 cases, a hypercoagulable state may occur. Antiphospholipid syndrome-related auto-antibodies (APSRAs) contribute to coagulopathy, but their role in COVID- 19 remains unclear. We aimed to investigate the prevalence of positive APSRAs and their effect on clinical outcomes in confirmed COVID-19 patients. Materials and Methods: In this cross-sectional study, severe hospitalized COVID-19 cases were enrolled. Demographic and clinical data were obtained from the day of admission. APSRAs including IgG and/or IgM anticardiolipin (aCL) and anti-ß2-glycoprotein1 (anti-ß2GP1) as well as lupus anticoagulant (LAC) were measured. Results: In this study, 54 severe COVID-19 cases with positive RT-PCR and chest CT scans were recruited. Positive APSRAs were found in 7 (12.9%) patients. Positive LAC was a more prevalent marker as compared to other tests (11.1%). The prevalence of positive aCL (IgM or IgG) and anti-ß2 GPI (IgM or IgG) was 1.8% (in an elderly woman). Lower oxygen saturation was found in the positive APSRAs group as opposed to the negative APSRAs group (70.3±9 vs. 84.8±9.7%). The mortality rate in the positive APSRAs group was significantly higher relative to the negative APSRAs group (83.3% vs. 27.1%; P-value: 0.01). Likewise, the mechanical ventilation requirement in the positive group was also higher (50% vs. 27.1%, P-value: 0.28). Conclusion: This study indicated that LAC might be associated with critical cases and high mortality of COVID-19. Nonetheless, the mortality was not related to macrothrombotic incidence.

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.

Chronic administration of methylphenidate did not affect memory and GDNF levels but increase astrogliosis in adult male rat's hippocampus.

BACKGROUND: ADHD is the most common developmental disorder affecting approximately three to seven percent of school-aged children and 2.5 percent of adults worldwide. The drug of choice for the pharmacotherapy of ADHD is Methylphenidate (MPH). However, there is growing concerns about side effects resulting from its potential interference with brain anatomical and behavioral development. AIM: This article focuses on the adverse effects of MPH on the rat's hippocampus. METHODS: The animals received an oral dose of 5 mg/kg MPH or normal saline, as the vehicle, on a daily basis for 30 days. Y-maze test, passive avoidance, Barnes maze and field potential recording were conducted. Western blot for detecting the neurotrophic factor of GDNF and immunohistochemistry of astrogliosis were performed. RESULTS: Our results revealed that MPH treatment suppressed the willingness of rats to explore new environments. Also, it had no effect on improving long-term potentiation, long-term memory and spatial memory in the MPH group as opposed to the control group. There was also a significant increase of astrogliosis in the treated rats' hippocampi. On the other hand, there was not a significant relationship between MPH administration and the decrement of the GDNF level. CONCLUSION: We encourage the need to conduct more research on the adverse effects of MPH on the brain.