Severe Hepatotoxicity in Mushroom Poisoning by Lepiota brunneoincarnata from Complete Recovery to Liver Transplantation: A Case Series with Review on Liver Function Tests and Liver Histopathology.

Background: In spite of the scientific evidence supporting health advantages of mushrooms, some of them are seriously poisonous. The clinical picture of mushroom intoxication ranges from minor gastrointestinal symptoms to organ failure, such as liver failure and death. Method: We provided demographics, clinicopathological characteristics, applied treatments, and outcomes of mushroom poisoning by Lepiota species in a series of 18 cases that were referred from Kermanshah and Lorestan provinces to Abu-Ali-Sina Hospital, Shiraz, Iran. Clinical and paraclinical data were collected by taking history and reviewing of medical documents. Pathologic findings were extracted through a review of hematoxylin and eosin pathologic slides. Results: The patients were between the ages of 18 and 67 years, composed of ten females and eight males. The most frequent clinical manifestations were nausea and vomiting followed by abdominal pain. Four cases presented decreased consciousness on admission. One of them passed away. Three other cases underwent liver transplantation, two of them died after transplantation, and one fully recovered without any major issues. All instances had elevated ALT levels, which ranged from 44 to 9,140 IU/L (mean: 3259 ± 2476), with most of them also having concurrent AST elevations (mean: 1,361 ± 1,532). Only few patients had modest elevations in alkaline phosphatase. Total and direct bilirubin elevations up to 47.6 and 24 mg/dL, respectively, were found in most cases. Decreased total protein and albumin concentrations and increased BUN and creatinine levels were observed in some patients. In addition, some instances revealed increased LDH, increased WBC, decreased hemoglobin, and decreased platelet count. Most patients had increased prothrombin time; hematuria and positive stool occult blood were observed in few patients. Histopathologic examination of three explanted livers revealed massive necrosis with moderate to severe macrovesicular steatosis, significant ductular reaction, and parenchymal inflammation. Other patients followed a recovery process with a considerable drop in liver enzymes, especially ALT, during hospitalization utilizing conservative treatment. They had no liver problems or relevant issues after a two-year follow-up. Conclusion: In our study, highly elevated liver enzymes with a significantly high ALT/AST ratio were observed in cases of mushroom poisoning by Lepiota species, leading to fulminant liver failure and death in some cases. These laboratory findings were correlated with liver necrosis and macrovesicular steatosis in explanted livers.

Zidovudine and Interferon Alfa based regimens for the treatment of adult T-cell leukemia/lymphoma (ATLL): a systematic review and meta-analysis.

BACKGROUND: ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens. METHODS: A systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses. RESULTS: We obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses' findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease. CONCLUSION: IFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate.

Splenic Lymphangioma Mimicking Lymphomatous Involvement: A Case Report with Review of the Literature.

Lymphangioma is a benign malformation of lymphatic vessels usually found in the head and neck areas or axilla. They may involve visceral organs with a lower percentage. Splenic lymphangioma is a rare tumor. This disease is often seen in children but may be diagnosed incidentally in adults. Most patients are asymptomatic, but in large and multifocal lesions, the patient may have some nonspecific symptoms such as abdominal pain, abdominal distention, nausea, vomiting, and loss of appetite. Physical examination may show no specific findings or detect palpable masses. The preoperative diagnosis of splenic lymphangioma is challenging. Histopathological evaluation and sometimes immunohistochemistry tests can result in a definitive diagnosis. In this study, we present an 18-year-old man, with Burkitt's lymphoma who underwent laparotomy and total splenectomy as a result of cystic lesions discovered accidentally during imaging with the final diagnosis of splenic lymphangioma after histopathological evaluation.

Identification of novel miRNAs potentially involved in the pathogenesis of adult T-cell leukemia/lymphoma using WGCNA followed by RT-qPCR test of hub genes.

BACKGROUND: Adult T-cell Lymphoma/Leukemia (ATLL) is characterized by the malignant proliferation of T-cells in Human T-Lymphotropic Virus Type 1 and a high mortality rate. Considering the emerging roles of microRNAs (miRNAs) in various malignancies, the analysis of high-throughput miRNA data employing computational algorithms helps to identify potential biomarkers. METHODS: Weighted gene co-expression network analysis was utilized to analyze miRNA microarray data from ATLL and healthy uninfected samples. To identify miRNAs involved in the progression of ATLL, module preservation analysis was used. Subsequently, based on the target genes of the identified miRNAs, the STRING database was employed to construct protein-protein interaction networks (PPIN). Real-time quantitative PCR was also performed to validate the expression of identified hub genes in the PPIN network. RESULTS: After constructing co-expression modules and then performing module preservation analysis, four out of 15 modules were determined as ATLL-specific modules. Next, the hub miRNA including hsa-miR-18a-3p, has-miR-187-5p, hsa-miR-196a-3p, and hsa-miR-346 were found as hub miRNAs. The protein-protein interaction networks were constructed for the target genes of each hub miRNA and hub genes were identified. Among them, UBB, RPS15A, and KMT2D were validated by Reverse-transcriptase PCR in ATLL patients. CONCLUSION: The results of the network analysis of miRNAs and their target genes revealed the major players in the pathogenesis of ATLL. Further studies are required to confirm the role of these molecular factors and to discover their potential benefits as treatment targets and diagnostic biomarkers.

Bayesian Optimization of Machine Learning Classification of Resting-State EEG Microstates in Schizophrenia: A Proof-of-Concept Preliminary Study Based on Secondary Analysis.

Resting-state electroencephalography (EEG) microstates reflect sub-second, quasi-stable states of brain activity. Several studies have reported alterations of microstate features in patients with schizophrenia (SZ). Based on these findings, it has been suggested that microstates may represent neurophysiological biomarkers for the classification of SZ. To explore this possibility, machine learning approaches can be employed. Bayesian optimization is a machine learning approach that selects the best-fitted machine learning model with tuned hyperparameters from existing models to improve the classification. In this proof-of-concept preliminary study based on secondary analysis, 20 microstate features were extracted from 14 SZ patients and 14 healthy controls' EEG signals. These parameters were then ranked as predictors based on their importance, and an optimized machine learning approach was applied to evaluate the performance of the classification. SZ patients had altered microstate features compared to healthy controls. Furthermore, Bayesian optimization outperformed conventional multivariate analyses and showed the highest accuracy (90.93%), AUC (0.90), sensitivity (91.37%), and specificity (90.48%), with reliable results using just six microstate predictors. Altogether, in this proof-of-concept study, we showed that machine learning with Bayesian optimization can be utilized to characterize EEG microstate alterations and contribute to the classification of SZ patients.

Development of Novel Gluten-Free Sausage Based on Chickpea, Corn Flour, and HPMC.

The present work was carried out to study the effectiveness of substitution of wheat flour with different levels of chickpea flour, corn flour, and hydroxypropyl methylcellulose (HPMC) for the production of gluten-free sausages. The prepared sausages were subjected to physicochemical, color, texture, thermal, and sensory analyses 24 h after production. Proximate chemical composition indicated that the protein content was raised by the addition of chickpea flour. The result of thermal analysis indicated that the addition of chickpea flour increased To, Tp, Tf, and ΔH and decreased ∆W 1. Textural properties revealed that hardness was higher in samples containing chickpea flour and adhesiveness, chewiness, and gumminess were lower in samples with chickpea flour and corn flour. Sensorial properties showed that there were no significant differences between samples except the sample containing 6% chickpea flour. Based on the obtained results, it seems that the sample containing 4% corn flour, 6% chickpea flour, and 0.3% HPMC had the best formulation.

Enhanced nuclear translocation and activation of aryl hydrocarbon receptor (AhR) in THP-1 monocytic cell line by a novel niosomal formulation of indole-3-carbinol.

Although niosomes structurally resemble liposomes, they are composed of nonionic surfactants which result in less toxicity and more stability. Here, we developed a novel niosomal formulation of I3C and investigated the nuclear translocation and activation of AhR among human acute myeloid leukaemia (AML) monocytic THP-1 cell line. Niosomal vesicles comprised of nonionic surfactants, cholesterol and I3C were prepared using thin film hydration (TFH) method and characterized according to the entrapment efficiency (EE %), size and zeta potential, by Dynamic light scattering method (DLS), and the surface morphology visualized by Transmission electron microscopy (TEM). In vitro release of I3C was evaluated and MTS assay was used to evaluate the viability of THP-1 cells. The nuclear translocation of AhR was assessed by immunocytochemistry (ICC) and Real-time RT-PCR was conducted using AhR target genes. The ratio of Cholesterol:Span 60 (1:1) niosomal formulations with the highest significant EE% were selected. I3C exerted cytotoxic effects on THP-1 cells in a dose- and time-dependent manner, while administration of niosomal I3C reduced these effects. Both niosomal and free I3C formulations facilitated the nuclear translocation of AhR. CYP1A1 was overexpressed in response to both free and niosomal I3C treatments, while IL1ß was overexpressed merely in niosomal I3C-treated THP-1 cells. Niosomal formulation of I3C resulted in reduced cytotoxicity effects by enhancing the functional effects of I3C on AhR in THP-1 cells, including its nuclear translocation and overexpression of the target genes.

Encapsulation of Leflunomide (LFD) in a novel niosomal formulation facilitated its delivery to THP-1 monocytic cells and enhanced Aryl hydrocarbon receptor (AhR) nuclear translocation and activation.

BACKGROUND: Leflunomide (LFD) is an Aryl hydrocarbon receptor (AhR) agonist and immunomodulatory drug with several side effects. Niosomes are novel drug delivery systems used to reduce the unfavorable effects of drugs by enhancing their bioavailability, controlling their release and targeting specific sites. OBJECTIVES: Here, we prepared niosomal formulations of LFD, evaluated their properties and delivered to THP-1 monocytic cells to study the activation and nuclear translocation of AhR. METHODS: Four types of non-ionic surfactants were utilized to formulate niosomes by thin film hydration (TFH) method. Entrapment efficiency (EE %) of niosomes were quantified and dynamic light scattering (DLS) was performed. Transmission electron microscopy (TEM) was used to identify the morphology of LFD niosomes. Dialysis method was used to measure LFD release rate. MTS assay was adopted to examine the viability of the cells upon each treatment. The nuclear transfer of AhR was investigated by Immunocytochemistry (ICC). The mRNA expression of IL1ß and CYP1A1 were evaluated using quantitative RT-PCR. RESULTS: Span 60: cholesterol (1:1) showed the highest EE% (70.00 ± 6.24), largest particles (419.00 ± 4.16 nm) and the best uniformity with the lowest PDI (0.291 ± 0.007). TEM micrographs of Span 60 (1:1) nanoparticles showed conventional spherical vesicles with internal aqueous spaces. The release rate of LFD from Span 60 (1:1) vesicles was slower. Although the viability of LFD niosome-treated THP-1 cells was decreased, they were associated with lower cytotoxic effects compared with the free LFD counterparts. Both free and niosomal LFD treatments intensified the nuclear translocation of AhR. The mRNA expression of CYP1A1 was overexpressed while IL1ß was downregulated in both free and niosomal LFD treated combinations. CONCLUSION: LFD encapsulation in Span 60: cholesterol (1:1) niosomal formulation could be introduced as a suitable vehicle of transferring LFD to THP-1 cells, with minimal cytotoxic effects, enhancing the AhR nuclear translocation and activation and inducing immunomodulatory properties. Graphical abstract The Graphical abstract; it demonstrates the workflow of the study and summary of results in brief.

Relationship of elongated styloid process in digital panoramic radiography with carotid intima thickness and carotid atheroma in Doppler ultrasonography in osteoporotic females.

STATEMENT OF THE PROBLEM: Cardiovascular disease and osteoporosis are major health dilemmas. Osteoporotic patients frequently display vascular calcification that consequently increases the cardiovascular morbidity and mortality. PURPOSE: This study aimed to investigate the relation of osteoporosis, vascular calcification (atheroma, intima-media thickness (IMT)) and elongated styloid process (ESP) in a sample of osteoporotic and normal female individuals. MATERIALS AND METHOD: This study recruited 78 women who were assessed for bone mass density (BMD). Sample included individuals with normal BMD (n=13, 17 %), osteopenia (n=36, 46 %), and osteoporosis (n=29, 37%). The presence of atheroma and IMT was examined using color Doppler ultrasonography (CD-US). In addition, digital panoramic radiographs (PRs) were obtained to assess ESP. RESULTS: In this study, 55 subjects (70%) with low BMD exhibited at least one side ESP. Femoral BMD decreased significantly in subjects with ESP (p= 0.03). Bilateral ESP was correlated with the presence of atheroma (p= 0.029). The CIMT was greater in patients with ESP, although the relation was not significant. CONCLUSION: The obtained data suggest referring the aged individuals with ESP for BMD assessment and individuals with low bone mass and ESP for more cardiovascular risk assessment.

Prevalence of substance use among Iranian high school students.

AIMS: This study assessed the rate of substance use among Iranian high school students. PARTICIPANTS: 397 high school students (200 girls and 197 boys) were selected randomly and were assessed. MEASUREMENTS: A confidential questionnaire was distributed, completed by the students, and collected in the same sessions in 2000. RESULTS: The mean ages for high school girls and boys were 15.85 and 17.28 years, respectively. Of the subjects, 30.23% reported usage of substance(s) once or more sometime during their lives: cigarettes (25.4%), alcohol (9.6%), opium (3.5%), hashish (2.8%), marijuana (1%), heroin (2%), LSD (0.5%), cocaine (1%), and morphine (0.8%). Only 13.86% of the students were currently using substances: cigarettes (8.3%), heroin (1%), morphine (0.3%), alcohol (4.3%), opium (0.8%), LSD (0.3%), cocaine (0.5%), hashish (0.8%), and marijuana (0.8%). Some used or were using more than one substance. CONCLUSIONS: Substance use was significantly higher among males than females. Cigarettes, alcohol, and opium were found to be the most prevalent forms of substance use. Seeking pleasure and release of tension were the most common reasons for substance use.