Takotsubo Cardiomyopathy and Autoimmune Disorders: A Systematic Scoping Review of Published Cases.

Introduction: Takotsubo cardiomyopathy (TCM) features transient left ventricular apical dysfunction or ballooning. The underlying mechanism remains elusive; however, evidence suggests the role of different physical and psychological stressors. We systematically reviewed patients presenting with TCM and autoimmunity to explore the link between the two conditions. Methods: We applied the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) to report this review. Using keywords related to autoimmune/immune-mediated diseases and TCM, we searched PubMed, Scopus, and WOS in March 2022. The final results were added to a data extraction sheet. Data were analyzed by SPSS version 26.0. Results: Our search yielded 121 studies, including 155 patients. Females were considerably predominant. Most patients had a history of autoimmune disease, and almost a third had a history of cardiovascular disease. Dyspnea and chest pain were the most common chief complaints. More than 70% of patients had experienced physical stress. Myasthenia gravis, systemic lupus erythematosus, and multiple sclerosis were the most frequently reported autoimmune diseases. Conclusion: There were similarities in age and sex compared to classic TCM. TCM should be considered as a differential diagnosis for ACS, especially in patients with a positive background of autoimmunity. A precise reporting system is required for further studies.

Cohort analysis of 50% lethal area (LA50) and associating factors in burn patients based on quality improvements and health policies.

Burn injuries are among the common traumatic injuries, which can be accompanied with lifelong morbidity and mortality. The Lethal Area Fifty Percent (LA50) index is another reliable outcome measurement tool that assesses the standard of medical care at burn centers. It is widely used as a benchmark for assessing the quality of burn care and is considered the percentage at which 50% of burn patients are expected to die because of burn-related injuries. We aimed to determine and compare the LA50 in burn patients admitted to Shiraz Burn Referral Centers in 2018-2021 and 2011-2018 with regard to improving the quality of special care and infection control in the new hospital. We conducted a retrospective cohort analysis on patients admitted to Amir al-Momenin Burn Injury Hospital in Shiraz, Fars, Southern Iran. Data were retrospectively gathered from March 2011 to January 2022, and subsequently analyzed with standard statistical analysis, and also multivariate and probability analysis. A total of 7382 patients with acute burns injuries were identified. Among them, 4852 (65.7%) patients were men, and the median age was 27 years [Q1-Q3 7-40; range 1-98]. Most of the patients were in the pediatric and early adulthood age range, with 76.2% being younger than 40 years old. The median TBSA was 24% [IQR 14, 43], and the median duration of hospitalization was 11 [IQR 11] days. Most injuries were secondary to flame and fire (33.5%; n = 2472). The mortality rate in our study was 19.0% (n = 1403). We evaluated our patients based on two main time intervals: March 2011 till February 2018 (n = 3409; 46.2%), and March 2018 to January 2022 (n = 3973; 53.8%). Based on multivariate analysis, the second interval of our study was significantly correlated with a more female patients, higher age, lower TBSA, less burn injuries due to scald, contact, but more frequent fire and flame injuries, and also lower mortality rate. Factors correlated with higher mortality included male gender, older age, shorter hospitalization duration, higher TBSA, etiology of fire and flame, and accidental burn injuries. A Baux score of 76.5 had a sensitivity of 81.1%, specificity of 87.3%, accuracy of 86.1% in predicting mortality among our patients. The mortality probability for the study intervals were 20.67% (SD 33.0%) for 2011-2018, and 17.02% (SD 29.9%) for 2018-2022 (P < 0.001). The LA50 was 52.15 ± 2 for all patients. This ammount was 50 ± 2% in 2011-2018, and 54 ± 2 in 2018-2022 (P < 0.001). The mean LA50 values showed significant improvements following significant modifications in our critical care for burn victims, including augmented intensive care unit capacity, prompt relocation of inhalation burn cases to the intensive care unit, establishing a well-trained multidisciplinary team, and improved infection control. To improve outcomes for burn patients in developing countries, major changes should be made in the management of burn patients and LA50 is a reliable assessment tool for evaluating the how these changes affect patient's outcomes.

Epidemiology of obesity and high blood pressure among school-age children from military families: the largest report from our region.

BACKGROUND: For the first time, we aimed to determine the epidemiology and associated factors of obesity and hypertension among children of military families in our region. METHODS: In this multi-centered study, children between the ages of 5 to 12 years old, entered the study. Data on baseline and clinical characteristics, history of disease and anthropometric measurements, were collected. RESULTS: Among 504 children, 44.2% were males. Mean (SD) age of participants was 7.9 ± 1.9 years. Overall, 5% were obese and 9.9% were overweight. In total, 16.3% had elevated BP, 12.5% had stage one and 0.2% had stage two hypertension. Age (beta = 0.306, OR = 1.35, 95% CI:1.14-1.61), obesity/overweight (OR = 5.58, 95% CI:2.59-12.0), history of hypertension in mother (OR = 43.24, 95% CI:5.99-312.11), low birth weight (OR = 7.96, 95% CI:2.59-12.0), physical activity (OR = 0.27, 95% CI:0.10-0.72), and consumption of fast food more than once a week (OR = 3.36, 95% CI:1.82-6.19), were associated with risk of hypertension. Furthermore, age (beta = 0.346, OR = 1.41, 95% CI:1.21-1.64), history of childhood obesity in the father (OR = 3.78, 95% CI: 1.77-8.06) and mother (OR = 2.44, 95% CI:1.07-5.56), and physical activity (OR = 0.27, 95% CI:0.11-0.66), were associated with obesity. CONCLUSION: Age, obesity/overweight, history of hypertension in the mother, birth weight, physical activity, and consumption of fast food, were associated with risk of hypertension. Moreover, age, history of childhood obesity in parents, and physical activity, were associated with obesity. Furthermore, we found that school-age children in military families have higher rates of hypertension and overweight compared to other reports from our region.

Current advances in stem cell therapy in the treatment of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease related to the central nervous system (CNS) with a significant global burden. In this illness, the immune system plays an essential role in its pathophysiology and progression. The currently available treatments are not recognized as curable options and, at best, might slow the progression of MS injuries to the CNS. However, stem cell treatment has provided a new avenue for treating MS. Stem cells may enhance CNS healing and regulate immunological responses. Likewise, stem cells can come from various sources, including adipose, neuronal, bone marrow, and embryonic tissues. Choosing the optimal cell source for stem cell therapy is still a difficult verdict. A type of stem cell known as mesenchymal stem cells (MSCs) is obtainable from different sources and has a strong immunomodulatory impact on the immune system. According to mounting data, the umbilical cord and adipose tissue may serve as appropriate sources for the isolation of MSCs. Human amniotic epithelial cells (hAECs), as novel stem cell sources with immune-regulatory effects, regenerative properties, and decreased antigenicity, can also be thought of as a new upcoming contender for MS treatment. Overall, the administration of stem cells in different sets of animal and clinical trials has shown immunomodulatory and neuroprotective results. Therefore, this review aims to discuss the different types of stem cells by focusing on MSCs and their mechanisms, which can be used to treat and improve the outcomes of MS disease.

Characterizing the immune responses of those who survived or succumbed to COVID-19: Can immunological signatures predict outcome?

BACKGROUND: Immunodeficiency has pivotal role in the pathogenesis of coronavirus disease 2019 (COVID-19). Several studies have indicated defects in the immune system of COVID-19 patients at different disease stages. Therefore, this study investigated whether alters in immune responses of COVID-19 patients may be considered as predicting factors for disease outcome. METHODS: The percentages of innate and adoptive immune cells in the recovered and dead patients with COVID-19, and healthy subjects were determined by flow cytometry. The levels of pro- and anti-inflammatory cytokines and other immune factors were also measured by enzyme-linked immunosorbent assay. RESULTS: At the first day of hospitalization, the frequencies of CD56dim CD16+ NK cells and CD56bright CD16dim/- NK cells in patients who died during treatment were significantly increased compared to recovered and healthy individuals (P < 0.0001). The recovered and dead patients had a significant increase in monocyte number in comparison with healthy subjects (P < 0.05). No significant change was observed in Th1 cell numbers between the recovered and dead patients while Th2, Th17 cell, and Treg percentages in death cases were significantly lower than healthy control and those recovered, unlike exhausted CD4 + and CD8 + T cells and activated CD4 + T cells (P < 0.0001-0.05). The activated CD8 + T cell was significantly higher in the recovered patients than healthy individuals (P < 0.0001-0.05). IL-1α, IL-1ß, IL-6, and TNF-α levels in patients were significantly increased (P < 0.0001-0.01). However, there were no differences in TNF-α and IL-1ß levels between dead and recovered patients. Unlike TGF-ß1 level, IL-10 was significantly increased in recovered patients (P < 0.05). Lymphocyte numbers in recovered patients were significantly increased compared to dead patients, unlike ESR value (P < 0.001-0.01). CRP value in recovered patients significantly differed from dead patients (P < 0.001). CONCLUSION: Changes in frequencies of some immune cells and levels of some immune factors may be considered as predictors of mortality in COVID-19 patients.

Glioma cells eradication by photoexcitation of bioengineered molybdenum trioxide nanoparticles synthesized by wet chemical and microwave route: Dose dependent photosensitizer bioactivity.

Here, we surveyed the usage of MoO3 nanostructure in role of a photosensitizer to eradicate glioma cells. This is the first endeavor upon survey of usage of nanostructured MoO3 to treat glioma in vitro. Here, we offer a simple way for preparation of bioactive MoO3 nanostructure via two different routes; wet chemical and microwave. The influence of diverse experimental factors like various alcoholic solvents and presence of capping agent was investigated on the final properties of synthesized products. Dimension and morphology of inorganic molybdenum trioxide nanostructures checked with TEM, HRTEM and also SEM images. Moreover, the cytotoxicity effect of optimized MoO3 nanoparticles was investigated on T98 and A172 cell lines. Both T98 and A172 cell lines indicated dose-dependent manner in the presence of increasing concentration of MoO3 nanostructures, but T98 cells were less sensitive to MoO3 in comparison with A172. Anti-glioma role of MoO3 nanostructures excited with the aid of UVC illumination studied in vitro as well. By studying the UV exposure lonely, it is evident that UV effects on cell viability about 50% in both cell lines after 24 h. Interestingly, by combining nanostructured MoO3 with UVC illumination, decrement in the proliferation value could be remarkably occurred in comparison with controls. The outcomes denote that the photodynamic therapy with the help of nanostructured MoO3 may be beneficial to treat glioma.

Effects of the programmed cell death 1 (PDCD1) polymorphisms in susceptibility to systemic lupus erythematosus.

The failure of immunological tolerance to self-antigens plays a fundamental role in the pathogenesis of systemic lupus erythematosus (SLE). PD-1 is an inhibitory receptor for regulating the immune system and preventing development of autoimmune disorders. This study aimed to determine the role of four single-nucleotide polymorphisms (SNPs) within programmed cell death 1 (PDCD1 or PD-1) gene and haplotypes defined by these SNPs in susceptibility to SLE in the Iranian population. Blood samples were obtained from 253 SLE and 564 healthy subjects. Red blood cells were lysed and genomic DNAs were extracted using salting-out method. Genotype determinations of PD1.1, PD1.3, PD1.5 and PD1.9 SNPs were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and 12 haplotypes were constructed by PDCD1 SNPs. Our results showed significant differences in PD1.5 genotype frequencies between patient and control groups (p < .001). The frequencies of PD1.5 C/C, C/T and T/T genotypes versus other genotypes in SLE patients significantly differed from healthy subjects (p < .001, p = .001 and p = .002, respectively). Allelic analysis indicated a significant association between the frequency of PD1.5C allele and development of SLE in our population (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.51-2.42, p < .001). At the haplotype level, GGCC, GACT and GGCT haplotypes were significantly different between SLE and control groups (OR = 2.14, 95% CI = 1.73-2.66, p < .001; OR = 9.76, 95% CI = 4.47-21.3, p < .001; and OR = 0.32, 95% CI = 0.24-0.42, p < .001, respectively). Based on these findings, PD1.5 SNP and some haplotypes of PDCD1 contribute to SLE risk in the Iranian population.

Cytotoxicity of temozolomide on human glioblastoma cells is enhanced by the concomitant exposure to an extremely low-frequency electromagnetic field (100Hz, 100G).

Glioblastoma multiforme (GBM) is the most malignant brain cancer that causes high mortality in humans. It responds poorly to the most common cancer treatments, such as surgery, chemo- and radiation therapy. Temozolomide (TMZ) is an alkylating agent that has been widely used to treat GBM; resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance. In this study, we evaluated the potential synergistic effect of 100µM TMZ and EMF (100Hz, 100G) on two human glioma cells line, i.e., U87 and T98G above single treatments, TMZ or EMF. Co-treatment synergistically enhanced apoptosis in U87 and T98G cells, by increasing the expression of P53, Bax, and Caspase-3 and decreasing that of Bcl-2 and Cyclin-D1. We also observed an increase in reactive oxygen species (ROS) production and the overexpression of the heme oxygenase-1 (HO-1) gene in comparison to controls. In conclusion, since EMF enhanced the apoptotic effect of TMZ, possibly through a redox regulation mechanism, the TMZ/EMF combination may be effective for glioma cancer treating. Further studies are needed to reveal the action mechanism of this possible novel therapeutic approach.

Caffeine: A novel green precursor for synthesis of magnetic CoFe2O4 nanoparticles and pH-sensitive magnetic alginate beads for drug delivery.

Hydrogel beads are promising delivery systems for encapsulation and release of drugs due to the mild process of their fabrication from biopolymers. Magnetic CoFe2O4 nanoparticles (MCFO, 9.72nm in diameter) were synthesized via a co-precipitation method using caffeine as a new environmentally friendly material in order to alkalinize the medium. Drug-targeting Magnetic beads based on CoFe2O4 nanoparticles, sodium alginate and chlorpheniramine maleate (CPAM) were synthesized in the presence of Ca2+ ions to obtain ionic cross-linked magnetic hydrogel beads. Nanoparticles as well as produced magnetic beads were thoroughly characterized by FTIR, XRD, SEM, nanosizer and VSM techniques. The swelling ratio of beads indicated pH-dependent property with maximum water absorbing at pH7.4. The in vitro release of beads exhibited significant behavior on the subject of nanoparticles concentration and alginate content. Biocompatibility of the CFO nanoparticles and MCFO/Alg beads are demonstrated through cytotoxicity test via MTT assay on U87 cell lines.

Effects of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) on glioblastoma cells (U87).

The impact of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) at various frequencies and amplitudes was investigated on cell cycle, apoptosis and viability of the Glioblastoma Multiforme (GBM) cell line (U87), in vitro. The GBM is a malignant brain tumor with high mortality in humans and poorly responsive to the most common type of cancer treatments, such as surgery, chemotherapy and radiation therapy. U87 cells with five experimental groups (I-V) were exposed to various ELF-PEMFs for 2, 4 and 24 h, as follows: (I) no exposure, control; (II) 50 Hz 100 ± 15 G; (III) 100 Hz 100 ± 15 G; (IV) 10 Hz 50 ± 10 G; (V) 50 Hz 50 ± 10 G. The morphology properties, cell viability and gene expression of proteins involved in cell cycle regulation (Cyclin-D1 and P53) and apoptosis (Caspase-3) were investigated. After 24 h, the cell viability and Cyclin-D1 expression increased in Group II (30%, 45%), whereas they decreased in Groups III (29%, 31%) and IV (21%, 34%); P53 and Caspase-3 elevated only in Group III; and no significant difference was observed in Group V, respectively, compared with the control (p < 0.05). The data suggest that the proliferation and apoptosis of human GBM are influenced by exposure to ELF-PEMFs in different time-dependent frequencies and amplitudes. The fact that some of the ELF-PEMFs frequencies and amplitudes favor U87 cells proliferation indicates precaution for the use of medical devices related to the MFs on cancer patients. On the other hand, some other ELF-PEMFs frequencies and intensities arresting U87 cells growth could open the way to develop novel therapeutic approaches.

Mesenchymal Stem Cell-Conditioned Medium Modulates Apoptotic and Stress-Related Gene Expression, Ameliorates Maturation and Allows for the Development of Immature Human Oocytes after Artificial Activation.

The aim of the present study was to determine whether mesenchymal stem cell-conditioned medium (MSC-CM) modulates apoptotic and stress-related gene expression, and ameliorates maturation and developmental potential of immature human oocytes after artificial activation. A total of 247 surplus immature germinal vesicle (GV) oocytes obtained from infertile women were allocated into two in vitro maturation (IVM) groups: 1: GV oocytes (n = 116) matured in vitro (fIVM), and 2: GV oocytes (n = 131) that were vitrified, then in vitro matured (vIVM). Also, two maturation media were used: Alpha-minimum essential medium (α-MEM) and human umbilical cord-derived MSCs (hUCM). After 36 h of incubation, the IVM oocytes were examined for nuclear maturation. In IVM-matured oocytes, cytoplasmic maturation was evaluated after artificial activation through Ionomycin. Moreover, the quantitative expressions of B-cell CLL/lymphoma 2 (BCL2), BCL2-associated X protein (BAX), superoxide dismutase (SOD), and Heat shock proteins (HSP70) in matured oocytes were assessed by quantitative Real-time polymerase chain reaction (qRT-PCR) and compared with fresh and vitrified in vivo matured oocytes, which were used as fIVM and vIVM controls, respectively. The highest maturation rate was found in hUCM in fIVM, and the lowest maturation rate was found using α-MEM in vIVM (85.18% and 71.42%, respectively). The cleavage rate in fIVM was higher than that in vIVM (83.4% vs. 72.0%). In addition, the cleavage rate in α-MEM was lower than that in the hUCM (66.0% vs. 89.4%). Furthermore, the difference between parthenote embryo arrested in 4-8 cells (p < 0.04) and the quality of embryo arrested in 8-cell (p < 0.007) were significant. The developmental stages of parthenote embryos in hUCM versus α-MEM were as follows: 2-4 cell (89.45% vs. 66.00%, respectively), 4-8 cell (44.31% vs. 29.11%, respectively), morula (12.27% vs. 2.63%, respectively), and blastocysts (2.5% vs. 0%, respectively). The messenger RNA (mRNA) expression levels of BCL2, BAX and SOD were significantly different (p < 0.05) between the matured IVM oocytes. Overall, hUCM showed potential efficacy in terms of ameliorating oocyte maturation and in promoting the development and mRNA expression of BAX, BCL2, and SOD.

Impact of inhomogeneous static magnetic field (31.7-232.0 mT) exposure on human neuroblastoma SH-SY5Y cells during cisplatin administration.

Beneficial or adverse effects of Static Magnetic Fields (SMFs) are a large concern for the scientific community. In particular, the effect of SMF exposure during anticancer therapies still needs to be fully elucidated. Here, we evaluate the effects of SMF at induction levels that cisPt-treated cancer patients experience during the imaging process conducted in Low field (200-500 mT), Open field (300-700 mT) and/or inhomogeneous High field (1.5-3 T) Magnetic Resonance Imaging (MRI) machines. Human adrenergic neuroblastoma SH-SY5Y cells treated with 0.1 µM cisPt (i.e. the lowest concentration capable of inducing apoptosis) were exposed to SMF and their response was studied in vitro. Exposure of 0.1 µM cisPt-treated cells to SMF for 2 h decreased cell viability (30%) and caused overexpression of the apoptosis-related cleaved caspase-3 protein (46%). Furthermore, increase in ROS (Reactive Oxygen Species) production (23%) and reduction in the number of mitochondria vs controls were seen. The sole exposure of SMF for up to 24 h had no effect on cell viability but increased ROS production and modified cellular shape. On the other hand, the toxicity of cisPt was significantly prevented during 24 h exposure to SMF as shown by the levels of cell viability, cleaved caspase-3 and ROS production. In conclusion, due to the cytoprotective effect of 31.7-232.0 mT SMF on low-cisPt-concentration-treated SH-SY5Y cells, our data suggest that exposure to various sources of SMF in cancer patients under a cisPt regimen should be strictly controlled.