Evaluation of antibiotic resistance, toxin-antitoxin systems, virulence factors, biofilm-forming strength and genetic linkage of Escherichia coli strains isolated from bloodstream infections of leukemia patients.

BACKGROUND: One of the most common complications in patients with febrile neutropenia, lymphoma, leukemia, and multiple myeloma is a bloodstream infection (BSI). OBJECTIVE: This study aimed to evaluate the antibiotic resistance patterns, virulence factors, biofilm-forming strength, and genetic linkage of Escherichia coli strains isolated from bloodstream infections (BSIs) of leukemia patients. METHODS: The study conducted in Iran from June 2021 to December 2022, isolated 67 E. coli strains from leukemia patients' bloodstream infections in hospitals in two different areas. Several techniques including disk diffusion and broth microdilution were used to identify patterns of antibiotic resistance, microtiter plate assay to measure biofilm formation, and PCR to evaluate the prevalence of different genes such as virulence factors, toxin-antitoxin systems, resistance to ß-lactams and fluoroquinolone antibiotics of E. coli strains. Additionally, the genetic linkage of the isolates was analyzed using the Enterobacterial Repeat Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) method. RESULTS: The results showed that higher frequency of BSI caused by E. coli in man than female patients, and patients with acute leukemia had a higher frequency of BSI. Ampicillin and Amoxicillin-clavulanic acid showed the highest resistance, while Imipenem was identified as a suitable antibiotic for treating BSIs by E. coli. Multidrug-resistant (MDR) phenotypes were present in 22% of the isolates, while 53% of the isolates were ESBL-producing with the blaCTX-M gene as the most frequent ß-lactamase gene. The fluoroquinolone resistance genes qnrB and qnrS were present in 50% and 28% of the isolates, respectively. More than 80% of the isolates showed the ability to form biofilms. The traT gene was more frequent than other virulence genes. The toxin-antitoxin system genes (mazF, ccdAB, and relB) showed a comparable frequency. The genetic diversity was detected in E. coli isolates. CONCLUSION: Our results demonstrate that highly diverse, resistant and pathogenic E. coli clones are circulating among leukemia patients in Iranian hospitals. More attention should be paid to the treatment and management of E. coli bloodstream infections in patients with leukemia.

On Patterns of Neuropsychiatric Symptoms in Patients With COVID-19: A Systematic Review of Case Reports.

Coronavirus disease 2019 (COVID-19) has various neuropsychiatric manifestations, including psychotic, mood, anxiety disorders, trauma-related disorders, and cognitive disorders, such as delirium. Although the psychosocial effects of the COVID-19 pandemic contribute to an increase in psychiatric comorbidities, the COVID-19 virus is also an independent risk factor. Previous studies have revealed that the virus can invade the neural tissue, which causes an imbalance of neurotransmitters that cause neuropsychiatric symptoms. The aim of this article is to conduct a systematic review to determine the patterns of neuropsychiatric manifestations of COVID-19, discussing the frequency and its impact on pre-existing psychiatric disorders. Thirty-nine case reports were collected and analyzed for a systematic review. They were full-text, peer-reviewed journal publications from November 2020 to February 2021. Fifty-three patients were included in our study. The most frequent symptom was abnormal/bizarre behavior (50.9%), followed by agitation/aggression (49.1%), and the third most common was altered mental status and delirium (47.2%). Only 48% of our patients had a pre-existing psychiatric disorder, including three not formally diagnosed but displayed psychiatric symptoms prior to the COVID-19 infection. Findings suggest a positive correlation of new-onset psychiatric symptoms with the SARS-CoV-2 virus. However, the exact pathophysiology of the virus itself causing neuropsychiatric manifestations needs to be investigated further.

Suicide amongst transplant recipients: Trends and unique risk factors.

INTRODUCTION: There are higher rates of depression and suicidal ideation among those with chronic diseases, including end-stage renal disease, diabetes mellitus and liver disease. Suicide is the tenth leading cause of death worldwide and is more prevalent among transplant recipients. Although transplantation has the potential to improve quality of life, many transplant recipients commit suicide each year. The extent to which sex, race, age, type of insurance coverage, time on waitlist, comorbidities, immunosuppressive regimen and graft loss contribute to suicide risk in this population remains understudied. METHODS: We queried UNOS data collected between 1990 and 2019 to determine what risk factors contribute to suicide in the transplant population. Suicide mortality rate was calculated by determining the fraction of organ recipients who died by suicide since 1990 and was expressed as deaths per 100 000. Two groups (suicide and all other cause mortality) were compared via univariate and multivariate statistical analysis. Time to graft loss was estimated using a Kaplan Meier Product Limit method. A propensity score analysis was performed to match patients who committed suicide to those who did not, allowing us to balance the relatively small sample of size of the suicide cohort with the larger all other cause mortality group to minimize the effect of confounding variables. We estimated years of organ life lost using the restricted mean. Statistical significance was defined by p < .05. RESULTS: The data included 135 432 transplant deaths in total; the majority were kidney recipients-82 305 (61%). We determined suicide rates of .28%, .31%, and .44% for kidney, liver and pancreas, respectively, with an overall rate of .3%. Across all three organs the most significant risk factor was male sex. Non-Hispanic whites were also at elevated risk (OR = 2.16, p < .003). In the liver and kidney transplant groups, the odds of committing suicide were reduced by 4% with advancing age. The odds of taking one's own life was inversely related to BMI in the kidney and pancreas groups. We observed a doubling of suicide rates from .3% in 2014 to .6% in 2018. There were no other statistically significant correlations. CONCLUSION: Suicide is more prevalent among transplant recipients than in the general population. White males in particular are most at risk. The highest rate of suicide was in pancreas recipients. Advancing age and increasing BMI conferred some protective effect. There were no significant associations between suicide incidence and glucocorticoid use, type of insurance coverage, time on waitlist or graft loss. The phenomenon has become more prevalent in recent years.

The mechanisms of mutual relationship between malignant hematologic cells and mesenchymal stem cells: Does it contradict the nursing role of mesenchymal stem cells?

Mesenchymal stem/stromal cells (MSCs) are known as the issue in biology because of some unpredictable characteristics in the different microenvironments especially in their bone marrow niche. MSCs are used in the regenerative medicine because of their unique potentials for trans-differentiation, immunomodulation, and paracrine capacity. But, their pathogenic and pro-survival effects in tumors/cancers including hematologic malignancies are indisputable. MSCs and/or their derivatives might be involved in tumor growth, metastasis and drug resistance in the leukemias. One of important relationship is MSCs and hematologic malignancy-derived cells which affects markedly the outcome of disease. The communication between these two cells may be contact-dependent and/or contact-independent. In this review, we studied the crosstalk between MSCs and malignant hematologic cells which results the final feedback either the progression or suppression of blood cell malignancy. Video abstract.

New Delhi metallo-ß-lactamase-1 among Escherichia coli strains isolated from leukemia patients in Iran: two case reports.

BACKGROUND: Escherichia coli has appeared as an important opportunistic pathogen responsible for nosocomial infections in patients with immunodeficiency, particularly in leukemia patients. New Delhi metallo-beta-lactamase is an enzyme originally found in Enterobacteriaceae. CASE PRESENTATION: In this study, 80 isolates of Escherichia coli and Klebsiella pneumoniae were collected over the course of 2 years from two medical centers in Tehran, Iran. Production of carbapenemase was detected in the isolates using modified Hodge test. New Delhi metallo-beta-lactamase-1 genes were detected by polymerase chain reaction amplification with specific primers. Two New Delhi metallo-beta-lactamase-1-producing Escherichia coli strains were isolated from two Iranian patients with leukemia. These two patients were 6 and 15 years old, one female and the other male, from two oncology centers in Iran. The isolates were resistant to carbapenems (imipenem, meropenem), and two isolates were positive for carbapenemase production by modified Hodge test. CONCLUSIONS: The emergence of New Delhi metallo-beta-lactamase-1-producing Escherichia coli is a threat for leukemia patients in oncology and hematology departments. We conclude that the incidence of multidrug resistant pathogens has increased among patients with leukemia and is life threatening.

Combined Parietal-Insular-Striatal Cortex Stroke with New-Onset Hallucinations: Supporting the Salience Network Model of Schizophrenia.

Brain imaging studies have identified multiple neuronal networks and circuits in the brain with altered functioning in patients with schizophrenia. These include the hippocampo-cerebello-cortical circuit, the prefrontal-thalamic-cerebellar circuit, functional integration in the bilateral caudate nucleus, and the salience network consisting of the insular cortex, parietal anterior cingulate cortex, and striatum, as well as limbic structures. Attributing psychotic symptoms to any of these networks in schizophrenia is confounded by the disruption of these networks in schizophrenic patients. Such attribution can be done with isolated dysfunction in any of these networks with concurrent psychotic symptoms. We present the case of a patient who presents with new-onset hallucinations and a stroke in brain regions similar to the salience network (insular cortex, parietal cortex, and striatum). The implication of these findings in isolating psychotic symptoms of the salience network is discussed.

Comparative Evaluation of Biochemical and Hematological Parameters of Pre-Storage Leukoreduction during RBC Storage.

Background: Some of the red cell storage lesions (RCSLs) take place during red blood cell (RBC) storage and may reduce the function of these cells dramatically, which mostly caused by residual leucocytes in blood components. This study was planned to observe the biochemical and hematological changes in pre-storage leukoreduced RBC (LR-RBC) compared with unfiltered RBC during in vitro storage. Materials and Methods: Ten unit RBCs were collected, processed and stored according to Iranian standard operating procedure (SOP) of Iranian Blood Transfusion Organization (IBTO). Every unit was split into two equal parts, unfiltered RBC and LR-RBC. Samples were collected and tested on weeks of storage. Biochemical parameters such as lactate dehydrogenase (LDH), lactate concentration and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity were measured by auto-analyzer. In addition, hematology analyzer was used to monitor the change of RBC indices such as (MCV), (MCH) and (MCHC). Results: In this study, both groups showed progressive increase of LDH and lactate levels, and also G6PD activity decreased during storage. Mean of LDH and lactate in unfiltered RBC was significantly increased compared with LR-RBC during all days of storage (p< 0.05). There was statically significant decrease in the G6PD enzyme activity between the two groups and weeks of storage (p< 0.05). However, the RBC indices remained within the expected levels in both groups. Conclusion: LR-RBC and RBC both exhibited RCSL during storage, but LR-RBC is effective in reducing Red cell storage lesion (RCSL) and also improves the quality of stored red blood cells.

Umbilical Cord Blood Platelet Lysate as Serum Substitute in Expansion of Human Mesenchymal Stem Cells.

OBJECTIVES: The diverse clinical applications for human mesenchymal stem cells (hMSCs) in cellular therapy and regenerative medicine warrant increased focus on developing adequate culture supplements devoid of animal-derived products. In the present study, we have investigated the feasibility of umbilical cord blood-platelet lysate (UCB-PL) as a standard substitute for fetal bovine serum (FBS) and human peripheral blood-PL (PB-PL). MATERIALS AND METHODS: In this experimental study, platelet concentrates (PC) from UCB and human PB donors were frozen, melted, and sterilized to obtain PL. Quality control included platelet cell counts, sterility testing (viral and microbial), total protein concentrations, growth factor levels, and PL stability. The effects of UCB-PL and PB-PL on hMSCs proliferation and differentiation into osteocytes, chondrocytes, and adipocytes were studied and the results compared with FBS. RESULTS: UCB-PL contained high levels of protein content, platelet-derived growth factor- AB (PDGF-AB), and transforming growth factor (TGF) compared to PB-PL. All growth factors were stable for at least nine months post-storage at -70˚C. hMSCs proliferation enhanced following treatment with UCB-PL. With all three supplements, hMSCs could differentiate into all three lineages. CONCLUSIONS: PB-PL and UCB-PL both were potent in hMSCs proliferation. However, PB promoted osteoblastic differentiation and UCB-PL induced chondrogenic differentiation. Because of availability, ease of use and feasible standardization of UCB-PL, we have suggested that UCB-PL be used as an alternative to FBS and PB-PL for the cultivation and expansion of hMSCs in cellular therapy.

Percutaneous Autologous Bone Marrow-Derived Mesenchymal Stromal Cell Implantation Is Safe for Reconstruction of Human Lower Limb Long Bone Atrophic Nonunion.

OBJECTIVE: Nonunion is defined as a minimum of a 9-month period of time since an injury with no visibly progressive signs of healing for 3 months. Recent studies show that application of mesenchymal stromal cells (MSCs) in the laboratory setting is effective for bone regeneration. Animal studies have shown that MSCs can be used to treat nonunions. For the first time in an Iranian population, the present study investigated the safety of MSC implantation to treat human lower limb long bone nonunion. MATERIALS AND METHODS: It is a prospective clinical trial for evaluating the safety of using autologus bone marrow derived mesenchymal stromal cells for treating nonunion. Orthopedic surgeons evaluated 12 patients with lower limb long bone nonunion for participation in this study. From these, 5 complied with the eligibility criteria and received MSCs. Under fluoroscopic guidance, patients received a one-time implantation of 20-50×106 MSCs into the nonunion site. All patients were followed by anterior-posterior and lateral X-rays from the affected limb, in addition to hematological, biochemical, and serological laboratory tests obtained before and 1, 3, 6, and 12 months after the implantation. Possible adverse effects that included local or systemic, serious or non-serious, and related or unrelated effects were recorded during this time period. RESULTS: From a safety perspective, all patients tolerated the MSCs implantation during the 12 months of the trial. Three patients had evidence of bony union based on the after implantation Xrays. CONCLUSION: The results have suggested that implantation of bone marrow-derived MSCs is a safe treatment for nonunion. A double-blind, controlled clinical trial is required to assess the efficacy of this treatment (Registration Number: NCT01206179).

The synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchymal stem cells.

PURPOSE: In this study, we examined chondrogenic regulation of 2 types of mesenchymal stem cells seeded on the bioengineered substrate in monolayer cultures under mechanically defined conditions to mimic the in vivo microenvironment of chondrocytes within articular cartilage tissues. METHODS: Human adipose-derived mesenchymal stem cells (ASCs) and bone marrow mesenchymal stem cells (BSCs) were exposed to 0.2 Pa shear stress, 3 MPa cyclic hydrostatic pressure, and combined loading with different sequences on chemically designed medical-grade silicone rubber, while no soluble growth factors were added to the culture medium. The expression levels of chondrogenic-specific genes of SOX9, aggrecan, and type II collagen (Col II) were measured. Results were compared to those of cells treated by biological growth factor. RESULTS: Gene expression patterns were dependent on the loading regime. Moreover, the source of mesenchymal stem cells (adipose or bone marrow) was influential in gene expression. Overall, enhanced expression of chondrogenic markers was found through application of mechanical stimuli. The response was generally found to be significantly promoted when the 2 loading regimes were superimposed. CONCLUSIONS: Differentiation of ASCs was shown by a modest increase in gene expression profiles. In general, BSCs expressed higher levels of chondrogenic gene expression than ASCs after 3 weeks. A greater effect on Col II and SOX9 mRNA expression was observed when combined loadings were applied. Results may be applied in determining the proper loading sequence for obtaining functional target cells in cartilage engineering applications.

Aqueous ferrofluid of magnetite nanoparticles: Fluorescence labeling and magnetophoretic control.

A method is presented for the preparation of a biocompatible ferrofluid containing dye-functionalized magnetite nanoparticles that can serve as fluorescent markers. This method entails the surface functionalization of magnetite nanoparticles using citric acid to produce a stable aqueous dispersion and the subsequent binding of fluorescent dyes to the surface of the particles. Several ferrofluid samples were prepared and characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), BET surface area analysis, transmission electron microscopy (TEM), and SQUID magnetometry. In addition, confocal fluorescence microscopy was used to study the response of the fluorescent nanoparticles to an applied magnetic field and their uptake by cells in vitro. Results are presented on the distribution of particle sizes, the fluorescent and magnetic properties of the nanoparticles, and the nature of their surface bonds. Biocompatible ferrofluids with fluorescent nanoparticles enable optical tracking of basic processes at the cellular level combined with magnetophoretic manipulation and should be of substantial value to researchers engaged in both fundamental and applied biomedical research.