Effective and Elaborative Induction Program for Mitigating Myths and Misconceptions Linked to Hematopoietic Stem Cell Transplantation in a Resource Limited Setting.

Since the first transplant in 1957 and hematopoietic stem cell transplantation (HSCT) is the curative modality for numerous hematological disorders. Nevertheless, it is not available for all patients. Besides unavailability of matched donors a lot of factors could hinder HSCT in a resource limited setting, as financial and administrative factors. In our daily practice we noticed other factors that hinder HSCT in our center, the common myths and misconceptions about HSCT and donation. This quasi-experimental study assessed, for the first time, common myths and misconceptions about HSCT among 218 medical and nursing students before and after an interventional educational program. The study tool was an investigators' developed self-administered questionnaire. Participants' male to female ratio was 1:2.5, and FAS was middle in 52.7%. Pretest high myths scores were reported in 53.4% and 90% of medical and nursing students that was reduced to 0% and 4% post-test, respectively. Pretest, 26.3% and 7% of medical and nursing students welling to donate HSC, that increased to 66% and 39% post-test, respectively. Rural residency, low and middle FAS associated with higher myths scores. Myths score is an independent effector of willingness to donate HSC among participants. In conclusion medical/nursing students had significant myths and misconceptions about HSCT that was corrected with the educational program. Thus, wide based educational programs about HSCT are mandatory to correct myths and augment HSC donation. www.clinicaltrrial.gov: clinical trial ID NCT05151406. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01634-5.

Genomic epidemiology and emergence of SARS-CoV-2 variants of concern in the United Arab Emirates.

Since the declaration of SARS-CoV-2 outbreak as a pandemic, the United Arab Emirates (UAE) public health authorities have adopted strict measures to reduce transmission as early as March 2020. As a result of these measures, flight suspension, nationwide RT-PCR and surveillance of viral sequences were extensively implemented. This study aims to characterize the epidemiology, transmission pattern, and emergence of variants of concerns (VOCs) and variants of interests (VOIs) of SARS-CoV-2 in the UAE, followed by the investigation of mutations associated with hospitalized cases. A total of 1274 samples were collected and sequenced from all seven emirates between the period of 25 April 2020 to 15 February 2021. Phylogenetic analysis demonstrated multiple introductions of SARS-CoV-2 into the UAE in the early pandemic, followed by a local spread of root clades (A, B, B.1 and B.1.1). As the international flight resumed, the frequencies of VOCs surged indicating the January peak of positive cases. We observed that the hospitalized cases were significantly associated with the presence of B.1.1.7 (p < 0.001), B.1.351 (p < 0.001) and A.23.1 (p = 0.009). Deceased cases are more likely to occur in the presence of B.1.351 (p < 0.001) and A.23.1 (p = 0.022). Logistic and ridge regression showed that 51 mutations are significantly associated with hospitalized cases with the highest proportion originated from S and ORF1a genes (31% and 29% respectively). Our study provides an epidemiological insight of the emergence of VOCs and VOIs following the borders reopening and worldwide travels. It provides reassurance that hospitalization is markedly more associated with the presence of VOCs. This study can contribute to understand the global transmission of SARS-CoV-2 variants.

Hepatitis E Virus Persistence and/or Replication in the Peripheral Blood Mononuclear Cells of Acute HEV-Infected Patients.

BACKGROUND: Hepatitis E virus (HEV) causes about 14 million infections with 300,000 deaths and 5,200 stillbirths worldwide annually. Extrahepatic manifestations are reported with HEV infections, such as renal, neurological, and hematological disorders. Recently, we reported that stool-derived HEV-1 replicates efficiently in human monocytes and macrophages in vitro. However, another study reports the presence of viral RNA but no evidence of replication in the PBMCs of acute hepatitis E (AHE) patients. Therefore, the replication of HEV in PBMCs during AHE infection is not completely understood. METHODS: PBMCs were isolated from AHE patients (n = 17) enrolled in Assiut University Hospitals, Egypt. The viral load, positive (+) and negative (-) HEV RNA strands and viral protein were assessed. The gene expression profile of PBMCs from AHE patients was assessed. In addition, the level of cytokines was measured in the plasma of the patients. RESULTS: HEV RNA was detected in the PBMCs of AHE patients. The median HEV load in the PBMCs was 1.34 × 103 IU/ml. A negative HEV RNA strand and HEV open reading frame 2 protein were recorded in 4/17 (23.5%) of the PBMCs. Upregulation of inflammatory transcripts and increased plasma cytokines were recorded in the AHE patients compared with healthy individuals with significantly elevated transcripts and plasma cytokines in the AHE with detectable (+) and (-) RNA strands compared with the AHE with the detectable (+) RNA strand only. There was no significant difference in terms of age, sex, and liver function tests between AHE patients with detectable (+) and (-) RNA strands in the PBMCs and AHE patients with the (+) RNA strand only. CONCLUSION: Our study shows evidence for in vivo HEV persistence and replication in the PBMCs of AHE patients. The replication of HEV in the PBMCs was associated with an enhanced immune response, which could affect the pathogenesis of HEV.

Evaluation of hepatitis E antigen kinetics and its diagnostic utility for prediction of the outcomes of hepatitis E virus genotype 1 infection.

HEV-Ag ELISA assay is a reliable diagnostic test in resource-limited areas. HEV genotype 1 (HEV-1) infections are either self-limited or progress to fulminant hepatic failure (FHF) and death if anti-HEV therapy is delayed. Limited data is available about the diagnostic utility of HEV Ag on HEV-1 infections. Herein wWe aimed to study the kinetics of HEV Ag during HEV-1 infections at different stages, i.e., acute HEV infection, recovery, and progression to FHF. Also, we evaluated the diagnostic utility of this marker to predict the outcomes of HEV-1 infections. Plasma of acute hepatitis E (AHE) patients were assessed for HEV RNA by RT-qPCR, HEV Ag, and anti-HEV IgM by ELISA. The kinetics of HEV Ag was monitored at different time points; acute phase of infection, recovery, FHF stage, and post-recovery. Our results showed that the level of HEV Ag was elevated in AHE patients with a significantly higher level in FHF patients than recovered patients. We identified a plasma HEV Ag threshold that can differentiate between self-limiting infection and FHF progression with 100% sensitivity and 88.89% specificity. HEV Ag and HEV RNA have similar kinetics during the acute phase and self-limiting infection. In the FHF stage, HEV Ag and anti-HEV IgM have similar patterns of kinetics which could be the cause of liver damage. In conclusion, the HEV Ag assay can be used as a biomarker for predicting the consequences of HEV-1 infections which could be diagnostically useful for taking the appropriate measures to reduce the complications, especially for high-risk groups.

Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus.

B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we hypothesized that an altered phenotype of B cell subsets is associated with T1D in children. Children with T1D (n = 29) and control children with normal blood glucose levels (n = 14) were recruited. The percentages of different circulating IL10-producing Breg subsets, including B10, immature transitional, and plasmablasts were determined using flow cytometry analysis. Furthermore, the association between different IL10-producing B cells and patient parameters was investigated. The percentage of circulating IL10+CD24hiCD27+ (B10) and IL10+CD24hiCD38hi (immature transitional) subsets of Breg cells was significantly lower in T1D patients than in healthy controls. Moreover, these cells were also negatively correlated with fasting blood glucose and HbA1c levels. Breg cells did not correlate with autoantibody levels in the serum. These findings suggest that certain Breg subsets are numerically deficient in children with T1D. This alteration in frequency is associated with deficient islet function and glycemia. These findings suggest that Breg cells may be involved in the loss of auto-tolerance and consequent destruction of pancreatic cells and could, therefore, be a potential target for immunotherapy.

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment.

Purpose. The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.

Management of intravesical self-inflicted sharp objects in children: 10-year single-center experience.

INTRODUCTION: Intravesical foreign bodies (FBs) are rare and have interesting pathology for urologists. There has been an increase in reports of intravesical FBs in the last few decades, but they are still considered to be rare in children, especially young girls. Here we present our experience in the assessment and management of intravesical self-inserted sharp objects in children. PATIENTS AND METHODS: We reviewed the records of children with self-introduced intravesical FBs admitted to our hospital during the last 10 years. Twenty-four cases were included in this study (20 girls and 4 boys). The presenting symptoms and methods of diagnosis and treatment were reviewed. RESULTS: The ages of the patients ranged from 4 to 12 years. In all cases, foreign bodies were self-inserted. All patients were subjected to KUB (kidney, ureter, bladder radiograph) and abdominal ultrasonography. Based on the KUB findings, the FBs in girls were found to be metal pins in 12, a hair clip in four, and a wooden pencil in three (Figure). In boys, a coiled electric wire was found in three, with a urinary calculus formed over one of them. There were small metallic objects in two cases (1 boy and 1 girl). Endoscopic removal of FBs was done successfully in 19 cases (18 girls and 1 boy), and open cystostomy was performed in four cases (3 boys and 1 girl). DISCUSSION: Intravesical FBs are important considerations in the differential diagnosis of pathological lower urinary tract symptoms. They represent significant challenges to urologists. Among children, the reasons for self-insertion of FBs might reflect psychiatric disorders. Routine psychiatric evaluations should be offered to all patients with intentional FB insertion to avoid missing any underlying psychiatric disorders. In our study, psychiatric evaluations have been advised for all the affected children and their parents. Self-inserted FBs are commonly seen in adults and are rarely encountered in children. To our knowledge, this is the largest reported series of children with self-inflicted intravesical FBs. In addition, all of the FBs in this study had one or more sharp edges that made their endoscopic extraction more difficult without causing bladder or urethral damage. In children, removal of intravesical FBs represents a great challenge, as the size of the pediatric urethra may hinder safe transurethral removal. Endoscopic handling of intravesical FBs is mostly unsuccessful in boys because of the long and narrow urethra, and open cystostomy might be the treatment of choice to save the urethra. In contrast, the short female urethra renders the endoscopic removal of intravesical FBs more successful. In this study, endoscopic removal of FBs was done successfully in 19 cases (18 girls and 1 boy), and open cystostomy was performed in four cases (3 boys and 1 girl). CONCLUSIONS: Although FBs in the urinary tract of children are very rare, they need to be considered during any evaluation of pathological lower urinary tract symptoms. Endoscopic management is feasible for most of these patients. The size, number, nature of foreign bodies, and any associated urinary calculi determine the treatment modality.

Molecular chaperone GRP78 enhances aggresome delivery to autophagosomes to promote drug resistance in multiple myeloma.

Despite the clinical benefit of the proteasome inhibitor bortezomib, multiple myeloma (MM) patients invariably relapse through poorly defined mechanisms. Myeloma cells inevitably develop chemoresistance that leads to disease relapse and patient-related deaths. Studies in tumor cell lines and biopsies obtained from patients refractory to therapy have revealed that myeloma cells adapt to stress by inducing expression of glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone with anti-apoptotic properties. Treatment of myeloma cells with bortezomib increased GRP78 levels and activated GRP78-dependent autophagy. Expression profiling indicated that GRP78-encoding HSPA5 was significantly upregulated in bortezomib-resistant cells. Co-treatment with the anti-diabetic agent metformin suppressed GRP78 and enhanced the anti-proliferative effect of bortezomib. Bortezomib treatment led to GRP78 co-localization with proteotoxic protein aggregates, known as aggresomes. Pharmacologic suppression, genetic ablation or mutational inactivation of GRP78 followed by bortezomib treatment led to the accumulation of aggresomes but impaired autophagy and enhanced anti-myeloma effect of bortezomib. GRP78 was co-immunoprecipitated with the KDEL receptor, an ER quality control regulator that binds proteins bearing the KDEL motif to mediate their retrieval from the Golgi complex back to the ER. Taken together, we demonstrate that inhibition of GRP78 functional activity disrupts autophagy and enhances the anti-myeloma effect of bortezomib.

Rare extraperitoneal involvement with fatal outcome in a case of bilateral luteinized thecoma of the ovaries with sclerosing peritonitis.

We report the case of a woman diagnosed with bilateral luteinized thecoma of the ovaries with sclerosing peritonitis, multiple intraperitoneal cystic lesions, and extraperitoneal lesions of the liver, inferior to the spleen, and high suspicion of bone marrow involvement. The patient developed profound pancytopenia with rapid clinical deterioration and a fatal outcome.