Histomorphometric Alterations Induced in the Testicular Tissues by Variable Sizes of Silver Nanoparticles.

OBJECTIVE: To investigate the histomorphometric alterations induced in testicular tissues by variable sizes of silver nanoparticles (SNPs). STUDY DESIGN: Male mice (BALB/C) were treated with SNPs (1 mg/kg) using 5 different sizes (10, 20, 40, 60, and 100 nm) for 35 days. Testicular biopsies from all mice under study were examined histomorphologically. RESULTS: SNPs sized 10 and 20 nm had provoked morphometric changes in the testes of the subjected mice together with the following histological alterations: seminiferous tubules, degeneration, spermatocyte cytoplasmic vacuolation, spermatocyte sloughing, and spermatid giant cell formation. Larger SNPs (40, 60, and 100 nm) induced little or no testicular histomorphometric alterations. CONCLUSION: The findings of the present work may indicate that subchronic exposure to SNPs could have a deleterious impact on the testicular tissues and spermatogenic process that could affect fertility and reproduction, with smaller SNPs being more toxic than larger ones.

Addition of Mitoquinone (MitoQ) to Fresh Human Sperm Enhances Sperm Motility without Attenuating Viability.

The preparation of human sperm in an andrology laboratory subjects it to oxidative stress. Reactive oxygen species are produced by mitochondria, making it susceptible to oxidative damage; hence, mitochondria-targeted antioxidants like Mitoquinone (MitoQ) might have therapeutic potential for oxidative-damage-associated disorders. The current research aims to establish whether MitoQ has any positive effects during in vitro preparation of fresh human sperm. Viability and motility are evaluated to determine the effective MitoQ concentration and to assess whether MitoQ supplementation is affected by sperm concentration by incubating normospermia semen samples at 37 °C for 2 h and 4 h, respectively. The effect of semen centrifugation following supplementation of 20 × 106 sperm/mL with 200 nM MitoQ is also assessed by measuring viability, motility and sperm DNA fragmentation. The best sperm motility is achieved after 2 h of incubation with 200 nM MitoQ at 37 °C. Sperm concentration of 20 × 106 sperm/mL is the best concentration where 200 nM MitoQ works efficiently. For semen centrifugation at 300× g for 20 min, supplementation with 200 nM MitoQ shows higher sperm motility. The current results demonstrate that MitoQ supplementation during in vitro human semen preparation procedures positively affects fresh sperm motility without affecting viability or increasing DNA fragmentation.

Characterization of BCL-X L , MCL-1, and BAX Protein Expression in Response to Neoadjuvant Chemotherapy in Breast Cancer.

The use of chemotherapy has improved the overall treatment of breast cancer, which is frequently administered in the form of neoadjuvant chemotherapy (NAC). Apoptosis is an established cell stress response to NAC in preclinical models; however, there is limited understanding of its role in clinical cancer, specifically, its contribution to favorable pathologic responses in breast cancer therapy. Here, we aimed to characterize the change in protein expression of 3 apoptosis-associated biomarkers, namely, BCL-X L , MCL-1, and BAX in breast cancer in response to NAC. For this, we utilized a set of 68 matched invasive breast cancer FFPE samples that were collected before (pre) and after (post) the exposure to NAC therapy that were characterized by incomplete pathologic response. Immunohistochemistry (IHC) analysis suggested that most of the samples show a decrease in the protein expression of all 3 markers following exposure to NAC as 90%, 69%, and 76% of the matched samples exhibited a decrease in expression for BCL-X L , MCL-1, and BAX, respectively. The median H-score of BCL-X L post-NAC was 150/300 compared with 225/300 pre-NAC ( P value <0.0001). The median H-score of MCL-1 declined from 200 pre-NAC to 160 post-NAC ( P value <0.0001). The median H-score of BAX protein expression decreased from 260 pre-NAC to 190 post-NAC ( P value <0.0001). There was no statistically significant association between the expression of these markers and stage, grade, and hormone receptor profiling (luminal status). Collectively, our data indicate that the expression of apoptosis regulatory proteins changes following exposure to NAC in breast cancer tissue, developing a partial pathologic response.

General pattern of paediatric poisoning in Jordan during 2018-2019.

Introduction: Acute accidental poisoning in children remains a significant public health issue and a predictable cause of morbidity around the world. To take preventive measures, it is necessary to identify the pattern of this problem. Objective: To determine the extent and characteristics of paediatric poisoning, an epidemiological investigation specific to each country is required. The goal of our research was to determine the current pattern of acute poisoning in children between (0-5) years old in Jordan. Methods: This retrospective study performs a descriptive analysis of the Jordan University Hospital's National Poison Information Center (NPIC) database and describes the epidemiology of acute poisoning in children between (0-5) years old during a period of two years (2018-2019). Results: Paediatric poisoning (0-5) years old accounts for approximately 88% of poisoning cases in Jordan between 2018 and 2019.Out of 3531 paediatric poisoning cases, 44.9% of cases were in children between (2-3) years old, 63.4% of subjects were male. 40.9% of calls were from governmental hospitals. Most cases occurred at home (98.7%) and were unintentional (98.6%). Medication poisoning was the commonest among cases (71.0%). Besides, 89.4% were asymptomatic at the time of call, and Central Nervous System (CNS) symptoms being the most common (3.6%) among the symptomatic cases. Conclusions: Most cases of paediatric poisoning handled by the NPIC was due to medications. To prevent or minimize these cases, it is necessary to educate parents and other caregivers about proper medication storage and use, and in case of poisoning, urgent referral to health facilities is required.

Non-Dexamethasone Corticosteroid Therapy's Effect on COVID-19 Prognosis in Cancer Patients: A Retrospective Study.

BACKGROUND: Anti-inflammatory corticosteroids are used in cancer treatment and COVID-19 infections. Data on the impact of non-dexamethasone corticosteroids on COVID-19 infection severity in cancer patients are minimal. This study investigates if corticosteroid treatment affects the disease severity in adult cancer patients. METHODS: A total of 116 COVID-19-infected cancer patients on hydrocortisone (H) or prednisone (P) were compared to 343 untreated patients. The study included patients who received corticosteroids before (B), after (A), or both before and after (B and A) COVID-19 infections. Ventilation support, hospitalization and mortality were investigated. RESULTS: Our data showed that a significantly greater number of patients taking H or P required ventilation support and hospitalization and that mortality rates were higher than the control group. Patients who received H or P after COVID-19 infection had a significantly worse prognosis than the other sub-groups and the control group. CONCLUSION: Corticosteroids impacted cancer patients' COVID-19 prognosis. Despite the limited sample size, H- and P-treated patients' corticosteroids performed worse than the control, especially if treatments were received after COVID-19 infection. Hence, when a cancer patient already on H or P treatment is diagnosed with COVID-19, we recommend switching to a steroid treatment as suggested by international guidelines.

Investigating the Utility of the SOFA Score and Creating a Modified SOFA Score for Predicting Mortality in the Intensive Care Units in a Tertiary Hospital in Jordan.

Background: The utility of the Sequential Organ Failure Assessment (SOFA) score in predicting mortality in the intensive care unit (ICU) has been demonstrated before, but serial testing in various settings is required to validate and improve the score. This study examined the utility of the SOFA score in predicting mortality in Jordanian ICU patients and aimed to find a modified score that required fewer laboratory tests. Methods: A prospective observational study was conducted at Jordan University Hospital (JUH). All adult patients admitted to JUH ICUs between June and December 2020 were included in the study. SOFA scores were measured daily during the whole ICU stay. A modified SOFA score (mSOFA) was constructed from the available laboratory, clinical, and demographic data. The performance of the SOFA, mSOFA, qSOFA, and SIRS in predicting ICU mortality was assessed using the area under the receiver operating characteristic curve (AUROC). Results: 194 patients were followed up. SOFA score (mean ± SD) at admission was significantly higher in non-survivors (7.5 ± 3.9) compared to survivors (2.4 ± 2.2) and performed the best in predicting ICU mortality (AUROC = 0.8756, 95% CI: 0.8117-0.9395) compared to qSOFA (AUROC = 0.746, 95% CI: 0.655-0.836) and SIRS (AUROC = 0.533, 95% CI: 0.425-0.641). The constructed mSOFA included points for the hepatic and CNS SOFA scores, in addition to one point each for the presence of chronic kidney disease or the use of breathing support; it performed as well as the SOFA score in this cohort or better than the SOFA score in a subgroup of patients with heart disease. Conclusion: SOFA score was a good predictor of mortality in a Jordanian ICU population and better than qSOFA, while SIRS could not predict mortality. Furthermore, the proposed mSOFA score which employed fewer laboratory tests could be used after validation from larger studies.

The Effect of Dexamethasone Treatment on COVID-19 Prognosis in Cancer Patients.

Background: Dexamethasone is used to treat cancer, relieve chemotherapy-induced nausea and vomiting, enhance cancer patients' appetites, and treat COVID-19 patients. There is little evidence of the impact of a dexamethasone treatment plan on the severity of COVID-19 infections in cancer patients. This study explores whether dexamethasone treatment plan influences the severity of COVID-19 in dexamethasone-treated cancer patients. Methods: The medical records of 108 cancer patients receiving dexamethasone at King Hussein Cancer Center with a COVID-19 infection and 343 without corticosteroid treatment were reviewed. Patients on dexamethasone within seven days before infection, after infection, or both were included. Ventilation support, hospitalization, and mortality within 28 days of a COVID-19 diagnosis were key severity factors. Results: We found that dexamethasone before a COVID-19 infection increased the risk of requiring ventilation assistance and mortality within 28 days by a factor of 5.8 (2.8−12.0) relative to control (p < 0.005). Continuing dexamethasone treatment after a COVID-19 infection, or starting it after infection, had a risk factor equivalent to control. Conclusion: Our data showed that dexamethasone therapy protocol affected COVID-19 prognoses in cancer patients, and it is preferable to not discontinue therapy after infection. A rigorous prospective comparison between early and late dexamethasone dosing is needed to determine the best protocol for treatment.

Androgen downregulates desmocollin-2 in association with induction of mesenchymal transition of breast MDA-MB-453 cancer cells.

Desmosomes are cellular structures that are critical in cell-cell adhesion and in maintaining tissue architecture. Changes in the expression of desmocollin-2 (DSC2) have been noted during tumor progression into an invasive phenotype and as cells undergo epithelial-mesenchymal transition. We have previously reported that breast MDA-MB-453 cancer cells, a luminal androgen receptor (AR) model of triple-negative breast cancer, acquire mesenchymal features when treated with the AR agonist, dihydrotestosterone (DHT). We have therefore investigated androgen regulation of the expression and cellular localization of DSC2 in MDA-MB-453 cells. Treatment of the cells with DHT resulted in a dose-dependent reduction in DSC2 protein levels and dispersion of its membrane localization concomitant with AR- and ß-catenin-mediated mesenchymal transition of cells. A significant correlation was revealed between decreased expression of AR and increased expression of DSC2 in patient samples. In addition, whereas lower expression of AR was associated with a reduced overall and recurrence-free survival of breast cancer patients, higher expression of DSC2 was found in invasive breast tumors than in normal breast cells and was correlated with lower patient survival. Upon knocking down DSC2, the cells became elongated, mesenchymal-like, and slightly, but insignificantly, more migratory. The addition of DHT further stimulated cell elongation and migration. DSC2 siRNA-transfected cells reverted to a normal epithelial morphology upon inhibition of ß-catenin. These results highlight the role of DSC2 in maintaining the epithelial morphology of MDA-MB-453 cells and the negative regulation of the desmosomal protein by DHT during stimulation of the androgen-induced, ß-catenin-mediated mesenchymal transition of the cells.

PD-L1 Expression Is a Favorable Prognostic Marker in Gastric Carcinoma.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. Although multidisciplinary therapeutic strategies have improved treatment outcomes, the overall prognosis for patients with GC remains poor. Recently, immunotherapeutic agents targeting immunosuppressive proteins such as anti-programmed death-1 receptor and anti-programmed death ligand-1 (PD-L1) have emerged as effective treatment options for various cancers, including GC. In addition to their therapeutic role, the expression of PD-L1 has been used as a predictive biomarker for programmed death-1/PD-L1 treatment response and has been shown to have a prognostic role in certain cancers. This study aims to evaluate the expression of PD-L1 in GC samples from Jordanian patients and assess its prognostic role as well as its correlation with clinicopathologic variables. Gastrectomy samples from 96 patients diagnosed with gastric adenocarcinoma were included in the study. Immunohistochemistry assay was employed for PD-L1 testing, and the scoring was based on a combined positive score (CPS). It was found that 66.7% of the study samples were positive for PD-L1 (CPS≥1). The expression of PD-L1 was not significantly associated with any of the assessed clinicopathologic variables; however, it was found to be an independent favorable prognostic factor for overall survival (hazard ratio: 0.481; 95% confidence interval: 0.231-1.001; P=0.050).

Application of Gas Chromatography-Mass Spectrometry for the Identification and Quantitation of Three Common Synthetic Cannabinoids in Seized Materials from the Jordanian Market.

Synthetic cannabinoids (SCs) were developed to mimic the effects of Δ9-tetrahydrocannabinol on humans. SCs were distributed in the form of herbal blends, with smoking being the main method of consumption. These synthetic compounds have a wide range of physical, behavioral, and harmful effects on the body. However, this study aimed to identify and quantify three common SCs including AB-FUBINACA, AB-CHMINACA, and XLR-11 in the seized materials from the Jordanian market by gas chromatography coupled with mass spectrometry (GC-MS). A liquid-liquid extraction sample preparation technique was applied to 100 different seized samples obtained from the Anti-Narcotics Department of Public Security in a period between 2017 and 2018. Profiling of the seized samples revealed different distributions of the targeted SCs in the obtained samples. Upon quantitation, concentrations of these SCs varied greatly within and among the samples. The use of GC-MS analysis provided a powerful technique in the detection and identification of SCs. This study revealed the current and trends of SC use in the Jordanian illicit substance market, which was previously unclear. Future studies are required to explore new SCs and their influence in different biological samples.

Association between occupational lead exposure and plasma levels of selected oxidative stress related parameters in Jordanian automobile workers.

OBJECTIVES: To study any possible correlation between blood lead levels and some oxidative stress parameters of selected groups of lead-exposed automobile occupational Jordanian workers. MATERIAL AND METHODS: Blood lead levels were determined for a total of 90 male automobile workers aged within the range of 25-45 years old along with the group of 20 agematched healthy males control. To get an idea about the antioxidant status of controls and lead-exposed workers, and to estimate the oxidative stress caused by exposure to lead, we measured the hydrogen peroxide (H2O2) concentration, superoxide dismutase (SOD) activity, lipid peroxidation as malondialdehyde (MDA) and total antioxidant capacity of controls and workers. RESULTS: The study showed that lead levels in the case of workers were approximately 4-5 times as high as in controls 14.5-21 µg×dl-1 vs. 4.3 µg×dl-1, respectively. There was a significant decrease (16-25%) in the level of plasma reduced glutathione and 21-33% decrease in total antioxidant capacity (TAOC) in all worker groups, as compared to controls. The results showed that the concentration of malondialdehyde (MDA) in plasma was higher (120-333%) in the case of workers than controls being the highest in automobile electronics and the lowest - in mechanics. Furthermore, there was 149-221% increase in hydrogen peroxide (H2O2) concentration, and 26-38% increase in SOD activity in the case of workers compared to the control group. CONCLUSIONS: There is a strong evidence for the associations between occupational lead exposure and various markers of oxidative stress in Jordanian automobile occupational workers. Thus, there is an urgent need to raise awareness and to initiate suitable protection guidelines for workers. Int J Occup Med Environ Health 2018;31(4):517-525.

Low Incidence of the DPD IVS14+1G>A Polymorphism in Jordanian Breast and Colorectal Cancer patients

Background: Dihydropyrimidine dehydrogenase (DPD) is a crucial enzyme in the catabolism of 5-fluorouracil (5-FU), a drug that is frequently used in cancer therapy. Patients with deficient DPD activity are at risk of developing severe 5-FU­associated toxicity. One possible cause of deficiency is genetic polymorphisms in the DPD gene, such as IVS14+1G>A. Aim: The present study was conducted to screen for the IVS14+1G>A polymorphism in cancer patients receiving 5-FU and a control group. Methods: A total of 40 cancer patients (30 colorectal cancer (CRC) and 10 breast cancer patients) were enrolled in this study. One hundred healthy controls were also tested using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). DNA sequence analysis was carried out to confirm the presence of the IVSI14+1G>A polymorphism. Results: Only one CRC patient showed heterozygous IVS14+1G>A polymorphism in the DPD gene. Conclusion: The results of this study demonstrated a very low frequency of the IVS14+1G>A polymorphism among Jordanian patients with colorectal and breast cancer.

Occupational exposure to pesticides and occurrence of the chromosomal translocation t(14;18) among farmers in Jordan.

BACKGROUND: An increased incidence of non-Hodgkin's lymphoma (NHL) has been reported in farmers and other occupational groups working with pesticides. In these individuals, an increased prevalence of the chromosomal translocation t(14;18)(q32;q21), one of the most common chromosomal abnormalities in NHL, has been detected in peripheral blood lymphocytes. This translocation juxtaposes the antiapoptotic BCL2 protein to the immunoglobulin heavy chain gene locus (IGH) leading to overexpression of BCL2. This causes an increase in cell survival, paving the way for malignant transformation. AIM OF THE STUDY: The present study aimed to evaluate the association between the occurrence of the chromosomal translocation t(14;18) and occupational exposure to pesticides among a group of Jordanian farmers. METHODS: A total of 192 male subjects including 96 agricultural workers and 96 control subjects participated in this study. BCL2-IGH t(14;18) fusions were detected by a nested polymerase chain reaction (PCR) assay targeting the major breakpoint region (MBR). RESULTS: We found that occupational exposure to pesticides in open-field farming and insecticide used on animals increased the frequency of the chromosomal translocation t(14;18). Farmers occupationally exposed to pesticides and insecticide were 13.5 times more likely to harbor t(14;18). 63.5% (61 of 96) of farmers compared to 11.5% (11 of 96) of controls carried the translocation (odds ratio: 13.5; 95% confidence interval (CI) = 6.3-28.6). We ruled out the influence of possible confounding factors such as age, duration of sun exposure, alcohol intake, smoking, and use of personal protective equipment. CONCLUSION: Our results indicate that pesticides increased the frequency of chromosomal translocation in the 14q32 region. Accordingly, the presented data agrees with previous suggestions from the literature that pesticides might be involved in the development of NHL through the t(14;18) pathway.

Morphometric alterations induced by the toxicity of variable sizes of silver nanoparticles / Alteraciones morfométricas inducidas por la toxicidad de diferentes tamaños de nanopartículas de plata

Silver nanoprticles (SNPs) are invested in medical, industrial and environmental applications. Little if any, is known about the morphometric alterations induced by the toxicity of SNPs. The aim of the present work is to find out the effect of variable size of SNPs on different morphometric parameters. Adult healthy male mice (BAL/C) were subjected to (10 nm, 20 nm, 40 nm 60 nm and 100 nm) SNPs for 35 days. Silver NPs caused non-significant decline on the average weight, significant decline in food consumption, increase in water intake, unilateral blindness, tanning fur color and cholestasis together with a decrease in the relative ratio of the liver, kidney and spleen weight to body weight. Mice subjected to 10 nm and 20 nm were more affected than mice receiving larger nanoparticles. These findings may indicate that SNPs could induce morphometric alterations that are size related wheresmaller SNPs have more impact than the larger ones.

Poco se sabe acerca de las alteraciones morfométricas inducidas por la toxicidad de las nanopartículas de plata (NPP). El objetivo fue investigar el efecto del tamaño variable de las NPP en diferentes parámetros morfométricos. Ratones machos adultos sanos (BAL/C) fueron sometidos a diferentes NPP de diferentes tamaños durante 35 días (10 nm, 20 nm, 40 nm 60 nm y 100 nm, respectivamente). Las NPP causaron una disminución no significativa del peso promedio, una disminución significativa en el consumo de alimentos, un aumento de la ingesta de agua, ceguera unilateral, cambios en el color de piel y colestasis junto con una disminución en el tamaño promedio del hígado, riñón y el peso del bazo, en relación al peso corporal. Los ratones sometidos a 10 nm y 20 nm fueron más afectados que los ratones que recibieron las nanopartículas más grandes. Estos resultados pueden indicar que las NPP podrían inducir alteraciones morfométricas que están relacionadas con el tamaño, en las cuales las NPP más pequeñas tienen un mayor impacto que las más grandes.