Beta Elemene induces cytotoxic effects in FLT3 ITD-mutated acute myeloid leukemia by modulating apoptosis.

OBJECTIVE: ß-Elemene, a sesquiterpene with a broad anti-cancer spectrum, is particularly effective against drug-resistant and complex tumors. It can also be efficient against FLT3-expressed acute myeloid leukemia. This research aims to determine whether ß-Elemene has cytotoxic effects on FLT3 ITD-mutated AML cells. MATERIALS AND METHODS: Cytotoxicity, cell morphology, mRNA analysis with apoptotic markers, and analysis of 43 distinct protein markers related to cell death, survival, and resistance were all performed to elucidate its mechanism. Additionally, in order to understand how ß-Elemene and FLT3 interact, molecular docking, molecular dynamics simulations, and computational ADME investigations were performed. RESULTS: ß-Elemene exhibited cytotoxic activity against FLT3-mutated MV4-11 and FLT3 wild-type THP-1 cells, with an IC50 of around 25 µg/ml. The molecular studies revealed that ß-Elemene inhibited cell proliferation by inducing p53, and the involvement of p21, p27, HTRA, and HSPs were also demonstrated. The interactive inhibition in proliferation was confirmed via molecular docking and dynamics analyses. ß-Elemene occupied the FLT3 enzymatic pocket with good stability at the FLT3 active site. CONCLUSIONS: We concluded from our observations that ß-Elemene causes cell death in ITD mutant AML cells, together with the effects of stress factors and inhibiting cell division.

Diagnostic Value of Serum Gamma Glutamyl Transpeptidase (GGT) for Early Diagnosis of Biliary Atresia.

Early differentiation of biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is of important as outcome of Kasai portoenterostomy is directly related to the age of surgery. We need to have a simple and cheap biochemical test in resource poor countries like Bangladesh, to pick up BA early. Serum gamma glutamyl transpeptidase (GGT) has been shown to be a useful marker to differentiate BA from INH. Objective of the study was to find out the diagnostic value of gamma glutamyl transpeptidase (GGT) in differentiating Biliary atresia (BA) from idiopathic neonatal hepatitis (INH). This observational cross section study was carried out at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Study period was from January 2014 to June 2015. Consecutive infants with neonatal cholestasis (defined as conjugated bilirubin >1.0mg/dL when total bilirubin was ≤5.0 or >20.0% to total bilirubin) were included in this study. Clinical details and the results of laboratory tests were recorded in a proforma. BA was diagnosed on the basis of liver biopsy. Different biochemical parameters especially the results of serum GGT level (normal up to 60U/L), were compared between two groups (BA and INH). Receiver Operator Characteristic (ROC) curve for GGT was constructed to find out the best cut off value to discriminate BA from INH by using SPSS (version 20.0). After confirming cholestasis, a total of 165 cases were enrolled for study. Among them 86 cases were diagnosed as INH or BA. Among these 86 cases, 38(44.2%) cases were BA and 48(55.8%) cases were INH. On comparing 38(44.2%) cases of BA with 48(55.8%) cases of INH it was found that low birth weight (13.0% vs. 31.0%, p<0.05), persistently acholic stools (76.0% vs. 44.0%, p=0.002) and mean GGT values (921 vs. 264, p<0.001) were significantly different between them. At a cut off value of 524U/L (8.7 times upper limit of normal) the area under curve (AUC) for GGT was 0.81 with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 81.7%, 72.9%, 70.5%, 83.3% and 76.1% respectively for the diagnosis of Biliary atresia. Serum GGT value of >524 U/L or 8.7 times upper limit of normal value was fairly good in differentiating BA from INH and can be used as a screening investigation in developing countries.

Patterns of Thyroid Cancer Mortality and Incidence in Saudi Arabia: A 30-Year Study.

Thyroid cancer is the most prevalent endocrine cancer among the female population in the Kingdom of Saudi Arabia (KSA) and the ninth most common in the male population in Saudi Arabia. Over the past years, an increasing incidence of thyroid cancer has been reported in Saudi Arabia. However, the etiology of thyroid cancer is still not clear. Therefore, this study aimed to estimate thyroid cancer incidence and mortality trends in Saudi Arabia from 1990 to 2019. The current study utilized the Global Burden of Disease and the Institute for Health Metrics and Evaluation databases to extract prevalence data of thyroid cancer in Saudi Arabia from 1990 to 2019. Moreover, the current project utilizes Global Burden of Disease (GBD) web-based tools to visualize these data. In total, 23,846 cases (17,220 females and 6626 males) were diagnosed with thyroid cancer in Saudi Arabia from 1990 to 2019. The incidence is higher in females than in males. Over these 30 years, women's incidence steadily increased by 15-fold versus a 22-fold increase in men. Moreover, there were 2056 deaths in total caused by thyroid cancer in KSA. The mortality rate in women steadily increased by threefold in the same period. However, the increase in mortality was higher in males (sixfold). A high percentage of YLLs was observed in males, with around 24.8% ranging from 30 to 34 and 40 to 45 years. Thyroid cancer incidence rates have increased exponentially between 1990 and 2019. The expansion of the incidence of thyroid cancer in Saudi Arabia could be due to the increased development in detection and diagnosis. The current study provided evidence of the need to increase awareness and diagnosis in the male population.

Role of somatostatin receptor SSRT5-AS1 in predicting biomarkers of primary androgen deprivation therapy on prostate cancer in Indonesian population.

INTRODUCTION: Androgen deprivation therapy (ADT) has been the pivotal strategy for treating advanced prostate cancers. Despite the high efficacy of ADT in prohibiting tumor growth, >50% cases of prostate cancer will develop into an aggressive variant known as castration resistant prostate cancer (CRPC). This study aimed to evaluate the potential role SSRT5-AS1 expression as a biomarker for response to ADT in prostate cancer. MATERIALS AND METHODS: In total, 36 patients diagnosed with prostate cancer at Dr. Sardjito General Hospital, Yogyakarta, Indonesia were enrolled from 2015 and 2019. The expression of SSRT5-AS1 in primary tumors was quantified using quantitative real-time polymerase chain reaction. RESULTS: The mean age of patients enrolled in this study was 69.07 ± 8.7 years, and the mean of prostate-specific antigen in patients was 141.22 ±112.28 ng/ml. Compared with the median, a higher expression of SSTR5-AS1 had more significant prognostic value than the variable shorter time to CRPC (p= 0.043). CONCLUSION: This study demonstrated that high expression of SSRT5-AS1 is a promising biomarker to predict response to ADT in patients with prostate cancer.

Persistent Fever and Cough in a Patient With Good's Syndrome: A Case Report.

Good's syndrome is a rare, acquired immunodeficiency condition characterized by thymoma and hypogammaglobulinemia, which increases the risk of recurrent infections. Immunoglobulin replacement therapy (IgRT) is the key treatment for recurrent infections. We describe the case of a 57-year-old male with a history of an anterior mediastinal mass and a persistent cough lasting for a few years. Based on the clinical history and immunological analysis, he was diagnosed with Good's syndrome. He was being managed conservatively with immunoglobulin until he underwent a thymectomy. Subsequently, he developed his first pneumonia. His conditions gradually worsened despite the initiation of IgRT. He was diagnosed to have hypersensitivity pneumonitis based on strong exposure history, consistent radiological images, and good clinical response to antigen avoidance and steroid therapy. To our knowledge, this is the first case of Good's syndrome with hypersensitivity pneumonitis that was unmasked after immune augmentation by the initiation of IgRT. Moreover, surgical intervention should not be considered unless unavoidable. Additionally, close clinical monitoring and laboratory testing are indicated, and IgRT should be considered when the patient begins to exhibit symptoms to prevent severe infections.

Magnetic Resonance Elastography-derived Stiffness Predicts Renal Function Loss and Is Associated With Microvascular Inflammation in Kidney Transplant Recipients.

Background: Organ stiffening can be caused by inflammation and fibrosis, processes that are common causes of transplant kidney dysfunction. Magnetic resonance elastography (MRE) is a contrast-free, noninvasive imaging modality that measures kidney stiffness. The objective of this study was to assess the ability of MRE to serve as a prognostic factor for renal outcomes. Methods: Patients were recruited from the St Michael's Hospital Kidney Transplant Clinic. Relevant baseline demographic, clinical, and Banff histologic information, along with follow-up estimated glomerular filtration rate (eGFR) data, were recorded. Two-dimensional gradient-echo MRE imaging was performed to obtain kidney "stiffness" maps. Binary logistic regression analyses were performed to examine for relationships between stiffness and microvascular inflammation score. Linear mixed-effects modeling was used to assess the relationship between stiffness and eGFR change over time controlling for other baseline variables. A G2-likelihood ratio Chi-squared test was performed to compare between the baseline models with and without "stiffness." Results: Sixty-eight transplant kidneys were scanned in 66 patients (mean age 56 ± 12 y, 24 females), with 38 allografts undergoing a contemporaneous biopsy. Mean transplant vintage was 7.0 ± 6.8 y. In biopsied allografts, MRE-derived allograft stiffness was associated only with microvascular inflammation (Banff g + ptc score, Spearman ρ = 0.43, P = 0.01), but no other histologic parameters. Stiffness was negatively associated with eGFR change over time (Stiffness × Time interaction ß = -0.80, P < 0.0001), a finding that remained significant even when adjusted for biopsy status and baseline variables (Stiffness × Time interaction ß = -0.46, P = 0.04). Conversely, the clinical models including "stiffness" showed significantly better fit (P = 0.04) compared with the baseline clinical models without "stiffness." Conclusions: MRE-derived renal stiffness provides important prognostic information regarding renal function loss for patients with allograft dysfunction, over and above what is provided by current clinical variables.

Occupational Stressors and Safety Behaviour among Oil and Gas Workers in Kuwait: The Mediating Role of Mental Health and Fatigue.

This paper provides an examination of direct and mediated relationships among occupational stressors (responsibilities towards family and living environment), mental health (anxiety and depression), fatigue (physical and mental fatigue), and safety behaviour (safety compliance and safety participation). In this cross-sectional study, data were collected by means of a questionnaire among oil and gas workers (foreign employees working at a remote oil and gas field site located in Kuwait), during a two-month period (November-December 2018). Regression analyses (bivariate and hierarchical), carried out on 387 responses, were employed to test the links between occupational stressors, mental health, fatigue, and safety behaviour in the hypothesised model. The results provide support for the direct relationship in the model, in that both responsibilities towards family and living environment predicted safety behaviour participation. Further, the results provide partial support for the mediated relationships in the model, as mental health and fatigue were found to mediate the relationship of responsibilities towards family and living environment with safety participation behaviour. It is concluded that occupational stressors have a negative effect on safety behaviour, while mental health and fatigue can operate as risk factors. Given this, it is recommended that organisations need to enhance remote oil and gas workers' safety behaviour by encouraging them to effectively balance their stress, mental health, and level of fatigue. This can be achieved by actions such as promoting spirituality, boosting workers' resilience, providing recreational facilities and encouraging communications.

Acute Severe Hyponatremia following Hysteroscopic Procedure in a Young Patient: A Case Report and Review of the Literature.

BACKGROUND: Hysteroscopic surgery is a minimally invasive procedure used to diagnose and treat intrauterine pathologies. It requires distension of the uterine cavity for the adequate visualization of the operative field. Glycine (1.5%) is one of the most commonly used solutions because it is nonconductive and also has good optical properties. However, acute hyponatremia is a critical complication that can develop after the absorption of a sufficient amount of the irrigation medium. Case Presentation. We report a case of a 43-year-old female patient who developed acute symptomatic hyponatremia (104 mEq/L) and pulmonary edema secondary to hysteroscopic resection of leiomyoma and hastily approached with rapid sodium correction measures. CONCLUSION: Multiple strategies can be taken to reduce the risk of fluid absorption and subsequent hyponatremia. Moreover, attention should be paid to the treatment approach for patients with acute hyponatremia following hysteroscopic procedures; rapid correction of acute hyponatremia for such patients might be safe, although there is no consensus in the literature, and further trials are needed.

Translation and validation of the Arabic version of the quality of oncology nursing care scale (QONCS): Psychometric testing in three Arabic countries.

BACKGROUND: In the Arab world, little is known about cancer patient's satisfaction with the care provided by the oncology nurses. The only explanation for this dearth of knowledge is lack of a specified, valid and reliable tool that can be utilized with all types of cancer. This regional study was conducted to translate and validate the Arabic version of quality of oncology nursing care scale (QONCS). METHODS: Brislin's model of translation was used with a cross-sectional, cross-cultural and psychometric design. A convenience sample of 517 from three countries (Jordan, Oman and Egypt) completed the study's surveys. RESULTS: The results indicated that the total QONCS-Ar was reliable with Cronbach's alpha 0.88 and 0.84, 0.87, 0.83, 0.89 and 0.86 for being supported and confirmed, with the religious and spiritual care, belonging, being valued and being respected domains respectively. Exploratory factor analysis supported the dimensional structure of the 34-item scale with five domains with Kaiser-Meyer-Oklin (KMO) measuring 0.872 and Bartlett's Test of Sphericity being significant (significant p<0.001) CONCLUSION: QONCS-Ar is a relatively short, valid, reliable and easy to use instrument that can be applied with all types of cancer, research and educational institutions in the Arabic region.

Antiviral activities of Cholistani plants against common poultry viruses.

Herbal medicines are becoming more popular and acceptable day by day due to their effectiveness, limited side effects, and cost-effectiveness. Cholistani plants are reported as a rich source of antibacterial, antifungal, antiprotozoal, antioxidant, and anticancer agents. The current study has evaluated antiviral potential of selected Cholistani plants. The whole plants were collected, ground and used in extract formation with n-hexane, ethyl acetate and n-butanol. All the extracts were concentrated by using a rotary evaporator and concentrate was finally dissolved in an appropriate vol of the same solvent. All of the extracts were tested for their antiviral potential by using 9-11 days old chick embryonated eggs. Each extract was tested against the Avian Influenza virus H9N2 strain (AIV), New Castle Disease virus Lasoota strain (NDV), Infectious bronchitis virus (IBV) and an Infectious bursal disease virus (IBDV). Hemagglutination test (HA) and Indirect Hemagglutination (IHA) tests were performed for different viruses. The overall order of the antiviral potential of Cholistani plants against viruses was NDV>IBV>IBDV>AIV. In terms of antiviral activity from extracts, the order of activity was n-butanol>ethyl acetate>n-hexane. The medicinal plants Achyranthes aspera, Neuroda procumbens, Panicum antidotale, Ochthochloa compressa and Suaeda fruticose were very effective against all four poultry viruses through their extracts. The low IC50 values of these extracts confirm the high antiviral potential against these viruses. It is worth to mention that Achyranthes aspera was found positive against IBDV through all its extracts which overcome the problem of unavailability of any known drug against IBDV. In short, the study proved that Cholistani plants are rich source of antiviral agent and their extracts can be used as good source of antiviral drugs both in crude and in purified form.

Radiotherapy Trial Set-up in the UK: Identifying Inefficiencies and Potential Solutions.

AIMS: Radiotherapy clinical trials are integral to the development of new treatments to improve the outcomes of patients with cancer. A collaborative study by the National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group and the National Institute for Health Research was carried out to understand better if and why inefficiencies occur in the set-up of radiotherapy trials in the UK. MATERIALS AND METHODS: Two online surveys collected information on the time taken for UK radiotherapy trials to reach key milestones during set-up and the research support currently being provided to radiotherapy centres to enable efficient clinical trial set-up. Semi-structured interviews with project managers and chief investigators identified better ways of working to improve trial set-up in the future. RESULTS: The timelines for the set-up of 39 UK radiotherapy trials were captured in an online survey showing that the median time from grant approval to trial opening was 600 days (range 169-1172). There were 38 responses from radiotherapy centres to a survey asking about the current support provided for radiotherapy research. Most of these centres have more than one type of staff member dedicated to supporting radiotherapy research. The most frequent barrier to radiotherapy trial set-up identified was lack of physicists' time and lack of time for clinical oncologists to carry out research activities. Four main themes around trial set-up were identified from semi-structured interviews: the importance of communication and building relationships, the previous experience of the chief investigator and clinical trials units, a lack of resources and having the time and personnel required to produce trial documentation and to process trial approval requests. CONCLUSIONS: This unique, collaborative project has provided up to date information about the current landscape of trial set-up and research support in the UK and identified several avenues on which to focus future efforts in order to support the excellent radiotherapy trial work carried out across the UK.

Soluble TNF-R1, VEGF and other cytokines as markers of disease activity in systemic lupus erythematosus and lupus nephritis.

BACKGROUND: Current non-invasive methods of assessing disease activity in systemic lupus erythematosus (SLE) are of limited sensitivity and specificity. Testing includes acute phase markers, autoantibodies and complement levels. Although measurements of dsDNA antibodies and complement C3/C4 levels are routine, they remain of limited value. Improved blood and urine markers may help in early detection of flare, distinction between flare and chronic damage, and monitoring response to therapy. METHODS: A total of 87 patients with SLE were tested for the following cytokines in serum and urine: monocyte chemoattractant protein 1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), soluble tumour necrosis factor receptor 1 (sTNF-R1), interferon-inducible protein 10 (IP-10), monocyte inhibitory protein 1α (MIP-1α) and vascular endothelial growth factor (VEGF). Patients attending the Lupus Unit at St Thomas' Hospital, London, UK were divided into active lupus nephritis (LN), inactive LN and non-renal SLE groups based on their renal pathology and SLE disease activity index (SLEDAI). Cytokine testing was performed using the FIDIS multiplex bead assay. RESULTS: The mean level of serum sTNF-R1 was higher in the active LN group compared with both inactive LN and non-renal SLE groups ( p < 0.001). For urine measurements there were significant differences between active LN and non-renal SLE for VEGF ( p = 0.016), after statistical correction for multiple testing. Both urinary and serum sTNF-R1 and IP-10 levels correlated with SLEDAI scores ( p < 0.001), while serum VEGF correlated weakly with SLEDAI ( p = 0.025). The optimum combination for differentiating active from inactive LN patients was serum VEGF, sTNF-R1, MCP-1 and glomerular filtration rate plus urinary sTNF-R1 and protein-creatinine ratio. CONCLUSION: These results indicate that for active LN, sTNF-R1 could be a useful serum cytokine marker, with potential for VEGF in the urine. This study has confirmed the ability of the multiplex bead technique to detect cytokines in a good analytical range, including very low and high levels, in both serum and urine. Combining serum and urine markers provided additional sensitivity in distinguishing active from inactive LN.

The burden of chronic pain after major head and neck tumor therapy.

INTRODUCTION: Little is known about the burden of chronic pain after major head and neck tumors' therapy. In this study, we aimed to estimate the prevalence of chronic pain, explore the factors associated with the presence of chronic pain, and assess the consequences of chronic pain on the patients' quality of life. METHODOLOGY: This was a cross-sectional survey among patients who had completed their therapy (e.g., surgery, radiotherapy, and chemotherapy) for major head and neck (larynx, nasopharynx, oropharynx, hypopharynx, oral cavity, tongue, and sinuses) tumors after at least 3 months. We collected relevant demographic and clinical data and administered the Brief Pain Inventory-Short Form, Neuropathic Pain Questionnaire-Short Form, and Pain Catastrophizing Scale questionnaires. Possible risk factors were explored using a classification tree model. RESULTS: A total of 102 patients (59 men, 42 women) were enrolled in this study between 3 and 72 months after tumor treatment. 30% of the patients reported having chronic pain after their major head and neck tumors' therapy. The average pain score in the last 24-hr was 3.4 (standard deviation = 2.7). The prevalence of patients with chronic pain was higher (42%) among those who had surgery. Factors associated with chronic pain were female sex, older age, surgery, advanced cancer stage, and radiotherapy. Patients who reported having chronic pain also reported having a lower quality of life manifested by impairments in general activity, mood, walking ability, normal work, and sleeping. Patients who reported having chronic pain had higher Pain Catastrophizing Scale scores. CONCLUSION: Our study highlighted the high burden of chronic pain after therapy for major head and neck tumors. We identified demographic and clinical factors that are associated with the presence of chronic pain. Further studies are required to better understand the risk factors to implement strategies to prevent, alleviate, and treat chronic pain associated with major head and neck tumor therapies.

Primary B-cell lymphoma of the uterine cervix: Presentation in Pap-test slide and cervical biopsy.

This case involved a 69-year-old female who presented with irritative urinary voiding. Imaging studies showed an 18-cm uterine mass centering on the cervix and extending into the bladder. The Pap test slide demonstrated necrotic background and degenerative changes in single and grouped atypical "small round blue cells" with high nuclear/cytoplasm ratio, scant cytoplasm, and hyperchromatic focally cleaved nuclei with occasional nuclear membrane "snout projections." Cervical biopsies showed similar findings. The tumor cells were positive for CD45, CD20, and PAX-5, and negative with epithelial, neuroendocrine, and muscle markers. A Ki-67 immunostain showed a markedly elevated proliferative index and the MUM1 stain was diffusely positive. Molecular study identified clonal immunoglobulin heavy chain gene rearrangement. Owing to its rarity, cervical lymphoma may sometimes be confused with other types of malignant neoplasms or inflammatory processes. Therefore, it is important to recognize the cytological features of cervical lymphomas and be aware of the potential diagnostic pitfalls for timely diagnosis and therapy. Diagn. Cytopathol. 2017;45:235-238. © 2016 Wiley Periodicals, Inc.

Undifferentiated embryonal sarcoma of the liver with an unusual presentation: case report and review of the literature.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant mesenchymal neoplasm, relatively unique to the liver that occurs primarily in children and teenagers. Delay in diagnosis is not uncommon due to lack of a characteristic clinical presentation, serological markers and radiological changes. We report a case of UESL in a 9-year-old girl who presented with right upper quadrant pain and a palpable mass. Laboratory and imaging workup revealed a complex hepatic cyst, increased IgE, transient peripheral eosinophilia and a normal alpha-fetoprotein (AFP). Initial empirical treatment with albendazole was implemented for presumed hydatid cyst disease, but the child failed to improve. Subsequent surgical resection resulted in the correct diagnosis of UESL. She received 6 months of chemotherapy and remains well with no evidence of tumor about 12 months after resection. We herein review the typical clinical, radiologic and pathologic features of this rare tumor.