PURPOSE: This study outlines CuE's cytotoxic activity against drug-resistant tumor cell lines. Three members of ABC transporters superfamily, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and ABCB5 were investigated, whose overexpression in tumors is tightly linked to multidrug resistance. Further factors of drug resistance studied were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR).
METHODS: Cytotoxicity assays (resazurin assays) were used to investigate the activity of Citrullus colocynthis and CuE towards multidrug resistant cancer cells. Molecular docking (In silico) has been carried out to explore the CuE's mode of binding to ABC transporters (P-gp, BCRP and ABCB5). The visualization of doxorubicin uptake was done by a Spinning Disc Confocal Microscope. The assessment of proteins expression was done by western blotting analysis. COMPARE and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to cucurbitacins (CuA, CuB, CuE, CuD, CuI, and CuK).
RESULTS: Multidrug-resistant cells overexpressing P-gp or BCRP were cross-resistant to CuE. By contrast, TP53 knock-out cells were sensitive to CuE. Remarkably, resistant cells transfected with oncogenic ΔEGFR or ABCB5 were hypersensitive (collateral sensitive) to CuE. In silico analyses demonstrated that CuE is a substrate for P-gp and BCRP. Immunoblot analyses highlighted that CuE targeted EGFR and silenced its downstream signaling cascades. The most striking result that emerged from the doxorubicin uptake by ABCB5 overexpressing cells is that CuE is an effective inhibitor for ABCB5 transporter when compared with verapamil. The COMPARE analyses of transcriptome-wide expression profiles of tumor cell lines of the NCI identified common genes involved in cell cycle regulation, cellular adhesion and intracellular communication for different cucurbitacins.
CONCLUSION: CuE represents a potential therapeutic candidate for the treatment of certain types of refractory tumors. To best of our knowledge, this is the first time to identify CuE and verapamil as inhibitors for ABCB5 transporter.
STUDY DESIGN: An observational study.
PLACE AND DURATION OF STUDY: Pediatric Oncology Ward, Shaukat Khanum Cancer Hospital, Lahore, from January 2015 to July 2017.
METHODOLOGY: Patients aged 1-15 years, diagnosed with ALL, were included. Studied variables were cytogenetic type and MRD outcome in patients with ALL. Patients under one year of age and more than 15 years, or those having comorbidities, were excluded.
RESULTS: Total 150 patients' data were retrieved from the Hospital database. One hundred and thirty-three belonged to age 1 to 5 years group (89%) and 17 (11%) were in 5 to 10 years group. The mean age of the patient was 4.3 +3.1 years. One hundred and two (68%) were males; whereas, 48 (32%) were females. Pre B acute lymphoblastic leukemia was diagnosed in 139 (93%) patients and 11(7%) were diagnosed with Pre T acute lymphoblastic leukemia. Standard risk was observed in 120 (80%) patients and 30 (20%) patients were on high risk as per National Cancer Institute (NCI) Guidelines. Regimen A was used in 125 (83.3%), Regimen B in 16 (10.7%), and Regimen C in 9 (6%) patients. BCR-ABL was positive in 2 (1.30%), TEL-AML in 68 (45%), MLL in 5 (3.30%), and normal in 54 (36%). MRD at day 29 was negative in 40 (93%) and positive in 3 (7%). The karyotyping was done in 128 (85%) patients, out of which 68 (53%) were hyperploids, 41 (32%) euploid, and 19 (15%) were hypoploid. Death was observed in 22 (15%) patients. Nineteen (86%) deaths were due to fungal and bacterial sepsis; and disease-related deaths were noted in 3 (14%) patients.
CONCLUSION: The role of MRD and cytogenetics in risk assessment has improved in the early prognosis determination.
METHODS: A cross-sectional market survey was conducted in 2017 of 233 sauces sold in Malaysian supermarkets. Information on the sodium content was collected from the product packaging and nutrient information panels of the sauces sold in the seven top supermarkets in the capital of Malaysia.
RESULTS: Of the 233 sauces surveyed, 116 did not include sodium content information on the nutrient information panel (49.8%). Soy sauce (particularly sweet soy sauce) and ketchup (particularly chilli sauce) were found to be the highest number of products surveyed in the analysis (N=54 and N=48, respectively). The highest sodium content information was displayed by fish/prawn sauce (budu/cencalok) (5192±3228 mg/100 g) which was followed by the light/thin soy sauce (5116±2084 mg/100 g), and followed by salty soy sauce (4780±988 mg/100 g). The sodium content information of the imported sauces was higher compared with local products produced in Malaysia. However, for sweet soy sauce, the sodium content information of the local products was higher compared with the imported products. Of the 116 sauces which displayed information regarding their sodium content, only 18.2% of the salty soy sauce and 25% of the light/thin soy sauce were found to be below the 2017 Malaysian sodium guidelines. Furthermore, only 21.7% of chilli ketchup and no tomato ketchup were below the 2017 UK salt guidelines.
CONCLUSIONS: Almost half of the sauces surveyed did not include sodium content information on the nutrient information panel. It is recommended that sodium content information is provided on all sauces sold in Malaysia. Also, manufacturers should be urged to reduce the sodium content level of their sauces to a minimum of 5%.
METHODS: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries.
RESULTS: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval.
CONCLUSIONS: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.
DATA SOURCES: A PubMed search was conducted using Clinical Queries with the key terms "Gianotti-Crosti syndrome" OR "papular acrodermatitis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. This paper is based on, but not limited to, the search results.
RESULTS: The eruption of Gianotti-Crosti syndrome is found predominantly on the cheeks, extensor surfaces of the extremities, and buttocks. There is a sparing of antecubital and popliteal fossae as well as palms, soles, and mucosal surfaces. Although often asymptomatic, the lesions may be mildly to moderately pruritic. Gianotti-Crosti syndrome is most common in children between 1 and 6 years of age. The Epstein-Barr virus and the hepatitis B virus are the most common pathogens associated with Gianotti-Crosti syndrome. No treatment for Gianotti-Crosti syndrome is necessary because it is self-limited. In an era of vaccine hesitancy and refusal, Gianotti-Crosti syndrome may be important to mention to parents, because it can occur and trigger alarmism.
CONCLUSIONS: Gianotti-Crosti syndrome is mainly a disease of early childhood, characterized by an acute onset of a papular or papulovesicular eruption with a symmetrical distribution. With the advent of more universal vaccination against hepatitis B virus, Epstein-Barr virus has become the most common etiologic agent of Gianotti-Crosti syndrome. Few cases of post-vaccination Gianotti-Crosti syndrome have been reported. Currently, the emphasis should be placed on its self-limiting attribution.
OBJECTIVE: To review the prevalence of illness, stress, and corresponding risk factors among educators in Malaysia.
METHOD: Scopus, ProQuest, PubMed, ScienceDirect, CAB, and other computerized databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies published between January 2013 and April 2019 on the prevalence and associated risk factors of illness and stress among educators (S1 Checklist). The keywords used included educator, teacher, lecturer, academic staff, teaching profession, university staff, academician, faculty, illness, injury, disease, pain, WMSD, dysphonia, hoarseness, stress, mental health, strain, health problem, disorder, and/or Malaysia. Selected studies were evaluated by quality assessment.
RESULTS: Twenty-two articles fulfilled the eligibility criteria. The prevalence of illness and stress was determined for low back pain (33.3-72.9%); upper back pain (33.33-56.4%); neck/shoulder pain (40.4-80.1%); upper arm discomfort (91.3%); forearm pain (89.6%); wrist pain (16.7-93.2%); hip pain (13.2-40.9%); thigh discomfort (91.8%); lower leg discomfort (90.5%); knee pain (23.7-88.0%); ankle/feet pain (19.3-87.7%); elbow pain (3.5-13.0%); voice disorder (10.4-13.0%) and stress (5.5-25.9%). Sex, education level, teaching experience, quality of life, anxiety, depression, coping styles, and others were reported as associated risk factors across the studies.
CONCLUSIONS: There appears to be a cause for concern regarding musculoskeletal disorders, voice disorder, and stress reported among educators in Malaysia. While most risk factors matched those reported in studies elsewhere, others such as school characteristics (school level, government or private school, and location [rural/urban]) have not been investigated.