A regional virtual case discussion forum in pediatric oncology: Experience of the Pediatric Oncology East and Mediterranean Group.

BACKGROUND: The Pediatric Oncology East and Mediterranean (POEM) group that aims to share expertise among pediatric oncology providers across the Middle East, North Africa, and East Asia region initiated a virtual Case Discussion Forum (CDF) in 2013. METHODS: Meeting records from September 2013 till June 2021 were reviewed. Detailed minutes were available starting August 2016; case data were analyzed including diagnoses, purpose of presentation and recommendations. A 38-item survey assessing perception of benefits, challenges, and opportunities of the forum was distributed to members of the POEM group and results analyzed. RESULTS: A total of 140 cases were presented from 14 countries. After August 2016, 67 cases were presented, and those were analyzed regarding reasons for discussion, barriers, and recommendations. Details are presented in this report, and the most common challenges identified were related to histopathologic/molecular diagnosis (24%), imaging interpretation (18%), resource limitations (12%), and surgical difficulties (9%). A survey was distributed to all POEM members in 28 countries, and 76 responded. The main benefit reported was the provision of recommendations regarding treatment and evaluation, while the main challenges reported were time zone difference and workload. Recognized opportunities included conducting regionally relevant research studies based on clinical problems identified during discussions, and setting guidelines for resource-adapted treatment regimens. CONCLUSIONS: The POEM CDF identified areas for multi-institutional regional studies and led to a twinning project between two centers in the region for improving diagnostic infrastructure. Such forums can identify specific resource limitations in pediatric cancer and direct efforts for targeted capacity building.

It is the time for quorum sensing inhibition as alternative strategy of antimicrobial therapy.

Multiple drug resistance poses a significant threat to public health worldwide, with a substantial increase in morbidity and mortality rates. Consequently, searching for novel strategies to control microbial pathogenicity is necessary. With the aid of auto-inducers (AIs), quorum sensing (QS) regulates bacterial virulence factors through cell-to-cell signaling networks. AIs are small signaling molecules produced during the stationary phase. When bacterial cultures reach a certain level of growth, these molecules regulate the expression of the bound genes by acting as mirrors that reflect the inoculum density.Gram-positive bacteria use the peptide derivatives of these signaling molecules, whereas Gram-negative bacteria use the fatty acid derivatives, and the majority of bacteria can use both types to modulate the expression of the target gene. Numerous natural and synthetic QS inhibitors (QSIs) have been developed to reduce microbial pathogenesis. Applications of QSI are vital to human health, as well as fisheries and aquaculture, agriculture, and water treatment. Video Abstract.

The Psychosocial Impact of the COVID-19 Pandemic on Families of Children With Cancer in the Low-income Setting.

The coronavirus disease 2019 (COVID-19) pandemic has had a profound effect on families' psychosocial well-being worldwide. This study aimed to investigate the pandemic's impact on families of children with cancer in a low-income setting in Syria. The study conducted a cross-sectional survey of 50 families of children with cancer receiving treatment at a nongovernmental organization-based pediatric oncology unit in Syria. The survey used the Corona Anxiety Scale (CAS) to assess the pandemic's impact on families' anxiety, and other items to evaluate the financial toxicity of the strict measures implemented during the pandemic's first months. The study's results revealed that the COVID-19 pandemic significantly negatively impacted the psychosocial well-being of families of children with cancer in Syria. Specifically, 22% of families reported a major increase in anxiety levels (CAS of >9), and the majority of families (84%) reported excessive indirect financial costs, including travel and living expenses. The study emphasizes the significant social and psychological impact of the COVID-19 pandemic on families of children with cancer in Syria, highlighting the need for additional psychosocial interventions to mitigate future global health crises or pandemics' impact on this vulnerable population. The interventions should prioritize promoting resilience and adaptive coping strategies.

Optimization of melanin pigment production from the halotolerant black yeast Hortaea werneckii AS1 isolated from solar salter in Alexandria.

BACKGROUND: Melanins are one of the magnificent natural pigments synthesized by a wide range of microorganisms including different species of fungi and bacteria. Marine black yeasts appear to be potential prospects for the synthesis of natural melanin pigment. As a result, the goal of this research was to isolate a marine black yeast melanin-producing strain and improve the culturing conditions in order to maximize the yield of such a valuable pigment. RESULTS: Among five locally isolated black yeast strains, the only one that demonstrated a potent remarkable melanin pigment production was identified using ITS rDNA as Hortaea werneckii AS1. The extracted pigment's physiochemical characterization and analytical investigation with Ultraviolet-Visible (UV) spectrophotometry, Fourier Transform-Infrared spectroscopy (FTIR), and Scanning Electron Microscope (SEM) confirmed its nature as a melanin pigment. The data obtained from the polynomial model's maximum point suggested that CaCl2, 1.125 g/L; trace element, 0.25 ml/L; and a culture volume 225 mL/500 mL at their optimal values were the critical three elements impacting melanin production. In comparison with the baseline settings, the response surface methodology (RSM) optimization approach resulted in a 2.0 - fold improvement in melanin output. CONCLUSIONS: A maximum melanin yield of 0.938 g/L proved the halotolerant H. werneckii AS1 potentiality as a source for natural melanin pigment synthesis 'when compared to some relevant black yeast strains' and hence, facilitating its incorporation in a variety of pharmaceutical and environmental applications.

Molecular cloning, heterologous expression, and in silico sequence analysis of Enterobacter GH19 class I chitinase (chiRAM gene).

BACKGROUND: Using in silico sequence analyses, the present study aims to clone and express the gene-encoding sequence of a GH19 chitinase from Enterobacter sp. in Escherichia coli. METHODS AND RESULTS: The putative open reading frame of a GH19 chitinase from Enterobacter sp. strain EGY1 was cloned and expressed into pGEM®-T and pET-28a (+) vectors, respectively using a degenerate primer. The isolated nucleotide sequence (1821 bp, GenBank accession no.: MK533791.2) was translated to a chiRAM protein (606 amino acids, UniProt accession no.: A0A4D6J2L9). The in silico protein sequence analysis of chiRAM revealed a class I GH19 chitinase: an N-terminus signal peptide (Met1-Ala23), a catalytic domain (Val83-Glu347 and the catalytic triad Glu149, Glu171, and Ser218), a proline-rich hinge region (Pro414 -Pro450), a polycystic kidney disease protein motif (Gly 465-Ser 533), a C-terminus chitin-binding domain (Ala553- Glu593), and conserved class I motifs (NYNY and AQETGG). A three-dimensional model was constructed by LOMETS MODELLER of PDB template: 2dkvA (class I chitinase of Oryza sativa L. japonica). Recombinant chiRAM was overexpressed as inclusion bodies (IBs) (~ 72 kDa; SDS-PAGE) in 1.0 mM IPTG induced E. coli BL21 (DE3) Rosetta strain at room temperature 18 h after induction. Optimized expression yielded active chiRAM with 1.974 ± 0.0002 U/mL, on shrimp colloidal chitin (SCC), in induced E. coli BL21 (DE3) Rosetta cells growing in SB medium. LC-MS/MS identified a band of 72 kDa in the soluble fraction with a 52.3% coverage sequence exclusive to the GH19 chitinase of Enterobacter cloacae (WP_063869339.1). CONCLUSIONS: Although chiRAM of Enterobacter sp. was successfully cloned and expressed in E. coli with appreciable chitinase activity, future studies should focus on minimizing IBs to facilitate chiRAM purification and characterization.

Methoxyisoflavan derivative from Trigonella stellata inhibited quorum sensing and virulence factors of Pseudomonas aeruginosa.

The number of deaths caused by multidrug-resistant Pseudomonas aeruginosa has risen in the recent decade. The development of quorum sensing inhibition (QSI) is a promising approach for controlling Pseudomonas infection. Therefore, this study mainly aimed to investigate how a plant-source material inhibits QSI to produce an antipathogenic effect for fighting microbial infections. The QSI effect of Trigonella stellata was assessed by using Chromobacterium violaceum ATCC 12472 reporter strain. Trigonella stellata exhibited high QSI activity, and an ethanolic extract of T. stellata was prepared for phytochemical isolation of the most active QSI compound. Nine pure compounds were isolated and identified as kaempferitrin (1), soyasaponin I (2), ß-sitosterol-3-O-glucoside (3), dihydromelilotoside (4), astrasikokioside I (5), methyl dihydromelilotoside (6), (3R, 4S)-4, 2', 4'-trihydroxy-7-methoxy-4'-O-ß-D-glucopyranosylisoflavan (7), (3S, 4R)-4, 2', 4'-trihydroxy-7-methoxyisoflavan (8, TMF), and (+)-D-pinitol (9). These compounds were screened against C. violaceum ATCC 12472, and TMF exhibited a potent QSI. The effect of TMF at sub-minimum inhibitory concentrations (MICs) was assessed against P. aeruginosa virulence factors, including biofilm, pyocyanin formation protease and hemolysin activity. TMF induced significant elimination of QS-associated virulence behavior. In addition, TMF at sub-MICs significantly reduced the relative expression of lasI, lasR, rhlI, and rhlR compared with that in untreated cells. Furthermore, molecular docking was performed to predict structural basis of the QSI activity of TMF. The study demonstrated the importance of T. stellata as a signal modulator and inhibitor of P. aeruginosa pathogenesis.

Occurrence and ecotoxicological risk assessment of pesticides in sediments of the Rosetta branch, Nile River, Egypt.

This study aimed to (1) monitor the occurrence and spatiotemporal variations of 100 pesticides in sediments collected monthly from July 2018 to June 2019 from sampling sites in El-Rahawy, Sabal, and Tala, along the Rosetta branch of the Nile River, Egypt, and (2) perform an ecological risk assessment for aquatic organisms upon exposure to the detected sediment pesticides based on the risk quotient (RQ) method. Out of the 100 pesticides monitored, 16 pesticides belonging to seven chemical families were detected, and 55% of the sediment samples were contaminated with one or more pesticide residues. The mean concentration (mg/kg dry weight (dw)) and detection frequency (%) of the four most frequently detected pesticides in the sediment samples were as follows: chlorpyrifos (0.18 mg/kg dw and 34%), p,p'-DDE (0.018 mg/kg dw and 30%), cypermethrin (0.03 mg/kg dw and 14%), and deltamethrin (0.026 mg/kg dw and 13%). The spatial distribution exhibited that El-Rahawy had the highest pesticide load (2.86 mg/kg dw) among the studied sites, whereas the temporal variations revealed that the highest total pesticide concentrations were detected in winter season (1.73 mg/kg dw). Meanwhile, 12 pesticides showed high RQs (>1), posing a potential ecological risk to aquatic species that live and feed on such sediments.

Treatment-induced cerebral sinus venous thrombosis in childhood acute lymphoblastic malignancies: New risk factors to consider.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is one of the many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, and consensus management, no recommendations exist to target the population at risk. METHODS: This is a retrospective chart review of 229 consecutive patients diagnosed with ALL with an age range of 1-21 years, treated at the Children's Cancer Center of Lebanon between October 2007 and February 2018. RESULTS: The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high-risk disease, maximum triglyceride (TG) level of >615 mg/dl, presence of mediastinal mass, and larger body surface area (BSA). With multivariate analysis, the only statistically significant risk factors were maximum TG level, BSA, presence of mediastinal mass, and risk stratification (intermediate/high risk). CONCLUSION: Our study was able to unveil TG level of >615 mg/dl, mediastinal mass, and a larger BSA as novel risk factors that have not been previously discussed in the literature.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.

Isolated Central Nervous System Relapse Following Treatment Reduction in Low-risk Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon.

The aim of this trial was to decrease the incidence of life-threatening infections by decreasing the dose and the duration of dexamethasone treatment during maintenance therapy. This was a prospective, nonrandomized trial of low-risk acute lymphoblastic leukemia patients 1 to 18 years of age who were treated at the Children's Cancer Center of Lebanon (CCCL). Patients consecutively diagnosed between 2002 and 2013 were divided into groups 1 and 2 receiving total dexamethasone doses of 1144 and 618 mg/m, respectively. A total of 84 patients were assigned to group 1 and 33 patients to group 2. The 5-year cumulative incidence of isolated central nervous system relapse increased from (n=0% [95% confidence interval: 0%-4.4%]) in group 1 to 9.1% [95% confidence interval: 3%-23%]; P=0.021) in group 2. Decreasing cumulative dose of dexamethasone for low-risk childhood acute lymphoblastic leukemia patients aiming to avoid serious viral infections led to a significant increase in isolated central nervous system relapse.

Port-a-Cath fracture and migration in paediatric cancer patients: incidence and management at a tertiary care centre - a 15-year experience.

INTRODUCTION: Port-a-Cath or chemoport provides prolonged central venous access for cancer patients requiring prolonged chemotherapy. Prolonged use of chemoport is associated with many complications. Dislodgement and migration of chemoport catheter is a rare and reportable complication with potentially serious consequences. METHODS: The medical charts of 1222 paediatric cancer patients admitted to the Children's Cancer Center in Lebanon who had chemoports inserted for long-term chemotherapy were retrospectively reviewed. Descriptive analysis of data was conducted. RESULTS: Chemoport fracture and migration were found in seven cases with an incidence of 0.57%. The duration of chemoport use before the event of dislodgement varied from 2 months to 102 months. Non-functioning chemoport was the most common presentation. Totally, six cases were managed successfully by loop snaring, three cases by paediatric cardiology team, and three cases by interventional radiology team. One case was managed surgically during chemoport removal. CONCLUSION: Fracture and migration of chemoport catheter is a rare complication of uncertain aetiology and with potentially serious consequences. Percutaneous retrieval, done by experienced cardiologist or interventional radiologist, is the first choice for management of this complication as it is considered as a safe and effective approach.

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome.

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age-adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.

Genetic polymorphisms in candidate genes are not associated with increased vincristine-related peripheral neuropathy in Arab children treated for acute childhood leukemia: a single institution study.

OBJECTIVE: The aim of this study was to evaluate the potential association between candidate genetic polymorphisms and vincristine-related peripheral neuropathy in Arab children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: This is a retrospective evaluation of 133 Arab children treated for ALL at the Children's Cancer Center of Lebanon. Incidence and severity of, as well as the timing (in weeks) at which grade 2 or higher peripheral neuropathy occurred were recorded. Genotyping for ABCB1 (rs1045642), ABCB1 (rs1128503), ABCC2 (rs717620), CEP72 (rs924607), ETAA1 (rs17032980), and MTNR1B (rs12786200) was performed. RESULTS: A total of 26 (19.5%) individuals developed peripheral neuropathy, three of which occurred during the induction phase. No statistically significant associations were revealed for any of the polymorphisms with either incidence of vincristine-related toxicity, toxicity severity, or time to the first episode of grade 2 or higher vincristine-related peripheral neuropathy. CONCLUSION: This study presents the first pharmacogenetic analysis of vincristine-related peripheral neuropathy in children with ALL in an Arab country. We have shown that genetic polymorphisms in candidate genes are not associated with peripheral neuropathy secondary to chronic therapy with high-dose vincristine (2 mg/m) during the continuation phase. Concerning CEP72, our results are in line with the findings from the St Jude cohort of children treated for ALL with higher vincristine doses during chronic treatment. Larger high-throughput genetic analyses may be warranted to evaluate variants in other candidate genes such as CYP3A5 and reveal new nonpreviously reported alleles that may be peculiar to this region of the world.

Production of di-(2-ethylhexyl) phthalate by Bacillus subtilis AD35: Isolation, purification, characterization and biological activities.

The emergence of extensive antibiotics resistant bacteria increased the demands for finding out new sources of antimicrobial agents. Marine niches were reported to be rich in many competent producers of significant bioactive compounds. On the course of screening program for new antimicrobials, a Bacillus strain was isolated from Alexandria sea shores, Egypt. According to the morphological, cultural and biochemical characteristics, 16S rRNA sequence analysis and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), the strain was identified as Bacillus subtilis and designated as B. subtilis AD35. One phthalate derivative namely Di-(2-ethylhexyl) phthalate (DEHP) was purified from the crude extract of B. subtilis AD35 by high performance liquid chromatography (HPLC) and the structural elucidation of this compound was confirmed on the basis of gas chromatography-mass spectroscopy (GC-MS), Fourier infrared spectroscopy (FT-IR) and UV spectrum. The results of MIC of the purified DEHP were as follow: 16 µg/ml (Salmonella typhimurium), 32 µg/ml (Methicillin resistant Staphylococcus aureus, MRSA), 0.25 µg/ml (Listeria monocytogenes), 0.5 µg/ml (Aeromonas hydrophila), 8 µg/ml (Staphylococcus aureus), 4 µg/ml (Staphylococcus epidermidis), 4 µg/ml (Escherichia coli), and 8 µg/ml (Pseudomonas aeruginosa). DEHP produced by B. subtilis AD35 up to a concentration of 2500 µg/ml exhibited no cytotoxic effect against normal Vero cells. In addition, it did not show an antiviral activity against HAV or a significant growth inhibitory effect toward human colorectal adenocarcinoma and human mammary gland adenocarcinoma cell-lines.

Statistically optimized ceftriaxone sodium biotransformation through Achromobacter xylosoxidans strain Cef6: an unusual insight for bioremediation.

The present study underlines a unique promising approach toward efficient biotransformation of ceftriaxone sodium (Ceftx), a highly frequent prescribed cephalosporin antibiotic, by a newly bacterium namely Achromobacter xylosoxidans strain Cef6 isolated from Ceftx contaminated raw materials in pharmaceutical industries. A three step sequential statistical-mathematical approach (Plackett-Burman design [PBD], Central Composite Design [CCD], and ridge-canonical analyses) was anticipated to optimize the biotransformation process. Ceftx concentration and medium volume: bottle volume ratio, two key determinants, significantly (p < 0.05) affected the process outcome deduced by regression analysis of PBD' data. CCD and ridge-canonical analyses localized the optimal levels of Ceftx concentration and medium volume: 250 ml bottle volume ratio to be 0.39 and 7.973 g Ceftx/L modified tryptic soy broth achieving Ceftx biotransformation (100%) after 39 h under aerobic static conditions at 30 °C, irrespectively deduced via HPLC analysis. Impressively, only one of five Ceftx byproducts was detected by the end of the biotransformation process. To the best of authors' knowledge, this is the first report addressing a detailed study regarding efficient biotransformation of Ceftx by single bacterium not bacterial consortium under aerobic conditions. Present data would greatly encourage applying this approach for decontamination of some Ceftx contaminated environmental sites.

Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No available consensus exists regarding its risk factors and appropriate management due to the rarity of cases. PROCEDURES: Out of 209 ALL patients aged 1-21 years treated at the Children's Cancer Center of Lebanon between May 2002 and May 2015, 13 developed CSVT during therapy. Patient characteristics, clinical management, and outcomes were studied. RESULTS: The incidence of CSVT was 6.2% (95% confidence interval [CI]: 3.4-10.4). Using univariate analysis, increased risk of CSVT was observed with age >10 years (odds ratio [OR]: 3.56, 95% CI: 1.13-11.2), T-cell immunophenotype (OR: 4.14, 95% CI: 1.16-14.7), and intermediate/high risk disease (OR: 3.4, 95% CI: 1.03-11.7). The only statistically significant risk factor by multivariate analysis was the treatment as per the intermediate-/high-risk protocol (HR: 15.6, 95% CI: 1.43-171.3). Most cases (77%) occurred in the postinduction phases of treatment while receiving a combination of asparaginase and dexamethasone rather than prednisone. Treatment with low molecular weight heparin (LMWH) for a minimum of 3 months and until significant radiological improvement is observed resulted in 100% survival rate. All but one patient had complete neurological recovery. CONCLUSIONS: CSVT is an important complication of childhood ALL therapy. Postinduction combined asparaginase and dexamethasone intensive treatment for intermediate-/high-risk patients was the most important risk factor. Treatment with LMWH for a minimum of 3 months, and until asparginase therapy is over, with major radiological improvement seems to be effective and feasible.

NUDT15 and TPMT genetic polymorphisms are related to 6-mercaptopurine intolerance in children treated for acute lymphoblastic leukemia at the Children's Cancer Center of Lebanon.

BACKGROUND: Interindividual variability in thiopurine-related toxicity could not be completely explained by thiopurine S-methyltransferase (TPMT) polymorphisms, as a number of patients who are homozygous wild type or normal for TPMT still develop toxicity that necessitates 6-mercaptopurine (MP) dose reduction or protocol interruption. Recently, few studies reported on an inherited nucleoside diphosphate-linked moiety X motif 15 (NUDT15) c.415C>T low-function variant that is associated with decreased thiopurine metabolism and leukopenia in childhood acute lymphoblastic leukemia (ALL) and other diseases. PROCEDURES: The aim of this study is to measure the frequency of TPMT and NUDT15 polymorphisms and assess whether they are predictors of MP intolerance in children treated for ALL. One hundred thirty-seven patients with ALL of whom 121 were Lebanese were evaluated. MP dose intensity was calculated as the ratio of the tolerated MP dose to planned dose during continuation phase to maintain an absolute neutrophil count (ANC) dose above 300 per µl. RESULTS: One patient was NUDT15 heterozygous TC and tolerated only 33.33% of the planned MP dose, which was statistically significantly different from the median-tolerated MP dose intensity of the rest of the cohort (76.00%). Three patients had the TPMT*3A haplotype and tolerated 40.00-66.66% of the planned MP dose, which was also statistically significantly different from the rest of the cohort. CONCLUSIONS: This is the first report on the association of TPMT and NUDT15 polymorphisms with MP dose intolerance in Arab patients with ALL. Genotyping for additional polymorphisms may be warranted for potential gene/allele-dose effect.

Metal Ion Removal from Wastewaters by Sorption on Activated Carbon, Cement Kiln Dust, and Sawdust.

This study assessed the efficiency of activated carbon, cement kiln dust (CKD), and sawdust for the removal of cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn) from aqueous solutions under mono-metal and competitive sorption systems and the removal of Cd, Cu, and Zn from different industrial wastewaters. Batch equilibrium experiments were conducted in a mono-metal and competitive sorption system. The efficiency of the sorbents in the removal of Cd, Cu, and Zn from industrial wastewaters was also investigated. Cement kiln dust expressed the highest affinity for the metals followed by activated carbon and sawdust. Competition among the metals changed their distribution coefficient (Kd) with the sorbents. Sorption of Pb and Cu was higher than Cd and Zn. The average metal removal from the wastewaters varied from 74, 61, and 60% for Cd, Cu, and Zn, respectively, to nearly 100%. The efficiencies of CKD and activated carbon in removing metals were higher than sawdust, suggesting their potential as low-cost sorbents for the removal of toxic metals from wastewaters.

Acute lymphoblastic leukemia in low and middle-income countries: disease characteristics and treatment results.

PURPOSE OF REVIEW: Acute lymphoblastic leukemia is the most common pediatric cancer. The cure rate of this disease is over 80% in developed countries utilizing protocols with very tolerable toxicity. Several factors contributed to this success, including the implementation of large collaborative clinical trials and the better understanding of disease biology allowing for risk-stratified treatment. We will review the current state of the treatment of acute lymphoblastic leukemia in low-income and medium-income countries. RECENT FINDINGS: The picture differs from country to country, but recent advances have been made in many countries and the cure rates have improved significantly. Tackling problems such as access to care, abandonment of treatment and toxicity of protocols and the development of centers of excellence are critical for continued improvement. Twinning with programs in developed countries and the creation of regional collaborative groups will allow the implementation of risk-directed therapy and better supportive care. SUMMARY: The experience in low-income countries shows that a structured approach to the treatment of acute lymphoblastic leukemia results in improved survival.