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Background Chronic liver disease (CLD) is one of the most significant causes of morbidity and mortality among the pediatric age group. The identification of the etiology of the disease is of utmost importance for the effective management of the disease. Objective To determine the various causes of CLD in pediatric patients attending a large public sector pediatric hospital. Patients and methods A prospective cross-sectional study was conducted at the National Institute of Child Health, Karachi, Pakistan from August 1, 2021, to February 28, 2022. All patients below 16 years of age of either gender with more than three months of symptoms duration on admission were enrolled. The diagnosis was labeled after the standard reference ranges for the pediatric age group. Results Of 136 patients, the mean age was 4.42 ± 3.92 years. More than half of the patients were males (76, 55.9%). Hepatitis B (31, 22.8%), idiopathic (23, 16.9%), glycogen storage disorder (GSD) (21, 15.4%), and Wilson disease (14, 10.3%) were the most common cause of CLD. A significant association of hepatitis was observed with age (p-value < 0.001), residence (p-value = 0.048), symptomatic (p-value < 0.001), total bilirubin level (p-value = 0.003), direct bilirubin level (p-value = 0.002), and albumin level (p-value = 0.003). Whereas a significant association of GSD was observed with age (p-value = 0.001), residence (p-value < 0.001), and serum glutamic pyruvic transaminase (SGPT) level (p-value = 0.033). Conclusion In our cohort, hepatitis B, idiopathic, GSD, and Wilson disease were the most common causes of CLD in pediatric patients. Moreover, age, residence, symptomatic, total bilirubin level, direct bilirubin level, SGPT, and albumin level were the important predictor variables.

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We aimed to examine the association between soft drink consumption and asthma and lung function among Qatari adults. In the cross-sectional study, we used data from 986 Qatari participants aged 20 years and above attending the Qatar Biobank Study. Usual consumption of soft drink was assessed using a food frequency questionnaire. Lung function was measured by spirometry and asthma was based on self-report. The associations between soft drink consumption and asthma and lung function were assessed using multivariable logistic and linear regression, respectively. In total, 65 participants out of 986 (6.6%) reported having asthma. A clear dose-response relationship between soft drink consumption and asthma was found. High soft drink consumers (≥7 times/week) were 2.60 (95% CI 1.20⁻5.63) times more likely to have asthma as compared to non-consumers. The association was partly mediated by BMI and inflammation. Diet soft drink consumption was positively associated with asthma (OR 1.12 (95% CI 1.02⁻1.23)) but not with lung function. Regular soft drink consumption was inversely associated with FEV1, but not with FVC. In conclusion, soft drink consumption is positively associated with asthma in Qatari adults. The association is partly mediated by obesity and inflammation. Limiting soft drink consumption should be taken into consideration for asthma prevention.

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Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(η(5) -Cp(xbiph) )Ir(phpy)(Cl)] (1-Cl), which contains π-bonded biphenyltetramethylcyclopentadienyl (Cp(xbiph) ) and C^N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(η(5) -Cp(xbiph) )Ir(phpy)(py)](+) (1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2 O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy.

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Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (Ir(III)) complexes [Ir(Cp(x))(XY)Cl](+/0) (Cp(x) = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cp(x) ring. In comparison, highly potent complex 4 (Cp(x) = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these Ir(III) complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 µM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic Ir(III) complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands.

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Artificial enzymes: half-sandwich arene ruthenium(II) and cyclopentadienyl iridium(III) complexes containing N,N-chelated ligands can use NADH as a source of hydride for the reduction of ketones. Moreover, cyclopentadienyl phenanthroline iridium(III) derivatives at micromolar concentrations are robust catalysts for the production of H(2) from NADH in water and can raise the NAD(+)/NADH ratio in cancer cells.

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