Association between granzyme B and perforin I polymorphisms and allograft outcomes in Hispanic kidney transplant recipients

Granzyme B (GZMB) and perforin 1 gene (PRF1) are key effector molecules of cytotoxic T lymphocytes, in causing acute and chronic solid organ transplant rejection. In this study, we analyzed the impact of GZMB and PRF1 polymorphism on kidney allograft outcomes. In all, 527 de novo kidney Hispanic allograft recipients were genotyped for PRF1 (rs10999426, rs35947132) and GZMB (rs8192917, rs7144366). PRF1 (rs10999426, rs35947132) G alleles and GG genotypes were negatively associated with allograft rejection, demonstrating protection against allograft rejection (OR = 0.61, p = 0.005 for rs1099946; OR = 0.4, p = 0.01 for rs 35947132). On the other hand, the GA heterozygosity of PRF1 was found marginally associated with the rejection group (OR = 1.53, p = 0.05 for rs10999426; OR = 2.24, p = 0.07 for rs35947132). There was a significant increase in allograft survival in time period studied for the PRF1 (rs10999426) GG genotype, while the GA heterozygosity was associated with graft failure. We found no association for polymorphic markers in GZMB gene with allograft rejection. Survival was significantly improved for patients who were homozygous TT for the GZMB (rs8192917) (TT vs. CC/TT, p = 0.041). The result suggests that PRF1 and GZMB gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.     

Variation in surface properties,metabolic capping,and antibacterial activity of biosynthesized silver nanoparticles: comparison of bio-fabrication potential in phytohormone-regulated cell cultures and naturally grown plants

We compared surface properties, metabolic capping and antibacterial activity of silver nanoparticles, synthesized through extracts of cell cultures of Fagonia indica and its naturally grown form. Extracts from cell cultures (produced with thidiazuron (TDZ) or melatonin (MLN)) were compared to the naturally grown whole plant extracts (WPEs) for their reducing potential, and their effects on physical and biochemical properties of the biosynthesized silver nanoparticles. UV-Vis spectroscopy revealed that the surface plasmon resonance peaked at λ = 415 nm for MLN-AgNPs, λ = 430 nm for TDZ-AgNPs and λ = 460–465 nm for WPE-AgNPs. Transmission electron microscopy and energy dispersive X-rays of AgNPs showed that compared to WPE-AgNPs (mean diameter = 22 nm), extracts from MLN- and TDZ-induced cell cultures produced particles with spherical shapes and smaller diameters (i.e. mean diameter = 15 nm and 19 nm, respectively). Size distribution analysis also showed that TDZ-AgNPs were nearer to a symmetric distribution in terms of diameter (skewness = 0.80) as compared to WPE-AgNPs (skewness = 0.9) and MLN-AgNPs (skewness = 1.4). Furthermore, MLN-induced cell culture extracts produced AgNPs in higher concentration (210 μg mL⁻¹) compared to AgNPs from TDZ-induced cell culture extracts (160 μg mL⁻¹) and WPE (138 μg mL⁻¹). Two-way comparisons of LC-MS/MS profiles of TDZ-AgNPs, MLN-AgNPs, and WPE-AgNPs revealed differences in their secondary metabolite profiles, which might account for differences in their differential response in bio-fabrication, and size distribution. Activity against different pathogenic bacterial strains, Escherichia coli, Bacillus cereus, Xanthomonas citri, Agrobacterium tumefaciens, Streptomyces griseus, and Erwinia carotovora suggested that MLN-AgNPs were more effective compared to TDZ- and WPE-AgNPs. These results indicated that phytohormones induced cell cultures can enhance the production, physical and biochemical properties of AgNPs.

We compared surface properties, metabolic capping and antibacterial activity of biosynthesized silver nanoparticles, synthesized through extracts of cell cultures of Fagonia indica and its naturally grown form.     

Evaluation of the antiparasitic activities of imidazol-2-ylidene–gold(I) complexes

A series of cationic gold(I)–carbene complexes with various 4,5-diarylimidazolylidene ligands were either newly prepared or repurposed for testing against protozoal Leishmania major, Toxoplasma gondii, and Trypanosoma brucei parasites. The syntheses of the new complexes 1b and 1c were described. Ferrocene compound 1a showed the highest activities against L. major amastigotes and T. gondii and distinct selectivity for T. gondii cells when compared with the activity against nonmalignant Vero cells. The ferrocene derivatives 1a–c are generally more active against the L. major amastigotes and the T. gondii tachyzoites than the other tested anisyl gold complexes and the approved drugs atovaquone and amphotericin B. Compounds 1a and 1e showed the highest selectivities for L. major amastigotes. Compounds 1d and 1f showed the highest selectivities for L. major promastigotes; 1f was the most active compound against L. major promastigotes of this series of compounds. The 3,4,5-trimethoxyphenyl analog 1b also exhibited a much greater selectivity for T. b. brucei cells when compared with its activity against human HeLa cells.     

Relationship of Right Ventricular Size and Function with Respiratory Status in Duchenne Muscular Dystrophy

The relationship between pulmonary function and right ventricle (RV) in Duchenne muscular dystrophy (DMD) has not been evaluated. Using cardiac magnetic resonance (CMR), we describe the relationship of RV size and function with spirometry in a DMD cohort. Fifty-seven boys undergoing CMR and pulmonary function testing within 1 month at a single center (2013–2015) were enrolled. Comparisons of RV ejection fraction (RVEF) and end-diastolic volume index (RVEDVI) were made across categories of percent forced vital capacity (FVC%), and relationships were assessed. Mean age was 15.5 ± 3.5 years. Spirometry and CMR were performed within 3.9 ± 4.1 days. Median FVC% was 92.0 % (67.5–116.5 %). Twenty-three (40 %) patients had abnormal FVC% (<80 %) of which 13 (57 %) had mild (FVC% 60–79 %), 6 (26 %) had moderate (FVC% 40–59 %), and 4 (17 %) had severe (FVC <40 %) reductions. Mean RVEF was 58.3 ± 3.7 %. Patients with abnormal FVC% were older and had lower RVEF and RVEDVI. Both RVEF and RVEDVI were significantly associated with FVC% (r = 0.31, p = 0.02 and r = 0.39, p = 0.003, respectively). In a large DMD cohort, RVEF and RVEDVI were related to FVC%. Worsening respiratory status may guide monitoring of cardiac function in these patients.     

Work related injuries in Qatar: a framework for prevention and control

Work related injuries (WRIs) are a growing public health concern that remains under-recognized, inadequately addressed and largely unmeasured in low and middle-income countries (LMIC’s). However, even in high-income countries, such as those in Gulf Cooperating Council (GCC) like Qatar, there are challenges in assuring the health and safety of its labor population. Countries in the GCC have been rapidly developing as a result of the economic boom from the petrochemical industry during the early seventies. Economic prosperity has propelled the migration of workers from less developed countries to make up for the human resource deficiency to develop its infrastructure, service and hospitality industries. Although these countries have gradually made huge gains in health, economy and human development index, including improvements in life expectancy, education, and standard of living, there remains a high incidence of work-related injuries especially in jobs in the construction and petrochemical sector. Currently, there is scarcity of literature on work-related injuries, especially empirical studies documenting the burden, characteristics and risk factors of work injuries and the work injured population, which includes large numbers of migrant workers in many GCC countries. This paper will focus on the current understanding of WRIs in those countries and identify the gaps in current approaches to workplace injury prevention, outlining current status of WRI prevention efforts in Qatar, and propose a framework of concerted action by multi-sectoral engagement.