The influence of polymorphisms in the drug transporter,ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia

Background

Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL.

Neural gain control measured through cortical gamma oscillations is associated with sensory sensitivity

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations. Recent studies in humans and nonhuman primates have shown that strong excitatory drive to the visual cortex leads to suppression of induced gamma oscillations, which may reflect inhibitory‐based gain control of network excitation. The efficiency of the gain control measured through gamma oscillations may in turn affect sensory sensitivity in everyday life. To test this prediction, we assessed the link between self‐reported sensitivity and changes in magneto‐encephalographic gamma oscillations as a function of motion velocity of high‐contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally elevated sensory sensitivity. We conclude that intensity‐related suppression of gamma response is a promising biomarker of homeostatic control of the excitation–inhibition balance in the visual cortex.     

Sleep disturbances in 22q11.2 deletion syndrome: a case with obstructive and central sleep apnea.

The 22q11.2 deletion syndrome is characterized by wide phenotypic variability, frequently involving characteristic craniofacial features, cardiac malformations, and learning difficulties. Skeletal anomalies are also common and include an obtuse angle of the cranial base, retrognathia, and cervical spine abnormalities. Despite these anomalies, sleep-disturbed breathing is not reported frequently in patients with 22q11.2 deletion syndrome. We describe a patient with an obstructive sleep disturbance that was successfully treated with a tonsillectomy followed by mandibular distraction osteogenesis. She also had central sleep apnea, initially attributed to spinal cord impingement from cervical instability. Posterior cervical fusion was associated with a decrease in the number of central apneic events.     

Factors pivotal for designing of nanoantimicrobials: an exposition

Understanding the interplay between bacterial pathogens and antimicrobials is a key to realize the control over infections causing morbidity and mortality. An important current issue of contemporary medicine and microbiology is the search for new strategies for adequate therapy of infectious diseases associated with rapidly emerging multidrug-resistant (MDR) pathogens. Recently, a great deal of progress has been made in the field of nanobiotechnology towards the development of various nanoantimicrobials (NAMs) as novel therapeutic solution. Current microbiological studies, employing either synthetic antibiotics or natural antimicrobial, have demonstrated the ability of NAMs to tackle the issue of MDR by reverting the mechanisms of resistance. The present review critically discusses the various factors that can contribute to modulate the effects of NAMs on microbes. It includes essential features of NAMs including but not limited to composition, surface charge, loading capacity, size, hydrophobicity/philicity, controlled release and functionalization. In contrast, how microbial structural differences, biofilm formation, persister cells and intracellular pathogens contribute towards sensitivity or resistance towards antimicrobials is comprehensively analysed. These multilateral factors should be considered earnestly in order to make NAMs a successful alternative of the conventional antibiotics.     

Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury

Recovery of endothelial integrity after vascular injury is vital for endothelial barrier function and vascular homeostasis. However, little is known about the molecular mechanisms of endothelial barrier repair following injury. To investigate the functional role of forkhead box M1 (FoxM1) in the mechanism of endothelial repair, we generated endothelial cell-restricted FoxM1-deficient mice (FoxM1 CKO mice). These mutant mice were viable and exhibited no overt phenotype. However, in response to the inflammatory mediator LPS, FoxM1 CKO mice displayed significantly protracted increase in lung vascular permeability and markedly increased mortality. Following LPS-induced vascular injury, FoxM1 CKO lungs demonstrated impaired cell proliferation in association with sustained expression of p27(Kip1) and decreased expression of cyclin B1 and Cdc25C. Endothelial cells isolated from FoxM1 CKO lungs failed to proliferate, and siRNA-mediated suppression of FoxM1 expression in human endothelial cells resulted in defective cell cycle progression. Deletion of FoxM1 in endothelial cells induced decreased expression of cyclins, Cdc2, and Cdc25C, increased p27(Kip1) expression, and decreased Cdk activities. Thus, FoxM1 plays a critical role in the mechanism of the restoration of endothelial barrier function following vascular injury. These data suggest that impairment in FoxM1 activation may be an important determinant of the persistent vascular barrier leakiness and edema formation associated with inflammatory diseases.