Sleep-Disordered Breathing and Stroke: Therapeutic Approaches

The majority of stroke patients have clinically significant obstructive sleep apnea (OSA). Also, recent evidence demonstrates that OSA serves as an independent risk factor for stroke. Treatment of OSA following stroke is associated with neurologic and functional improvements, as well as long-term reduced risk of cardiovascular events. Identification of stroke patients at risk of OSA and subsequent diagnosis and treatment is essential in stroke recovery and reducing recurrent stroke risk. Continuous positive airway pressure (CPAP), the standard modality of treating OSA, is highly effective, but is often inadequately tolerated by stroke patients. Education and medical provider support are essential in establishing CPAP use in this population. However, in cases where CPAP therapy is not feasible, it is important for clinicians to be familiar with alternative modalities in treating OSA.     

Effects of the inhibition of cytosolic phospholipase A<Subscript>2</Subscript>α in non-small cell lung cancer cells

Purpose  

The aim of this study was to investigate the expression of cPLA₂α in non-small lung cancer cell lines and tissues, and we sought to determine the in vitro effects of the pyrrolidine-2 inhibitor on cPLA₂α sensitivity in three different non-small lung cancer cell lines.     

Pulse oximetry screening to detect critical congenital heart diseases in asymptomatic neonates

BackgroundCritical congenital heart diseases (CCHDs), 10% to 25% of all CHD, are duct-dependent defects that are life threatening without intervention in the neonatal period or infancy. One third of neonates with CCHDs are discharged home undetected and have a poorer outcome. Pulse oximetry screening before discharge is increasingly being used to diagnose CCHDs in developed countries.MethodsThis prospective observational study conducted at a tertiary care hospital from September 2016 to March 2019 screened all asymptomatic intramural neonates after 24 hours of life using a Masimo pulse oximeter with signal extraction technology using the standard American Academy of Pediatrics algorithm. A positive screen was followed by a confirmatory echocardiography (gold standard) and a negative screen by clinical examination at 6, 10 and 14 weeks and identification of readmissions during the study period.ResultsA total of 1855 neonates (82.99% of the eligible 2235 neonates) underwent screening at a mean (SD) age at screening of 32.4 (6.8) hours and took a mean (SD) time of 3.5 (1.2) minutes. The sensitivity, specificity, positive and negative predictive value of pulse oximetry screening for detection of CCHDs in asymptomatic neonates was 75% (95% CI: 28.91% to 96.59%), 99.29% (95% CI: 98.79% to 99.60%), 18.75% (95% CI: 5.80% to 43.80%) and 99.94% (95% CI: 99.66 to 99.99%), respectively.ConclusionPulse oximetry screening of asymptomatic neonates between 24 and 48 hours of life improved the detection of CCHDs with high specificity and negative predictive value, moderate sensitivity and a reasonably low false positivity rate.     

Therapeutic potential of peptides with neutralizing ability towards the venom and toxin (CaTx-I) of crotalus adamanteus

The CaTx-I (PLA2) toxin of Crotalus adamanteus venom is responsible for most of the symptoms observed during envenomation. Synthetic peptides were designed and screened for venom (0.8 μg/ml) and CaTx-I (0.1 μM) inhibition at varying doses of the peptide (10000- 0.0001 μM) using a Cayman chemical human secretory phospholipase A2 (sPLA2, Type II) assay kit. Further, in vitro neutralization studies were evaluated by a fixed dose of peptide (1 μM) against venom (0.8 μg/ml) and toxin (0.1 μM). Among the linear peptides (PIP-18, cyclic C and PIP59-67) that showed potent neutralizing effects against the venom/toxin of C. adamanteus. PIP-18 [IC50, 1.23 μM] and cyclic C [IC50, 1.27 μM] peptides possessed the strongest inhibitory effect against CaTx-I. A fixed dose of CaTx-I (75 μg/kg) was administered intraperitoneally (i.p.) into mice followed by an i.p. injection of peptides PIP-18 and cyclic C at (6 μg/mouse), venom (150 μg/kg) and toxin CaTx-I alone served as references. Mice treated with PIP-18 and cyclic C showed a very strong neutralizing effect and markedly reduced mortality compared to the control after 24 h. The CA venom and CaTx-I injected mice showed severe toxicity after 24 h. Peptides PIP-18 and cyclic C were non-hemolytic at 100 μM. They produced a significant decrease in lipid peroxidase (LPx) and enhancement of superoxide dismutase (SOD), catalase (CAT) and Glutathione-s-transferase (GST) levels indicating their antioxidant property against venom-induced changes in mice. This study confirmed the potent snake venom neutralizing properties of peptides.     

Synthesis and biological evaluation of α, β-unsaturated ketone as potential antifungal agents

Abstract  With the aim of developing potential antifungals, a series of chalcones incorporating sulfur either as part of a heteroaromatic ring (thiophene) or as a side chain (thiomethyl group) were synthesized and tested for their in vitro activity. Some of the compounds showed appreciable activity against a fluconazole-resistant strain, and could act as new hits for the design of better analogs. Graphical Abstract  Synthesis and biological evaluation of α,β-unsaturated ketone as potential antifungal agentsSeema Bag, S.Ramar, Mariam S. Degani*With an aim to develop new chemical entities with potent antifungal activity against Candida albicans strains, a series of chalcones incorporating sulfur either as part of a heteroaromatic ring (thiophene) or as a side chain (thiomethyl group) were synthesized. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.