CuO Bionanocomposite with Enhanced Stability and Antibacterial Activity against Extended-Spectrum Beta-Lactamase Strains

Worldwide, bacterial resistance to beta-lactam antibiotics is the greatest challenge in public health care. To overcome the issue, metal-based nanoparticles were extensively used as an alternative to traditional antibiotics. However, their unstable nature limits their use. In the present study a very simple, environmentally friendly, one-pot synthesis method that avoids the use of organic solvents has been proposed to design stable, novel nanocomposites. Formulation was done by mixing biogenic copper oxide (CuO) nanomaterial with glycerol and phospholipids isolated from egg yolk in an appropriate ratio at optimum conditions. Characterization was done using dynamic light scattering DLS, Zeta potential, high performance liquid chromatography (HPLC), and transmission electron microscopy (TEM). Further, its antibacterial activity was evaluated against the extended-spectrum beta-lactamase strains based on zone of inhibition and minimal inhibitory concentration (MIC) indices. Results from this study have demonstrated the formulation of stable nanocomposites with a zeta potential of 34.9 mV. TEM results indicated clear dispersed particles with an average of 59.3 ± 5 nm size. Furthermore, HPLC analysis of the egg yolk extract exhibits the presence of phospholipids in the sample and has significance in terms of stability. The newly formed nanocomposite has momentous antibacterial activity with MIC 62.5 μg/mL. The results suggest that it could be a good candidate for drug delivery in terms of bactericidal therapeutic applications.     

Association between anemia and postoperative complications in infants undergoing pyloromyotomy

BackgroundAlthough preoperative anemia has been suggested to predict postsurgical morbidity and mortality among infants < 1 year of age, the data were drawn from heterogeneous patient cohorts including severely ill infants undergoing complex, high-risk procedures. We aimed to determine whether untreated preoperative anemia was associated with increased risk of postoperative complications in infants < 1 year of age who underwent pyloromyotomy, a common and relatively simple surgery.MethodsInfants < 1 year of age undergoing pyloromyotomy were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program-Pediatric database. Preoperative anemia was defined as a hematocrit ≤ 40% for infants 0–30 days of age and ≤ 30% for infants more than 30 days of age. Patients who received pre- or postoperative blood transfusions were excluded.ResultsWe identified 2948 patients who met our inclusion criteria, of whom 843 were anemic (29%). The overall rate of complications in this cohort was 6%. The most common postoperative complications were readmission (97 cases), surgical site infection (43), reoperation (39), prolonged hospital stay (24), urinary tract infection (3), 30-day mortality (3) and cardiac arrest (2). We found no differences in the incidence of complications in anemic versus nonanemic patients on bivariate analysis or multivariable logistic regression (adjusted odds ratio = 1.2; 95% confidence interval: 0.8–1.7; P = 0.319).ConclusionsIn relatively healthy infants undergoing pyloromyotomy, untreated preoperative anemia was not associated with postoperative compilations and should not be considered a significant risk factor.Level of evidence III.     

Radon inhalation decreases DNA damage induced by oxidative stress in mouse organs via the activation of antioxidative functions

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m³ (for one, three, or 10 days). The 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m³ radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m³ radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20–40% (2 kBq/m³ for three days or 20 kBq/m³ for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15–60% and 15–45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage.     

Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells

Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Repression of HPV oncoproteins would therefore result in reactivation of tumor suppressor pathways and cause apoptosis in cancer cells. Withaferin A (WA), the active component of the medicinal plant Withania Somnifera, has exhibited inhibitory effects against several different cancers. We examined the activity of WA on human cervical cancer cells in vitro and in vivo. WA potently inhibited proliferation of the cervical cancer cells, CaSki (IC(50) 0.45 ± 0.05 μM). Mechanistically, WA was found to (i) downregulate expression of HPV E6 and E7 oncoproteins, (ii) induce accumulation of p53, (iii) increase levels of p21(cip1/waf1) and its interaction with proliferating cell nuclear antigen (PCNA), (iv) cause G(2)/M cell cycle arrest, associated with modulation of cyclin B1, p34(cdc2) and PCNA levels, (v) decrease the levels of STAT3 and its phosphorylation at Tyr(705) and Ser(727) and (vi) alter expression levels of p53-mediated apoptotic markers-Bcl2, Bax, caspase-3 and cleaved PARP. In vivo, WA resulted in reduction of nearly 70% of the tumor volume in athymic nude mice with essentially similar trend in the modulation of molecular markers as in vitro. This is the first demonstration indicating that WA significantly downregulates expression of HPV E6/E7 oncogenes and restores the p53 pathway, resulting in apoptosis of cervical cancer cells. Together, our data suggest that WA can be exploited as a potent therapeutic agent for the treatment and prevention of cervical cancer without deleterious effects.     

Panel of synaptic protein ELISAs for evaluating neurological phenotype

The purpose of this study was to develop ELISAs for key neural proteins, three synaptic and one glial, that exist in different intracellular compartments, which would be used as a measure of synaptic phenotype. These assays would be valuable to neurologically phenotype transgenic mouse models of human disease and also human disease itself using minimal amounts of post-mortem tissue. We showed that supernatant from crude brain tissue homogenates extracted in RIPA buffer containing 0.1% SDS bind to synaptophysin, synaptosome-associated protein of 25 kDa (SNAP-25), post-synaptic density-95 (PSD-95), and glial fibrillary acidic protein (GFAP) antibody pairs with high affinity and selectivity. Overall, RIPA + 0.1% SDS were more efficient than RIPA + 2% SDS or a buffer containing only 1% Triton-X-100. Diluting the brain extracts resulted in dose-dependent binding to the antibody pairs for each neural protein, with EC50s that varied from 8.6 μg protein for PSD-95 to 0.23 μg for GFAP. The assays were used to measure synaptic marker protein levels at various times during mouse development and GFAP in a model of disease accompanied by neuroinflammation. Comparison of ELISAs with Western blots by measuring marker levels in brain extract from developing mice showed a greater relative difference in values derived from ELISA. These ELISAs should be valuable to phenotype the synapse in neurological disease and their rodent models.     

Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells

P-glycoprotein-mediated multidrug resistance (MDR) is a major limiting factor in the efficacy of most microtubule-targeting agents. Here, we investigated the novel, synthetic, and small-molecule microtubule-destabilizing agent, 2-(2-amino-5-(1-ethyl-1H-indol-5-yl) pyrimidin-4-yl) phenol (YHHU0895), for its anti-tumor activity and potential for overcoming P-glycoprotein-mediated MDR. YHHU0895 inhibited purified tubulin polymerization through binding to tubulin at the colchicine-binding site and significantly inhibited human tumor cell proliferation. Notably, P-glycoprotein-overexpressing KBV200 and K562/ADR cells, which are strongly resistant to colchicine, vinorelbine and paclitaxel, were sensitive to YHHU0895 both in vitro and in vivo. These findings indicate that YHHU0895 is a novel type of microtubule-destabilizing agent that has the potential for the treatment of patients with drug resistance mediated by P-glycoprotein.     

Awareness and Prevention of Osteoporosis Among South Asian Women

We examined awareness of osteoporosis prevention among peri- and post-menopausal South Asian women attending two community centers in the Dallas/Fort-Worth Metroplex. We conducted a quasi-experimental study (final N = 61) assessing knowledge about osteoporosis among South Asian women (≥40 years). The mean age was 52.3 years (SD = 8.72). Over 50% were college educated and 64% had no health insurance. We administered a baseline knowledge test, followed by a health education intervention and, 2 weeks later, by a post-test. Participants received one point for each correct answer and scores were added (≤14). Participants showed a significant increase in osteoporosis knowledge post intervention (paired t ₆₀ = −9.5, P < .01). For example, women reported highest knowledge gains on the following: adequate calcium intake is achievable from two glasses of milk a day; very thin women are at risk for developing osteoporosis, and family history of osteoporosis is a risk factor. Intervention completers were better prepared to prevent and manage osteoporosis. Results indicate the efficacy of educational intervention in improving osteoporosis awareness; and point to the potential for knowledge acquisition aimed at developing community-based prevention strategies at the community level.     

Resident Education Curriculum in Pediatric and Adolescent Gynecology: The Short Curriculum 2.0

The degree of exposure to pediatric and adolescent gynecology (PAG) varies across residency programs in obstetrics and gynecology and pediatrics. Nevertheless, these programs are responsible for training residents and providing opportunities within their programs to fulfill PAG learning objectives. To that end, the North American Society for Pediatric and Adolescent Gynecology has taken a leadership role in PAG resident education by creating and systematically updating the Short Curriculum. This curriculum outlines specific learning objectives that are central to PAG education and lists essential resources for learners' reference. This updated curriculum replaces the previous 2014 publication with added content, resources, and updated references. Additionally, attention to the needs of learners in pediatrics and adolescent medicine is given greater emphasis in this revised North American Society for Pediatric and Adolescent Gynecology Short Curriculum 2.0.