Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study

Metformin (MET), an antidiabetic drug, is emerging as a promising anticancer agent. This study was initiated to investigate the antitumor effects and potential molecular targets of MET in mice bearing solid Ehrlich carcinoma (SEC) as a model of breast cancer (BC) and to explore the potential of zein nanoparticles (ZNs) as a carrier for improving the anticancer effect of MET. ZNs were fabricated through ethanol injection followed by probe sonication method. The optimum ZN formulation (ZN8) was spherical and contained 5 mg zein and 30 mg sodium deoxycholate with a small particle size and high entrapment efficiency percentage and zeta potential. A stability study showed that ZN8 was stable for up to three months. In vitro release profiles proved the sustained effect of ZN8 compared to the MET solution. Treatment of SEC-bearing mice with ZN8 produced a more pronounced anticancer effect which was mediated by upregulation of P53 and miRNA-543 as well as downregulation of NF-κB and miRNA-191-5p gene expression. Furthermore, ZN8 produced a marked elevation in pAMPK and caspase-3 levels as well as a significant decrease in cyclin D1, COX-2, and PGE2 levels. The acquired findings verified the potency of MET-loaded ZNs as a treatment approach for BC

Microscale Physiological Events on the Human Cortical Surface

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit

Impact of the International Nosocomial Infection Control Consortium (INICC)’s multidimensional approach on rates of ventilator-associated pneumonia in intensive care units in 22 hospitals of 14 cities of the Kingdom of Saudi Arabia

To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and use of INICC Surveillance Online System (ISOS) on ventilator-associated pneumonia (VAP) rates in Saudi Arabia from September 2013 to February 2017. A multicenter, prospective, before–after surveillance study on 14,961 patients in 37 intensive care units (ICUs) of 22 hospitals. During baseline, we performed outcome surveillance of VAP applying the definitions of the CDC/NHSN. During intervention, we implemented the IMA and the ISOS, which included: (1) a bundle of infection prevention practice interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback on VAP rates and consequences and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using generalized linear mixed models to estimate the effect of intervention. The baseline rate of 7.84 VAPs per 1000 mechanical-ventilator (MV)-days―with 20,927 MV-days and 164 VAPs―, was reduced to 4.74 VAPs per 1000 MV-days―with 118,929 MV-days and 771 VAPs―, accounting for a 39% rate reduction (IDR 0.61; 95% CI 0.5–0.7; P 0.001). Implementing the IMA was associated with significant reductions in VAP rates in ICUs of Saudi Arabia