Steenlamb1613

The vertebrate heart is regulated by excitatory adrenergic and inhibitory cholinergic innervations, as well as non-adrenergic non-cholinergic (NANC) factors that may be circulating in the blood or released from the autonomic nerves. As an example of NANC signaling, an increased histaminergic tone, acting through stimulation of H2 receptors, contributes markedly to the rise in heart rate during digestion in pythons. In addition to the direct effects of histamine, it is also known that histamine can reinforce the cholinergic and adrenergic signaling. Thus, to further our understanding of the histaminergic regulation of the cardiovascular response in pythons, we designed a series of in vivo experiments complemented by in vitro experiments on sinoatrial and vascular ring preparations. We demonstrate the tachycardic mechanism of histamine works partly through a direct binding of cardiac H2 receptors and in part through a myocardial histamine-induced catecholamine release, which strengthens the sympathetic adrenergic signaling pathway.

Endothelial cell (EC) dysfunction underlies the pathology of multiple disease conditions including cardiovascular and pulmonary diseases. Dysfunctional ECs have a distinctive gene expression profile compared to healthy ECs. RNAi therapy is a powerful therapeutic approach that can be used to silence multiple genes of interests simultaneously. However, the delivery of RNAi to ECs in vivo continues to be a major challenge. Here, we optimized a polymer formulation based on poly(β-amino ester)s (pBAEs) to deliver siRNA to vascular ECs.

We developed a library of bioinspired oligopeptide-modified pBAE nanoparticles (NPs) with different physicochemical proprieties and screened them for cellular uptake and efficacy of RNAi delivery in vitro using ECs, vascular smooth muscle cells, and THP-1 monocytes. From the screening, the lysine-/histidine-oligopeptide modified pBAE (C6-KH) NP was selected and further tested ex vivo using mouse aorta and in mice to determine efficiency of siRNA delivery in vivo.

The in vitro screening study showed that C6-KH was most efficient in delivering siRNA to ECs. Ex vivo study showed that C6-KH nanoparticles containing siRNAs accumulated in the endothelial layer of mouse aortas. In vivo study showed that C6-KH nanoparticles carrying siICAM2 injected via tail-vein in mice significantly reduced ICAM2 level in the artery endothelium (55%), lung (52%), and kidney (31%), but not in the liver, heart, and thymus, indicating a tissue-specific delivery pattern.

We demonstrate that C6-KH pBAE can used for delivery of siRNAs to the artery endothelium and lung, while minimizing potential side or toxic effects in the liver and heart.

We demonstrate that C6-KH pBAE can used for delivery of siRNAs to the artery endothelium and lung, while minimizing potential side or toxic effects in the liver and heart.In recent years, nontraditional mental healthcare services and tools (e.g., mobile apps, peer counselors, online support groups) have been developed to increase access to and utilization of behavioral health services. This study investigates how adolescents and younger adults use and perceive various nontraditional mental healthcare services in comparison to traditional services and in comparison to each other. A questionnaire-based study was conducted that included 203 participants between the ages of 17 and 37 (M = 25.01, SD = 5.04). Results showed that while usage rates of nontraditional mental health services were considerably high, the highest rates were reported for traditional services. Similarly, participants reported high levels of willingness to use nontraditional services, yet the highest levels of willingness were reported for traditional services. These findings suggest that the integration of nontraditional services with traditional services may be particularly impactful for young people.Early identification and treatment of mental illness symptoms results in better outcomes, yet few screeners are available that can be efficiently used in community settings. The Mental Illness Needs Detection (MIND) Screener was developed to identify the need for mental health treatment and administered to 820 adults across the USA. Confirmatory factor analysis supported the internal consistency of the MIND. selleck The MIND significantly correlated with the Kessler-10 (K10; a well-validated screener), reported mental illness, mental health treatment, and the need for treatment. The MIND's ability to accurately assess treatment needs was further demonstrated through high sensitivity (84%; 83%), specificity (71%; 62%), and AUC values (0.77; 0.73) when compared to both the K10 and reported need for treatment, respectively. These findings support the validity and reliability of the MIND and indicate its promise as a means of detecting a wide range of mental health needs across a variety of settings.

Despite significant investment in colorectal cancer (CRC) screening, 40% of US adults are not up-to-date. Commitment devices, which are psychologically tailored approaches to enforce health goals, may be an effective method to increase CRC screening.

Compare the effectiveness of a commitment device (patient self-ordering fecal immunochemical test (FIT) kits) to standard CRC screening outreach.

A retrospective observational study.

Participants were > 49years and < 75years, had no history of CRC, and were eligible for CRC screening.

An electronic screening reminder with an embedded order button allowed participants to order FIT kits directly from a patient portal. Those who used the order button were promptly sent a kit; those who did not were later mailed kits.

Primary outcome was completion of FIT kits. Secondary outcomes included number of days to completion, completion of follow-up for positive results, and CRC diagnosis; we also examined prior use of FIT kit. We used inverse probability ot portals such as this can complement existing CRC outreach strategies.

Inflorescence explants of date palm proved to be a promising tool for micropropagation of elite cultivars or rare males and females as organogenesis and somatic embryogenesis could be achieved. These plant materials are abundantly available every year and can be used as cheap and potent explants. Nevertheless, many difficulties could be faced in this protocol according to selection of the spathe size and age, media components, growth regulators, etc. The aim of this study was to determine the influence of various cytokinins on direct organs induction of three date palm cultivars (Selmi, Barhee, and Medjool) from immature inflorescence. An additional objective of this study was to investigate the effect of cytokinins and auxins on growth and development of Medjool cultivar.

Various combinations of cytokinins were investigated on three date palm inflorescences as N6-(2-isopentenyl) adenine (2iP), kinetin, benzyleadenine (BA), and thidiazuron (N-phenyl-N'-1,2,3-thidiazol-5-yl urea) (TDZ). TDZ alone or in combination with BA proved to be superior for direct organogenesis in all three cultivars so that another combination of TDZ with BA was conducted.