Efficient activation of neutrophils is a key requirement for effective immune responses. We found that neutrophils released cellular adenosine triphosphate (ATP) in response to exogenous stimuli such as formylated bacterial peptides and inflammatory mediators that activated Fcγ, interleukin-8, C5a complement, and leukotriene B₄ receptors. Stimulation of the formyl peptide receptor (FPR) led to ATP release through pannexin-1 (panx1) hemichannels, and FPRs colocalized with P2Y2 nucleotide receptors on the cell surface to form a purinergic signaling system that facilitated neutrophil activation. Disruption of this purinergic signaling system by inhibiting or silencing panx1 hemichannels or P2Y2 receptors blocked neutrophil activation and impaired innate host responses to bacterial infection. Thus, purinergic signaling is a fundamental mechanism required for neutrophil activation and immune defense.

The sodium/iodide symporter (NIS) mediates iodide uptake in lactating breast tissue and is expressed in some breast cancers. We have previously demonstrated that all-trans retinoic acid (tRA) stimulates NIS gene expression and the selective cytotoxic effect of β-emitting radioiodide-131 (131I) in both in vitro and in vivo MCF-7 breast cancer cell systems. We studied the ability of natural and synthetic retinoids, in combination with other nuclear receptor ligands, to achieve greater and more sustained induction of NIS in MCF-7 cells and enhance 131I-mediated cytotoxicity. Selective stimulation of retinoic acid receptor (RAR) β/γ produced marked NIS induction; and selective stimulation of RARα, RARγ, or retinoid X receptor produced more modest induction. Maximal NIS induction was seen with 9-cis retinoic acid and AGN190168, a RAR β/γ-agonist. Dexamethasone (Dex), but not the other nuclear receptor ligands, in combination with tRA synergistically induced iodide uptake and NIS mRNA expression, predominantly by prolonging NIS mRNA half-life. The addition of Dex reduced the EC50 of tRA for NIS stimulation to approximately 7%, such that 10 −7m tRA with addition of Dex enhanced iodide uptake and selective cytotoxicity of 131I greater than 10−6m tRA alone. AGN190168 combined with Dex synergistically increased iodide uptake and significantly prolonged induction (5 d) of iodide uptake compared with that induced by the combination of tRA/Dex or 9-cis retinoic acid/Dex. The addition of Dex reduced the effective dose of retinoid and prolonged the induction of NIS, especially with AGN190168, suggesting higher efficacy of 131I after combination treatment.

: Peripheral Nerve Injuries (PNI) frequently occur secondary to traumatic injuries. Recovery from these injuries can be expectedly poor, especially in proximal injuries. In order to study and improve peripheral nerve regeneration, scientists rely on peripheral nerve models to identify and test therapeutic interventions. In this review, we discuss the best described and most commonly used peripheral nerve models that scientists have and continue to use to study peripheral nerve physiology and function.

Mobile device technology has revolutionized interpersonal communication, but the application of this technology to the physician-patient relationship remains limited due to concerns over patient confidentiality and the security of digital information. Nevertheless, there is a continued focus on improving communication between doctors and patients in all fields of medicine as a means of improving patient care. In this study, we implement a novel communications platform to demonstrate that instantaneously sharing perioperative information with surgical patients and members of their support networks can improve patient care and strengthen the physician-patient relationship. 423 consecutive patients scheduled to undergo elective surgical procedures were offered complimentary registration to a secure, web-based service designed to distribute perioperative updates to a group of recipients designated by each patient via Short Message Service (SMS) and/or email. Messages were created by attending surgeons and delivered instantaneously through the web-based platform. In the postoperative period, patients and their designated message recipients, as well as participating healthcare providers, were asked to complete a survey designed to assess their experience with the messaging system. Survey results were statistically analyzed to determine satisfaction rates. Of the qualifying 423 patients, 313 opted to enroll in the study. On average, patients selected a total of 3.5 recipients to receive perioperative updates. A total of 1,195 electronic messages were generated for distribution to designated recipients during the study period and delivered to recipients located around the world. There were no documented errors or failures in message delivery. Satisfaction surveys were completed by 190 users of the service (73 %). Respondents identified themselves as either patients (n = 48, 25.5 %), family/friends (n = 120, 63.8 %), or healthcare providers (n = 15, 12 %). Satisfaction with the service was high: 94.2 % of users “enjoyed this software” and and 94.2 % of family/friends “felt more connected to their loved ones during surgery.” 92.5 % would “recommend their loved ones sign up for this service

We present a low-cost clinically viable ventilator design, AmbuBox, using a controllable pneumatic enclosure and standard manual resuscitators that are readily available (AmbuBag), which can be rapidly deployed during pandemic and mass-casualty events with a minimal set of components to manufacture and assemble. The AmbuBox is designed to address the existing challenges presented in the existing low-cost ventilator designs by offering an easy-to-install and simple-to-operate apparatus while maintaining a long lifespan with high-precision flow control. As an outcome, a mass-producible prototype of the AmbuBox has been devised, characterized, and validated in a bench test setup using a lung simulator. This prototype will be further investigated through clinical testing. Given the potentially urgent need for inexpensive and rapidly deployable ventilators globally, the overall design, operational principle, and device characterization of the AmbuBox system have been described in detail with open access online. Moreover, the fabrication and assembly methods have been incorporated to enable short-term producibility by a generic local manufacturing facility. In addition, a full list of all components used in the AmbuBox has been included to reflect its low-cost nature.