This study investigated nicotine dependence as an independent risk factor for upper aerodigestive tract (UADT) cancers, including lung and head and neck cancers (HNC). The study aimed to isolate the ...direct effect of nicotine dependence, independent of tobacco smoking.
A case-control study with a total of 4957 participants was conducted in Ontario, Canada, of which 2964 categorized as either current or former smokers were used in the analysis. Nicotine dependence of ever-smokers (2360 UADT cases and 604 controls) was measured using the Fagerström Test for Nicotine Dependence. Using mediation analyses and adjusted logistic regression models, we decomposed the direct effect of nicotine dependence and the mediated effect of smoking duration to quantify the risks of lung and HNC. The role of human papillomavirus (HPV) and cancer subtypes were assessed.
Most individual nicotine dependence behaviours showed positive associations with lung cancer with approximately 1.8 to 3.5-fold risk increase, and to lesser extent with 1.4 to 2.3-fold risk for HNC. Nicotine dependence is partially accountable for increased risks of lung cancer (OR = 1.20, 95%CI = 1.13-1.28) and HNC (1.12, 95%CI = 1.04-1.19). Nicotine dependence had a greater effect on the risk of HPV-negative oropharyngeal cancer (OR = 3.06, 95%CI = 1.65-5.66) in comparison to HPV-positive oropharyngeal cancer (OR = 1.05, 95%CI = 0.67-1.65). The direct effects of nicotine dependence remained significant after accounting for cumulative tobacco exposures.
Nicotine dependence increases the risks of lung and HNC cancers after accounting for tobacco smoking, suggesting potential toxic effects of nicotine. These results are informative for the safety consideration of nicotine exposures.
The present research adopts an attachment theory perspective to advance new insights into the effectiveness of advertising strategies that depict interpersonal relationships. Although pictures, and ...specifically pictures of relationships (e.g., friends), make up an increasingly large portion of advertisements, scant research has examined how depictions of relationships impact consumer evaluations of advertised products. The present research demonstrates that the effectiveness of ads which depict interpersonal relationships, including romantic partnerships and friendships, is associated with consumers' interpersonal attachment styles. Specifically, individuals with highly anxious attachment styles are unlikely to purchase products shown in relational ads; whereas, individuals with less anxious and more secure attachment styles are more likely to purchase these products. Importantly, perceptions of fit (i.e., the extent to which an advertised product is perceived as a good fit with oneself) mediate the relationship between interpersonal attachment style and consumers' likelihood of purchasing products shown in advertisements that portray relationships.
•The effectiveness of relational ads is associated with consumers' attachment styles.•Attachment styles are associated with responses to products shown in relational ads.•Securely attached people feel that products in relational ads fit well with oneself.•Anxiously attached people feel that products in relational ads are not a fit for them.•Perceived fit mediates the relationship between attachment and purchase likelihood.
Phubbing (phone snubbing) has become a commonplace behavior. The more we are phubbed the more likely we are to phub others. The extraordinary attention-grabbing ability of the smartphone would only ...be an interesting story if not for its impact on social media use and, ultimately, stress and depression. In Study 1 (n = 258,
= 20), we develop a parsimonious and valid measure of phubbing. Extant "phubbing" measures all lack important qualities needed to be able to assess phubbing with a brief and valid scale that can be replicated and used in a variety of research settings. In Study 2 (n = 157,
= 39), we test and extend the David and Roberts (2017) phubbing model, while further validating our perceived phubbing measure. We use Social Exchange Theory and Kardefelt-Winther's (2014) model of compensatory internet use as theoretical support for our expected findings. Results find that phubbed individuals experience a sense of social exclusion that, paradoxically, is associated with an increased use of social media. This increased use of social media is associated with higher reported levels of anxiety and depression. Future research directions and study limitations are discussed.
Cochlear implants are among the most successful neural prosthetic devices to date but exhibit poor frequency selectivity and the inability to consistently activate apical (low frequency) spiral ...ganglion neurons. These issues can limit hearing performance in many cochlear implant patients, especially for understanding speech in noisy environments and in perceiving or appreciating more complex inputs such as music and multiple talkers. For cochlear implants, electrical current must pass through the bony wall of the cochlea, leading to widespread activation of auditory nerve fibers. Cochlear implants also cannot be implanted in some individuals with an obstruction or severe malformations of the cochlea. Alternatively, intraneural stimulation delivered via an auditory nerve implant could provide direct contact with neural fibers and thus reduce unwanted current spread. More confined current during stimulation can increase selectivity of frequency fiber activation. Furthermore, devices such as the Utah Slanted Electrode Array can provide access to the full cross section of the auditory nerve, including low frequency fibers that are difficult to reach using a cochlear implant. However, further scientific and preclinical research of these Utah Slanted Electrode Array devices is limited by the lack of a chronic large animal model for the auditory nerve implant, especially one that leverages an appropriate surgical approach relevant for human translation. This paper presents a newly developed transbullar translabyrinthine surgical approach for implanting the auditory nerve implant into the cat auditory nerve. In our first of a series of studies, we demonstrate a surgical approach in non-recovery experiments that enables implantation of the auditory nerve implant into the auditory nerve, without damaging the device and enabling effective activation of the auditory nerve fibers, as measured by electrode impedances and electrically evoked auditory brainstem responses. These positive results motivate performing future chronic cat studies to assess the long-term stability and function of these auditory nerve implant devices, as well as development of novel stimulation strategies that can be translated to human patients.
Haemostasis occurs at sites of vascular injury, where flowing blood forms a clot, a dynamic and heterogeneous fibrin-based biomaterial. Paramount in the clot's capability to stem haemorrhage are its ...changing mechanical properties, the major drivers of which are the contractile forces exerted by platelets against the fibrin scaffold. However, how platelets transduce microenvironmental cues to mediate contraction and alter clot mechanics is unknown. This is clinically relevant, as overly softened and stiffened clots are associated with bleeding and thrombotic disorders. Here, we report a high-throughput hydrogel-based platelet-contraction cytometer that quantifies single-platelet contraction forces in different clot microenvironments. We also show that platelets, via the Rho/ROCK pathway, synergistically couple mechanical and biochemical inputs to mediate contraction. Moreover, highly contractile platelet subpopulations present in healthy controls are conspicuously absent in a subset of patients with undiagnosed bleeding disorders, and therefore may function as a clinical diagnostic biophysical biomarker.
We examined the structural plasticity of excitatory synapses from corticostriatal and thalamostriatal pathways and their postsynaptic targets in adult Sprague-Dawley rats to understand how these ...striatal circuits change in l-DOPA-induced dyskinesias (LIDs). We present here detailed electron and light microscopic analyses that provide new insight into the nature of the structural and synaptic remodeling of medium spiny neurons in response to LIDs. Numerous studies have implicated enhanced glutamate signaling and persistent long-term potentiation as central to the behavioral sensitization phenomenon of LIDs. Moreover, experience-dependent alterations in behavior are thought to involve structural modifications, specifically alterations in patterns of synaptic connectivity. Thus, we hypothesized that in the striatum of rats with LIDs, one of two major glutamatergic pathways would form new or altered contacts, especially onto the spines of medium spiny neuron (MSNs). Our data provide compelling evidence for a dramatic rewiring of the striatum of dyskinetic rats and that this rewiring involves corticostriatal but not thalamostriatal contacts onto MSNs. There is a dramatic increase in corticostriatal contacts onto spines and dendrites that appear to be directly linked to dyskinetic behaviors, since they were not seen in the striatum of animals that did not develop dyskinesia. There is also an aberrant increase in spines receiving more than one excitatory contact(i.e., multisynaptic spines) in the dyskinetic animals compared with the 6-hydroxydopamine-treated and control rats. Such alterations could substantially impair the ability of striatal neurons to gate cortically driven signals and contribute to the loss of bidirectional synaptic plasticity.
Leveraging Bagozzi's (1992) appraisal framework, this research contributes to our understanding of the effects of demarketing. In particular, it examines the impact of a proenvironmental demarketing ...effort which calls attention to potential electricity saving ideas, on perceptions, and consumption. A pair of cross-validated studies indicates that proenvironmental demarketing may enhance consumers' perceptions of the firm and subsequently affect consumption behavior. Specifically, study one suggests that proenvironmental demarketing leads to enhanced perception of an organization's trustworthiness, market orientation, and environmental-sensitivity, while study two indicates that proenvironmental demarketing may lead to a reduction in electricity consumption.
Background
Recruitment manoeuvres involve transient elevations in airway pressure applied during mechanical ventilation to open (‘recruit’) collapsed lung units and increase the number of alveoli ...participating in tidal ventilation. Recruitment manoeuvres are often used to treat patients in intensive care who have acute respiratory distress syndrome (ARDS), but the effect of this treatment on clinical outcomes has not been well established. This systematic review is an update of a Cochrane review originally published in 2009.
Objectives
Our primary objective was to determine the effects of recruitment manoeuvres on mortality in adults with acute respiratory distress syndrome.
Our secondary objective was to determine, in the same population, the effects of recruitment manoeuvres on oxygenation and adverse events (e.g. rate of barotrauma).
Search methods
For this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), the Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCO), Latin American and Caribbean Health Sciences (LILACS) and the International Standard Randomized Controlled Trial Number (ISRCTN) registry from inception to August 2016.
Selection criteria
We included randomized controlled trials (RCTs) of adults who were mechanically ventilated that compared recruitment manoeuvres versus standard care for patients given a diagnosis of ARDS.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.
Main results
Ten trials met the inclusion criteria for this review (n = 1658 participants). We found five trials to be at low risk of bias and five to be at moderate risk of bias. Six of the trials included recruitment manoeuvres as part of an open lung ventilation strategy that was different from control ventilation in aspects other than the recruitment manoeuvre (such as mode of ventilation, higher positive end‐expiratory pressure (PEEP) titration and lower tidal volume or plateau pressure). Six studies reported mortality outcomes. Pooled data from five trials (1370 participants) showed a reduction in intensive care unit (ICU) mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.72 to 0.97, P = 0.02, low‐quality evidence), pooled data from five trials (1450 participants) showed no difference in 28‐day mortality (RR 0.86, 95% CI 0.74 to 1.01, P = 0.06, low‐quality evidence) and pooled data from four trials (1313 participants) showed no difference in in‐hospital mortality (RR 0.88, 95% CI 0.77 to 1.01, P = 0.07, low‐quality evidence). Data revealed no differences in risk of barotrauma (RR 1.09, 95% CI 0.78 to 1.53, P = 0.60, seven studies, 1508 participants, moderate‐quality evidence).
Authors' conclusions
We identified significant clinical heterogeneity in the 10 included trials. Results are based upon the findings of several (five) trials that included an "open lung ventilation strategy", whereby the intervention group differed from the control group in aspects other than the recruitment manoeuvre (including co‐interventions such as higher PEEP, different modes of ventilation and higher plateau pressure), making interpretation of the results difficult. A ventilation strategy that included recruitment manoeuvres in participants with ARDS reduced intensive care unit mortality without increasing the risk of barotrauma but had no effect on 28‐day and hospital mortality. We downgraded the quality of the evidence to low, as most of the included trials provided co‐interventions as part of an open lung ventilation strategy, and this might have influenced results of the outcome.
Infection by DNA viruses can elicit DNA damage responses (DDRs) in host cells. In some cases the DDR presents a block to viral replication that must be overcome, and in other cases the infecting ...agent exploits the DDR to facilitate replication. We find that low multiplicity infection with the autonomous parvovirus minute virus of mice (MVM) results in the activation of a DDR, characterized by the phosphorylation of H2AX, Nbs1, RPA32, Chk2 and p53. These proteins are recruited to MVM replication centers, where they co-localize with the main viral replication protein, NS1. The response is seen in both human and murine cell lines following infection with either the MVMp or MVMi strains. Replication of the virus is required for DNA damage signaling. Damage response proteins, including the ATM kinase, accumulate in viral-induced replication centers. Using mutant cell lines and specific kinase inhibitors, we show that ATM is the main transducer of the signaling events in the normal murine host. ATM inhibitors restrict MVM replication and ameliorate virus-induced cell cycle arrest, suggesting that DNA damage signaling facilitates virus replication, perhaps in part by promoting cell cycle arrest. Thus it appears that MVM exploits the cellular DNA damage response machinery early in infection to enhance its replication in host cells.
Abnormal sickle red blood cell (sRBC) biomechanics, including pathological deformability and adhesion, correlate with clinical severity in sickle cell disease (SCD). Clinical intravenous fluids ...(IVFs) of various tonicities are often used during treatment of vaso-occlusive pain episodes (VOE), the major cause of morbidity in SCD. However, evidence-based guidelines are lacking, and there is no consensus regarding which IVFs to use during VOE. Further, it is unknown how altering extracellular fluid tonicity with IVFs affects sRBC biomechanics in the microcirculation, where vaso-occlusion takes place. Here, we report how altering extracellular fluid tonicity with admixtures of clinical IVFs affects sRBC biomechanical properties by leveraging novel in vitro microfluidic models of the microcirculation, including 1 capable of deoxygenating the sRBC environment to monitor changes in microchannel occlusion risk and an “endothelialized” microvascular model that measures alterations in sRBC/endothelium adhesion under postcapillary venular conditions. Admixtures with higher tonicities (sodium = 141 mEq/L) affected sRBC biomechanics by decreasing sRBC deformability, increasing sRBC occlusion under normoxic and hypoxic conditions, and increasing sRBC adhesion in our microfluidic human microvasculature models. Admixtures with excessive hypotonicity (sodium = 103 mEq/L), in contrast, decreased sRBC adhesion, but overswelling prolonged sRBC transit times in capillary-sized microchannels. Admixtures with intermediate tonicities (sodium = 111-122 mEq/L) resulted in optimal changes in sRBC biomechanics, thereby reducing the risk for vaso-occlusion in our models. These results have significant translational implications for patients with SCD and warrant a large-scale prospective clinical study addressing optimal IVF management during VOE in SCD.
•Intravenous fluids are used when treating VOE, but guidelines are lacking, and how IVF tonicity affects sickle red cell biomechanics is unknown.•Modifying extracellular fluid tonicity alters deformability, adhesivity, and occlusion risk for sRBCs in microfluidic vascular models.
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