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Background Laboratory-based r espiratory pathogen (RP) results are often available too late to influence clinical decisions such as hospitalisation or antibiotic treatment due to time delay in transport of specimens and testing schedules. Ward-based i.e. point of care (POC) testing providing rapid results may alter the clinical management pathway. Methods FilmArray® RP polymerase chain reaction (PCR) systems were placed in three in-patient and out-patient medical areas. Patients presenting with influenza-like illness /upper respiratory tract infection +/− lower RTI were recruited between January–July 2015. FilmArray® POC testing occurred on even days of the month (intervention) or routine, laboratory-based RP PCR testing +/− atypical serology on odd days (control). The primary outcome was length of hospital stay. The secondary outcomes were impact on the use of antimicrobials, readmissions, all-cause mortality, length of ward stay and turn-around time (TAT) (time to result from admission). Results Of 606 eligible patients, 545 (89.9%) were included; 211 in the control arm and 334 in the intervention arm. 20% of control arm patients and 24% of intervention arm patients had an RP detected. POC testing was not associated with the primary outcome measure, length of stay, but reduced the TAT from 39.5 h to 19.0 h, p  < 0.001. Only the prescribing decision differed between study arms, p < 0.001. When antivirals were given, the intervention was associated with a reduction in the median time to the first dose of 36 h and allowed appropriate treatment of mycoplasma infection. Conclusions We found no association between respiratory PCR POC testing and length of stay or most of the secondary outcomes except the antimicrobial prescribing decision. This was probably due to a delay in initiating FilmArray® testing. Despite this, POC testing allowed time-critical antivirals to be given significantly faster, appropriate mycoplasma treatment and results were available considerably faster than routine, laboratory-based testing. Ward-staff of all grades performed POC testing without difficulty suggesting potential use across many divergent healthcare settings. Further studies evaluating the implementation of rapid respiratory PCR POC testing and the effect on length of stay and antimicrobial use are required. Trial registration ISRCTN10470967 , Retrospectively Registered, 30/6/2015.

The mammalian target of rapamycin (mTOR) and Akt proteins regulate various steps of muscle development and growth, but the physiological relevance and the downstream effectors are under investigation. Here we show that S6 kinase 1 (S6K1), a protein kinase activated by nutrients and insulin-like growth factors (IGFs), is essential for the control of muscle cytoplasmic volume by Akt and mTOR. Deletion of S6K1 does not affect myoblast cell proliferation but reduces myoblast size to the same extent as that observed with mTOR inhibition by rapamycin. In the differentiated state, S6K1(-/-) myotubes have a normal number of nuclei but are smaller, and their hypertrophic response to IGF1, nutrients and membrane-targeted Akt is blunted. These growth defects reveal that mTOR requires distinct effectors for the control of muscle cell cycle and size, potentially opening new avenues of therapeutic intervention against neoplasia or muscle atrophy.

Background: Technological advancements are rapidly propelling the field of genome research forward, while lawmakers attempt to keep apace with the risks these advances bear. Balancing normative concerns of maximizing data utility and protecting human subjects, whose privacy is at risk due to the identifiability of DNA data, are central to policy decisions. Research on genome research participants making real-time data sharing decisions is limited; yet, these perspectives could provide critical information to ongoing deliberations. Methods: We conducted a randomized trial of 3 consent types affording varying levels of control over data release decisions. After debriefing participants about the randomization process, we invited them to a follow-up interview to assess their attitudes toward genetic research, privacy and data sharing. Results: Participants were more restrictive in their reported data sharing preferences than in their actual data sharing decisions. They saw both benefits and risks associated with sharing their genomic data, but risks were seen as less concrete or happening in the future, and were largely outweighed by purported benefits. Conclusion: Policymakers must respect that participants’ assessment of the risks and benefits of data sharing and their privacy-utility determinations, which are associated with their final data release decisions, vary. In order to advance the ethical conduct of genome research, proposed policy changes should carefully consider these stakeholder perspectives.

Despite growing concerns toward maintaining participants' privacy, individual investigators collecting tissue and other biological specimens for genomic analysis are encouraged to obtain informed consent for broad data sharing. Our purpose was to assess the effect on research enrollment and data sharing decisions of three different consent types (traditional, binary, or tiered) with varying levels of control and choices regarding data sharing. A single-blinded, randomized controlled trial was conducted with 323 eligible adult participants being recruited into one of six genome studies at Baylor College of Medicine in Houston, Texas, between January 2008 and August 2009. Participants were randomly assigned to one of three experimental consent documents (traditional, n = 110; binary, n = 103; and tiered, n = 110). Debriefing in follow-up visits provided participants a detailed review of all consent types and the chance to change data sharing choices or decline genome study participation. Before debriefing, 83.9% of participants chose public data release. After debriefing, 53.1% chose public data release, 33.1% chose restricted (controlled access database) release, and 13.7% opted out of data sharing. Only one participant declined genome study participation due to data sharing concerns. Our findings indicate that most participants are willing to publicly release their genomic data; however, a significant portion prefers restricted release. These results suggest discordance between existing data sharing policies and participants' judgments and desires.

▪ Abstract  Prolactin (PRL) is a paradoxical hormone. Historically known as the pituitary hormone of lactation, it has had attributed to it more than 300 separate actions, which can be correlated to the quasi-ubiquitous distribution of its receptor. Meanwhile, PRL-related knockout models have mainly highlighted its irreplaceable role in functions of lactation and reproduction, which suggests that most of its other reported target tissues are presumably modulated by, rather than strictly dependent on, PRL. The multiplicity of PRL actions in animals is in direct opposition to the paucity of arguments that suggest its involvement in human pathophysiology other than effects on reproduction. Although many experimental data argue for a role of PRL in the progression of some tumors, such as breast and prostate cancers, drugs lowering circulating PRL levels are ineffective. This observation opens new avenues for research into the understanding of whether local production of PRL is involved in tumor growth and, if so, how extrapituitary PRL synthesis is regulated. Finally, the physiological relevance of PRL variants, such as the antiangiogenic 16K-like PRL fragments, needs to be elucidated. This review is aimed at critically discussing how these recent findings have renewed the manner in which PRL should be considered as a multifunctional hormone.

Growth hormone (GH) participates in the postnatal regulation of skeletal muscle growth, although the mechanism of action is unclear. Here we show that the mass of skeletal muscles lacking GH receptors is reduced because of a decrease in myofiber size with normal myofiber number. GH signaling controls the size of the differentiated myotubes in a cell-autonomous manner while having no effect on size, proliferation, and differentiation of the myoblast precursor cells. The GH hypertrophic action leads to an increased myonuclear number, indicating that GH facilitates fusion of myoblasts with nascent myotubes. NFATc2, a transcription factor regulating this phase of fusion, is required for GH action because GH is unable to induce hypertrophy of NFATc2-/-myotubes. Finally, we provide three lines of evidence suggesting that GH facilitates cell fusion independent of insulin-like growth factor 1 (IGF-1) up-regulation. First, GH does not regulate IGF-1 expression in myotubes; second, GH action is not mediated by a secreted factor in conditioned medium; third, GH and IGF-1 hypertrophic effects are additive and rely on different signaling pathways. Taken together, these data unravel a specific function of GH in the control of cell fusion, an essential process for muscle growth.

BackgroundThere is strong evidence of FFR-guided treatment in multi-vessel disease. The presence of a concomitant CTO may influence the FFR measurement in donor vessel. We sought to investigate the influence of collateral regression after successful CTO recanalisation on donor vessel pressure-derived indices.Methods28 out of 34 consecutive patients underwent successful PCI to RCA CTOs and completed the follow up study (at 3 months post CTO-PCI). Resting Pd/Pa,iFR and FFR were measured pre and post successful CTO PCI and at follow-up in donor vessels.ResultsThe mean resting Pd/Pa, iFR and FFR pre and post-RCA CTO PCI and at follow-up procedures in major donor vessel were (0.893, 0.862, 0.764), (0.907, 0.886, 0.753) and (0.918, 0.901, 0.787) respectively. The mean resting Pd/Pa, iFR and FFR pre and post-RCA CTO PCI and at follow-up procedures in minor donor vessel were (0.979, 0.966, 0.890), (0.983, 0.979, 0.880) and (0.981, 0.974, 0.898) respectively. Changes in pressure-derived indices are summarised in table 1.Abstract 8 Table 1Changes in coronary pressure-derived measurements in donor vessel pre and post RCA CTO PCI and at fellow-up (FU: follow-up; PdPa: resting Pd/Pa; PCI: percutaneous coronary intervention; IFR: instantaneous wave-free ratio; FFR: fractional flow reserve; CTO: chronic total occlusion)ConclusionSuccessful recanalisation of a RCA CTO results in a significant increase in coronary pressure-derived indices of the major donor vessel at follow-up associated with a regression of collateral function. The expected change and the optimal timing to perform PCI in donor vessel should be considered when planning multi-vessel revascularisation in this setting.

BackgroundThe presence of a concomitant CTO may influence the FFR measurement in donor vessel. We sought to investigate the immediate physiological impact of CTO recanalisation on donor vessel pressure-derived indices.Methods34 out of 40 consecutive patients underwent successful PCI to RCA CTOs. Resting Pd/Pa,iFR and FFR were measured pre and post-successful CTO PCI in donor vessels and collateral FFR in the CTO vessel.ResultsThe angiographic details are as outlined in table 1. The mean resting Pd/Pa, iFR and FFR pre and post CTO PCI in major donor vessel were (0.891,0.858, 0.759) and (0.903, 0.882, 0.746) (p=0.109, p=0.012, p=0.388) respectively. iFR in the major donor vessel increased from 0.858 to 0.882 (difference, 0.02412; p=0.012). The mean resting Pd/Pa, iFR and FFR pre and post CTO PCI in minor donor vessel were (0.982, 0.969, 0.894) and (0.985, 0.979, 0.885), (p=0.534, p=0.152, p=0.183) respectively. The mean collateral FFR was 0.310. The mean total ischaemic burden on baseline cardiac MRI in RCA territory was 12.6%.ConclusionSuccessful recanalisation of a RCA CTO results in a significant increase in the iFR of the major donor vessel but no significant difference was seen in resting Pd/Pa and FFR. Complete collateral regression was not observed in all patients immediately post RCA CTO PCI and this may account for the non-significant change in FFR values.Abstract 20 Table 1Angiographic characteristics (CTO: chronic total occlusion; RCA: right coronary artery; LAD: left anterior descending artery; LCX: left circumflex artery; PCI: percutaneous coronary intervention)

Excess local tissue production of prolactin may be associated with development and progression of breast and prostate cancers. Pure prolactin-receptor antagonists, such as described here, block prolactin signaling, and may provide a novel therapeutic approach to these cancers, as well as a means of treating drug-resistant forms of hyperprolactinemia. Prolactin is a polypeptide hormone whose major biological actions are related to normal lactation and reproduction. Abnormally high prolactin levels, referred to as hyperprolactinemia, can result in various reproductive disorders. Currently, therapeutic management of hyperprolactinemia relies on dopamine agonists, since dopamine is the primary physiological suppressor of pituitary prolactin production. Epidemiologic studies have shown that prolactin levels in the high-normal range, as well as medications that interfere with dopamine action (e.g. certain antipsychotic drugs), might correlate with increased breast cancer risk. In addition to circulating prolactin, it is now well established that prolactin is also produced locally within various tissues, including breast and prostate. Increasing evidence, mainly from animal studies at present, suggests that excess locally produced prolactin may promote the growth of breast and prostate tumors via an autocrine or paracrine mechanism. These findings have renewed the interest in finding alternative strategies to suppress prolactin actions when dopamine agonists are ineffective. Our studies of the relationship between prolactin structure and function have resulted in the development of pure prolactin-receptor antagonists. These molecules prevent endogenous prolactin from exerting its actions via a competitive mechanism for receptor binding. In this review, we discuss the possible future therapeutic utility of this novel class of compounds. Key Points Experimental, clinical and/or epidemiologic evidence supports the role of prolactin as a promoter of benign and malignant tumors of the breast and the prostate; recent data have shown that this effect involves prolactin produced locally by these tissues, indicating that the autocrine loop of action of this hormone may be a new therapeutic target Dopamine agonists, the classical drugs used to decrease prolactin production and release from the pituitary, do not affect production of prolactin in nonpituitary tissues Prolactin-receptor antagonists are engineered prolactin mutants designed to bind but not activate this receptor, with the aim of preventing the actions of endogenous prolactin by competing for receptor binding We have recently developed a new generation of human prolactin mutants that have no residual agonistic activity: in contrast to first-generation antagonists, these new compounds behave as pure antagonists Potential indications for this novel class of compounds involve breast and prostate tumors, as well as prolactin-secreting pituitary tumors that are resistant to dopamine-agonist treatment

Learning environments overtly or implicitly address patient-centered values and have been the focus of research for more than 40 years, often in studies about the \"hidden curriculum.\" However, many of these studies occurred at single medical schools and used time-intensive ethnographic methods. This field of inquiry lacks survey methods and information about how learning environments differ across medical schools. To examine patient-centered characteristics of learning environments at 9 U.S. medical schools. Cross-sectional internet-based survey. Eight-hundred and twenty-three third- and fourth-year medical students in the classes of 2002 and 2003. We measured the patient-centeredness of learning environments with the Communication, Curriculum, and Culture (C3) Instrument, a 29-item validated measure that characterizes the degree to which a medical school's environment fosters patient-centered care. The C3 Instrument contains 3 content areas (role modeling, students' experiences, and support for students' patient-centered behaviors), and is designed to measure these areas independent of respondents' attitudes about patient-centered care. We also collected demographic and attitudinal information from respondents. The variability of C3 scores across schools in each of the 3 content areas of the instrument was striking and statistically significant (P values ranged from .001 to .004). In addition, the patterns of scores on the 3 content areas differed from school to school. The 9 schools demonstrated unique and different learning environments both in terms of magnitude and patterns of characteristics. Further multiinstitutional study of hidden curricula is needed to further establish the degree of variability that exists, and to assist educators in making informed choices about how to intervene at their own schools.