Conceptual definitions of indicators for the nursing outcome "Knowledge: Fall Prevention".
to construct conceptual definitions for indicators of nursing outcome Knowledge: Fall Prevention, selected for evaluation of hospitalized patients with the nursing diagnosis Risk for falls. integrative literature review performed in the LILACS, MEDLINE and Web of Science databases, comprising articles published in English, Spanish and Portuguese languages from 2005 to 2015. the final sample of the study was composed of 17 articles. The conceptualizations were constructed for 14 indicators of nursing outcome Knowledge: Fall Prevention focused on hospitalized patients. the theoretical support of the Nursing Outcomes Classification (NOC), through the process of constructing the conceptual definitions of the indicators of its results, allows nurses to accurately implement this classification in clinical practice and to evaluate the effectiveness of their interventions through the change of the patients' status over time.


The Association of Shelter Veterinarians veterinary medical care guidelines for spay-neuter programs.
As efforts to reduce the overpopulation and euthanasia of unwanted and unowned dogs and cats have increased, greater attention has been focused on spay-neuter programs throughout the United States. Because of the wide range of geographic and demographic needs, a wide variety of programs have been developed to increase delivery of spay-neuter services to targeted populations of animals, including stationary and mobile clinics, MASH-style operations, shelter services, feral cat programs, and services provided through private practitioners. In an effort to ensure a consistent level of care, the Association of Shelter Veterinarians convened a task force of veterinarians to develop veterinary medical care guidelines for spay-neuter programs. The guidelines consist of recommendations for preoperative care (eg, patient transport and housing, patient selection, client communication, record keeping, and medical considerations), anesthetic management (eg, equipment, monitoring, perioperative considerations, anesthetic protocols, and emergency preparedness), surgical care (eg, operating-area environment; surgical-pack preparation; patient preparation; surgeon preparation; surgical procedures for pediatric, juvenile, and adult patients; and identification of neutered animals), and postoperative care (eg, analgesia, recovery, and release). These guidelines are based on current principles of anesthesiology, critical care medicine, microbiology, and surgical practice, as determined from published evidence and expert opinion. They represent acceptable practices that are attainable in spay-neuter programs.


From data to knowledge in e-health applications: an integrated system for medical information modelling and retrieval.
The system described in this paper uses the technological advances in information technology in order to influence and improve healthcare practice by enabling the flexible modelling, direct representation and adaptable use of medical knowledge. It aims at resolving a number of difficulties encountered by current information repositories, such as costly customization, reusability, high maintenance and poor information modelling, by employing the architecture of the functional data model (FDM), while maintaining full interoperability with existing systems by means of XML. On the information-modelling front the system supports a variety of modelling techniques that are especially relevant to medical applications, such as complex objects, incomplete or missing information, partially structured data and multimedia content. A prototype implementation of the system has been developed which consists of a multimedia-enhanced version of the functional database language FDL, and a web-based, two-way translator interface between the application's native language and XML. This interface provides full interoperability with other, heterogeneous systems over the web, thus, significantly reducing the complexity of developing distributed healthcare systems and e-health applications.


Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis.
To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV.


The RFTS domain of Raf2 is required for Cul4 interaction and heterochromatin integrity in fission yeast.
Centromeric heterochromatin assembly in fission yeast is critical for faithful chromosome segregation at mitosis. Its assembly requires a concerted pathway of events whereby the RNA interference (RNAi) pathway guides H3K9 methylation to target sequences. H3K9 methylation, a hallmark of heterochromatin structure, is mediated by the single histone methyltransferase Clr4 (equivalent to metazoan Suv3-9), a component of the CLRC complex. Loss of or defects in CLRC components disrupts heterochromatin formation due to loss of H3K9 methylation, thus an intact, fully functional CLRC complex is required for heterochromatin integrity. Despite its importance, little is known about the contribution of the CLRC component Raf2 to H3K9 methylation and heterochromatin assembly. We demonstrate that Raf2 is concentrated at centromeres and contrary to other analyses, we find that loss of Raf2 does not affect CENP-ACnp1 localisation or recruitment to centromeres. Our sequence alignments show that Raf2 contains a Replication Foci Targeting Sequence (RFTS) domain homologous to the RFTS domain of the human DNA methyltransferase DNMT1. We show that the Raf2 RFTS domain is required for centromeric heterochromatin formation as its mutation disrupts H3K9 methylation but not the processing of centromeric transcripts into small interfering RNAs (siRNAs) by the RNAi pathway. Analysis of biochemical interactions demonstrates that the RFTS domain mediates an interaction between Raf2 and the CLRC component Cul4. We conclude that the RFTS domain of Raf2 is a protein interaction module that plays an important role in heterochromatin formation at centromeres.


Feeding the critically ill patient.
Critically ill patients are usually unable to maintain adequate volitional intake to meet their metabolic demands. As such, provision of nutrition is part of the medical care of these patients. This review provides detail and interpretation of current data on specialized nutrition therapy in critically ill patients, with focus on recently published studies. The authors used literature searches, personal contact with critical care nutrition experts, and knowledge of unpublished data for this review. Published and unpublished nutrition studies, consisting of observational and randomized controlled trials, are reviewed. The authors used consensus to summarize the evidence behind specialized nutrition. In addition, the authors provide recommendations for nutritional care of the critically ill patient. Current evidence suggests that enteral nutrition, started as soon as possible after acute resuscitative efforts, may serve therapeutic roles beyond providing calories and protein. Although many new studies have further advanced our knowledge in this area, the appropriate level of standardization has not yet been achieved for nutrition therapy, as it has in other areas of critical care. Protocolized nutrition therapy should be modified for each institution based on available expertise, local barriers, and existing culture in the ICU to optimize evidence-based nutrition care for each critically ill patient.


Differential sensitivity to trypsin of human bone-derived cells in culture: surface changes detected by partitioning in aqueous two-phase systems.
Human bone-derived cells, grown in monolayer culture, were dissociated by incubations with trypsin/EDTA and subjected to thin-layer counter-current distribution in a 'low potential' aqueous two-phase system. Two major populations of cells were detected. The number of cells in the second (more hydrophobic) population increased with length of trypsinization and time in culture. Cells allowed to 'regain' surface molecules lost by trypsinization did not produce the second population. Cells occupying the second population after a short period of trypsinization had a lower rate of division than peak 1 cells but showed a higher rate of protein synthesis per rate of division than peak 1 cells. These results show that the cells have markedly different sensitivities to trypsin digestion which may be related to cell division rate of growth. The possible relationship between this and osteoblast development are discussed.


The Limited Effect of Mindfulness-Based Interventions on Anxiety in Children and Adolescents: A Meta-Analysis.
Anxiety disorders are common mental health problems amongst youth with harmful impacts often extending into adulthood. Mindfulness-based interventions (MBIs) have become increasingly popular for addressing mental health issues, particularly in schools; however, it remains unclear how effective they are for reducing youth anxiety. This meta-analysis aimed to evaluate the efficacy and effect moderators of MBIs on anxiety outcomes in children and adolescents. Eligible studies were published randomised controlled trials (RCTs) of MBIs conducted with participants aged 18 years or younger, investigating anxiety outcomes using a well-validated anxiety scale. A systematic search of RCTs published through to February 2019 identified 20 studies for inclusion (n = 1582). A random effects model was used to synthesise MBI effects. Stratified meta-analyses as well as individual, random effects meta-regressions were performed to examine how effects varied by age group, intervention setting, control type, research location, and intervention dosage. Although, across all studies, there was a small beneficial effect of MBIs on anxiety post treatment (d = 0.26), this was significantly moderated by research location, with RCTs conducted in Iran producing large effects (d = 1.25), and RCTs conducted in Western countries demonstrating no significant beneficial effect compared to controls (very small, d = 0.05). Effects were non-significant at follow-up assessment points. Post-treatment effects were significant for MBIs conducted with children (d = 0.41) and for MBIs when compared to passive controls (d = 0.33), but non-significant for adolescents (d = 0.21), for MBIs conducted in schools (d = 0.30) and in clinics (d = 0.13), and when MBIs were compared to active controls (d = 0.12). Results suggest that MBIs are likely to have a small to medium, yet temporary effect in reducing anxiety symptoms in children (not adolescents), but amongst Western youth populations the most likely outcome, from RCTs to date, is that MBIs produce no beneficial effect in anxiety reduction. Results revealed a lack of evidence to support investment in school-based MBIs to address youth anxiety.


[Structure, ontogeny and vascularization of the flowers and inflorescences of Drimys granadensis (Winteraceae)].
Structure, ontogeny and vascularization of the flowers and inflorescences of Drimys granadensis (Winteraceae). Drimys granadensis is a widespread species in montane forests of South and Central America. In this research, the structure, ontogeny, phyllotaxis and vascularization of the flowers and inflorescences of this species was studied in a population from the Eastern hills of Sabana de Bogota, Colombia. The methods used applied both optical microscopy, with astra blue-fuchsin staining, and scanning electron microscopy, using critical point dryed and gold-paladium metallized samples. Besides, results were compared with those of Drimys winteri, a widely studied species distributed in Chile and Argentina. Additionally, we studied the detail of the floral anatomy to determine the bracteal or calicine identity of the caliptra. I confirmed the proliferative status of the monothelic inflorescence, discarding alternative explanations of the terminal flower identity. I found that uniflorescences have an acropetal development until the terminal meristem becomes the terminal flower, then this flower develops rapidly resulting in a determined uniflorescence. I found pseudosyphonosthelic vascularization in peduncles and pedicels. Besides, I discovered some evidence in the vascular and anatomical structures, to consider the caliptra as the fusion product of various structures and therefore of calicine origin. The caliptra showed a whorled phyllotaxis, but the petals, stamens and carpels presented a spiral condition; phyllotaxis change was explained by the long time lapse between the initiation of the calyx and the corolla. I found great similarities among the inflorescences of D. granadensis and D. winteri; they were different in the proliferation start time, and in the frequent presence of nomophylls in D. granadensis, in contrast to the presence of reduced bracts and bracteoles in D. winteri inflorescences.


Disappearing acts: the social networks of formerly homeless individuals with co-occurring disorders.
Studies of the social lives of men and women living with co-occurring disorders (substance abuse and serious mental illness) suggest that social networks critically influence recovery. In this paper, we examine some of the reasons that the social networks of individuals with co-occurring disorders are small, and the impact of small networks for this population. Using a social capital framework with cross-case analysis, we analyze 72 in-depth qualitative interviews with 39 formerly homeless mentally ill men and women who were substance abusers. All were participants in the New York Services Study (NYSS), a federally funded study of mentally ill adults in New York City. The patterns suggest that networks shrunk because (1) social network members died prematurely, (2) study participants withdrew or pushed others away, and (3) friends and family members faced so many obstacles of their own that they could not provide resources for the study participants. We suggest that as networks diminished, some participants responded by attempting to rebuild their networks, even if the networks provided negative social capital, and others isolated themselves socially to escape the pressures and disappointments of interaction.


Bone health of middle-aged and older surfers.
Given the lack of research investigating surfing and bone health, we aimed to assess the bone mineral density (BMD) of middle-aged and older surfers. In a cross-sectional observational design, we compared a group of middle-aged and older surfers to a group of non-surfers, age- and sex-matched controls. Participants were males, aged between 50 and 75 years. Volunteers were assessed for body mass index, bone-specific physical activity questionnaire (BPAQ) scores, daily calcium intake, and alcohol intake. Primary outcomes included BMD at the femur and lumbar spine (LS), and T-score, assessed via dual-energy X-ray absorptiometry. Bone biomarkers were also analyzed. A total of 104 participants (59 surfers and 45 controls) were assessed. Groups were similar with regards to all demographic characteristics except for percentage of lean mass (higher in surfers, mean difference [MD] +2.57%; 95% CI 0.05-5.09; p=0.046) and current BPAQ score (lower in surfers; MD -0.967; 95% CI -0.395 to -1.539; p=0.001). Surfers had a mean surfing experience of 41.2 (SD ±11.8) years and mean surfing exposure of 26.9 (SD ±15.0) hours/month. Controls were divided into two groups, according to their main physical activity: weight-bearing/high intensity (WBHI) and non-weight-bearing/low intensity (NWBLI). When compared to NWBLI controls, surfers had higher LS BMD (MD +0.064; 95% CI 0.002-0.126; p=0.041) and higher T-score (MD +0.40; 95% CI 0.01-0.80; p=0.042); however, surfers had a lower T-score than the WBHI group (MD -0.52; 95% CI -0.02 to -1.0; p=0.039). No other differences were found between groups. The findings of this study support our hypothesis that regular surfing may be an effective physical activity for middle-aged and older men to decrease bone deterioration related to aging, as we identified positive results for surfers in relation to primary outcomes.


Event-Based 3D Motion Flow Estimation Using 4D Spatio Temporal Subspaces Properties.
State of the art scene flow estimation techniques are based on projections of the 3D motion on image using luminance-sampled at the frame rate of the cameras-as the principal source of information. We introduce in this paper a pure time based approach to estimate the flow from 3D point clouds primarily output by neuromorphic event-based stereo camera rigs, or by any existing 3D depth sensor even if it does not provide nor use luminance. This method formulates the scene flow problem by applying a local piecewise regularization of the scene flow. The formulation provides a unifying framework to estimate scene flow from synchronous and asynchronous 3D point clouds. It relies on the properties of 4D space time using a decomposition into its subspaces. This method naturally exploits the properties of the neuromorphic asynchronous event based vision sensors that allows continuous time 3D point clouds reconstruction. The approach can also handle the motion of deformable object. Experiments using different 3D sensors are presented.


Analysis of anticancer platinum(II)-complexes by microemulsion electrokinetic chromatography: separation of diastereomers and estimation of octanol-water partition coefficients.
Microemulsion electrokinetic chromatography (MEEKC) was applied for the separation and lipophilicity estimation of oxaliplatin and eight novel anticancer oxaliplatin derivatives. Solubility and permeability have to be balanced in modern drug development, and the octanol-water partition coefficient (log P) still represents one of the most useful quantifiable parameters providing a reasonable estimation of a drug's lipophilicity. Therefore, the capacity factors from MEEKC were correlated to log P values derived by the traditional shake flask method. The MEEKC method was accomplished using a microemulsion of heptane/sodium dodecyl sulfate (SDS)/butanol in phosphate buffer at pH 7.4 and 37 degrees C with all analytes being in a neutral state during the run. This experimental setup allowed a baseline separation of all platinum complexes within 11 min. Remarkably, beside the very good resolution and precision of the measurements, separation of diastereomers of the complexes and quantification of the diastereomeric ratios could be achieved. Correlating the capacity factors with the corresponding log P values resulted in a linear dependency with a correlation factor of r = 0.9935. Consequently, the applied MEEKC method was found to be a highly valuable technique not only for the separation of platinum complexes but as well for the estimation of the octanol-water partition coefficient with many advantages in comparison to other methods.


Taming Time: Configuring Cancer Patients as Research Subjects.
This article explores how incurable cancer patients in the affluent Danish welfare state are recruited to clinical trials. We show that patients' impending death constitutes their potential for being configured as research subjects. To produce valuable data, patients who enroll in trials and health care professionals must engage in daily "time practices" that prolong the threshold between life and death. When death becomes inevitable, the limit of configuring dying cancer patients as research subjects is reached. Navigating this temporal logic, health care professionals balance the boundary between patients' instrumental worth as research subjects and their intrinsic worth as dying cancer patients. Whereas previous studies have critically uncovered how clinical trials operate at socioeconomic margins, we point to the ways in which clinical trials operate through temporal margins. We argue that clinical trials are dependent on configuring marginal societal spaces and marginal bodies from which to produce knowledge.


Inflammation-induced TRIM21 represses hepatic steatosis by promoting the ubiquitination of lipogenic regulators.
Nonalcoholic steatohepatitis (NASH) is a leading cause for chronic liver diseases. Current therapeutic options are limited due to an incomplete mechanistic understanding of how steatosis transitions to NASH. Here we show that the TRIM21 E3 ubiquitin ligase is induced by the synergistic actions of proinflammatory TNF-α and fatty acids in livers of humans and mice with NASH. TRIM21 ubiquitinates and degrades ChREBP, SREBP1, ACC1, and FASN, key regulators of de novo lipogenesis, and A1CF, an alternative splicing regulator of the high-activity ketohexokinase-C (KHK-C) isoform and rate-limiting enzyme of fructose metabolism. TRIM21-mediated degradation of these lipogenic activators improved steatosis and hyperglycemia as well as fructose and glucose tolerance. Our study identifies TRIM21 as a negative regulator of liver steatosis in NASH and provides mechanistic insights into an immunometabolic crosstalk that limits fatty acid synthesis and fructose metabolism during metabolic stress. Thus, enhancing this natural counteracting force of steatosis through inhibition of key lipogenic activators via TRIM21-mediated ubiquitination may provide a therapeutic opportunity to treat NASH.


Mechanics at the glass-to-gel transition of thermoresponsive microgel suspensions.
We study the rheology of systems of thermoresponsive microgels which can transition between a repulsive glass and an attractive gel state. We find marked differences between these two colloidal solids, within the same experimental system, due to the different origins for their dynamic arrest. While the rigidity of the repulsive systems depends solely on particle volume fraction, we find that the change in linear elasticity upon introducing attractive bonds in the system scales linearly with the adhesive bond strength which can be tuned with the temperature in our experiments. And while the glasses yield reversibly and with a rate-dependent energy dissipation, bond-reorganisation in the gels is suppressed so that their rupture is irreversible and accompanied by a high, but rate-independent, dissipation. These results highlight how colloids with responsive interactions can be employed to shed new light onto solid-solid transitions.


Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion.
The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05) and 53% (P<0.001) respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025) lower by 9.4 fold (89%) in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84-95%, P<0.005) in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.


Parent Partners: Evaluation of a Novel Peer-Support Intervention for the Caregivers of Children Hospitalized for Behavioral Health Conditions.
Nearly 10% of all hospitalized children have a primary behavioral health diagnosis, but the effectiveness of treatment can be limited by caregivers' challenges navigating the behavioral health system. In this study, we assessed a novel peer-support intervention ("parent partners") designed for the caregivers of children admitted to an inpatient psychiatric unit. We used a mixed-methods approach including 1) document review and interviews to assess implementation and 2) a difference-in-differences analysis using claims for Medicaid-enrolled children admitted to the intervention inpatient psychiatric unit and matched comparison children admitted to other inpatient psychiatric units to assess the impacts on health care use after discharge. Ninety-six percent of caregivers who were offered the intervention engaged with a parent partner. The primary challenges to implementation were accommodating the needs of parent partners to address behavioral health crises among their own children and initial limited engagement from behavioral health clinicians. The intervention leaders reported success in addressing these through adjustments to staffing policies, training parent partners in engagement with clinicians, and incorporating parent partners into team rounds. We did not find a statistically significant difference in follow-up outpatient behavioral health visits (adjusted treatment to comparison difference +3% [90% CI = -2%, +9%]), readmissions (+5% [-33%, +43%]), or behavioral health ED visits (-15% [-44%, +14%]). This novel intervention was implemented successfully, and although our study did not find statistically significant impacts on health care use after discharge, the findings for ED visits are suggestive of benefits. Parent peer support in inpatient settings warrants additional investigation.


Predictive validity of the Short-Term Assessment of Risk and Treatability (START) for multiple adverse outcomes: The effect of diagnosis.
The Short-Term Assessment of Risk and Treatability (START) assists risk assessment for seven risk outcomes based on scoring of risk and protective factors and assignment of clinically-informed risk levels. Its predictive validity for violence and self-harm has been established in males with schizophrenia, but accuracy across pathologically diverse samples is unknown. Routine START assessments and 3-month risk outcome data of N = 527 adult, inpatients in a UK secure mental health facility were collected. The sample was divided into diagnostic groups; predictive validity was established using receiver operating characteristics regression (rocreg) analysis in which potential covariates were controlled. In most single-diagnosis groups START risk factors ('vulnerabilities'), protective factors ('strengths'), and clinically-informed estimates predicted multiple risk outcomes with effect sizes similar to previous research. Self-harm was not predicted among patients with an organic diagnosis. The START risk estimates predicted physical aggression in all diagnostic groups, and verbal aggression, self-harm and self-neglect in most diagnostic groups. The START can assist assessment of aggressive, self-harm, and self-neglect across a range of diagnostic groups. Further research with larger sample sizes of those with multiple diagnoses is required.


Relative phase noise estimation and mitigation in Raman amplified coherent optical communication system.
The interplay between the stochastic intensity fluctuation of Raman pump laser and cross-phase modulation (XPM) effect in transmission optical fiber leads to additional phase noise, namely, relative phase noise (RPN) of signal in multi-level modulated coherent optical communication system. Both theoretical analysis and quantitative simulation have been performed to investigate the characteristics and impact of RPN. Being low-pass in nature, RPN is different from XPM induced phase noise in PSK/OOK hybrid system, and has not been considered yet. The noise power of RPN can accumulate incoherently along transmission links. With a proper signal model, we study the impact of RPN to the coherent optical communication system through Monte Carlo simulation. RPN will cause more cycle slips in Viterbi-and-Viterbi (V-V) phase estimation (PE), and the quantitative analysis of cycle slip probability is carried out. When using sliding window V-V without any optimization, the Q factor penalty of RPN on DQPSK signal can be as large as around 5 dB in strong RPN condition. However, it can be reduced by over 3 dB when using an optimal block size or optimal averaging weights.


Hinges, swivels and switches: the role of prolines in signalling via transmembrane alpha-helices.
Extracellular signals are transduced across membranes via conformational changes in the transmembrane domains (TMs) of ion channels and G-protein-coupled receptors (GPCRs). Experimental and simulation studies indicate that such conformational switches in transmembrane (alpha-helices can be generated by proline-containing motifs that form molecular hinges. Computational approaches tested on model channel-forming peptides (e.g. alamethicin) reveal functional mechanisms in gap-junction proteins (such as connexin) and voltage-gated K+ channels. Similarly, functionally important roles for proline-based switches in TM6 and TM7 were identified in GPCRs. However, hinges in transmembrane helices are not confined to proline-containing sequence motifs, as evidenced by a non-proline hinge in the M2 helix of the nicotinic acetylcholine receptor. This helix lines the pore and plays a key role in the gating of this channel.


Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.
We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions.


Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype.
Gene targeting was used to create a null allele at the epidermal growth factor receptor locus (Egfr). The phenotype was dependent on genetic background. EGFR deficiency on a CF-1 background resulted in peri-implantation death due to degeneration of the inner cell mass. On a 129/Sv background, homozygous mutants died at mid-gestation due to placental defects; on a CD-1 background, the mutants lived for up to 3 weeks and showed abnormalities in skin, kidney, brain, liver, and gastrointestinal tract. The multiple abnormalities associated with EGFR deficiency indicate that the receptor is involved in a wide range of cellular activities.


Effects of locus coeruleus stimulation on the responses of SI neurons of the rat to controlled natural and electrical stimulation of the skin.
1. The effects of microstimulation of the locus coeruleus (LC) region on the spontaneous discharge and the response of SI neurons to natural and electrical stimulation of the skin have been investigated in 26 urethane anesthetized Sprague-Dawley rats. In particular, one or two air puffs, 5-10 msec in duration, 1-2 psi, usually separated by an interval of 40 msec, were applied on the hairy skin of the wrist or the forepaw at the presentation rate of 1/sec. For units unresponsive to air puffs, similar presentation of low intensity electrical stimuli (0.2-5.0 V, 0.2-0.4 msec pulses) were applied through two needles inserted on the most effective area of the skin. Both natural and electrical stimulations of the skin were applied under control conditions, as well as 50 msec after a 250 msec train of 0.3 msec pulses at 40 Hz. 20-30 microA applied stereotaxically to the LC complex through a tungsten microelectrode. 2. Not all cortical units exhibited spontaneous discharge. Most of the units, however, which were spontaneously active, were inhibited by electrical stimulation of the LC complex, while the remaining ones were excited. The sites of stimulation, which included either the LC proper or the locus subcoeruleus, were identified following both anatomical and physiological criteria. 3. SI neurons recorded at sites between 400 and 950 microns below the surface of the cortex, thus being most likely granule cells of layers III and IV, responded to cutaneous stimuli with spikes which occurred with a latency of 20-30 msec in response to single air puffs and a latency of 15-20 msec in response to single electrical pulses to the skin. In both instances the response to the second stimulus applied at the interstimulus interval of 40 msec was markedly reduced or abolished due to postexcitatory inhibition following the response to the first stimulus (in-field inhibition). In contrast, units particularly located at or below 1000 microns from the cortical surface, which were of very large size probably corresponding to large layer V pyramidal cells, were often difficult to activate with air puffs applied at the centre of the receptive field (RF) and were submitted to electrical stimulation of the skin. 4. Among the 59 isolated SI units tested either to air puffs (45 neurons) or to electrical skin stimulation (14 neurons), 15 units (i.e., 25.4%) were facilitated, while 12 units (i.e., 20.3%) were inhibited following stimulation of the LC complex. 5. A marked feature of the facilitatory effects which usually involved the predominant response to the first air puff, but also the smaller response to the second puff, was that the increase in the number of spikes per stimulus was accompanied by a temporal focusing of the responses characterized by a clear tightening of the latency and narrowing of the peak of activity, which was often accompanied by some level of tonic inhibition of the background discharge. Thus, LC stimulation increased the signal-to-noise ratio of SI neuronal responses to skin stimulation. When inhibitory effects were induced by LC stimulation, they clearly affected the unit response to the first air puff, which was severely depressed. However, the response to the second puff could be facilitated, suggesting that LC stimulation might have produced inhibition of those inhibitory interneurons responsible for the postexcitatory inhibition of the units under examination. Evidence for spatial focusing of the response was not easily documented. In some units, however, LC stimulation produced either facilitation of the responses to puffs at the receptive field center and inhibition of the responses to puffs at the edge at the receptive field or vice versa. 6. Since the LC complex contains in the rat a predominant population of noradrenergic neurons, it is likely that the effects described above were mainly due to activation of these noradrenergic neurons. 7. (ABSTRACT TRUNCATED)


Melanin inhibits cytotoxic effects of doxorubicin and daunorubicin in MOLT 4 cells.
In the present study we have developed a simple method to elucidate the melanin binding ability of different chemotherapeutic agents. The anthracyclines, doxorubicin and daunorubicin, or the alkylating agent cisplatin were preincubated with melanin (Sepia). Melanin and free drug was then separated through centrifugation and the cytotoxic effects of corresponding drug were evaluated in a MTT (3-(4,5-dimetyltiazol-2-yl)-2,5-difenyl-tetrazoliumbromide) assay using MOLT-4 cells. Our results show that melanin pretreatment shifted the IC50 value for doxorubicin from 0.06 to 0.97 microM and for daunorubicin from 0.04 to 0.80 microM. In contrast, the IC50 values of cisplatin was not influenced by melanin pre-treatment indicating that cisplatin does not bind to melanin. By comparing equi-active concentrations from concentration-response curves with or without melanin pretreatment an approximate binding capacity of melanin could be estimated. Our results show that melanin binds about 900 nmol/mg doxorubicin and 760 nmol/mg daunorubicin. Chloroquine, which is known to bind to melanin with high affinity, was found to inhibit melanin binding of both daunorubicin and doxorubicin, thereby leading to an increased sensitivity of the anthracyclines. The clinical implications of melanin binding regarding unwanted accumulation of anthracyclines in the skin as well as chemoprotective effects against chemotherapy are discussed.


Genes Linked to Production of Secondary Metabolites in Talaromyces atroroseus Revealed Using CRISPR-Cas9.
The full potential of fungal secondary metabolism has until recently been impeded by the lack of universal genetic tools for most species. However, the emergence of several CRISPR-Cas9-based genome editing systems adapted for several genera of filamentous fungi have now opened the doors for future efforts in discovery of novel natural products and elucidation and engineering of their biosynthetic pathways in fungi where no genetic tools are in place. So far, most studies have focused on demonstrating the performance of CRISPR-Cas9 in various fungal model species, and recently we presented a versatile CRISPR-Cas9 system that can be successfully applied in several diverse Aspergillus species. Here we take it one step further and show that our system can be used also in a phylogenetically distinct and largely unexplored species from the genus of Talaromyces. Specifically, we exploit CRISPR-Cas9-based genome editing to identify a new gene in T. atroroseus responsible for production of polyketide-nonribosomal peptide hybrid products, hence, linking fungal secondary metabolites to their genetic origin in a species where no genetic engineering has previously been performed.


Therapeutic potential of krait venom.
Kraits belong to Elapideae and are widely distributed in East and South-East Asian countries. Krait venom possesses neurotoxins, membrane toxins, cardiotoxins, three finger toxins, metalloproteinases, cholinesterases, L-amino acid oxidases and serine proteases. The therapeutic potential of krait venom in pathophysiological conditions such as microbial and parasitic infections, cancer, arthritis, inflammation and blood coagulation disorder is discussed in this review. More intensive new research ventures are required to establish the therapeutic potential of krait venom in complex and emerging diseases.


MARPLE, a point-of-care, strain-level disease diagnostics and surveillance tool for complex fungal pathogens.
Effective disease management depends on timely and accurate diagnosis to guide control measures. The capacity to distinguish between individuals in a pathogen population with specific properties such as fungicide resistance, toxin production and virulence profiles is often essential to inform disease management approaches. The genomics revolution has led to technologies that can rapidly produce high-resolution genotypic information to define individual variants of a pathogen species. However, their application to complex fungal pathogens has remained limited due to the frequent inability to culture these pathogens in the absence of their host and their large genome sizes. Here, we describe the development of Mobile And Real-time PLant disEase (MARPLE) diagnostics, a portable, genomics-based, point-of-care approach specifically tailored to identify individual strains of complex fungal plant pathogens. We used targeted sequencing to overcome limitations associated with the size of fungal genomes and their often obligately biotrophic nature. Focusing on the wheat yellow rust pathogen, Puccinia striiformis f.sp. tritici (Pst), we demonstrate that our approach can be used to rapidly define individual strains, assign strains to distinct genetic lineages that have been shown to correlate tightly with their virulence profiles and monitor genes of importance. MARPLE diagnostics enables rapid identification of individual pathogen strains and has the potential to monitor those with specific properties such as fungicide resistance directly from field-collected infected plant tissue in situ. Generating results within 48 h of field sampling, this new strategy has far-reaching implications for tracking plant health threats.


Salivary Alpha-Amylase Correlates with Subjective Heat Pain Perception.
Self-reports of pain are important for an adequate therapy. This is a problem with patients and infants who are restricted in providing an accurate verbal estimation of their pain. Reliable, real-time, economical, and non-invasive physiological correlates might contribute to a more comprehensive description of pain. Salivary alpha-amylase constitutes one candidate biomarker, which reflects predominantly sympathetic nervous system alterations under stressful conditions and can be measured non-invasively. The current study investigated the effects of acute heat pain on salivary alpha-amylase activity. Heat pain tolerance was measured on the non-dominant forearm. Participants completed visual analog scales on pain intensity and unpleasantness. Saliva samples were collected directly after pain induction. Twenty-seven healthy volunteers were recruited for this study. While salivary alpha-amylase levels correlated positively with intensity and unpleasantness ratings in response to acute heat pain stimuli, there was no corresponding association with pain tolerance. Salivary alpha-amylase is suggested to be an indirect physiologic correlate of subjective heat pain perception. Future studies should address the role of salivary alpha-amylase depending on the origin of pain, the concerned tissue, and other pain assessment methods.


Head size, age and gender adjustment in MRI studies: a necessary nuisance?
Imaging studies of cerebral volumes often adjust for factors such as age that may confound between-subject comparisons. However the use of nuisance covariates in imaging studies is inconsistent, which can make interpreting results across studies difficult. Using magnetic resonance images of 78 healthy controls we assessed the effects of age, gender, head size and scanner upgrade on region of interest (ROI) volumetry, cortical thickness and voxel-based morphometric (VBM) measures. We found numerous significant associations between these variables and volumetric measures: cerebral volumes and cortical thicknesses decreased with increasing age, men had larger volumes and smaller thicknesses than women, and increasing head size was associated with larger volumes. The relationships between most ROIs and head size volumes were non-linear. With age, gender, head size and upgrade in one model we found that volumes and thicknesses decreased with increasing age, women had larger volumes than men (VBM, whole-brain and white matter volumes), increasing head size was associated with larger volumes but not cortical thickness, and scanner upgrade had an effect on thickness and some volume measures. The effects of gender on cortical thickness when adjusting for head size, age and upgrade showed some non-significant effect (women>men), whereas the independent effect of head size showed little pattern. We conclude that age and head size should be considered in ROI volume studies, age, gender and upgrade should be considered for cortical thickness studies and all variables require consideration for VBM analyses. Division of all volumes by head size is unlikely to be adequate owing to their non-proportional relationship.


Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation.
O-GlcNAcylation is a newly discovered histone modification implicated in transcriptional regulation, but no structural information on the physical effect of GlcNAcylation on chromatin exists. Here, we generate synthetic, pure GlcNAcylated histones and nucleosomes and reveal that GlcNAcylation can modulate structure through direct destabilization of H2A/H2B dimers in the nucleosome, thus promoting an 'open' chromatin state. The results suggest that a plausible molecular basis for one role of histone O-GlcNAcylation in epigenetic regulation is to lower the barrier for RNA polymerase passage and hence increase transcription.


Early Recovery Following Total and Unicompartmental Knee Arthroplasty Assessed Using Novel Patient-Reported Measures.
The early postoperative recovery period following unicompartmental (UKA) and total knee arthroplasty (TKA) is an important area for research with increasingly sensitive metrics and new technologies. This study uses 2 recently developed patient-reported scores to compare the recovery following UKA and TKA. Two consecutive cohorts of 37 UKAs and 33 TKAs completed the Oxford Arthroplasty Early Recovery Score (OARS) and the Oxford Arthroplasty Early Change Score (OACS) on days 1, 2, 3, 7, 14, and week 6. The Short Form-36 version 2 was also completed on weeks 1, 2, and 6. Improvements within cohorts and comparisons between cohorts were assessed. For both UKA and TKA the speed of recovery was rapid early on and then progressively decreased. At all time points, the UKA cohort reported similar or significantly better scores than the TKA cohort. The overall OARS (P < .001) showed that UKA recovered, shown as improvement on the OARS, 2-3 times faster than TKA. OARS subscales demonstrated that UKA had better Function/Mobility (P = .003) particularly early in the recovery, and better Nausea/Feeling Unwell (P < .001) and Fatigue/Sleep (P = .009) later in the recovery. UKA also had less pain at 2 weeks (P = .03). There was no significant difference between UKA and TKA OACS. UKA had significantly better scores in 3 of the 8 Short Form-36 domains, with the largest difference being in Role-Emotional (P = .003). The OARS is useful for the assessment of postoperative recovery. This study provides direct evidence that recovery following UKA is better and 2-3 times faster than following TKA. All differences may be explained by the less invasive nature of UKA.


Exposure-based cycling crash, near miss and injury rates: the Safer Cycling Prospective Cohort Study protocol.
There are clear personal, social and environmental benefits of cycling. However, safety concerns are among the frequently cited barriers to cycling. In Australia, there are no exposure-based measures of the rates of crash or 'near miss' experienced by cyclists. A prospective cohort study over 12 months, with all data collected via web-based online data entry. Two thousand adults aged 18 years and older, living in New South Wales (Australia), who usually bicycle at least once a month, will be recruited from March to November 2011. In the 12 months following enrolment, cyclists will be surveyed on six occasions (weeks 8, 16, 24, 32, 40 and 48 from the week of the enrolment survey). In these survey weeks, cyclists will be asked to provide daily reports of distance travelled; time, location and duration of trips; infrastructure used; crashes, near misses and crash-related injuries. Information on crashes and injuries will also be sought for the intervening period between the last and current survey. A subsample of participants will receive bicycle trip computers to provide objective measurement of distance travelled. This study protocol describes the prospective cohort study developed to assess near misses, crashes and injuries among cyclists by time and distance travelled and by type of infrastructure used, with recruited participants entering data remotely using the internet. We expect to be able to calculate event rates according to exposure overall and for different infrastructure types and to report in-depth information about event causation.


Teaching the physical examination: a longitudinal strategy for tomorrow's physicians.
The physical examination is an essential clinical skill. The traditional approach to teaching the physical exam has involved a comprehensive "head-to-toe" checklist, which is often used to assess students before they begin their clinical clerkships. This method has been criticized for its lack of clinical context and for promoting rote memorization without critical thinking. In response to these concerns, Gowda and colleagues surveyed a national sample of clinical skills educators in order to develop a consensus "core" physical exam, which they report in this issue. The core physical exam is intended to be performed for every patient admitted by students during their medicine clerkships and to be supplemented by symptom-driven "clusters" of additional history and physical exam maneuvers.In this commentary, the authors review the strengths and limitations of this Core + Clusters technique as well as the head-to-toe approach. They propose that the head-to-toe still has a place in medical education, particularly for beginning students with little knowledge of pathophysiology and for patients with vague or multiple symptoms. The authors suggest that the ideal curriculum would include teaching both the head-to-toe and the Core + Clusters exams in sequence. This iterative approach to physical exam teaching would allow a student to assess a patient in a comprehensive manner while incorporating more clinical reasoning as further medical knowledge is acquired.


COX-2 inhibitors and the heart: are all coxibs the same?
The selective COX-2 inhibitors (coxibs) were originally developed to minimise the adverse effects of conventional non-steroidal anti-inflammatory drugs (NSAIDs) while maintaining the same analgesic and anti-inflammatory properties. Many large studies confirmed the improved gastric side effect profile of coxibs compared with non-selective NSAIDs; however, reports of increased cardiovascular morbidity and mortality followed, and the manufacturer Merck was forced to withdraw rofecoxib (Vioxx) from the market. Other coxibs have also either perished or had restrictions placed on their use. However, there seem to be significant differences between coxibs regarding their cardiovascular profiles, and the evidence for a class effect is dubious. In this paper, the current body of knowledge regarding the cardiovascular toxicities of coxibs is reviewed. The take home message for prescribing NSAIDs and those coxibs still on the market seems to be one of caution rather than contraindication, except in patients with significant cardiovascular risk factors.


Imaging in Suspected Renal Colic: Systematic Review of the Literature and Multispecialty Consensus.
Renal colic is common and computed tomography (CT) is frequently used when the diagnosis of kidney stone is suspected. CT is accurate but exposes patients to ionizing radiation and has not been shown to alter either interventional approaches or hospital admission rates. This multiorganizational transdisciplinary collaboration seeks evidence-based, multispecialty consensus on optimal imaging across different clinical scenarios in patients with suspected renal colic in the acute setting. In conjunction with the American College of Emergency Physicians (ACEP) Emergency Quality Network, we formed a 9-member panel with 3 physician representatives each from ACEP, the American College of Radiology, and the American Urology Association. A systematic literature review was used as the basis for a 3-step modified Delphi process to seek consensus on optimal imaging in 29 specific clinical scenarios. From an initial search yielding 6,337 records, there were 232 relevant articles of acceptable evidence quality to guide the literature summary. At the completion of the Delphi process consensus, out of the 29 scenarios agreement was rated as perfect in 15 (52%), excellent in 8 (28%), good in 3 (10%), and moderate in 3 (10%). There were no scenarios in which at least moderate consensus was not reached. CT was recommended in 7 scenarios (24%), with ultrasonography in 9 (31%) and no further imaging needed in 12 (45%). Evidence and multispecialty consensus support ultrasonography or no further imaging in specific clinical scenarios, with reduced-radiation-dose CT to be used when CT is needed for patients with suspected renal colic.


Triple oxygen isotope analysis of nitrate using the denitrifier method and thermal decomposition of N2O.
Interaction with ozone transfers its anomalous (non-mass-dependent) 17O enrichment to atmospheric nitrogen oxides and nitrate. The 17O anomaly (Delta17O) in nitrate can be used to identify atmospheric nitrate inputs into terrestrial and aquatic environments as well as to study the role of ozone in the atmosphere's reactive nitrogen cycle. We report here on an online method for analysis of the 17O anomaly, using a strain of denitrifiers to convert nitrate to N2O, which decomposes quantitatively to N2 and O2 in a gold furnace at 800 degrees C, followed by gas chromatographic separation and isotope analysis of O2. This method requires approximately 50 nmol of nitrate, 2-3 orders of magnitude less than previous offline thermal decomposition methods to achieve a similar analytical precision of 0.5 per thousand for Delta17O. There is no significant memory effect, but calibration via nitrate or N2O reference materials is required for scale normalization. The N2O decomposition method is shown to be well-suited for nitrate analysis in freshwater and seawater samples from various environments.


Modular 32-channel transceiver coil array for cardiac MRI at 7.0T.
To design and evaluate a modular transceiver coil array with 32 independent channels for cardiac MRI at 7.0T. The modular coil array comprises eight independent building blocks, each containing four transceiver loop elements. Numerical simulations were used for B1 (+) field homogenization and radiofrequency (RF) safety validation. RF characteristics were examined in a phantom study. The array's suitability for accelerated high spatial resolution two-dimensional (2D) FLASH CINE imaging of the heart was examined in a volunteer study. Transmission field adjustments and RF characteristics were found to be suitable for the volunteer study. The signal-to-noise intrinsic to 7.0T together with the coil performance afforded a spatial resolution of 1.1 × 1.1 × 2.5 mm(3) for 2D CINE FLASH MRI, which is by a factor of 6 superior to standardized CINE protocols used in clinical practice at 1.5T. The 32-channel transceiver array supports one-dimensional acceleration factors of up to R = 4 without impairing image quality significantly. The modular 32-channel transceiver cardiac array supports accelerated and high spatial resolution cardiac MRI. The array is compatible with multichannel transmission and provides a technological basis for future clinical assessment of parallel transmission techniques at 7.0T.


Shared decision making in senior medical students: results from a national survey.
To explore perceptions and experiences of Peruvian medical students about observed, preferred, and feasible decision-making approaches. We surveyed senior medical students from 19 teaching hospitals in 4 major cities in Peru. The self-administered questionnaire collected demographic information, current approach, exposure to role models for and training in shared decision making, and perceptions of the pertinence and feasibility of the different decision-making approaches in general as well as in challenging scenarios. A total of 327 senior medical students (51% female) were included. The mean age was 25 years. Among all respondents, 2% reported receiving both theoretical and practical training in shared decision making. While 46% of students identified their current decision-making approach as clinician-as-perfect-agent, 50% of students identified their teachers with the paternalistic approach. Remarkably, 53% of students thought shared decision making should be the preferred approach and 50% considered it feasible in Peru. Among the 10 challenging scenarios, shared decision making reached a plurality (40%) in only one scenario (terminally ill patients). Despite limited exposure and training, Peruvian medical students aspire to practice shared decision making but their current attitude reflects the less participatory approaches they see role modeled by their teachers.


Measurements of the associated production of a Z boson and b jets in pp collisions at s = 8 TeV.
Measurements of the associated production of a Z boson with at least one jet originating from a b quark in proton-proton collisions at s = 8 TeV are presented. Differential cross sections are measured with data collected by the CMS experiment corresponding to an integrated luminosity of 19.8 fb - 1 . Z bosons are reconstructed through their decays to electrons and muons. Cross sections are measured as a function of observables characterizing the kinematics of the b jet and the Z boson. Ratios of differential cross sections for the associated production with at least one b jet to the associated production with any jet are also presented. The production of a Z boson with at least two b jets is investigated, and differential cross sections are measured for the dijet system. Results are compared to theoretical predictions, testing two different flavour schemes for the choice of initial-state partons.


Fractional dextran and protein clearances in glomerulonephritis and in diabetic nephropathy.
The renal clearance of dextran and protein of different molecular sizes has been measured in 42 proteinuric patients with diabetes and glomerulonephritis. In both patient groups the fractional low molecular (radii 3.0-3.6 nm) dextran clearances were significantly decreased whereas the fractional high molecular (radii 5.1-7.8 nm) dextran clearances were increased as compared with the controls. A porosity/charge index was constructed by calculating the ratio of fractional clearances of neutral to anionic macromolecules (theta D3.6/theta ALB, theta D5.1/theta IgG). In diabetic patients the relation between the fractional clearances of neutral and anionic macromolecules was dependent on glomerular filtration rate. It seems likely that the altered glomerular permeability in diabetic nephropathy is associated with a decrease of charge as renal function deteriorates. In glomerulonephritis the process is different and there is a high degree of variation from case to case.


Emotional labor: relevant theory for occupational health practice in post-industrial America.
The occupational experience of workers in service-oriented jobs can have profound effects on their health and well being, such as burnout, inauthenticity, and job dissatisfaction. The growing service economy and resultant proliferation of service-oriented jobs in current times and in the future must be acknowledged and investigated. The move from an economy driven by manufacturing industries to one dominated by service industries has taken place and currently prevails in the United States. In recognizing this shift in the "work" experience of the American work force, the changing nature of work related hazards must also be considered. Emotional labor has come to be known as an appreciable aspect of work involving direct interactions with clients and customers that can lead to adverse psychosocial outcomes. These relationships reveal the potential unpleasantness of service employment in which the performance of emotional labor is unavoidable. Although worker attributes can influence the emotional experience on the job, emotional labor is also likely to threaten the well being of workers through significantly high demands to express organizationally desired emotions and low control over what emotions can be felt and displayed. Recognition and investigation of emotional labor is necessary to understand its effects on worker populations. Conceptual models featuring emotional labor are available to guide research. However, discrimination among them based on utility and application in relation to identified study objectives and needs is essential.


Pushing the limits forward: transradial superficial femoral artery stenting.
Percutaneous revascularization of superficial femoral artery (SFA) is increasingly carried out to treat patients with peripheral vascular disease and either intermittent claudication or critical limb ischemia. Transradial vascular access is increasingly adopted for invasive procedures due to reduced access-site complications and improved patient's comfort, compared with transfemoral. However, compared with coronary interventions, the adoption of transradial access in peripheral procedures is limited. Concerning SFA interventions, transradial access is usually prevented by the distance between the vascular access and the target lesion, which extends over the length of the currently available devices. Thanks to technical improvements, resulting in specifically dedicated low-profile equipment with adequate shaft length availability, transradial access is now feasible for the treatment of selected SFA lesions. We report the first two cases of SFA stenting performed by transradial access with a new specifically developed self-expanding nitinol stent with extended delivery system length. This report suggests that, with proper technique and specifically dedicated equipment, transradial SFA stenting is feasible. Treatment of SFA disease by transradial route, allowing for immediate post-procedure walking and simultaneous bilateral interventions, may represent an alternative for effective treatment of selected patients with SFA lesions.


Phylogenetic analysis of porcine epidemic diarrhea virus field strains prevailing recently in China.
Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), which is characterized by severe diarrhea, dehydration and high mortality in the affected pigs. Recently, clinical outbreaks of diarrhea in suckling piglets emerged in pig-producing areas of China. In this study, molecular detection of PEDV was conducted using RT-PCR (targeting the M gene) on samples collected from piglets with watery diarrhea from 15 pig farms, and phylogenetic analysis of PEDV field strains was carried out based on their M and S genes. In addition, the complete genome sequence of a PEDV field strain was determined. PEDV was detected in 92.7 % of the samples (267/288). The 15 M genes that were amplified shared 99.6-100 % nucleotide identity and 99.1-100 % amino acid similarity with each other. The 15 S genes exhibited 98.6-99.9 % homology, both at the nucleotide level and at the deduced amino acid level. Phylogenetic analysis showed that all of the amplified M genes grouped in cluster 3, together with some Chinese, Korean and Thai strains, while all of the amplified S genes were in cluster 3 and were closely related to Korean strains. Compared with previous PEDV strains, all of the S genes have common characteristics, namely, a 4-aa (GENQ) insertion between positions 55 and 56, a 1-aa (N) insertion between positions 135 and 136, and a 2-aa (DG) deletion between positions 155 and 156, similar or identical to Korean KNU-serial strains reported in recent years. The genome of the sequenced PEDV field strain is 28,038 nucleotides in length, excluding the poly (A) tail. Our findings suggest that a novel PEDV with a characteristic variant S gene is responsible for recent outbreaks of clinical diarrhea in piglets in China.


Unstructured treatment interruption of antiretroviral therapy in clinical practice: a systematic review.
To characterize the frequency, reasons, risk factors, and consequences of unstructured anti-retroviral treatment interruptions. Systematic review. Seventy studies were included. The median proportion of patients interrupting treatment was 23% for a median duration of 150 days. The most frequently reported reasons for interruptions were drug toxicity, adverse events, and side-effects; studies from developing countries additionally cited treatment costs and pharmacy stock-outs as concerns. Younger age and injecting drug use was a frequently reported risk factor. Other risk factors included CD4 count, socioeconomic variables, and pharmacy stock outs. Treatment interruptions increased the risk of death, opportunistic infections, virologic failure, resistance development, and poor immunological recovery. Proposed interventions to minimize interruptions included counseling, mental health services, services for women, men, and ethnic minorities. One intervention study found that the use of short message service reminders decrease the prevalence of treatment interruption from 19% to 10%. Finally, several studies from Africa stressed the importance of reliable and free access to medication. Treatment interruptions are common and contribute to worsening patient outcomes. HIV/AIDS programmes should consider assessing their causes and frequency as part of routine monitoring. Future research should focus on evaluating interventions to address the most frequently reported reasons for interruptions.


THE QUANTITATIVE CHANGES IN THE PROTEINS IN THE BLOOD PLASMA OF HORSES IN THE COURSE OF IMMUNIZATION.
Gravimetric determinations were recorded for the total and several individual proteins (in the sodium oxalate plasma) fractioned with ammonium sulphate and sodium chloride. At precipitation, the plasma salt mixture had been diluted to a final volume of ten times the amount of plasma employed. Coagulations were on aliquot portions of filtrates, and the individual protein constituents (except serumalbumin) were calculated by difference. The eleven horses had been subjected to simultaneous immunization against diphtheria and tetanus toxins, each horse being subsequently continued on the toxin to which it responded best. Test bleedings of about 500 cubic centimeters only were made until maximum antitoxic potency (with almost coincident greatest variation See PDF for Structure in the contents of the several proteins) had been attained; routine bleedings of four to ten liters for antitoxin production were then instituted. The two refractory, one medium and the eight horses yielding a highly potent antitoxic plasma, all showed an increase of from 40 to 114 per cent. in the total serumglobulin. For the refractory animals, this increase was 59.3 and 87.9 per cents. In one refractory and in one high horse, the serumglobulin maximum preceded the highest concentration in antitoxin. In seven of the horses, the greatest increase in the total serumglobulin was coincident with the maximum antitoxic potency. The serumglobulin increase, however, tended relatively to precede that of the antitoxin. In the two other horses, both maxima also were observed together; no "intermediate" bleedings were made in these two instances. The greatest absolute increase in the serumglobulin was observed in the most potent plasma obtained in the series; the second place, however, went to a refractory horse. Subsequent to the maxima, the serumglobulin content was maintained at high concentration, in spite of repeated bleedings; it then only roughly paralleled the antitoxic variations in the plasma of the individual animals. At dilutions of the plasma in the precipitated mixtures of 1:15, 1:5 and 1:10, the ammonium sulphate "euglobulin" fraction amounted to about 60 to 70, 20 to 24 and 10 to 15 per cents., respectively, of the total serumglobulin in both the normal and the antitoxic plasma. In an 850 unit plasma, an increase in the "euglobulin" over the normal percentage was observed, but the high content of protein in this plasma probably influenced the precipitation limits. The influence of the protein concentration is indicated by the different percentages for the "euglobulin" obtained for the three dilutions of 1:15, 1:5 and 1:10. The "euglobulin" then was not increased to a greater extent than the "pseudoglobulin" as the result of immunization, as has at times been maintained. See PDF for Structure The "euglobulin" precipitated by saturating the plasma with sodium chloride (at ultimate dilution of the plasma 1:10) was much greater in normal plasma than the ammonium sulphate "euglobulin" at the same dilution. There was a tendency in early immunization for this sodium chloride "euglobulin" to increase along with the total serumglobulin; it rapidly diminished, however, until at the height of immunization and maximum serumglobulin concentration, it may have reached less than half the normal absolute amount. The serum albumin was diminished a third to a half the normal along with the serumglobulin increase. Subsequent to the anti- See PDF for Structure toxic and serumglobulin maxima, figures as low as a fifth of the original serumalbumin content have been noted. It is suggested that this diminution of the sodium chloride "euglobulin" and the serumalbumin is a physiological compensation for the greater viscosity of the plasma because of the increase in the more soluble serumglobulins. No characteristic alteration in the fibrinogen of the plasma was observed during immunization. Individual variations up to 0.5 gram per 100 cubic centimeters of plasma have been recorded. The influence of repeated bleedings does not essentially influence the protein changes induced by immunization. These remarkable regenerative processes are worthy of note. The results of our investigation indicate that in "forced" immunization, the same characteristic quantitative changes can occur in the blood proteins of both refractory horses and those yielding a highly potent antitoxic plasma. We cannot conclude, however, that the serumglobulin increase does not represent an accumulation of antitoxin, at least in part; it is possible that other antibodies may be formed either prior to or along with the specific antitoxin and that these may constitute a portion of the increase in the more soluble serumglobulin with which protein such substances are associated.


Association of obesity with chronic kidney disease in elderly patients with nonalcoholic fatty liver disease.
This study investigated an association between obesity and impaired renal functions in elderly patients with nonalcoholic fatty liver disease (NAFLD) and evaluated the risk factors for chronic kidney disease (CKD) in these patients. A cross-sectional study was performed involving 515 elderly patients (≥ 60 years old) with NAFLD. Demographics, body mass index (BMI), medical history, and laboratory parameters were compared for groups stratified by obesity (≥ 28 kg/m2) or CKD. An association between obesity and CKD was analyzed, and a multivariate logistic regression analysis was conducted for risk factors associated with CKD. In the overall population, 28.7% were obese and 54.8% had CKD; there were more women (58.8%) than men. The prevalence of hypertension and diabetes was similar between the obese and nonobese groups and between the CKD and non-CKD groups. Obese patients had significantly higher levels of serum uric acid and estimated glomerular filtration rates when compared with the nonobese group. When compared with those without CKD, patients with CKD were significantly older in addition to having higher BMI and serum uric acid levels. The multivariate logistic regression analysis indicated that CKD was positively associated with age, BMI, and serum uric acid levels. Elderly obese patients with NAFLD are at a higher risk of CKD. NAFLD patients with advanced age, greater BMI, or higher serum uric acid levels are more prone to developing CKD. The renal function of NAFLD patients should be closely monitored.


Association of leukocyte-depleted blood transfusions with infectious complications after cardiac surgery.
To test the hypothesis that leukocyte-mediated immunosuppression may contribute to postoperative infections after blood transfusions, we compared the incidence of postoperative infections in patients undergoing elective coronary artery bypass graft (CABG) surgery who received either leukocyte-depleted (LD-RBCC) or non-LD transfusions of red blood cell concentrates (RBCC) within 48 h of surgery. Data for all primary elective CABG patients between 1995 and 1998 who received allogeneic RBCC transfusions in the first 48 h after surgery were collected. Patients were divided into two groups (group LD: LD-RBCC transfusions only; group non-LD: non-LD-RBCC transfusions only were excluded). Patients who received a combination of LD and non-LD-RBCC transfusions, or any blood products other than RBCC were excluded. Infectious complications recorded included pneumonia, acute respiratory distress syndrome, mediastinitis, leg wound/sternal wound infection, nosocomial infection, catheter-related infection, urinary tract infection, decubitus ulcers, and bacteremia/fungemia. One hundred forty-two patients received only LD-RBCC transfusions, and 1,765 patients received only non-LD-RBCC transfusions. Power analysis demonstrated that the sample size attained 80% power to detect an odds ratio of 2.1 at a significance level of p < 0.05. Infection rates were not significantly different between the non-LD and LD groups (7.57% vs. 9.52%, p = 0.40). Leukocyte depletion status of RBCC transfusions was not a predictor of infectious complications (p = 0.73). However, total units of RBCC received was highly associated with increased infection (p = 0.0001). No association between postoperative infections and the use of leukocyte-depleted blood was identified. However, an increased incidence of postoperative infections was observed to be associated with blood transfusions in general.


What Messages Do Patients Remember? Relationships Among Patients' Perceptions of Physical Therapists' Messages, Patient Characteristics, Satisfaction, and Outcome.
Based on a behavioral medicine perspective, modern recommendations for physical therapists treating patients with spinal pain include performing a trustworthy physical examination, conveying the message that back pain is benign, and stressing that activity is a key to recovery. However, little evidence is available on how patients perceive these biopsychosocial messages and how patients' perceptions of these messages relate to their recovery. The aim of this study was to explore the relationships between perceptions of treatment delivery that are related to an evidence-based approach and psychological factors, treatment outcome, and treatment satisfaction. A cohort study with 3 measurement points was conducted. Data on 281 participants were collected. High catastrophizing and lower mood in the participants were correlated to "not perceiving the biopsychosocial message" measured at 6 weeks after treatment start. Participants who did not perceive the biopsychosocial message were at higher risk for disability and had lower treatment satisfaction 6 months after treatment start even when controlling for pretreatment pain intensity. "Not perceiving the biopsychosocial message" was not a mediator for treatment outcome and treatment satisfaction. Physical therapists' treatment orientations or attitudes were not related to the perception of the message by the patients. There was no measure of actual practice behavior. Maladaptive cognitions and negative emotions appear to affect the way information provided during treatment is perceived by patients. The way information is perceived by patients influences treatment outcome and treatment satisfaction. Physical therapists are advised to check that patients with higher levels of catastrophizing and lower mood are correctly perceiving and interpreting a biopsychosocial message.


Anaphylaxis Triggers and Treatments by Grade Level and Staff Training: Findings from the EPIPEN4SCHOOLS Pilot Survey.
This pilot survey was designed to evaluate the characteristics of anaphylactic events and epinephrine autoinjector (EAI) use in children in U.S. schools. A cross-sectional, web-based, pilot survey of schools participating in the EPIPEN4SCHOOLS® program (Mylan Specialty L.P., Canonsburg, PA) assessed characteristics of anaphylactic events and EAI use during the 2013-2014 academic year. Respondents reported 757 anaphylactic events experienced by students; student grade level was noted for 724 events. Of these events, 32.3% (234/724) were experienced by students in grade school, 18.6% (135/724) by students in middle school, and 49.0% (355/724) by students in high school. Frequency of food-related triggers was consistently high across grade levels. However, many events experienced by students in high school (22.3%, 79/355), middle school (15.0%, 20/135), and grade school (14.1%, 33/234) had an unknown trigger. In 36.0% of schools (2008/5579), only the school nurse and select staff received training to recognize anaphylaxis; most staff or all staff received training in 28.9% (1610/5579) and 30.9% (1722/5579) of schools, respectively. In a majority of schools (54.2%, 3003/5544), only the school nurse and select staff were permitted to administer epinephrine, whereas most staff or all staff were permitted to administer epinephrine in 15.8% (876/5544) and 21.9% (1212/5544) of schools, respectively. Risk of anaphylaxis may be particularly high during adolescence, and some students encounter staff members who are untrained in anaphylaxis recognition or management, or both. These findings support the need for continued anaphylaxis training for the protection of all students, staff, and visitors.


Precision oncology in Latin America: current situation, challenges and perspectives.
Anti-cancer cytotoxic treatments like platinum-derived compounds often show low therapeutic efficacy, high-risk side effects and resistance. Hence, targeted treatments designed to attack only tumour cells avoiding these harmful side effects are highly needed in clinical practice. Due to this, precision oncology has arisen as an approach to specifically target alterations present only in cancer cells, minimising side effects for patients. It involves the use of molecular biomarkers present in each kind of tumour for diagnosis, prognosis and treatment. Since these biomarkers are specific for each cancer type, physicians use them to stratify, diagnose or take the best therapeutic options for each patient depending on the features of the specific tumour. This review aims to describe the current situation, limitations, advantages and perspectives about precision oncology in Latin America. For many years, many biomarkers have been used in a clinical setting in developed countries. However, in Latin American countries, their broad application has not been affordable partially due to financial and technical limitations associated with precarious health systems and poor access of low-income populations to quality health care. Furthermore, the genetic mixture in Latin American populations could generate differences in treatment responses from one population to another (pharmacoethnicity) and this should be evaluated before establishing precision therapy in particular populations. Some research groups in the region have done a lot of work in this field and these data should be taken as a starting point to establish networks oriented to finding clinically useful cancer biomarkers in Latin American populations. Latin America must create policies allowing excluded populations to gain access to health systems and next generation anti-cancer drugs, i.e. high-cost targeted therapies to improve survival. Also, cancer clinical research must be oriented to establish cancer biomarkers adapted to specific populations with different ethnicity, allowing the improvement of patient outcomes.


Plate-nanolattices at the theoretical limit of stiffness and strength.
Though beam-based lattices have dominated mechanical metamaterials for the past two decades, low structural efficiency limits their performance to fractions of the Hashin-Shtrikman and Suquet upper bounds, i.e. the theoretical stiffness and strength limits of any isotropic cellular topology, respectively. While plate-based designs are predicted to reach the upper bounds, experimental verification has remained elusive due to significant manufacturing challenges. Here, we present a new class of nanolattices, constructed from closed-cell plate-architectures. Carbon plate-nanolattices are fabricated via two-photon lithography and pyrolysis and shown to reach the Hashin-Shtrikman and Suquet upper bounds, via in situ mechanical compression, nano-computed tomography and micro-Raman spectroscopy. Demonstrating specific strengths surpassing those of bulk diamond and average performance improvements up to 639% over the best beam-nanolattices, this study provides detailed experimental evidence of plate architectures as a superior mechanical metamaterial topology.


Employment of mid-level providers in primary care and control of diabetes.
Examine potential associations between inclusion of mid-level providers in United States Veterans Affairs (VA) primary care programs and diabetes control. We established a cohort of diabetes patients (alive October 1, 1999) using the VA Diabetes Registry and VA corporate databases. 1999 VA Survey of Primary Care Practices data were combined with individual-patient information. We used a two-level hierarchical model to determine the relationship between staffing characteristics and hemoglobin A1c (HbA1c), among 88,682 patients from 198 clinics. Inclusion of nurse practitioners (NPs) at relatively limited levels (% of all providers who are NPs) in the primary care program was significantly associated with HbA1c lower by 0.31 percentage points (95% CI, -0.50% to -0.12%) compared to programs that did not include NPs. Having some level of NP staffing vs. no NP staffing was associated HbA1c lower by 0.25%. Inclusion of physician assistants (PAs) in primary care programs was generally not associated with a statistically significant difference in HbA1c. The exception is that moderate levels of PA staffing were associated with slightly higher HbA1c [0.18%, 95% CI, 0.02-0.34)]. Diabetes control among primary care patients appeared to benefit from inclusion of NPs, while an analogous association was not found for PAs.


Continuing evolution of Burkholderia mallei through genome reduction and large-scale rearrangements.
Burkholderia mallei (Bm), the causative agent of the predominately equine disease glanders, is a genetically uniform species that is very closely related to the much more diverse species Burkholderia pseudomallei (Bp), an opportunistic human pathogen and the primary cause of melioidosis. To gain insight into the relative lack of genetic diversity within Bm, we performed whole-genome comparative analysis of seven Bm strains and contrasted these with eight Bp strains. The Bm core genome (shared by all seven strains) is smaller in size than that of Bp, but the inverse is true for the variable gene sets that are distributed across strains. Interestingly, the biological roles of the Bm variable gene sets are much more homogeneous than those of Bp. The Bm variable genes are found mostly in contiguous regions flanked by insertion sequence (IS) elements, which appear to mediate excision and subsequent elimination of groups of genes that are under reduced selection in the mammalian host. The analysis suggests that the Bm genome continues to evolve through random IS-mediated recombination events, and differences in gene content may contribute to differences in virulence observed among Bm strains. The results are consistent with the view that Bm recently evolved from a single strain of Bp upon introduction into an animal host followed by expansion of IS elements, prophage elimination, and genome rearrangements and reduction mediated by homologous recombination across IS elements.


The impact of a supportive leadership program in a policing organisation from the participants' perspective.
The aim of this study is to explore the implementation of an organisational level intervention, focussing on Supportive Leadership (SL), in an Australian police organisation from the perspective of supervisors and managers. The impact of the intervention was explored using a qualitative methodology using semi-structured telephone interviews with 44 participants who had attended the Supportive Leadership Workshop, designed to improve awareness of good management practices. Data was subjected to thematic analysis using a social constructivist theoretical orientation. Findings showed that SL as a concept was generally accepted by a majority of participants and that they had integrated a number of SL strategies into their work practices. The participants also identified the importance of senior personnel role-modelling SL and the negative impact of non-role modelling. RESEARCH LIMITATIONS AND IMPLICATIONS: The major limitation of the study was the non-random sample of voluntary participants. However, the nature of conducting applied studies in police organisations is inherently difficult due to confidentiality and their paramilitary nature. This study highlights the need for future studies in police leadership and occupational stress that directly explore issues from the perspective of the supervisors and managers. Interventions such as SL need support and role modelling from senior management to enhance their credibility. ORIGINAL VALUE: This paper reports on an applied intervention that received major support and funding within a police organisation. It is of value to other organizations considering similar interventions because it highlights issues that could be addressed to further enhance the program.


Analysis of therapeutic effectiveness and prognostic factor on argon-helium cryoablation combined with transcatheter arterial chemoembolization for the treatment of advanced hepatocellular carcinoma.
The objective of this study was to evaluate the effectiveness on argon-helium cryoablation combined with transcatheter arterial chemoembolization (TACE) in treating advanced hepatocellular carcinoma (HCC) and its influence factor. This trial was approved by the Guangzhou Panyu Central Hospital Ethics Committee. This was a prospective, single-center study conducted in Guangzhou Panyu Central Hospital. After informed consent was obtained, the prospective randomized clinical data of 120 patients with advanced HCC were collected. Based on the therapeutic scheme, the patients were divided into control group (TACE + argon-helium cryoablation) and observed group (TACE group). All the patients were followed up for 60 months. The pre- and post-operative cancer situation, hepatic function situation, complete remission (CR) rate, total effective rate, and survival time were evaluated. The short-term and long-term effectiveness were compared between the two groups. Both the CR rate and total effective rate of the combination group were significantly higher than those of TACE group (P < 0.05). Liver function damage of the combination group was lower than those of TACE group. The survival rate of the combination group was significantly longer than that of TACE group P < 0.05). The Cox regression model revealed that ages, tumor diameter, tumor periportal location, and liver function (Child-Pugh) were significant variables influencing survival time P < 0.05). For the treatment of advanced HCC, argon-helium cryoablation combined with TACE is obviously effective and safe. The ages, tumor diameter, tumor periportal location, and grade of liver function (Child-Pugh) have obvious impacted the treatment effectiveness.


Practical applications of quantitative microbial risk assessment (QMRA) for water safety plans.
The absence of indicator organisms in drinking water does not provide sufficient guarantee for microbial safety. Therefore the water utilities are implementing water safety plans (WSP) to safeguard drinking water quality. Quantitative microbial risk assessment (QMRA) can be used to provide objective quantitative input for the WSP. This study presents several applications of treatment modelling in QMRA to answer the risk managers questions raised in the WSP. QMRA can estimate how safe the water is, how much the safety varies and how certain the estimate of safety is. This can be used in the WSP system assessment to determine whether treatment is meeting health-based targets with the required level of certainty. Quantitative data analysis showed that short events of only 8 hours per year can dominate the yearly average health risk for the consumer. QMRA also helps the design of physical and microbial monitoring. The study showed that the required monitoring frequency increases with increasing treatment efficacy. Daily monitoring can be sufficient to verify a treatment process achieving 2 log reduction of pathogens, but a process achieving 4 log reduction needs to be monitored every 15 minutes. Similarly, QMRA helps to prepare adequate corrective actions by determining the acceptable 'down time' of a process. For example, for a process achieving 2.5 log reduction a down time of maximum 6 hours per year is acceptable. These applications illustrate how QMRA can contribute to efficient and effective management of microbial drinking water safety.


Helper bacteria halt and disarm mushroom pathogens by linearizing structurally diverse cyclolipopeptides.
The bacterial pathogen Pseudomonas tolaasii severely damages white button mushrooms by secretion of the pore-forming toxin tolaasin, the main virulence factor of brown blotch disease. Yet, fungus-associated helper bacteria of the genus Mycetocola (Mycetocola tolaasinivorans and Mycetocola lacteus) may protect their host by an unknown detoxification mechanism. By a combination of metabolic profiling, imaging mass spectrometry, structure elucidation, and bioassays, we found that the helper bacteria inactivate tolaasin by linearizing the lipocyclopeptide. Furthermore, we found that Mycetocola spp. impair the dissemination of the pathogen by cleavage of the lactone ring of pseudodesmin. The role of pseudodesmin as a major swarming factor was corroborated by identification and inactivation of the corresponding biosynthetic gene cluster. Activity-guided fractionation of the Mycetocola proteome, matrix-assisted laser desorption/ionization (MALDI) analyses, and heterologous enzyme production identified the lactonase responsible for toxin cleavage. We revealed an antivirulence strategy in the context of a tripartite interaction that has high ecological and agricultural relevance.


Inhibition of Rho kinase suppresses capsular contraction following lens injury in mice.
We investigated the effect of systemic fasudil hydrochloride and an inhibitor of nuclear translocation of myocardin-related transcription factor-A (MRTF-A) on capsular contraction in a puncture-injured lens in mice. Lens injury of an anterior capsular break was achieved in male adult C57Bl/6 mice under general and topical anesthesia at 1 h after systemic fasudil hydrochloride (intraperitoneal, 10 mg/kg body weight) or vehicle administration. The mice were allowed to heal after instillation of ofloxacin ointment, for 5 and 10 days with daily administration of fasudil hydrochloride or vehicle. In another series of experiment, we examined the effect of systemic administration of an MRTF-A inhibitor (CCG-203971, 100 mg/kg twice a day) on fibrogenic reaction and tissue contraction in an injured lens on day 5 or 10. The eye was processed for histology and immunohistochemistry for SM22, proliferating cell nuclear antigen (PCNA), or MRTF-A. In hematoxylin and eosin - stained samples, the distance between each edge of the break of the anterior capsule was measured and statistically analyzed. A cluster of lens cell accumulation was formed adjacent to the edge of the capsular break on day 5. It contained cells labeled for SM22 and PCNA. The size of the cell cluster was larger in fasudil group of mice than in control mice on day 5. Systemic fasudil or CCG-203971 suppressed an excess contraction of the capsular break at certain time points. Systemic administration of fasudil hydrochloride could be a treatment strategy of postoperative capsular contraction following cataract-intraocular lens surgery.


Quality of life in adults with congenital heart disease: biopsychosocial determinants and sex-related differences.
To assess the quality of life (QoL) in adults with congenital heart disease (ACHD) and to explore the sex-related differences and biopsychosocial determinants in an Asian cohort. Prospective cross-sectional clinical study. One tertiary medical centre in Taiwan. The QoL of ACHD (≥20 years) was investigated using the Taiwanese version of the QoL questionnaire designed by the WHO, which assesses four domains of QoL (physical, psychological, social and environmental). Personality, psychological distress and family support were assessed using the Maudsley Personality Inventory, Brief Symptom Rating Scale, and the Family APGAR score, respectively. A total of 289 patients (age 33.2 ± 10.6 years; 36% men) were studied. ACHD women had significantly lower QoL scores in the physical and psychological domains compared to the age-matched general population, whereas no differences were observed between ACHD men and the general population. Multivariate analysis showed that female gender was associated with poorer physical QoL; the sex difference in the psychological QoL was mediated by psychological distress. Interaction analysis showed that the effect of family support on the psychological domain of QoL may be different by sex. The determinants of QoL varied between different domains. Extroversion personality trait, psychological distress and family support were common determinants of most domains of QoL. In ACHD, female gender was associated with poor physical and psychological QoL. The common denominators for QoL were primarily personality trait, psychological distress and family support, but not disease severity.


Bioethics in Africa: A contextually enlightened analysis of three cases.
Across sub-Saharan Africa, bioethics is an emerging field of scholarly inquiry, informed by contextual features distinct to the region. A cultural mix comprised of Euro-American influences, indigenous traditions, Christian faiths and Muslim communities, a bioethics for the sub-Saharan region must be responsive to this milieu. This paper asks, what values and methods can best promote the practice of bioethics in Africa? We set forth a strategy that leans one way or another in response to contextual features of a particular setting. Since our aim is to be responsive to context, we begin with a series of cases and develop values and methods in response to each case as we work through its ethical analysis. Section I introduces a case involving setting priorities for public funding of services that produce large benefits for a small group of people, using the example of dialysis in Ghana. Section II presents a situation involving determining the permissibility of a double standard of quality for healthcare devices in rich and poor nations, using the example of explanting pacemakers from deceased people in wealthy nations for use by people in low- and middle-income nations. Section III describes a scenario where international groups clash with religious and spiritual healers over the chaining of people with severe mental illness at prayer camps and healing centers in Ghana. Section IV articulates a three-pronged strategy for engaging in bioethics brought to light by the case analyses and defends it against objections. Throughout the paper, we tag certain views 'African' and others 'Western' to indicate ethical beliefs commonly found in these regions and less commonly found elsewhere. We do not mean to imply that all Africans hold a certain ethical stance or that all Westerners do; nor do we mean to suggest that people outside these regions do not hold the views in question.