Pharmacokinetics/pharmacodynamics of antofloxacin hydrochloride in a neutropenic murine thigh model of Staphylococcus aureus infection.
Antofloxacin hydrochloride is a new fluoroquinolone antibiotic with broad-spectrum in vitro activity. Using the neutropenic murine thigh infection model, we defined the pharmacodynamic profile and property of antofloxacin hydrochloride against Staphylococcus aureus. Single-dose pharmacokinetic studies of antofloxacin hydrochloride were carried out in thigh infected mice. Therapy was initiated at 2 h postinoculation with 5-640 mg/kg per d fractionated for different dosing regimens. The thighs were removed for bacterial measurement after 24 h of therapy, the best pharmacokinetic/ pharmacodynamic (PK/PD) index correlated with the efficacy was determined by nonlinear regression analysis. A sigmoid E(max) dose-response model was used to estimate the daily dose and AUC(24 h)/MIC (minimal inhibitory concentration) required to achieve a static effect. The PK was linear with similar elimination half-life over the dose range studied. The AUC(24 h)/MIC ratio was the PK/PD parameter that best correlated with efficacy (R(2)=92.3%, 90.8% for the two organisms, compared with C(max)/MIC and T>MIC [%], respectively). The 24 h static dose ranged from 34.3 to 153.7 mg/kg per d for all S aureus strains, the total AUC(24 h)/MIC ratio to achieve bacteriostatic effect varied from 31.7 to 122.5 (mean, 65.7+/-30.6). Antofloxacin hydrochloride showed powerful antibacterial activity against the S aureus isolates used in our neutropenic infected mice model. Our data suggested that the AUC/MIC ratio appeared to be most closely linked to the bacterial outcome (R(2)>90%), and a total AUC(24 h)/MIC ratio of 65.7 appears to be the target value to achieve a net bactericidal activity against S aureus, similar to the results of other fluoroquinolones.


Global burden of diabetes mellitus from 1990 to 2019 attributable to dietary factors: An analysis of the Global Burden of Disease Study 2019.
To analyse spatial and temporal changes in the global burden of diabetes mellitus (DM) attributable to dietary factors from 1990 to 2019. The burden of DM was analysed in terms of age-standardized disability-adjusted life-year (DALY) rates and age-standardized death rates (ASDRs), which were obtained from the Global Burden of Disease Study 2019, and their corresponding estimated annual percentage changes (EAPCs). The ASDR exhibited a decreasing trend (EAPC = -0.02), while the age-standardized DALY rate exhibited an increasing trend (EAPC = 0.65). Forty-four percent of the burden of DM was attributable to dietary factors, with the three largest contributors being high intake of red meat, high intake of processed meat, and low intake of fruit. Residence in a region with a high sociodemographic index (SDI) was associated with a diet low in whole grains and high in red meat and processed meat, while residence in a low-SDI region was associated with a diet low in whole grains and fruits, and high in red meat. The age-standardized DALYs of DM attributable to dietary factors increased between 1990 and 2019 but differed among areas. The three largest dietary contributors to the burden of DM were high intake of red meat, high intake of processed meat, and low intake of fruit.


Human-Guided Learning for Probabilistic Logic Models.
Advice-giving has been long explored in the artificial intelligence community to build robust learning algorithms when the data is noisy, incorrect or even insufficient. While logic based systems were effectively used in building expert systems, the role of the human has been restricted to being a "mere labeler" in recent times. We hypothesize and demonstrate that probabilistic logic can provide an effective and natural way for the expert to specify domain advice. Specifically, we consider different types of advice-giving in relational domains where noise could arise due to systematic errors or class-imbalance inherent in the domains. The advice is provided as logical statements or privileged features that are thenexplicitly considered by an iterative learning algorithm at every update. Our empirical evidence shows that human advice can effectively accelerate learning in noisy, structured domains where so far humans have been merely used as labelers or as designers of the (initial or final) structure of the model.


A diffusion tensor-based method facilitating volumetric assessment of fiber orientations in skeletal muscle.
The purpose of this study was to develop a DTI-based method to quantitatively assess fiber angles and changes therein in leg muscles in order to facilitate longitudinal studies on muscle fiber architectural adaptations in healthy subjects. The upper legs of five volunteers were scanned twice on the same day. The right lower legs of five volunteers were scanned twice with the ankle in three positions, i.e. -15° dorsiflexion, 0° neutral position, and 30° plantarflexion. The MRI protocols consisted of a noise scan, a 3-point mDixon scan and a DTI scan. Fiber-angle color maps were generated for four muscles in the upper legs and two muscles in the lower leg. Voxel-wise fiber angles (θ) were calculated from the angle between the principal eigenvector of the diffusion tensor and a reference line defined between the origo and insertion points of each muscle. Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation (CV%), minimal detectable change (MDC), standard error (SE) and Friedman test were used for assessing the feasibility of this method and in order to have an indication of the repeatability and the sensitivity. Bland-Altman analysis showed good repeatability (CV%<10 and 0.7≤ICC≤0.9) with exception of the Tibialis Anterior (TA) muscle in dorsiflexion position(CV%: 12.2) and the Semitendinosus (ST) muscle (left leg) (CV%: 11.4). The best repeatability metrics were found for the SOL muscle in neutral position (CV%: 2.6). Changes in average θ in TA and SOL with ankle positions were observed in accordance with expected agonist and antagonist functions of both muscles. For example, for the anterior left compartment the change in fiber angle Δθ with respect to the neutral position Δθ = -1.6° ± 0.8° and 2.2° ± 2.8° (p = 0.008), for dorsiflexion and plantarflexion, respectively. Our method facilitates fast inspection and quantification of muscle fiber angles in the lower and upper leg muscles in rest and detection of changes in lower-leg muscle fiber angles with varying ankle angles.


Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders.
Prenatal infection is an environmental risk factor for various brain disorders with neurodevelopmental components, including autism spectrum disorder and schizophrenia. Modeling this association in animals shows that maternal immune activation negatively affects fetal brain development and leads to the emergence of behavioral disturbances later in life. Recent discoveries in these preclinical models suggest that epigenetic modifications may be a critical molecular mechanism by which prenatal immune activation can mediate changes in brain development and functions, even across generations. This review discusses the potential epigenetic mechanisms underlying the effects of prenatal infections, thereby highlighting how infection-mediated epigenetic reprogramming may contribute to the transgenerational transmission of pathological traits. The identification of epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders appears relevant to brain disorders independently of existing diagnostic classifications and may help identifying complex patterns of transgenerational disease transmission beyond genetic inheritance. The consideration of ancestral infectious histories may be of great clinical interest and may be pivotal for developing new preventive treatment strategies against infection-mediated neurodevelopmental disorders.


Accelerated hypothesis generation for multistructure data via preference analysis.
Random hypothesis generation is integral to many robust geometric model fitting techniques. Unfortunately, it is also computationally expensive, especially for higher order geometric models and heavily contaminated data. We propose a fundamentally new approach to accelerate hypothesis sampling by guiding it with information derived from residual sorting. We show that residual sorting innately encodes the probability of two points having arisen from the same model, and is obtained without recourse to domain knowledge (e.g., keypoint matching scores) typically used in previous sampling enhancement methods. More crucially, our approach encourages sampling within coherent structures and thus can very rapidly generate all-inlier minimal subsets that maximize the robust criterion. Sampling within coherent structures also affords a natural ability to handle multistructure data, a condition that is usually detrimental to other methods. The result is a sampling scheme that offers substantial speed-ups on common computer vision tasks such as homography and fundamental matrix estimation. We show on many computer vision data, especially those with multiple structures, that ours is the only method capable of retrieving satisfactory results within realistic time budgets.


A high rate clarifier for load levelling in sewerage systems.
The combining of chemically assisted clarification with a proprietary physical separation technology has led to a high rate process for clarifying flocculated sewage and other waste streams. This hybrid physico-chemical system, known as the CDS Fine Solids Separation (FSS) System, was developed over a two year period within a sewage treatment plant environment. This paper summarises the results of a recent field trial of the system with a Victorian water authority which experiences heavy loading of sewers in a coastal town during holiday periods. The trial sought to evaluate the FSS as a tool for smoothing the load on the 11 km long sewer to the sewage treatment plant (STP). The FSS system could possibly enable the costly augmentation of the sewer to be deferred, particularly as the capacity of the existing sewer pipe is satisfactory for most of the year. Water quality parameters were determined for a range of flowrates and operational conditions over a two month period. Large reductions were achieved in TSS, TP, FC, turbidity and BOD5, with only minimal reductions in NH3 and TON. These results showed that the FSS could meet the authority's objectives for load levelling and would provide a 20-25% increase in effective sewer capacity. The data are also discussed in terms of possible use of the effluent from the FSS for water reuse applications.


The nitrative and oxidative stress in blood platelets isolated from breast cancer patients: the protectory action of aronia melanocarpa extract.
Since mechanisms involved in the relationship between oxidative stress and breast cancer are still unclear, the aim of our present study was to evaluate oxidative/nitrative modifications of blood platelet proteins by measuring the level of biomarkers of oxidative/nitrative stress such as carbonyl groups, thiol groups and 3-nitrotyrosine in proteins in patients with benign breast diseases and in patients with invasive breast cancer, and compare with the control group. Levels of carbonyl groups and 3-nitrotyrosine residues in platelet proteins were measured by ELISA and a competition ELISA, respectively. The method with 5,5′-dithio-bis(2-nitro-benzoic acid) has been used to analyse free thiol groups in platelet proteins. Patients were hospitalized in the Department of Oncological Surgery, Medical University of Lodz, Poland. Exogenous antioxidants reduce oxidative stress, therefore we also investigated in a model system in vitro the effects of a polyphenol rich extract of Aronia melanocarpa (Rosaceae, final concentration of 50 µg/ml, 5 min, 37°C) on modified blood platelet proteins as well from patients with breast cancer and from the healthy group. We demonstrated in platelet proteins from patients with invasive breast cancer a higher level of carbonyl groups than in the control healthy group (p < 0.02). The level of 3-nitrotyrosine in platelet proteins from patients with invasive breast cancer was also significantly higher than in the healthy subject group (p < 0.001). In contrast, the amount of thiol groups in platelet proteins from patients was significantly lower (about < 50%) than in control blood platelets. In a model system in vitro we also observed that the extract from berries of A. melanocarpa (50 µg/ml, 5 min, 37°C) due to antioxidant action, significantly reduced the oxidative/nitrative stress (measured by thiol groups and 3-nitrotyrosine) in platelets, not only from the healthy group, but also from patients with benign breast diseases and in patients with invasive breast cancer.


Comparative transcriptome meta-analysis reveals a set of genes involved in the responses to multiple pathogens in maize.
Maize production is constantly threatened by the presence of different fungal pathogens worldwide. Genetic resistance is the most favorable approach to reducing yield losses resulted from fungal diseases. The molecular mechanism underlying disease resistance in maize remains largely unknown. The objective of this study was to identify key genes/pathways that are consistently associated with multiple fungal pathogen infections in maize. Here, we conducted a meta-analysis of gene expression profiles from seven publicly available RNA-seq datasets of different fungal pathogen infections in maize. We identified 267 common differentially expressed genes (co-DEGs) in the four maize leaf infection experiments and 115 co-DEGs in all the seven experiments. Functional enrichment analysis showed that the co-DEGs were mainly involved in the biosynthesis of diterpenoid and phenylpropanoid. Further investigation revealed a set of genes associated with terpenoid phytoalexin and lignin biosynthesis, as well as potential pattern recognition receptors and nutrient transporter genes, which were consistently up-regulated after inoculation with different pathogens. In addition, we constructed a weighted gene co-expression network and identified several hub genes encoding transcription factors and protein kinases. Our results provide valuable insights into the pathways and genes influenced by different fungal pathogens, which might facilitate mining multiple disease resistance genes in maize.


Autoradiographic cytokinetics of colonic mucosal hyperplasia in mice.
The cytokinetics of a naturally occurring hyperplastic disease of the colon in mice were determined by autoradiography and compared to kinetic changes seen by others in nonneoplastic and neoplastic colonic disease. Cell cycle parameters were determined using the fraction-labeled mitosis method. Labeling index, labeling pattern, and migration rates were also evaluated. During colonic hyperplasia, there was an increase in variation of DNA synthesis times, resulting in prolongation of the S phase. There also was prolongation of the total cell cycle time and G1 phase. In addition, labeling index was increased 2-fold, the proliferative zone was extended to include the entire crypt column and surface mucosa, and the migration rate was accelerated. These findings parallel the "atypical" cytokinetics found in human and murine neoplastic and preneoplastic disorders of the colon and may be a typical proliferative response of mucosa to a variety of stimuli.


CANGS: a user-friendly utility for processing and analyzing 454 GS-FLX data in biodiversity studies.
Next generation sequencing (NGS) technologies have substantially increased the sequence output while the costs were dramatically reduced. In addition to the use in whole genome sequencing, the 454 GS-FLX platform is becoming a widely used tool for biodiversity surveys based on amplicon sequencing. In order to use NGS for biodiversity surveys, software tools are required, which perform quality control, trimming of the sequence reads, removal of PCR primers, and generation of input files for downstream analyses. A user-friendly software utility that carries out these steps is still lacking. We developed CANGS (Cleaning and Analyzing Next Generation Sequences) a flexible and user-friendly integrated software utility: CANGS is designed for amplicon based biodiversity surveys using the 454 sequencing platform. CANGS filters low quality sequences, removes PCR primers, filters singletons, identifies barcodes, and generates input files for downstream analyses. The downstream analyses rely either on third party software (e.g.: rarefaction analyses) or CANGS-specific scripts. The latter include modules linking 454 sequences with the name of the closest taxonomic reference retrieved from the NCBI database and the sequence divergence between them. Our software can be easily adapted to handle sequencing projects with different amplicon sizes, primer sequences, and quality thresholds, which makes this software especially useful for non-bioinformaticians. CANGS performs PCR primer clipping, filtering of low quality sequences, links sequences to NCBI taxonomy and provides input files for common rarefaction analysis software programs. CANGS is written in Perl and runs on Mac OS X/Linux and is available at http://i122server.vu-wien.ac.at/pop/software.html.


Empathy for others' suffering and its mediators in mental health professionals.
Empathy is a complex cognitive and affective process that allows humans to experience concern for others, comprehend their emotions, and eventually help them. In addition to studies with healthy subjects and various neuropsychiatric populations, a few reports have examined this domain focusing on mental health workers, whose daily work requires the development of a saliently empathic character. Building on this research line, the present population-based study aimed to (a) assess different dimensions of empathy for pain in mental health workers relative to general-physicians and non-medical workers; and (b) evaluate their relationship with relevant factors, such as moral profile, age, gender, years of experience, and workplace type. Relative to both control groups, mental health workers exhibited higher empathic concern and discomfort for others' suffering, and they favored harsher punishment to harmful actions. Furthermore, this was the only group in which empathy variability was explained by moral judgments, years of experience, and workplace type. Taken together, these results indicate that empathy is continuously at stake in mental health care scenarios, as it can be affected by contextual factors and social contingencies. More generally, they highlight the importance of studying this domain in populations characterized by extreme empathic demands.


Toxicity of brominated volatile organics to freshwater biota.
As part of a larger study investigating the fate and effects of brominated volatile organic compounds (VOCs) in contaminated groundwaters discharging to surface waters, the toxicity of 1,2 dibromoethene (DBE) and 1,1,2-tribromoethene (TriBE) to freshwater aquatic biota was investigated. Their toxicity to bacteria (Microtox(R)), microalgae (Chlorella sp.), cladocerans (Ceriodaphnia dubia), duckweed (Lemna sp.) and midges (Chironomus tepperi) was determined after careful optimization of the test conditions to minimize chemical losses throughout the tests. In addition, concentrations of DBE and TriBE were carefully monitored throughout the bioassays to ensure accurate calculation of toxicity values. 1,2-Dibromoethene showed low toxicity to most species, with concentrations to cause 50% lethality or effect (LC/EC50 values) ranging from 28 to 420 mg/L, 10% lethality or effect (LC/EC10 values) ranging from 18 to 94 mg/L and no-observed-effect concentrations (NOECs) ranging from 22 to 82 mg/L. 1,1,2-Tribromoethene was more toxic than DBE, with LC/EC50 values of 2.4 to 18 mg/L, LC/EC10 values of 0.94 to 11 mg/L and NOECs of 0.29 to 13 mg/L. Using these limited data, together with data from the only other published study on TriBE, moderate-reliability water quality guidelines (WQGs) were estimated from species sensitivity distributions. The proposed guideline trigger values for 95% species protection with 50% confidence were 2 mg/L for DBE and 0.03 mg/L for TriBE. The maximum concentrations of DBE and TriBE in nearby surface waters (3 and 1 microg /L, respectively) were well below these WQGs, so the risk to the freshwater environment receiving contaminated groundwater inflows was considered to be low, with hazard quotients <1 for both VOCs. Environ.


[The involvement of the zona pellucida in unexplained infertile women].
Unexplained infertility (*UI) was a common problem before the IVF era. A couple was declared as UI only after they passed all the routine common tests and no reason was found for the infertility. The introduction of ICSI in the IVF clinics enabled the investigation of the quality of the couple's gametes. Thus, the definition of the term UI was refined and the number of couples encompassed by this term decreased dramatically. Zona Pellucida (ZP) incompetence was described as one of the causes of UI. We recently (2004) published a case study of an UI couple due to this cause. The oocytes of the woman collapsed during the preparation of the oocytes for sperm injection. These oocytes suffered from irregular ZP and abnormal appearance. Only after gentle treatment of the oocyte-cumulus complex and ICSI fertilization, embryo development and delivery of normal newborn was achieved. This woman and others who suffer from UI did not conceive in a natural way since the ZP of the ovulated eggs did not bind sperm cells and, thereby, were not fertilized. It only recently became possible to find the reason for the infertility of the couple and the solution, through the use of highly advanced technology in the IVF-ICSI process. One of the reasons for the deformatted ZP is the malfunction of the gene that encodes the 4 glycoproteins, which compose the ZP. This is now under investigation in our Institute.


Oral and systemic photoprotection.
Photoprotection can be provided not only by ultraviolet (UV) blockers but also by oral substances. Epidemiologically identified associations between foods and skin cancer and interventional experiments have discovered mechanisms of UV skin damage. These approaches have identified oral substances that are photoprotective in humans. UV inhibits adenosine triphosphate (ATP) production causing an energy crisis, which prevents optimal skin immunity and DNA repair. Enhancing ATP production with oral nicotinamide protects from UV immunosuppression, enhances DNA repair and reduces skin cancer in humans. Reactive oxygen species also contribute to photodamage. Nontoxic substances consumed in the diet, or available as oral supplements, can protect the skin by multiple potential mechanisms. These substances include polyphenols in fruit, vegetables, wine, tea and caffeine-containing foods. UV-induced prostaglandin E2 (PGE2 ) contributes to photodamage. Nonsteroidal anti-inflammatory drugs and food substances reduce production of this lipid mediator. Fish oils are photoprotective, at least partially by reducing PGE2 . Orally consumed substances, either in the diet or as supplements, can influence cutaneous responses to UV. A current research goal is to develop an oral supplement that could be used in conjunction with other sun protective strategies in order to provide improved protection from sunlight.


S. aureus biofilm metabolic activity correlates positively with patients' eosinophil frequencies and disease severity in chronic rhinosinusitis.
Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinus mucosa. Recalcitrant CRS patients are unresponsive to medical and surgical interventions and often present with nasal polyps, tissue eosinophilia, and Staphylococcus aureus dominant mucosal biofilms. However, S. aureus sinonasal mucosal colonisation occurs in the absence of inflammation, questioning the role of S. aureus in CRS pathogenesis. Here, we aimed to investigate the relationship between S. aureus biofilm metabolic activity and virulence genes, innate immune cells, and disease severity in CRS. Biospecimens, including sinonasal tissue and nasal swabs, and clinical datasets, including disease severity scores, were obtained from CRS patients and non-CRS controls. S. aureus isolates were grown into biofilms in vitro, characterised, and sequenced. The patients' innate immune response was evaluated using flow cytometry. S. aureus was isolated in 6/19 (31.58%) controls and 23/53 (43.40%) CRS patients of 72 recruited patients. We found increased S. aureus biofilm metabolic activity in relation to increased eosinophil cell frequencies and disease severity in recalcitrant CRS cases. Mast cell frequencies were higher in tissue samples of patients carrying S. aureus harbouring lukF.PV, sea, and fnbB genes. Patients with S. aureus harbouring lukF.PV and sdrE genes had more severe disease. This offers insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.


Frontline Nurses' Post-Traumatic Stress Disorder and Associated Predictive Factors During the Second Wave of COVID-19 in Central, Uganda.
Prior to the COVID-19 pandemic, the Ugandan healthcare system was already under severe strain due to a lack of human resources, poor working conditions, and poor management. At the center of these challenges are nurses, the backbone of the health system. This study investigated post-traumatic stress disorder and associated predictive factors during the second wave of COVID-19 among frontline nurses in the country. This was a hospital-based cross-sectional study conducted among 601 nurses between May and June 2021. Post-traumatic stress disorder was assessed using PTSD Checklist-Civilian. The bivariate and multivariate logistic regression analyses were conducted to determine the factors predicting PTSD. P-values less than 0.05 were considered statistically significant at 95% CI. The estimated prevalence of post-traumatic stress disorder was 65.7%. In the multivariate logistic regression, the predictive factors of PTSD among the study participants were social support (AOR: 0.49; 95% CI: 034-0.60; p ≤ 0.001), fear of getting infected with COVID-19 (AOR: 3.10; 95% CI: 2.17-4.43; p < 0.001) and increased workload (AOR: 1.65; 95% CI: 1.16-2.34; p < 0.001). The results of the study highlight the impact of COVID-19 on the mental health of front-line nurses. Assessing PTSD among nurses may increase the understanding of COVID-19 induced mental health issues. Identifying the risk factors like lack of social support and heavy workload and providing treatment is essential given that various waves of COVID-19 seem inevitable. Supportive strategies like counseling should be provided to the nurses to prevent or manage PTSD.


A new age of peer reviewed scientific journals.
The principles of peer reviewed scientific publications date back two and one-half centuries to the origins of Medical Essays and Observations published by the Royal Society of Edinburgh (1731). This year (2012) is notable in that perhaps the most prestigious and best-known medical journal, the New England Journal of Medicine, crossed the second century mark. The methodologies of peer review have undeniably served medicine well and helped to usher in unimaginable advances in human health. Despite such illustrious history, the winds of change are in the air.


Triglycerides Paradox Among the Oldest Old: "The Lower the Better?"
Currently, most treatment guidelines suggest lowering hypertriglyceridemia of any severity, even in elderly individuals. However associations of serum triglycerides (TGs) with adverse health and mortality risk decrease with age, it remains unclear among the oldest old (aged 80 years and older). The study was to investigate the relationship of serum TG concentrations with cognitive function, activities of daily living (ADLs), frailty, and mortality among the oldest old in a prospective cohort study. Longitudinal prospective cohort study. Community-based setting in longevity areas in China. A total of 930 (mean age = 94.0 years) Chinese oldest old. The TG concentrations were measured at baseline survey in 2009. Cognitive function, ADLs, frailty, and mortality were determined over 5 years of follow-up. Cox proportional hazards models and competing risk models were performed to explore the association, adjusting for potential confounders. Each 1-mmol/L increase in TGs was associated with a nearly 20% lower risk of cognitive decline, ADL decline, and frailty aggravation during the 5 years of follow-up. Consistently, higher TGs (each 1 mmol/L) was associated with lower 5-year all-cause mortality after fully adjustment (hazard ratio [HR] = 0.79; 95% confidence interval [CI] = 0.69-0.89). Nonelevated TG concentrations (less than 2.26 mmol/L) were associated with higher mortality risk (HR = 1.72; 95% CI = 1.22-2.44), relative to TGs of 2.26 mmol/L or more. We observed similar results regarding TG concentrations and mortality in 1-year lag analysis and when excluding participants with identified chronic disease. In the oldest old, a higher concentration of TGs was associated with a lower risk of cognitive decline, ADL decline, frailty aggravation, and mortality. This paradox suggests the clinical importance of revisiting the concept of "the lower the better" for the oldest old. J Am Geriatr Soc 67:741-748, 2019.


Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial.
Polycystic ovary syndrome (PCOS) is the most common cause of infertility due to menstrual dysfunction, and the most promising treatments for this disease are insulin sensitising agents. Myo-inositol and D-chiro-inositol are insulin sensitizing agents used in PCOS treatment. In the present paper, we aimed to compare the effects myo-inositol and D-chiro-inositol on oocyte quality in euglycemic PCOS patients. Eighty-four euglycemic PCOS patients, undergoing ovulation induction for ICSI, were recruited for this study. Forty-three participants received MyoInositol 2 g twice a day and forty-one patients received D-chiro inositol 0.6 g twice a day. The results of our study showed that the total number of oocytes retrieved did not differ in the two treatments groups. However, the number of mature oocytes was significantly increased in the myo-inositol group compared to D-chiro-inositol. Concurrently, the number of immature oocytes decreased in myo-inositol treated patients. Furthermore, the myo-inositol-treated group showed an increase in the mean number of top quality embryos and in the total number of pregnancies compared to the D-chiro-inositol-treated group. Our data show that, in PCOS patients having a normal insulin response, myo-inositol treatment rather than D-chiro-inositol is able to improve oocyte and embryo quality during ovarian stimulation protocols.


Why do so few older people with aortic stenosis have valve replacement surgery?
Many older patients with severe aortic stenosis do not have valve replacement surgery. To determine the proportion of older people with symptomatic aortic stenosis referred for specialist assessment and the reasons for non-referral. Retrospective study of all patients over 75 attending the geriatric department of an English teaching hospital. Confirmation was by reviewing all echocardiographic reports. Of 40 patients with symptomatic aortic stenosis, only four had undergone surgery. Seven patients refused operation; five were medically unfit (for reasons other than heart failure) and reasons for not referring could not be found in 13 casenotes. Of the 15 patients referred to a cardiologist, eight were considered suitable for surgery. Only one in five patients over 75 with echocardiographically-confirmed aortic stenosis was considered for surgery. Prospective studies are needed to determine why patients and geriatricians do not seek specialist assessment for this treatable condition.


ATP requirement for acidic resistance in Escherichia coli.
ATP participates in many cellular metabolic processes as a major substrate to supply energy. Many systems for acidic resistance (AR) under extremely acidic conditions have been reported, but the role of ATP has not been examined. To clarify whether or not ATP is necessary for the AR in Escherichia coli, the AR of mutants deficient in genes for ATP biosynthesis was investigated in this study. The deletion of purA or purB, each of which encodes enzymes to produce AMP from inosinate (IMP), markedly decreased the AR. The content of ATP in these mutants decreased rapidly at pH 2.5 compared to that of the wild type. The AR was again decreased significantly by the mutation of adk, which encoded an enzyme to produce ADP from AMP. The DNA damage in the purA and purB mutants was higher than that in the wild type. These results demonstrated that metabolic processes that require ATP participate in survival under extremely acidic conditions, and that one such system is the ATP-dependent DNA repair system.


Sirolimus improves pain in NF1 patients with severe plexiform neurofibromas.
Plexiform neurofibromas (PNs) are common and potentially debilitating complications of neurofibromatosis 1 (NF1). These benign nerve-sheath tumors are associated with significant pain and morbidity because they compress vital structures. The mammalian target of rapamycin (mTOR) pathway is a major mediator involved in tumor growth in NF1. We present 3 cases of patients with NF1, aged 8, 16, and 17 years, followed for inoperable and symptomatic PNs; patients received sirolimus for life-threatening and painful neurofibromas after multidisciplinary consultation. Epidemiologic, clinical, and radiologic data were retrospectively collected. The volume of PNs did not differ between baseline and 12-month follow-up and pain was alleviated, with withdrawal of analgesics in 2 cases at 6 months, and significantly decreased for the third case. Sirolimus for inoperable symptomatic PNs in patients with NF1 permitted stabilization of mass and produced unpredictable and important alleviation of pain in all cases with good tolerance. This treatment was proposed in extreme cases, in absence of therapeutic alternatives, after multidisciplinary consensus. The mTOR pathway may be both a major mediator of NF1 tumor growth and regulator of nociceptor sensitivity. mTOR inhibitors clinically used as anticancer and immunosuppressant drugs could be a potential treatment of chronic pain.


When the Lyon(ized chromosome) roars: ongoing expression from an inactive X chromosome.
A tribute to Mary Lyon was held in October 2016. Many remarked about Lyon's foresight regarding many intricacies of the X-chromosome inactivation process. One such example is that a year after her original 1961 hypothesis she proposed that genes with Y homologues should escape from X inactivation to achieve dosage compensation between males and females. Fifty-five years later we have learned many details about these escapees that we attempt to summarize in this review, with a particular focus on recent findings. We now know that escapees are not rare, particularly on the human X, and that most lack functionally equivalent Y homologues, leading to their increasingly recognized role in sexually dimorphic traits. Newer sequencing technologies have expanded profiling of primary tissues that will better enable connections to sex-biased disorders as well as provide additional insights into the X-inactivation process. Chromosome organization, nuclear location and chromatin environments distinguish escapees from other X-inactivated genes. Nevertheless, several big questions remain, including what dictates their distinct epigenetic environment, the underlying basis of species differences in escapee regulation, how different classes of escapees are distinguished, and the roles that local sequences and chromosome ultrastructure play in escapee regulation.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'.


Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo.
Apoptosis-inducing factor (AIF) is a novel mediator in apoptosis. AIF is a flavoprotein that is normally confined to the mitochondrial intermembrane space, yet translocates to the nucleus in several in vitro models of apoptosis. To investigate the role of AIF in the apoptotic process in vivo, we induced retinal detachment (RD) by subretinal injection of sodium hyaluronate, either in Brown Norway rats or in C3H mice. Apoptotic DNA fragmentation, as determined by terminal nick-end labeling, was most prominent 3 days after RD. The subcellular localization of AIF was examined by immunohistochemistry and immunoelectron microscopy. In normal photoreceptor cells, AIF was present in the mitochondrion-rich inner segment. However, AIF was found in the nucleus after RD. Photoreceptor apoptosis developed similarly in C3H control mice, and in mice bearing the gld or lpr mutations, indicating that cell death occurs independently from the CD95/CD95 ligand system. Both the mitochondrio-nuclear transition of AIF localization and the nuclear DNA fragmentation were inhibited by subretinal application of brain-derived neurotrophic factor. To our knowledge, this is the first description of AIF relocalization occurring in a clinically relevant, in vivo model of apoptosis.


Convergence and contrast in the community structure of Bacteria, Fungi and Archaea along a tropical elevation-climate gradient.
Changes in species richness along climatological gradients have been instrumental in developing theories about the general drivers of biodiversity. Previous studies on microbial communities along climate gradients on mountainsides have revealed positive, negative and neutral richness trends. We examined changes in richness and composition of Fungi, Bacteria and Archaea in soil along a 50-1000 m elevation, 280-3280 mm/yr precipitation gradient in Hawai'i. Soil properties and their drivers are exceptionally well understood along this gradient. All three microbial groups responded strongly to the gradient, with community ordinations being similar along axes of environmental conditions (pH, rainfall) and resource availability (nitrogen, phosphorus). However, the form of the richness-climate relationship varied between Fungi (positive linear), Bacteria (unimodal) and Archaea (negative linear). These differences were related to resource-ecology and limiting conditions for each group, with fungal richness increasing most strongly with soil carbon, ammonia-oxidizing Archaea increasing with nitrogen mineralization rate, and Bacteria increasing with both carbon and pH. Reponses to the gradient became increasingly variable at finer taxonomic scales and within any taxonomic group most individual OTUs occurred in narrow climate-elevation ranges. These results show that microbial responses to climate gradients are heterogeneous due to complexity of underlying environmental changes and the diverse ecologies of microbial taxa.


[Syndrome of apparent mineralocorticoid excess caused by a deficiency of 11 beta-hydroxysteroid dehydrogenase: clinical and genetic study in a Chilean family followed for 19 years].
An 11-year old girl was seen in 1981 with hypokalemia, low renin, low aldosterone, and severe hypertension. A medical adrenalectomy with dexamethasone and aminoglutethimide, and the blockade of mineralocorticoid receptors with spironolactone improved her condition, but the blockade of glucocorticoid receptors with RU-486 worsened it. An aldosterone infusion induced no changes. A sister was born in 1982 with similar findings. Both patients had an impaired ability to convert cortisol to cortisone after an oral load of 200 mg cortisol. In urine, an elevated ratio for metabolites of cortisol to metabolites of cortisone was found. These data suggested a defect in the activity of renal 11 beta-hydroxysteroid dehydrogenase. Both parents were asymptomatic, phenotypically normal and non-consanguineous. Their urinary metabolites of cortisol and cortisone were normal before and after stimulation with ACTH. However, the mother reached a peak plasma cortisone concentration 3 SD below the mean reached by normal subjects after an oral 200-mg cortisol load, a fact that suggests that this test could be used to detect heterozygotes. The genetic studies revealed a homozygous mutation on exon 3 of the HSD11K gene, which by substituting TGC for CGC changes Arg 213 for Cys and induces a loss of 84% of the enzymatic activity in transfected cells. Both unrelated parents had the same heterozygous mutation. Both patients have been treated with dexamethasone but have also required spironolactone. The older sister has also required high doses of nifedipine to lower her blood pressure. After 19 years of follow-up, the older sister has become normotensive and normokalemic under therapy, and reached a final height of 140 cm at age 17. The younger sister has increased her mean blood pressure at a rate of 1 mm Hg per year, in spite of treatment. Her final height is 143.5 cm.


[Treatment of Ampullary Adenocarcinoma].
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.


Prognostic Value of S-100β Protein for Prediction of Post-Concussion Symptoms after a Mild Traumatic Brain Injury: Systematic Review and Meta-Analysis.
This systematic review and meta-analysis aimed to determine the prognostic value of S-100β protein to identify patients with post-concussion symptoms after a mild traumatic brain injury (mTBI). A search strategy was submitted to seven databases from their inception to October 2016. Individual patient data were requested. Cohort studies evaluating the association between S-100β protein level and post-concussion symptoms assessed at least seven days after the mTBI were considered. Outcomes were dichotomized as persistent (≥3 months) or early (≥7 days <3 months). Our search strategy yielded 23,298 citations of which 29 studies including between seven and 223 patients (n = 2505) were included. Post-concussion syndrome (PCS) (16 studies) and neuropsychological symptoms (9 studies) were the most frequently assessed outcomes. The odds of having persistent PCS (odds ratio [OR] 0.62, 95% confidence interval [CI]: 0.34-1.12, p = 0.11, I2 0% [n = five studies]) in patients with an elevated S-100β protein serum level were not significantly different from those of patients with normal values while the odds of having early PCS (OR 1.67, 95% CI: 0.98-2.85, p = 0.06, I2 38% [n = five studies]) were close to statistical significance. Similarly, having an elevated S-100β protein serum level was not associated with the odds of returning to work at six months (OR 2.31, 95% CI: 0.50-10.64, p = 0.28, I2 22% [n = two studies]). Overall risk of bias was considered moderate. Results suggest that the prognostic biomarker S-100β protein has a low clinical value to identify patients at risk of persistent post-concussion symptoms. Variability in injury to S-100ß protein sample time, mTBI populations, and outcomes assessed could potentially explain the lack of association and needs further evaluation.


Characterization of emissions from diffusion flare systems.
Emissions from flares typical of those found at oil-field battery sites in Alberta, Canada, were investigated to determine the degree to which the flared gases were burned and to characterize the products of combustion in the emissions. The study consisted of laboratory, pilot-scale, and field-scale investigations. Combustion of all hydrocarbon fuels in both laboratory and pilot-scale tests produced a complex variety of hydrocarbon products within the flame, primarily by pyrolytic reactions. Acetylene, ethylene, benzene, styrene, ethynyl benzene, and naphthalene were some of the major constituents produced by conversion of more than 10% of the methane within the flames. The majority of the hydrocarbons produced within the flames of pure gas fuels were effectively destroyed in the outer combustion zone, resulting in combustion efficiencies greater than 98% as measured in the emissions. The addition of liquid hydrocarbon fuels or condensates to pure gas streams had the largest effect on impairing the ability of the resulting flame to destroy the pyrolytically produced hydrocarbons, as well as the original hydrocarbon fuels directed to the flare. Crosswinds were also found to reduce the combustion efficiency (CE) of the co-flowing gas/condensate flames by causing more unburned fuel and the pyrolytically produced hydrocarbons to escape into the emissions. Flaring of solution gas at oil-field battery sites was found to burn with an efficiency of 62-82%, depending on either how much fuel was directed to flare or how much liquid hydrocarbon was in the knockout drum. Benzene, styrene, ethynyl benzene, ethynyl-methyl benzenes, toluene, xylenes, acenaphthalene, biphenyl, and fluorene were, in most cases, the most abundant compounds found in any of the emissions examined in the field flare testing. The emissions from sour solution gas flaring also contained reduced sulfur compounds and thiophenes.


Effect of yacon (Smallanthus sonchifolius) on colonic transit time in healthy volunteers.
Yacon is a root crop which contains high amounts of fructooligosaccharides (FOS). The aim of this study was to investigate the effects of yacon syrup on colon transit time in healthy volunteers. In a placebo-controlled, double-blind study yacon was administered to 16 healthy individuals (8 males, 8 females) in a dose of 20 g daily (equal to 6.4 g FOS) in a 2-week crossover design. Each period was interrupted by a 2-week wash-out phase. Transit time was assessed by a radio-opaque marker technique. Transit time (mean +/- SEM) through the gastrointestinal tract was significantly decreased from 59.7 +/- 4.3 to 38.4 +/- 4.2 h (p < 0.001). Yacon was well tolerated with an excellent side effect profile. Bloating is not an uncommon side effect observed with FOS, but bloating-related disturbances were not significantly more often reported with yacon compared to placebo. Stool frequency increased from 1.1 +/- 0.1 to 1.3 +/- 0.2 times per day and the consistency showed a tendency for softer stools as assessed by a numerical depicted stool protocol. Neither parameter did, however, reach statistical significance. Yacon markedly accelerates colonic transit in healthy individuals. Further studies are needed in constipated patients to confirm these preliminary data. Due to the low caloric content of yacon, the root could be a useful treatment in constipated diabetics or obese patients.


Consumer satisfaction with occupational health services: should it be measured?
To find answers in the literature to the questions if, why, and how consumer satisfaction with occupational health services (OHSs) should be measured. Publications about the concept of consumer satisfaction with health care and surveys of consumer satisfaction with occupational health care were reviewed. For care providers, surveys of consumer satisfaction can be useful to improve quality or as indicators of non-compliant behaviour among patients. For clients, satisfaction surveys can be helpful for choosing between healthcare providers. Satisfaction is made up of an affective component of evaluation and a cognitive component of expectations. Also, in occupational health care, patient satisfaction is measured by dimensions such as the humanness and competence of the care provider similar to health care in general. However, there are dimensions that are specific to occupational health-such as the perceived independence of the physician, unclear reasons for visiting an OHS, and the perceived extent of knowledge of OHS professionals about the patient's working conditions. Dimensions of client satisfaction are mostly similar to patient satisfaction but include more businesslike aspects. They are different for the two groups of client, employers and employees. To measure consumer satisfaction in occupational healthcare specific questionnaires must be constructed. To achieve the highest possible reader satisfaction guidelines are provided for construction of a questionnaire. Consumer satisfaction is a complex theoretical concept, but it is relatively easy to measure in practice and can be a valuable tool for quality improvement. Consumers' evaluations of occupational health services will become increasingly important due to changes in the organisation of occupational health care. Occupational healthcare providers are encouraged to measure the consumer satisfaction of their services.


Zinc Promotes Osteoblast Differentiation in Human Mesenchymal Stem Cells Via Activation of the cAMP-PKA-CREB Signaling Pathway.
The crucial trace element zinc stimulates osteogenesis in vitro and in vivo. However, the pathways mediating these effects remain poorly understood. This study aimed to investigate the effects of zinc on osteoblast differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs) and to identify the molecular mechanisms of these effects. In hBMSCs, zinc exposure resulted in a dose-dependent increase in osteogenesis and increased mRNA and protein levels of the master transcriptional factor RUNX2. Analyzing the upstream signaling pathways of RUNX2, we found that protein kinase A (PKA) signaling inhibition blocked zinc-induced osteogenic effects. Zinc exposure increased transcriptional activity and protein levels of phospho-CREB and enhanced translocation of phospho-CREB into the nucleus. These effects were reversed by H-89, a potent inhibitor of PKA. Moreover, zinc exposure led to dose-dependent increases in levels of intracellular cyclic adenosine monophosphate (cAMP). These findings indicate that zinc activates the PKA signaling pathway by triggering an increase in intracellular cAMP, leading to enhanced osteogenic differentiation in hBMSCs. Our results suggest that zinc exerts osteogenic effects in hBMSCs by activation of RUNX2 via the cAMP-PKA-CREB signaling pathway. Zinc supplementation may offer a promise as a potential pharmaceutical therapy for osteoporosis and other bone loss conditions.


Growth arrest and morphological change of human breast cancer cells by dibutyryl cyclic AMP and L-arginine.
The growth in vitro of human breast cancer cells, line MCF-7, was inhibited by a daily supplement of L-arginine (1 milligram per milliliter). Arginine acted synergistically with dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) (10(-6) molar) to enhance the growth inhibitory effect: the cell replication ceased completely within 2 days after treatment. The growth arrest accompanied a change in cell morphology and was preceded by increases in the cellular concentration of cyclic AMP, adenylate cyclase, and type II cyclic AMP-dependent protein kinase activities as well as a decrease of estrogen binding activity. The results suggest that growth of human breast cancer cells is subject to cyclic AMP-mediated regulation and that arginine may play a specific role in this process.


Derepression of a mouse alpha-fetoprotein expression vector in COS-1 cells by amplification of specific cis-acting sequences of the AFP promoter.
The existence of trans-acting regulatory factors has been demonstrated by in vivo competition with cis-acting sequences from both viral and eukaryotic genomes. Plasmids containing a functional SV40 origin of replication when transfected into permissive SV40 T-antigen producing COS-1 cells will amplify to high copy numbers (5,000 to 10,000) without inflicting toxic effects upon the host cell. This amplification vector (pSVori) has been used to amplify cis-acting regulatory elements which can act as competitors for positive and negative trans-acting factors in vivo. Using this amplification system we conducted experiments to determine whether amplification of alpha-fetoprotein (AFP) and albumin cis-acting promoter sequences could activate a corresponding co-transfected AFP-promoter-CAT or Alb-promoter-CAT expression vector in COS-1 cells. We used pMoMLV(-1009)AFPcat, or p(-308)Albcat-MoMLV as reporter genes and pSVori to amplify specific promoter sequences of the AFP or albumin promoter. Our experiments indicated that amplification of a region from -53 to -202 of the AFP promoter resulted in the activation of the pMoMLV(-1009)AFPcat and p(-308)Albcat-MoMLV expression vectors in COS-1 cells. Surprisingly, amplification of the albumin promoter sequences failed to activate either the pMoMLV(-1009)AFPcat or p(-308)Albcat-MoMLV plasmids.


Are lipoprotein disturbances in chronic hemodialyzed patients only renal failure related?
Chronically hemodialyzed (HD) patients frequently suffer from quantitative and even more often qualitative serum lipids disorders. Mostly they have increased triglycerides and VLDL-cholesterol, slightly increased or normal total and LDL-cholesterol and decreased HDL-cholesterol concentrations. The study compared lipid profile between two groups of chronic HD patients coming from regionally distinct areas, the continental and the maritime one. The aim was to examine the hypothetic influence of their different dietary habits on lipid profile. The study included 72 patients from continental region (39 men) and 50 from maritime part of the country (30 men). Patients suffering from diabetes mellitus, hypothyroidism, liver disease, alcoholics as well as sevelamer treated patients were not included. Prior to a HD session the patients were determined fasting total cholesterol, triglycerides, HDL- and LDL-cholesterol, total proteins, albumins and C-reactive protein serum concentrations. All patients were undergoing bicarbonate hemodialysis with polysulphone dialysers of low permeability. The continental group of patients were somewhat older, undergoing HD for longer period of time, of lower height, greater weight, greater body mass index, higher total (4.70 +/- 0.91:4.42 +/- 1.02 mmol/L), and LDL-cholesterol (2.78 +/- 0.74:2.66 +/- 0.75 mmol/L) concentrations, while lower triglycerides (1.72 +/- 0.84:1.81 +/- 0.83 mmol/L) and HDL-cholesterol (1.13 +/- 0.42:1.16 +/- 0.54 mmol/L). However all the differences were without statistical significance. Chi-square test showed that the continental group of patients consumed more often pork, bacon, smoked and cured meats, margarine, butter, walnuts, almonds, garlic, cream and full-fat cheese than fish. They prepare food more often with lard and sunflower oil. Almost every fourth continental patient received statins, while only every 25th in the maritime group of patients. There were not any statistically significant Chi-square values for differences in frequencies of patients with total cholesterol greater than 5.2 mmol/L, triglycerides above 1.6 mmol/L, HDL-cholesterol less than 1.1 mmol/L, LDL-cholesterol greater than 2.6 mmol/L, obesity and malnutrition between the two groups. Based on the results of this study we have concluded that diet has significant influence on lipid profile of HD patients. Even though the continental and the maritime groups of patients differed significantly in diet, they were similar in plasmatic lipoprotein concentrations. However, this similarity was ascribed only to statin treatment, which was more frequent in the continental group of patients. The influence of ESRD and HD as a method of renal replacement therapy on lipid profile was not more dominant than diet.


Biogeography and Photosynthetic Biomass of Arctic Marine Pico-Eukaroytes during Summer of the Record Sea Ice Minimum 2012.
Information on recent photosynthetic biomass distribution and biogeography of Arctic marine pico-eukaryotes (0.2-3 μm) is needed to better understand consequences of environmental change for Arctic marine ecosystems. We analysed pico-eukaryote biomass and community composition in Fram Strait and large parts of the Central Arctic Ocean (Nansen Basin, Amundsen Basin) using chlorophyll a (Chl a) measurements, automated ribosomal intergenic spacer analysis (ARISA) and 454-pyrosequencing. Samples were collected during summer 2012, the year with the most recent record sea ice minimum. Chl a concentrations were highest in eastern Fram Strait and pico-plankton accounted for 60-90% of Chl a biomass during the observation period. ARISA-patterns and 454-pyrosequencing revealed that pico-eukaryote distribution is closely related to water mass distribution in the euphotic zone of the Arctic Ocean. Phaeocystaceae, Micromonas sp., Dinophyceae and Syndiniales constitute a high proportion of sequence reads, while sequence abundance of autotrophic Phaeocystaceae and mixotrophic Micromonas sp. was inversely correlated. Highest sequence abundances of Phaeocystaceae were observed in the warm Atlantic Waters in Fram Strait, while Micromonas sp. dominated the abundant biosphere in the arctic halocline. Our results are of particular interest considering existing hypotheses that environmental conditions in Nansen Basin might become more similar to the current conditions in Fram Strait. We propose that in response, biodiversity and biomass of pico-eukaryotes in Nansen Basin could resemble those currently observed in Fram Strait in the future. This would significantly alter biogeochemical cycles in a large part of the Central Arctic Ocean.


Herbage intake regulation and growth of rabbits raised on grasslands: back to basics and looking forward.
Organic agriculture is developing worldwide, and organic rabbit production has developed within this context. It entails raising rabbits in moving cages or paddocks, which enables them to graze grasslands. As organic farmers currently lack basic technical information, the objective of this article is to characterize herbage intake, feed intake and the growth rate of rabbits raised on grasslands in different environmental and management contexts (weather conditions, grassland type and complete feed supplementation). Three experiments were performed with moving cages at an experimental station. From weaning, rabbits grazed a natural grassland, a tall fescue grassland and a sainfoin grassland in experiments 1, 2 and 3, respectively. Rabbit diets were supplemented with a complete pelleted feed limited to 69 g dry matter (DM)/rabbit per day in experiment 1 and 52 g DM/rabbit per day in experiments 2 and 3. Herbage allowance and fiber, DM and protein contents, as well as rabbit intake and live weight, were measured weekly. Mean herbage DM intake per rabbit per day differed significantly (P<0.001) between experiments. It was highest in experiment 1 (78.5 g DM/day) and was 43.9 and 51.2 g DM/day in experiments 2 and 3, respectively. Herbage allowance was the most significant determinant of herbage DM intake during grazing, followed by rabbit metabolic weight (live weight0.75) and herbage protein and fiber contents. Across experiments, a 10 g DM increase in herbage allowance and a 100 g increase in rabbit metabolic weight corresponded to a mean increase of 6.8 and 9.6 g of herbage DM intake, respectively. When including complete feed, daily mean DM intakes differed significantly among experiments (P<0.001), ranging from 96.1 g DM/rabbit per day in experiment 2 to 163.6 g DM/rabbit per day in experiment 1. Metabolic weight of rabbits raised on grasslands increased linearly over time in all three experiments, yielding daily mean growth rates of 26.2, 19.2 and 28.5 g/day in experiments 1, 2 and 3, respectively. The highest growth rate was obtained on the sainfoin grassland despite lower concentrate supplementation. Thus, it seems possible to reduce complete feed supplementation without reducing animal performance. This possibility requires improving our knowledge about organic rabbit production systems and especially grazing and animal health management.


[Pathologo-anatomic morphometric diagnosis of senile dementia and Alzheimer's disease].
The numbers of senile plaques, neurofibrillar bundles, and neurofibrillar "skeletons" in a certain constant volume of the left temporal pole cortex were calculated in 131 psychically healthy subjects who died at an age of 41 to 101 years, and in 111 subjects who suffered at lifetime from debilitating diseases of the type of senile dementia (dotage) and Alzheimer's disease. Each senile plaque was estimated at 0.1 point, and each neurofibrillar bundle and neurofibrillar "skeleton" at 1.0 point. In each case the points were summed up. In 86% of the cases of senile dementia and Alzheimer's disease the total of the points exceeded the maxima found in the psychically healthy subjects. This gives one grounds to recommend this method for making reliable pathoanatomic diagnoses of debilitating diseases of the type of senile dementia or Alzheimer's disease.


Systematic review about 10 interventions in dermatitis. A document from the Latin American Society of Allergy, Asthma, and Immunology.
The Latin American Society of Allergy, Asthma, and Immunology (SLAAI) conducted a systematic search in the Medline and LILACS' database in order to get articles linked to 10 current questions about dermatitis. The assessment of the quality of the evidence and the strength of the recommendations was made through the GRADE system. The completeness and transparency of the recommendations for this clinical guide were assessed with the AGREE Reports Verification Checklist. The final document was shared with physicians, allergists, dermatologists, and pediatricians, and with patients and academic institutions such as universities and medical scientific societies for external assessment. According to the review, clinical scales should be used to measure the severity of the dermatitis, and some interventions such as the use of probiotics may benefit the patient; nevertheless, more studies are required before this management option can be used in the everyday practice. Other interventions such as dietary restrictions and the use of antihistamines seem to be well-founded only in particular cases and they should not be a general recommendation for all patients. This practical guide presents recommendations for the treatment of atopic dermatitis; these recommendations can be helpful for medical staff, patients, and health systems.


Alpha-blockade during congenital heart surgery admissions: analysis from national database.
The effects of alpha-blockade on haemodynamics during and following congenital heart surgery are well documented, but data on patient outcomes, mortality, and hospital charges are limited. The purpose of this study was to characterise the use of alpha-blockade during congenital heart surgery admissions and to determine its association with common clinical outcomes. A cross-sectional study was conducted using the Pediatric Health Information System database. De-identified data for patients under 18 years of age with a cardiac diagnosis who underwent congenital heart surgery were obtained from 2004 to 2015. Patients were subdivided on the basis of receiving alpha-blockade with either phenoxybenzamine or phentolamine during admission or not. Continuous and categorical variables were analysed using Mann−Whitney U-tests and Fisher exact tests, respectively. Characteristics between subgroups were compared using univariate analysis. Regression analyses were conducted to determine the impact of alpha-blockade on ICU length of stay, hospital length of stay, billed charges, and mortality. Of the 81,313 admissions, 4309 (5.3%) utilised alpha-blockade. Phentolamine was utilised in 4290 admissions. In univariate analysis, ICU length of stay, total length of stay, inpatient mortality, and billed charges were all significantly higher in the alpha-blockade admissions. However, regression analyses demonstrated that other factors were behind these increased. Alpha-blockade was significantly, independently associated with a 1.5 days reduction in ICU length of stay (p < 0.01) and a 3.5 days reduction in total length of stay (p < 0.01). Alpha-blockade was significantly, independently associated with a reduction in mortality (odds ratio 0.8, 95% confidence interval 0.7−0.9). Alpha-blockade was not independently associated with any significant change in billed charges. Alpha-blockade is used in a subset of paediatric cardiac surgeries and is independently associated with significant reductions in ICU length of stay, hospital length of stay, and mortality without significantly altering billed charges.


Ultrastructural blood-brain barrier alterations and edema formation in acute spinal cord trauma.
Endothelial changes leading to edema formation are examined in the primate spinal cord (Macaca mulatta) following a lesion created by a 20-gm weight falling 15 cm onto the exposed dura. Intravascular perfusion of a paraformaldehydeglutaraldehyde solution followed by carbon black provides adequate fixation of vascular structures and glial elements. Myelin is poorly preserved. Ultrastructural alterations of the blood-brain barrier consist of loss of integrity of the endothelial tight junctions. Edema caused by vascular disruption and parenchymatous extravasation of intravascular contents is observed along with glial swelling. Interglial gap junctions persist in areas of marked cellular seperation and do not impede the migration of edema fluid.


Implications of the Implicit Association Test D-Transformation for Psychological Assessment.
Psychometricians strive to eliminate random error from their psychological inventories. When random error affecting tests is diminished, tests more accurately characterize people on the psychological dimension of interest. We document an unusual property of the scoring algorithm for a measure used to assess a wide range of psychological states. The "D-score" algorithm for coding the Implicit Association Test (IAT) requires the presence of random noise in order to obtain variability. Without consequential degrees of random noise, all individuals receive extreme scores. We present results from an algebraic proof, a computer simulation, and an online survey of implicit racial attitudes to show how trial error can bias IAT assessments. We argue as a result that the D-score algorithm should not be used for formal assessment purposes, and we offer an alternative to this approach based on multiple regression. Our critique focuses primarily on the IAT designed to measure unconscious racial attitudes, but it applies to any IAT developed to provide psychological assessments within clinical, organizational, and developmental branches of psychology-and in any other field where the IAT might be used.


Design and Fabrication of Optical Flow Cell for Multiplex Detection of β-lactamase in Microchannels.
Miniaturized quantitative assays offer multiplexing capability in a microfluidic device for high-throughput applications such as antimicrobial resistance (AMR) studies. The detection of these multiple microchannels in a single microfluidic device becomes crucial for point-of-care (POC) testing and clinical diagnostics. This paper showcases an optical flow cell for detection of parallel microchannels in a microfluidic chip. The flow cell operates by measuring the light intensity from the microchannels based on Beer-Lambert law in a linearly moving chip. While this platform could be tailored for a wide variety of applications, here we show the design, fabrication and working principle of the device. β-lactamase, an indicator of bacterial resistance to β-lactam antibiotics, especially in milk, is shown as an example. The flow cell has a small footprint and uses low-powered, low-cost components, which makes it ideally suited for use in portable devices that require multiple sample detection in a single chip.


Comparison of metal/polymer back reflectors with half-sphere, blazed, and pyramid gratings for light trapping in III-V solar cells.
We report on the fabrication of diffraction gratings for application as back contact reflectors. The gratings are designed for thin-film solar cells incorporating absorbers with bandgap slightly lower than GaAs, i.e. InAs quantum dot or GaInNAs solar cells. Light trapping in the solar cells enables the increase of the absorption leading to higher short circuit current densities and higher efficiencies. We study metal/polymer back reflectors with half-sphere, blazed, and pyramid gratings, which were fabricated either by photolithography or by nanoimprint lithography. The gratings are compared in terms of the total and the specular reflectance, which determine their diffraction capabilities, i.e. the feature responsible for increasing the absorption. The pyramid grating showed the highest diffuse reflection of light compared to the half-sphere structure and the blazed grating. The diffraction efficiency measurements were in agreement with the numerical simulations. The validated model enables designing such metal/polymer back reflectors for other type of solar cells by refining the optimal dimensions of the gratings for different wavelength ranges.


Next generation sequencing in functional genomics.
Genome-wide sequencing has enabled modern biomedical research to relate more and more events in healthy as well as disease-affected cells and tissues to the genomic sequence. Now next generation sequencing (NGS) extends that reach into multiple almost complete genomes of the same species, revealing more and more details about how individual genomes as well as individual aspects of their regulation differ from each other. The inclusion of NGS-based transcriptome sequencing, chromatin-immunoprecipitation (ChIP) of transcription factor binding and epigenetic analyses (usually based on DNA methylation or histone modification ChIP) completes the picture with unprecedented resolution enabling the detection of even subtle differences such as alternative splicing of individual exons. Functional genomics aims at the elucidation of the molecular basis of biological functions and requires analyses that go far beyond the primary analysis of the reads such as mapping to a genome template sequence. The various and complex interactions between the genome, gene products and metabolites define biological function, which necessitates inclusion of results other than sequence tags in quite elaborative approaches. However, the extra efforts pay off in revealing mechanisms as well as providing the foundation for new strategies in systems biology and personalized medicine. This review emphasizes the particular contribution NGS-based technologies make to functional genomics research with a special focus on gene regulation by transcription factor binding sites.


Infection Rate in 1033 Elective Neurosurgical Procedures at a University Hospital in South China.
Objective Infection following surgery is a serious complication, especially in neurosurgery. The aim of the study is to report the change of incidence rates of infection in patients undergoing elective neurosurgical procedures at a university hospital in South China as well as the risk factors. Material and Methods The medical records and postoperative courses for patients undergoing 1,033 neurosurgical procedures from 2008 to 2014 were reviewed retrospectively to determine the incidence of neurosurgical infection, the identity of the offending organisms, and the factors associated with infection. Results A total of 33 patients (40 cases) experienced postoperative infection representing 3.19% of the study population. Twenty cases were incision infections (1.94%), and 20 were cranial/spinal infections (1.94%) including 15 intracranial infections and 5 intraspinal infections. The 2.4-fold greater incidence of postoperative infection in 2008 to 2010 was compared with that in 2011 to 2014 with perioperative antibiotic prophylaxis (p <0.01). The neurosurgical procedure associated with the highest rate of infection was cranioplasty (6.85%); the lowest rate of infection was associated with functional neurosurgery (1.08%). The most common offending organism was Staphylococcus aureus (27.5%). Foreign body implantation, operative time > 4 hours, and cerebrospinal fluid (CSF) leak (13 infections in 158 patients; p <0.001) were risk factors for infections (p <0.05). Conclusion The neurosurgical infection rate is usually low with perioperative antibiotic prophylaxis even in developing countries. Less foreign body implantation, shorter operative times, and controlling CSF leak could reduce infection rates.


[From phylogenesis to physiology: dopamine receptors].
Communication between neurones requires specialised proteins called receptors which fix the neuromediator (e.g. dopamine) and transmit a message to the cell interior. For a given neuromediator there exist several types and subtypes of receptors, which make up multigenic families. These gene families have come to be thanks to successive duplications of one initial gene in the course of evolution. Thus dopamine receptors of the D1 class include up to four subtypes in vertebrates. The cloning and subsequent study of D1 genes in a sample of species representative of the major evolutionary stages in vertebrates has led to the localisation of the duplication phases of the genes at the origin of the functional diversity of these receptors.


Enzyme-functionalized biomimetic apatites: concept and perspectives in view of innovative medical approaches.
Biomimetic nanocrystalline calcium-deficient apatite compounds are particularly attractive for the setup of bioactive bone-repair scaffolds due to their high similarity to bone mineral in terms of chemical composition, structural and substructural features. As such, along with the increasingly appealing development of moderate temperature engineered routes for sample processing, they have widened the armamentarium of orthopedic and maxillofacial surgeons in the field of bone tissue engineering. This was made possible by exploiting the exceptional surface reactivity of biomimetic apatite nanocrystals, capable of easily exchanging ions or adsorbing (bio)molecules, thus leading to highly-versatile drug delivery systems. In this contribution we focus on the preparation of hybrid materials combining biomimetic nanocrystalline apatites and enzymes (lysozyme and subtilisin). This paper reports physico-chemical data as well as cytotoxicity evaluations towards Cal-72 osteoblast-like cells and finally antimicrobial assessments towards selected strains of interest in bone surgery. Biomimetic apatite/enzyme hybrids could be prepared in varying buffers. They were found to be non-cytotoxic toward osteoblastic cells and the enzymes retained their biological activity (e.g. bond cleavage or antibacterial properties) despite the immobilization and drying processes. Release properties were also examined. Beyond these illustrative examples, the concept of biomimetic apatites functionalized with enzymes is thus shown to be useable in practice, e.g. for antimicrobial purposes, thus widening possible therapeutic perspectives.


Effects of participative decision making in central supply department: a case study.
This is an account of an effort to develop a culture of quality in a small service department of a major provincial hospital--in the belief that this could only be brought about by encouraging workers to take a larger degree of control over their work and the way in which it is carried out. The charge nurse, finding herself in a situation which amounted to a crisis in the work of the department and the lives of the staff, introduced a process which sought to establish that control. This account is derived from the journal of the charge nurse over the period of five months during which the changes occurred.


Bee-venom allergy in children: long-term predictive value of standardized challenge tests.
Venom immunotherapy (VIT) is able to protect insect venom-allergic patients against life-threatening sting reactions. Standardized sting challenges can be used as a diagnostic tool to check whether VIT is required. No data are available on the long-term predictive value of sting challenge tests. The purpose of this study was to investigate the long-term predictive value of sequential bee-sting challenges with respect to the ability to predict future sting reactions in bee-venom (BV) allergic children. Between 1988 and 1992, 92 BV-allergic children had been challenged with sequential bee stings at intervals of 2-6 weeks to determine the necessity of VIT. In 1996, all 92 families were followed-up using standardized telephone interviews. Until the follow-up, 61 children (66.3%) had experienced at least one natural bee sting. Based on the results of the initial challenge tests, 13 of the 61 patients had been started on VIT. Two of these 13 (15.4%) developed systemic reactions 1 year after VIT of 5 years, of which one was mild and one was severe. Among the 48 re-stung patients who were not treated with VIT, three children (6.3%) experienced mild systemic reactions, whereas 45 children reported no more than a local reaction. The long-term predictive value of sequential bee-sting challenge tests for systemic reactions in children not treated with VIT remained at a level of 93.8% (95% confidence interval: 82.8-98.7%) even over a period of more than 6 years. Based on this data, we conclude that sequential bee-sting challenges are a powerful tool to determine the necessity for VIT in BV-allergic children.


Radiologic Evaluation of the Distal Radius Indices in Early And Late Childhood.
The osseous anatomy of the distal radius is well documented in adults. Three commonly discussed variables are the volar tilt (also known as palmar tilt or palmar inclination), radial inclination, and radial height. These values are not well defined in the growing skeleton. We studied the radiographic measurements of normal distal radius osseous anatomy in children and identified how these values change with age. 372 patients (215 males and 157 females) between the ages of 8 and 16 were included in the study. Normal values of volar tilt, radial inclination, and radial epiphyseal height were defined for each age group. Regression analysis showed that volar tilt increased significantly by increase in age (P <0.001). Radial inclination and radial epiphyseal height both showed significant increase with increase in age (P<0.001). This is the first study to define these radiographic values in children and their change with age.


Xanthophyll biosynthetic mutants of Arabidopsis thaliana: altered nonphotochemical quenching of chlorophyll fluorescence is due to changes in Photosystem II antenna size and stability.
Xanthophylls (oxygen derivatives of carotenes) are essential components of the plant photosynthetic apparatus. Lutein, the most abundant xanthophyll, is attached primarily to the bulk antenna complex, light-harvesting complex (LHC) II. We have used mutations in Arabidopsis thaliana that selectively eliminate (and substitute) specific xanthophylls in order to study their function(s) in vivo. These include two lutein-deficient mutants, lut1 and lut2, the epoxy xanthophyll-deficient aba1 mutant and the lut2aba1 double mutant. Photosystem stoichiometry, antenna sizes and xanthophyll cycle activity have been related to alterations in nonphotochemical quenching of chlorophyll fluorescence (NPQ). Nondenaturing polyacrylamide gel electrophoresis indicates reduced stability of trimeric LHC II in the absence of lutein (and/or epoxy xanthophylls). Photosystem (antenna) size and stoichiometry is altered in all mutants relative to wild type (WT). Maximal DeltapH-dependent NPQ (qE) is reduced in the following order: WT>aba1>lut1 approximately lut2>lut2aba1, paralleling reduction in Photosystem (PS) II antenna size. Finally, light-activation of NPQ shows that zeaxanthin and antheraxanthin present constitutively in lut mutants are not qE active, and hence, the same can be inferred of the lutein they replace. Thus, a direct involvement of lutein in the mechanism of qE is unlikely. Rather, altered NPQ in xanthophyll biosynthetic mutants is explained by disturbed macro-organization of LHC II and reduced PS II-antenna size in the absence of the optimal, wild-type xanthophyll composition. These data suggest the evolutionary conservation of lutein content in plants was selected for due to its unique ability to optimize antenna structure, stability and macro-organization for efficient regulation of light-harvesting under natural environmental conditions.


Epineurial vs. perineurial repair.
Previous work concerning the efficacy of different types of nerve repair has been reviewed. We describe a model in which epineurial and perineurial suture techniques were studied by quantitative ultramicroscopy and electrophysiology. In this model, we believe suture of the perineurium was shown to have a slight advantage over suture of the epineurium. Microscopic control and fascicular alignment are advocated to increase the percentage of axons growing into the distal stump and the periphery. The model described should lend itself to the study of other traumatic peripheral neuropathies.


Outcome in dogs undergoing adrenalectomy for small adrenal gland tumours without vascular invasion.
Veterinary studies have reported the outcome of adrenalectomies in dogs; however, these studies typically include a wide variety of adrenal tumour sizes, including cases with or without vascular invasion. The purpose of this study was to report outcome in a cohort of dogs with histologically confirmed small adrenal tumours without vascular invasion treated with adrenalectomy. This retrospective study was conducted using data from the University of Florida and University of California-Davis databases between 2010 and 2017. Dogs were included if they underwent excision of an adrenal gland tumour with a maximal diameter ≤ 3 cm, without evidence of vascular invasion to any location as assessed via computed tomography. Fifty-one dogs met the inclusion criteria. The short-term survival rate of dogs undergoing adrenalectomy was 92.2%, and one-year disease-specific survival was 83.3%. Twenty-eight of 51 (54.9%) dogs were diagnosed with a malignancy. Minor complications were observed commonly intra-operatively and post-operatively. Major complications were observed in six dogs, and included sudden death, respiratory arrest, acute kidney injury, haemorrhage, hypotension and aspiration pneumonia. Short-term mortality occurred in four dogs. Sudden death and haemorrhage were the most common major complications leading to death. While adrenalectomy is sometimes controversial because of the high perioperative mortality rates previously reported, the results of this study support that adrenalectomy for small tumours with no vascular invasion can be performed with low risk.


Posterior fossa tumors with pathological laughter.
Of two patients with posterior fossa tumor and pathological laughter, one had extrinsic compression of the brain stem; the other had an intrinsic brain-stem lesion. Surgical removal of the epidermoid from the cerebellopontine angle cured the laughter. The euphoria of multiple sclerosis with paroxysmal laughter and a feeling of joy is to be differentiated from cases in which pathological laughter is a presenting complaint.


Immunohistochemical analysis of the mouse celiac ganglion: An integrative relay station of the peripheral nervous system.
Celiac ganglia are important sites of signal integration and transduction. Their complex neurochemical anatomy has been studied extensively in guinea pigs but not in mice. The goal of this study was to provide detailed neurochemical characterization of mouse celiac ganglia and noradrenergic nerves in two target tissues, spleen and stomach. A vast majority of mouse celiac neurons express a noradrenergic phenotype, which includes tyrosine hydroxylase (TH), vesicular monoamine transporter 2, and the norepinephrine transporter. Over 80% of these neuron also express neuropeptide Y (NPY), and this coexpression is maintained by dissociated neurons in culture. Likewise, TH and NPY were colocalized in noradrenergic nerves throughout the spleen and in stomach blood vessels. Somatostatin was not detected in principal neurons but did occur in small, TH-negative cells presumed to be interneurons and in a few varicose nerve fibers. Cholinergic nerves provided the most abundant input to the ganglia, and small percentages of these also contained nitric oxide synthase or vasoactive intestinal polypeptide. A low-to-moderate density of nerves also stained separately for the latter markers. Additionally, nerve bundles and varicose nerve fibers containing the sensory neuropeptides, calcitonin gene-related polypeptide, and substance P, occurred at variable density throughout the ganglia. Collectively, these findings demonstrate that principal neurons of mouse celiac ganglia have less neurochemical diversity than reported for guinea pig and other species but receive input from nerves expressing an array of neurochemical markers. This profile suggests celiac neurons integrate input from many sources to influence target tissues by releasing primarily norepinephrine and NPY.


Association Between Midlife Physical Activity and Incident Kidney Disease: The Atherosclerosis Risk in Communities (ARIC) Study.
Physical activity is associated with lower risk for cardiovascular disease, diabetes, and hypertension, which have shared risk factor profiles with chronic kidney disease (CKD). However, there are conflicting findings regarding the relationship between physical activity and CKD. The objective was to evaluate the association between physical activity and CKD development over long-term follow-up using the Atherosclerosis Risk in Communities (ARIC) Study. Prospective cohort study. 14,537 participants aged 45 to 64 years. Baseline physical activity status was assessed using the modified Baecke Physical Activity Questionnaire at visit 1 (1987-1989) and categorized according to the 2018 Physical Activity Guidelines for Americans to group participants as inactive, insufficiently active, active, and highly active. Incident CKD defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 at follow-up and≥25% decline in eGFR relative to baseline, CKD-related hospitalization or death, or initiation of kidney replacement therapy. Cox proportional hazards regression. At baseline, 37.8%, 24.2%, 22.7%, and 15.3% of participants were classified as inactive, insufficiently active, active, and highly active, respectively. During a median follow-up of 24 years, 33.2% of participants developed CKD. After adjusting for age, sex, race-center, education, smoking status, diet quality, diabetes, coronary heart disease, hypertension, antihypertensive medication, body mass index, and baseline eGFR, higher categories of physical activity were associated with lower risk for CKD compared with the inactive group (HRs for insufficiently active, 0.95 [95% CI, 0.88-1.02]; active, 0.93 [95% CI, 0.86-1.01]; highly active, 0.89 [95% CI, 0.81-0.97]; P for trend = 0.007). Observational design and self-reported physical activity that was based on leisure time activity only. Due to low numbers, participants who were not Black or White were excluded. Highly active participants had lower risk for developing CKD compared with inactive participants.


Malnutrition and the oral health of children in Ogbomosho, Nigeria.
Fifty-two Nigerian children, forty-five of whom were severely malnourished were examined to ascertain their level of oral health. Enamel hypoplasia, dental caries, gingivitis and periodontitis were given special attention in this study, and each of these disorders was found to be more frequently seen in the malnourished child. In a followup study of the malnourished children treated at the Baptist nutritional center there was improvement in the children's oral health, manifested by improvement of their gingivitis and periodontitis as the child's nutritional level and general health improved. Other oral findings were noted and recorded, including two patients with cancrum oris (noma) and others with angular chelitis, cleft palate, fungal infections, and a peculiar intrinsic black stain of the teeth, among others.


Pathogenic roles for fungal melanins.
Melanins represent virulence factors for several pathogenic fungi; the number of examples is growing. Thus, albino mutants of several genera (in one case, mutated precisely in the melanizing enzyme) exhibit decreased virulence in mice. We consider the phenomenon in relation to known chemical properties of melanin, beginning with biosynthesis from ortho-hydroquinone precursors which, when oxidized enzymatically to quinones, polymerize spontaneously to melanin. It follows that melanizing intermediates are cross-linking reagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appressorium) of certain plant pathogens. Polymeric melanins undergo reversible oxidation-reduction reactions between cell wall-penetrating quinone and hydroquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. The amount of buffering per cell approximately neutralizes the amount of oxidant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to trap unpaired electrons. We have suggested that the oxidation state of external melanin may be regulated by external Fe(II). An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H(2)O(2). Thus, problems in fungal pathogenesis have led to evolving hypotheses regarding melanin functioning.


Understanding the impact of a collective leadership intervention on team working and safety culture in healthcare teams: a realist evaluation protocol.
There is accumulating evidence for the value of collective and shared approaches to leadership across sectors and settings. However, relatively little research has explored collective leadership in healthcare and thus, there is little understanding of what works for healthcare teams, why, how and to what extent. This study describes the approach that will be adopted to the realist evaluation of a collective leadership intervention with four heterogenous healthcare teams in four different settings. A realist evaluation will be conducted. Realist evaluation is a theory-based approach to evaluation. It enables the use of mixed-methods to explore the research question of interest. Development of an initial programme theory (IPT) constitutes the first phase of the approach. This IPT will be informed by interviews with members of teams identified as working collectively, an examination of extant literature using realist synthesis, and will be refined through consultation with an expert panel. A multiple case study design will be adopted to explore the impact of the intervention, including quantitative scales on teamworking, leadership and safety culture, realist interviews with key informants and observations of teams during intervention sessions. Analysis of data will be guided by the IPT to refine the theory and context-mechanism-outcome configurations. Findings from the cases will be compared to identify patterns or demi-regularities and to explore if the intervention operates differently in different contexts. This analysis and synthesis of findings across the teams will inform the development of a middle range theory that will not only add to our understanding of how collective leadership influences teamwork and patient safety, but also provide guidance for future collective leadership interventions. Favourable ethical opinion has been received from the University College Dublin Ethics Committee. Results will be disseminated via publication in peer-review journals, national and international conferences and to stakeholders/interest groups.


Origin of the mixing ratio dependence of power conversion efficiency in bulk heterojunction organic solar cells with low donor concentration.
We studied the origin of the improvement in device performance of thermally evaporated bulk heterojunction organic photovoltaic devices (OPVs) with low donor concentration. Samples with three different donor-acceptor mixing ratios, 0:10 (C70-only), 1:9 (low-doped) and 3:7 (high-doped), were fabricated with 1,1-bis-(4-bis(4-methyl-phenyl)-amino-phenyl)-cyclohexane (TAPC):C70. The power conversion efficiencies (PCEs) of these samples were 1.14%, 2.74% and 0.69%, respectively. To determine why the low-doped device showed a high PCE, we measured various properties of the devices in terms of the effective energy band gap, activation energy, charge carrier mobility and recombination loss. We found that the activation energy for charge carrier transport was increased as we increased the TAPC concentration in the blends whereas the hole and electron mobilities became more balanced as the TAPC concentration was increased. Furthermore, the recombination loss parameter alpha (from the light intensity dependence) remained alpha to approximately 0.9 in the low-doped device, but it decreased to alpha to approximately 0.77 in the high-doped device, indicating a large recombination loss as a result of space charge. Therefore, the improved PCE of low-doped OPVs can be attributed to the balance between carrier mobilities with no increase in recombination loss.


A statewide teleradiology system reduces radiation exposure and charges in transferred trauma patients.
Trauma transfer patients routinely undergo repeat imaging because of inefficiencies within the radiology system. In 2009, the virtual private network (VPN) telemedicine system was adopted throughout Oregon allowing virtual image transfer between hospitals. The startup cost was a nominal $3,000 per hospital. A retrospective review from 2007 to 2012 included 400 randomly selected adult trauma transfer patients based on a power analysis (200 pre/200 post). The primary outcome evaluated was reduction in repeat computed tomography (CT) scans. Secondary outcomes included cost savings, emergency department (ED) length of stay (LOS), and spared radiation. All data were analyzed using Mann-Whitney U and chi-square tests. P less than .05 indicated significance. Spared radiation was calculated as a weighted average per body region, and savings was calculated using charges obtained from Oregon Health and Science University radiology current procedural terminology codes. Four-hundred patients were included. Injury Severity Score, age, ED and overall LOS, mortality, trauma type, and gender were not statistically different between groups. The percentage of patients with repeat CT scans decreased after VPN implementation: CT abdomen (13.2% vs 2.8%, P < .01) and cervical spine (34.4% vs 18.2%, P < .01). Post-VPN, the total charges saved in 2012 for trauma transfer patients was $333,500, whereas the average radiation dose spared per person was 1.8 mSV. Length of stay in the ED for patients with Injury Severity Score less than 15 transferring to the ICU was decreased (P < .05). Implementation of a statewide teleradiology network resulted in fewer total repeat CT scans, significant savings, decrease in radiation exposure, and decreased LOS in the ED for patients with less complex injuries. The potential for health care savings by widespread adoption of a VPN is significant.


RNA-based phylogenetic methods: application to mammalian mitochondrial RNA sequences.
The PHASE software package allows phylogenetic tree construction with a number of evolutionary models designed specifically for use with RNA sequences that have conserved secondary structure. Evolution in the paired regions of RNAs occurs via compensatory substitutions, hence changes on either side of a pair are correlated. Accounting for this correlation is important for phylogenetic inference because it affects the likelihood calculation. In the present study we use the complete set of tRNA and rRNA sequences from 69 complete mammalian mitochondrial genomes. The likelihood calculation uses two evolutionary models simultaneously for different parts of the sequence: a paired-site model for the paired sites and a single-site model for the unpaired sites. We use Bayesian phylogenetic methods and a Markov chain Monte Carlo algorithm is used to obtain the most probable trees and posterior probabilities of clades. The results are well resolved for almost all the important branches on the mammalian tree. They support the arrangement of mammalian orders within the four supra-ordinal clades that have been identified by studies of much larger data sets mainly comprising nuclear genes. Groups such as the hedgehogs and the murid rodents, which have been problematic in previous studies with mitochondrial proteins, appear in their expected position with the other members of their order. Our choice of genes and evolutionary model appears to be more reliable and less subject to biases caused by variation in base composition than previous studies with mitochondrial genomes.