Unplanned return to the operating room.
Unplanned return to the operating room (OR) has been suggested as one of the indicators that could be used to assess the quality of surgery in a hospital setting. The present study was undertaken in order to try to identify those factors that were important in determining the need for the return to the OR in patients undergoing a series of colorectal surgical procedures. All patients who returned to the OR following an index colorectal procedure during a 15-year period on a colorectal service, were identified from the unit's database. The site of original disease, presentation, type of surgery performed, reason for re-operation and post-surgical morbidity and mortality were examined. Overall there were 2011 colorectal surgical admissions, and of these 19 males (61.2 years) and 18 females (67.4 years) underwent an unplanned return to the OR. In 34 patients the index operation was performed by a consultant surgeon. A total of 46% of index operations were performed in an emergency setting. The majority of patients had colorectal cancer. Most lesions were situated in the sigmoid colon or rectum. Postoperative adhesive obstruction was the commonest reason for return to the OR. No patient re-obstructed following re-operation. Overall eight wounds dehisced and five patients suffered anastomotic leakage. Intra-abdominal sepsis was found in 12 patients. Twenty-one patients developed urinary tract infections. Twenty-eight patients were discharged well, two patients were discharged dying with advanced malignancy and there were seven postoperative deaths (18.9%). Unplanned return to the OR is a function of both the patient's presenting problem and the surgical skill and judgement of the surgeon. It is thus in part determined by the patient casemix in a unit, service or institution.


Ovaries of patients recently treated with alkylating agent chemotherapy indicate the presence of acute follicle activation, elucidating its role among other proposed mechanisms of follicle loss.
To investigate mechanisms of primordial follicle (PMF) loss in vivo in human ovaries shortly after alkylating agent (AA) chemotherapy. Cohort study. Tertiary university medical center. Ninety-six women aged 15-39 years who underwent ovarian tissue cryopreservation for fertility preservation. Fresh ovarian tissue samples were harvested from women treated with AA (n = 24) or non-AA (n = 24) chemotherapy <6 months after treatment and age-matched untreated women (n = 48). Differential follicle counts, time from chemotherapy exposure, immunostaining for apoptosis (cleaved caspase-3) and FOXO3A on tissue harvested within ultrashort time intervals (4-12 days), collagen (Sirius red) and neovascularization (CD34). AA-treated ovaries had significant loss of PMFs, and significant increase in absolute numbers of growing follicles compared with untreated control ovaries. The number of growing follicles was inversely correlated with time from chemotherapy. Representative staining for FOXO3A observed decreased nuclear localization in PMF oocytes in AA-treated ovaries removed within the ultrashort time interval compared with untreated ovaries. Neither significant loss of PMFs, increase in growing follicles, nor decrease in nuclear FOXO3A were observed in non-AA-treated ovaries. No increased expression of cleaved caspase-3 was seen in PMFs within the ultrashort time interval after AA or non-AA chemotherapy. Significant stromal fibrosis and neovascularization were observed in AA-treated ovaries only after follicle loss had already occurred (4-6 months). Follicle activation occurs in vivo in ovaries of patients treated with AA, indicating a pathologic mechanism which may contribute to chemotherapy-induced follicle loss.


The next frontier: Moving human fear conditioning research online.
Fear conditioning is a significant area of research that has featured prominently among the topics published in Biological Psychology over the last 50 years. This work has greatly contributed to our understanding of human anxiety and stressor-related disorders. While mainly conducted in the laboratory, recently, there have been initial attempts to conduct fear conditioning experiments online, with around 10 studies published on the subject, primarily in the last two years. These studies have demonstrated the potential of online fear conditioning research, although challenges to ensure that this research meets the same methodological standards as in-person experimentation remain, despite recent progress. We expect that in the coming years new outcome measures will become available online including the measurement of eye-tracking, pupillometry and probe reaction time and that compliance monitoring will be improved. This exciting new approach opens new possibilities for large-scale data collection among hard-to-reach populations and has the potential to transform the future of fear conditioning research.


The Physical Exercise as a Strategy of Reduce Costs with Medicine for Aged.
To provide a critical reflection from the literature review to describe the current panorama on the importance of physical exercises in the improvement of the quality of life of the aged, besides the use of medications. While aging brings a high cost to health and demographic pyramid changes, so does the disease. As aging is a biological process and many diseases develop at this time of life, the aged are the fastest growing segment of the Brazilian population due to the natural susceptibility of the organism. With this increase, health costs in the country also increase. In everyday practice, medicine has often been characterized as a therapeutic intervention instrument for the first choice, and a consequence, generates significant and significant economic and social damages. Search in databases using analysis descriptors as exercises and medicine for the aged. The involvement of the aged in physical exercise programs is an important adjunct to reduce the progressive degeneration associated with natural aging, becoming a powerful instrument to guarantee a healthy, active and independent lifestyle. The physical activity was inversely associated with the number of medications, the more physical activity and fewer drug expenses. The need to implement programs for orientation and for the promotion of health through physical activity was also verified.


Infections and cardiovascular disease: is Bartonella henselae contributing to this matter?
Cardiovascular disease is still the major cause of death worldwide despite the remarkable progress in its prevention and treatment. Endothelial progenitor cells (EPCs) have recently emerged as key players of vascular repair and regenerative medicine applied to cardiovascular disease. A large amount of effort has been put into discovering the factors that could aid or impair the number and function of EPCs, and also into characterizing these cells at the molecular level in order to facilitate their therapeutic applications in vascular disease. Interestingly, the major cardiovascular risk factors have been associated with reduced number and function of EPCs. The bacterial contribution to cardiovascular disease represents a long-standing controversy. The discovery that Bartonella henselae can infect and damage EPCs revitalizes the enduring debate about the microbiological contribution to atherosclerosis, thus allowing the hypothesis that this infection could impair the cardiovascular regenerative potential and increase the risk for cardiovascular disease. In this review, we summarize the rationale suggesting that Bartonella henselae could favour atherogenesis by infecting and damaging EPCs, thus reducing their vascular repair potential. These mechanisms suggest a novel link between communicable and non-communicable human diseases, and put forward the possibility that Bartonella henselae could enhance the susceptibility and worsen the prognosis in cardiovascular disease.


A Rationally and Computationally Designed Fluorescent Biosensor for d-Serine.
Solute-binding proteins (SBPs) have evolved to balance the demands of ligand affinity, thermostability, and conformational change to accomplish diverse functions in small molecule transport, sensing, and chemotaxis. Although the ligand-induced conformational changes that occur in SBPs make them useful components in biosensors, they are challenging targets for protein engineering and design. Here, we have engineered a d-alanine-specific SBP into a fluorescence biosensor with specificity for the signaling molecule d-serine (D-serFS). This was achieved through binding site and remote mutations that improved affinity (KD = 6.7 ± 0.5 μM), specificity (40-fold increase vs glycine), thermostability (Tm = 79 °C), and dynamic range (∼14%). This sensor allowed measurement of physiologically relevant changes in d-serine concentration using two-photon excitation fluorescence microscopy in rat brain hippocampal slices. This work illustrates the functional trade-offs between protein dynamics, ligand affinity, and thermostability and how these must be balanced to achieve desirable activities in the engineering of complex, dynamic proteins.


Comparative Study of Drug-eluting Beads versus Conventional Transarterial Chemoembolization for Treating Peculiar Anatomical Sites of Gastric Cancer Liver Metastasis.
BACKGROUND This study aimed to assess the relative safety and short-term efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (c-TACE) for treating peculiar anatomical sites of gastric cancer liver metastasis. MATERIAL AND METHODS Of the 68 patients with gastric cancer liver metastases confirmed by imaging and pathology, 35 were treated with DEB-TACE and 33 with c-TACE. The DEB-TACE group comprised 26 males and 9 females aged 28-75 years (56.8±6.3), and the c-TACE group included 19 males and 14 females aged 33-77 (60.2±9.4) years. Liver functions of the 2 groups were compared between pre-TACE and 1-week and 1-month after TACE. Computed tomography and magnetic resonance imaging were reexamined at 1, 3, and 6 months after TACE, and short-term efficacy was assessed based on modified response evaluation criteria in solid tumors. RESULTS One month following DEB-TACE and c-TACE, the number of cases with objective response (OR) was 29 cases (29 out of 35 cases, 82.9%) and 20 cases (20 out of 33 cases, 60.6%) and disease control (DC) in the 2 groups was 33 cases (33 out of 35 cases, 94.3%) and 26 cases (26 out of 33 cases, 78.8%) respectively (P=0.041, P=0.031). Alanine transaminase (ALT) and Aspartate transaminase (AST) significantly increased in the DEB-TACE and c-TACE groups 1 week later (P<0.001). There were no serious complications in the 2 groups; incidences of nausea and vomiting were significantly lower, but instances of fever were markedly elevated in the DEB-TACE group (P=0.023, P=0.016, respectively). CONCLUSIONS The safety, feasibility, and short-term efficacy of DEB-TACE and c-TACE in the treatment of gastric cancer liver metastasis are clear. DEB-TACE leads to less incidences of nausea and vomiting but more incidences of fever than c-TACE.


Mechanisms of combined action of different chemopreventive dietary compounds: a review.
Consumption of fruits and vegetables has generally been associated with a decrease in cancer incidence and cardiovascular disease. Over the years, numerous bioactive compounds have been identified that contribute to these beneficial health effects. More recently, evidence is emerging that specific combinations of phytochemicals may be far more effective in protecting against cancer than isolated compounds. Combinatorial effects have been observed where any one of the single agents is inactive. Apart from interactions among dietary micronutrients, drug-phytochemical interactions have also been observed, indicating possibilities for improved cancer therapeutic strategies. Our understanding of the molecular mechanisms underlying such synergistic effects is still limited, but it appears that different combinations of complementary modes of actions are involved. In this review, we discuss the molecular mechanisms that are likely to be involved in cancer chemoprevention and summarize the most important findings of those studies that report synergistic chemopreventive effects of dietary compounds.


Advancing Point-of-Care Ultrasound Training in Medical Schools: Ultrasound-Guided Subclavian Vein Access Training Using Formalin-Embalmed Cadavers.
This brief report examines the feasibility of using formalin-embalmed cadavers in training medical students to use ultrasound guidance to access the subclavian. This novel educational approach is discussed in the context of the ongoing integration of point-of-care ultrasound training into medical education. Additionally, this report explores how cadavers can provide practical, effective, and hands-on skills training opportunities for medical students to learn to perform common clinical procedures under ultrasound guidance. This report presents subjective and objective data evaluating the utility of teaching medical students to perform ultrasound-guided subclavian vein access on formalin-embalmed cadavers. Rocky Vista University College of Osteopathic Medicine in Ivins, UT. Twenty-five first-year medical students at Rocky Vista University. None. Pre and posttraining questionnaires were administered to assess each participant's self-confidence in using ultrasonography to access the subclavian vein of a cadaver. A statistically significant increase in participant self-confidence was observed across all questionnaire items from pre to posttraining. Objective evaluation consisted of a supervised skills test. Participants were evaluated on their ability to visualize the subclavian vein with ultrasound and achieve flashback of blood/embalming fluid into a syringe. During skills testing, the number of needle sticks and the time taken to achieve flashback were recorded for each participant. Twenty-three of the 25 participants were able to successfully complete the skills testing assessment. The formalin-embalmed cadaver can be a readily available and effective learning tool for medical education programs seeking to provide training opportunities in ultrasound-guided clinical procedures. The use of cadavers allows learners to train in a low stress and anatomically authentic environment without risk of patient discomfort.


Initial Modified Pulmonary Index Score Predicts Hospital Length of Stay for Asthma Subjects Admitted to the Pediatric Intensive Care Unit.
Scoring systems are frequently used to assess the severity of pediatric asthma exacerbations. The modified pulmonary index score (MPIS) has been found to be highly correlated with length of stay (LOS) in the pediatric intensive care unit (PICU). We sought to evaluate the use of the MPIS to predict hospital LOS for patients admitted to our PICU. We retrospectively reviewed the medical records of pediatric asthma subjects aged 2-17 y admitted to our PICU between June 2014 and November 2017. We divided subjects a priori into 3 groups (low: MPIS 0-5; medium: MPIS 6-9; high: MPIS ≥ 10) based upon each subject's first MPIS documented in the PICU. Hospital LOS, PICU LOS, time on continuous albuterol, and increased respiratory support were compared between groups. 143 subjects were included. There were no differences for demographics, medical history, cause of exacerbations, or mean heart rate between groups. There were significant differences between groups for mean breathing frequency (P < .001), [Formula: see text] (P = .01), and [Formula: see text] (P < .004). There were significant differences between groups for route of admission (P = .02), high-flow nasal cannula use (P < .001), and use of a helium-oxygen mixture (P < .001). There were significant differences between groups for median hospital LOS (1.2 vs 2.3 vs 3.4 d, P < .001), PICU LOS (0.39 vs 1.3 vs 2 d, P < .001), and time on continuous albuterol (7.4 vs 20.6 vs 34.7 h, P < .001). After adjusting for demographics and medical history, the incidence risk ratio for hospital LOS was 2.09 for PICU admission for an MPIS of 6-9 and 2.68 for an MPIS ≥ 10 when compared to an MPIS < 6. The MPIS thresholds used in our pathway appropriately predicted LOS in our cohort of subjects with asthma admitted to the PICU. Higher MPIS was associated with increased hospital LOS, PICU LOS, and time on continuous albuterol.


The role of GTP-binding protein activity in fast central synaptic transmission.
Guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are involved in exocytosis, endocytosis, and recycling of vesicles in yeast and mammalian secretory cells. However, little is known about their contribution to fast synaptic transmission. We loaded guanine nucleotide analogs directly into a giant nerve terminal in rat brainstem slices. Inhibition of G-protein activity had no effect on basal synaptic transmission, but augmented synaptic depression and significantly slowed recovery from depression. A nonhydrolyzable GTP analog blocked recovery of transmission from activity-dependent depression. Neither effect was accompanied by a change in presynaptic calcium currents. Thus, G proteins contribute to fast synaptic transmission by refilling synaptic vesicles depleted after massive exocytosis.


Evaluating the environmental impacts of a nano-enhanced field emission display using life cycle assessment: a screening-level study.
Carbon nanotube (CNT) field emission displays (FEDs) are currently in the product development stage and are expected to be commercialized in the near future because they offer image quality and viewing angles comparable to a cathode ray tube (CRT) while using a thinner structure, similar to a liquid crystal display (LCD), and enable more efficient power consumption during use. To address concerns regarding the environmental performance of CNT-FEDs, a screening-level, cradle-to-grave life cycle assessment (LCA) was conducted based on a functional unit of 10,000 viewing hours, the viewing lifespan of a CNT-FED. Contribution analysis suggests the impacts for material acquisition and manufacturing are greater than the combined impacts for use and end-of-life. A scenario analysis of the CNT paste composition identifies the metal components used in the paste are key contributors to the impacts of the upstream stages due to the impacts associated with metal preparation. Further improvement of the manufacturing impacts is possible by considering the use of plant-based oils, such as rapeseed oil, as alternatives to organic solvents for dispersion of CNTs. Given the differences in viewing lifespan, the impacts of the CNT-FED were compared with a LCD and a CRT display to provide more insight on how to improve the CNT-FED to make it a viable product alternative. When compared with CRT technology, CNT-FEDs show better environmental performance, whereas a comparison with LCD technology indicates the environmental impacts are roughly the same. Based on the results, the enhanced viewing capabilities of CNT-FEDs will be a more viable display option if manufacturers can increase the product's expected viewing lifespan.


Monocyte surface expression of Fcgamma receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus.
More than half of systemic lupus erythematosus (SLE) patients show evidence of excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection of IFN-I proteins in serum is unreliable, and the measurement of interferon-stimulated gene (ISG) expression is expensive and time consuming. The aim of this study was to identify a surrogate marker for IFN-I activity in clinical samples for monitoring disease activity and response to therapy. Monocyte surface expression of Fcgamma receptors (FcgammaRs), chemokine receptors, and activation markers were analyzed with flow cytometry in whole blood from patients with SLE and healthy controls. FcgammaR expression also was measured in peripheral blood mononuclear cells (PBMCs) from healthy controls cultured with Toll-like receptor (TLR) agonists, cytokines, or serum from SLE patients. Expression of ISGs was analyzed with real-time PCR. Circulating CD14+ monocytes from SLE patients showed increased surface expression of FcgammaRI (CD64). The mean fluorescent intensity of CD64 staining correlated highly with the ISG expression (MX1, IFI44, and Ly6E). In vitro, IFN-I as well as TLR7 and TLR9 agonists, induced CD64 expression on monocytes from healthy controls. Exposure of monocytes from healthy controls to SLE sera also upregulated the expression of CD64 in an IFN-I-dependent manner. Decreased CD64 expression was observed concomitant with the reduction of ISG expression after high-dose corticosteroid therapy. Expression of CD64 on circulating monocytes is IFN-I inducible and highly correlated with ISG expression. Flow-cytometry analysis of CD64 expression on circulating monocytes is a convenient and rapid approach for estimating IFN-I levels in SLE patients.


[Validity assessment of a low level phonological processing test material in preschool children].
The BISC (Bielefelder Screening) is a German test to evaluate phonological skills believed to be a prerequisite for future reading and writing skills. BISC results may indicate an elevated risk for dyslexia. Our research group has put forward test material in order to specifically examine low-level phonological processing LLPP. In this study we analysed whether BISC and low-level phonological processing correlate. A retrospective correlation analysis was carried out on primary school children's test results of the BISC and the newly developed low-level phonological processing test material. Spearman's rho was 0.52 between total LLPP and total BISC. The subscales correlated with a rho below 0.5. Results indicate that a low level phonological processing and higher level phonological processing can be differentiated. Future studies will have to clarify whether these results can be used to construct specifically targeting therapy strategies and whether the LLPP test material can be used to assess the risk of subsequent dyslexia also.


Computer-aided manufacturing and focused ion beam technology enable machining of complex micro- and nano-structures.
We present a novel framework for the fabrication of geometrically complex structures at the micro- and nano-scale which relies on the synergy of integrated computer-aided design and manufacturing systems (CAD/CAM) and focused ion beam (FIB) technology in a scanning electron microscope. Here we utilise industry standard G-code syntax, for the first time, to FIB machining by designing geometries with CAD, defining machining strategies and exporting G-codes with CAM and generating a coordinate list-based beam path by using a custom-built interpreter program. This allows the fabrication of complex structures from CAD models using syntax which is readily understood in the general fabrication industry. The use of G-code allows optimization of the beam path towards a reduction of beam blanking operations and tracing of contours, leading to minimized re-deposition of material. We give a detailed description of the method, use an application example to demonstrate advantages and prospects of the approach and provide the free and open-source interpreter program CAM2FIB for application of this method. We contrast and compare various existing available milling strategies and demonstrate the versatility of G-code based programming.


Psychoemotional aspects of mastectomy: a review of recent literature.
The author reviews the recent literature on the psychological aspects of mastectomy, including psychological reactions to the procedure and appropriate intervention strategies. He discusses individual and familial fears and concerns related to mastectomy and emphasizes the importance of preoperative counseling and postoperative rehabilitation.


Synaptic relationships between axon terminals from the mediodorsal thalamic nucleus and gamma-aminobutyric acidergic cortical cells in the prelimbic cortex of the rat.
Although the reciprocal interconnections between the prefrontal cortex and the mediodorsal nucleus of the thalamus (MD) are well known, the involvement of inhibitory cortical interneurons in the neural circuit has not been fully defined. To address this issue, we conducted three combined neuroanatomical studies on the rat brain. First, the frequency and the spatial distribution of synapses made by reconstructed dendrites of nonpyramidal neurons were identified by impregnation of cortical cells with the Golgi method and identification of thalamocortical terminals by degeneration following thalamic lesions. Terminals from MD were found to make synaptic contacts with small dendritic shafts or spines of Golgi-impregnated nonpyramidal cells with very sparse dendritic spines. Second, a combined study that used anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and postembedding gamma-aminobutyric acid (GABA) immunocytochemistry indicated that PHA-L-labeled terminals from MD made synaptic junctions with GABA-immunoreactive dendritic shafts and spines. Nonlabeled dendritic spines were found to receive both axonal inputs from MD with PHA-L labelings and from GABAergic cells. In addition, synapses were found between dendritic shafts and axon terminals that were both immunoreactive for GABA. Third, synaptic connections between corticothalamic neurons that project to MD and GABAergic terminals were investigated by using wheat germ agglutinin conjugated to horseradish peroxidase and postembedding GABA immunocytochemistry. GABAergic terminals in the prelimbic cortex made symmetrical synaptic contacts with retrogradely labeled corticothalamic neurons to MD. All of the synapses were found on cell somata and thick dendritic trunks. These results provide the first demonstration of synaptic contacts in the prelimbic cortex not only between thalamocortical terminals from MD and GABAergic interneurons but also between GABAergic terminals and corticothalamic neurons that project to MD. The anatomical findings indicate that GABAergic interneurons have a modulatory influence on excitatory reverberation between MD and the prefrontal cortex.


Object-based attentional modulation of biological motion processing: spatiotemporal dynamics using functional magnetic resonance imaging and electroencephalography.
Although it is well documented that the ability to perceive biological motion is mediated by the lateral temporal cortex, whether and when neural activity in this brain region is modulated by attention is unknown. In particular, it is unclear whether the processing of biological motion requires attention or whether such stimuli are processed preattentively. Here, we used functional magnetic resonance imaging, high-density electroencephalography, and cortically constrained source estimation methods to investigate the spatiotemporal effects of attention on the processing of biological motion. Directing attention to tool motion in overlapping movies of biological motion and tool motion suppressed the blood oxygenation level-dependent (BOLD) response of the right superior temporal sulcus (STS)/middle temporal gyrus (MTG), while directing attention to biological motion suppressed the BOLD response of the left inferior temporal sulcus (ITS)/MTG. Similarly, category-based modulation of the cortical current source density estimates from the right STS/MTG and left ITS was observed beginning at approximately 450 ms following stimulus onset. Our results indicate that the cortical processing of biological motion is strongly modulated by attention. These findings argue against preattentive processing of biological motion in the presence of stimuli that compete for attention. Our findings also suggest that the attention-based segregation of motion category-specific responses only emerges relatively late (several hundred milliseconds) in processing.


Smoke-free air laws and asthma prevalence, symptoms, and severity among nonsmoking youth.
We investigated the association between smoke-free laws and asthma prevalence, symptoms, and severity among nonsmoking youth (aged 3-15 years). We examined data from the 1999-2006 National Health and Nutrition Examination Survey, a cross-sectional survey designed to monitor the health and nutritional status of the US population. Survey locations were dichotomized as having or not having at least 1 smoke-free workplace, restaurant, or bar law at the county or state level that covered the entire county population. Asthma prevalence was assessed as self-reported current asthma and as ever having asthma with current symptoms. Asthmatic symptoms included persistent wheeze, chronic night cough, and wheeze-medication use. We also examined asthma severity (asthma attack or emergency-department visit for asthma) and persistent ear infection. Smoke-free laws were not associated with current asthma but were significantly associated with lower odds of asthmatic symptoms (odds ratio [OR]: 0.67 [95% confidence interval (CI): 0.48-0.93]) among nonsmoking youth. The association between smoke-free laws and ever having asthma with current symptoms approached significance (OR: 0.74 [95% CI: 0.53-1.03]). Smoke-free laws were associated with lower odds of asthma attacks (OR: 0.66 [95% CI: 0.28-1.56]) and emergency-department visits for asthma (OR: 0.55 [95% CI: 0.27-1.13]), although these results were not statistically significant. Our results suggest that smoke-free laws reduce asthmatic symptoms, including persistent wheeze, chronic night cough, and wheeze-medication use in nonsmoking youth.


Using induced pluripotent stem cells to explore genetic and epigenetic variation associated with Alzheimer's disease.
It is thought that both genetic and epigenetic variation play a role in Alzheimer's disease initiation and progression. With the advent of somatic cell reprogramming into induced pluripotent stem cells it is now possible to generate patient-derived cells that are able to more accurately model and recapitulate disease. Furthermore, by combining this with recent advances in (epi)genome editing technologies, it is possible to begin to examine the functional consequence of previously nominated genetic variants and infer epigenetic causality from recently identified epigenetic variants. In this review, we explore the role of genetic and epigenetic variation in Alzheimer's disease and how the functional relevance of nominated loci can be investigated using induced pluripotent stem cells and (epi)genome editing techniques.


Analysis of Transient Flow to an Extended Fully Penetrating Well at Constant-Head Pumping.
Vertical wells with radial extension at the well bottom can improve the rate of water production. No study has yet investigated the effects of the transient state and anisotropy in directional hydraulic conductivities on the wellbore flux rate for this type of well. This study derives a semianalytical transient drawdown solution for constant-head pumping at a fully penetrating well radially extended at the bottom of a confined, anisotropic aquifer by applying Laplace transform and separation of variables as well as conducting a Fourier analysis. The results of this new solution indicate that transient and steady-state wellbore flux rates can be increased by a factor of two for greater radial extension of the well. Compared with an isotropic aquifer (a ratio of vertical and horizontal hydraulic conductivities equal to one), an anisotropic aquifer with the ratio less than one may produce a higher transient wellbore flux rate and lower steady-state wellbore flux rate. Moreover, the time required to achieve the steady-state wellbore flux rate can be substantially affected by anisotropy of the aquifer.


Impact of drug-resistant tuberculosis treatment on hearing function in South African adults: Bedaquiline versus kanamycin.
Ototoxicity linked to medications used to treat tuberculosis (TB) remains a global challenge. The aim was to describe the audiological function in a group of adults with drug-resistant tuberculosis (DR-TB) on bedaquiline (G-BDQ) treatment attending a TB hospital in South Africa and compare this with patients on kanamycin (G-KCIN). A quantitative paradigm was adopted within a non-experimental retrospective record review design. The sample consisted of 30 records of adults with DR-TB between the ages of 18 and 50 years, recruited from a Tropical Diseases Hospital in South Africa. Data were analysed through both descriptive and inferential statistical measures. Clear and statistically significant differences in the audiological function were found between the two groups. The group receiving G-KCIN presented with ototoxicity that was clearly demonstrated by sensorineural hearing loss of high-frequency worsening of thresholds in over 73% of the records, which was statistically (p 0.05) and clinically significant, over the three testing sessions, demonstrating the cumulative effects of dosage. Increased evidence of tinnitus was also found in this group. The group receiving G-BDQ presented with neither statistically (p 0.05) nor clinically significant changes in hearing thresholds across all frequencies over the same monitoring timeframe. Additionally, only one report (7%) of tinnitus was found in this group. The results indicating that bedaquiline does not cause hearing loss when compared with G-KCIN highlight the need for increased availability of bedaquiline for the treatment of DR-TB within the South African context, to preserve both the quantity and quality of life of those infected.


Towards smart work zones: Creating safe and efficient work zones in the technology era.
Work Zones (WZs) have long been identified as a source of traffic fatalities and delays. Despite considerable technological advances that have alleviated many operational challenges associated with a WZ, social concerns about safety and mobility near WZs remain. Notably, the concept of a Smart Work Zone (SWZ) emerged from the compelling need to improve the safety and mobility of traffic and other WZ participants. This study reviewed the literature to assimilate studies related to SWZ Systems (SWZSs), report their findings, and ascertain a future path forward. To accomplish this, the existing WZ-related literature base was clustered into safety and traffic mobility topics using Latent Dirichlet Allocation (LDA) modeling. A thorough investigation of the pivotal inferences for the research topics was undertaken to comprehend current SWZ technologies and the need for further research. The review uncovered the prominent features of SWZSs reported in the literature and the hindrances to their adoption. The most reported hindrances are the cost and effort associated with development, installation, and relocation. We uncover that Connected Autonomous Vehicles, vehicle-to-vehicle, and vehicle-to-infrastructure communication, along with technology-based worker training are the most promising next frontier for SWZ. Significant research gaps exist in the literature regarding developing and implementing SWZS. Additionally, little effort has been directed toward developing workers' skills and competency. Practical approaches such as Virtual Reality (VR)-based training are necessary to bring workers up to pace with the developing SWZ technologies. Future research should be directed towards interconnecting and implementing available safety technologies to automate WZ safety and management. Workers should be trained using more practical techniques. In this context, using VR will enable the simulation of hazardous events in a safe environment while also improving workers' skill retention.


Development of TaqMan real-time PCR assay for detection and quantitation of reticuloendotheliosis virus.
A highly sensitive real-time PCR method was developed in this study for reticuloendotheliosis virus (REV) detection and quantitation. The real-time PCR method, with a minimum detection limit of 10 proviral DNA copies, was 100 times more sensitive than the conventional PCR. It was also shown to be highly specific, as no positive signals were detected for other common avian DNA viruses. The coefficients of variation of intra- and inter-assay reproducibility were both less than 2%. The chicken β-actin gene was co-amplified and used as the internal control to monitor the efficiency of DNA extraction and PCR amplification. Specific pathogen free chickens were infected with REV at different ages and the blood was detected with the real-time PCR method. High levels of proviral DNA were detected in the blood of REV-infected chickens during the experiment and chickens infected early had higher proviral loads from 2 weeks post-infection compared with late infected chickens. This study provides an excellent research and diagnostic tool that can be used for REV detection and quantitation.


The development of scales to measure childhood cancer survivors' readiness for transition to long-term follow-up care as adults.
To develop and validate scales to measure constructs that survivors of childhood cancer report as barriers and/or facilitators to the process of transitioning from paediatric to adult-oriented long-term follow-up (LTFU) care. Qualitative interviews provided a dataset that were used to develop items for three new scales that measure cancer worry, self-management skills and expectations about adult care. These scales were field-tested in a sample of 250 survivors aged 15-26 years recruited from three Canadian hospitals between July 2011 and January 2012. Rasch Measurement Theory (RMT) analysis was used to identify the items that represent the best indicators of each scale using tests of validity (i.e. thresholds for item response options, item fit statistics, item locations, differential item function) and reliability (Person Separation Index). Traditional psychometric tests of measurement performance were also conducted. RMT led to the refinement of a 6-item Cancer Worry scale (focused on worry about cancer-related issues such as late effects), a 15-item Self-Management Skills scale (focused on skills an adolescent needs to acquire to manage their own health care), and a 12-item Expectations scale (about the nature of adult LTFU care). Our study provides preliminary evidence about the reliability and validity of these new scales (e.g. Person Separation Index ≥ 0.81; Cronbach's α ≥ 0.81; test-retest reliability ≥ 0.85). There is limited knowledge about the transition experience of childhood cancer survivors. These scales can be used to investigate barriers survivors face in the process of transition from paediatric to adult care.


Spatial Compounding of Volumetric Data Enables Freehand Optoacoustic Angiography of Large-Scale Vascular Networks.
Optoacoustic tomography systems have attained unprecedented volumetric imaging speeds, thus enabling insights into rapid biological dynamics and marking a milestone in the clinical translation of this modality. Fast imaging performance often comes at the cost of limited field-of-view, which may hinder potential applications looking at larger tissue volumes. The imaged field-of-view can potentially be expanded via scanning and using additional hardware to track the position of the imaging probe. However, this approach turns impractical for high-resolution volumetric scans performed in a freehand mode along arbitrary trajectories. We have developed an accurate framework for spatial compounding of time-lapse optoacoustic data. The method exploits the frequency-domain properties of vascular networks in optoacoustic images and estimates the relative motion and orientation of the imaging probe. This allows rapidly combining sequential volumetric frames into large area scans without additional tracking hardware. The approach is universally applicable for compounding volumetric data acquired with calibrated scanning systems but also in a freehand mode with up to six degrees of freedom. Robust performance is demonstrated for whole-body mouse imaging with spiral volumetric optoacoustic tomography and for freehand visualization of vascular networks in humans using volumetric imaging probes. The newly introduced capability for angiographic observations at multiple spatial and temporal scales is expected to greatly facilitate the use of optoacoustic imaging technology in pre-clinical research and clinical diagnostics. The technique can equally benefit other biomedical imaging modalities, such as scanning fluorescence microscopy, optical coherence tomography or ultrasonography, thus optimizing their trade-offs between fast imaging performance and field-of-view.


Altering the crystal morphology of silicalite-1 through microemulsion-based synthesis.
The crystal morphology of silicalite-1 was adjusted through a microemulsion-based hydrothermal synthesis. The surfactant cetyltrimethylammonium bromide (CTAB) with cosurfactant butanol was used to form water-in-oil microemulsions containing the silicalite-1 synthesis gel. The crystal morphology of silicalite-1 was adjusted from coffin-shaped to novel rod-shaped and to irregular-shaped nanoparticles by varying the microemulsion composition. Silicalite-1 synthesized in the microemulsion has a smaller size and a more narrow size distribution than that produced by conventional synthesis without the microemulsion. The novel morphology of silicalite-1 may facilitate assembly into films and find applications in separation and catalysis.


Weaning from mechanical ventilatory support: refinement of a model.
The American Association of Critical-Care Nurses sponsored the third National Study Group to advance the science of weaning from mechanical ventilatory support and to guide clinical practice. The study group proposed a model of weaning in 1994 to provide an organizing framework for scientific inquiry. Since the model was first proposed, the ongoing work of the study group has led to refinement of the model. The purpose of this brief communication is to inform critical care clinicians and researchers about the refinements.


A novel X-linked four-repeat tauopathy with Parkinsonism and spasticity.
The parkinsonian syndromes comprise a highly heterogeneous group of disorders. Although 15 loci are linked to predominantly familial Parkinson's disease (PD), additional PD loci are likely to exist. We recently identified a multigenerational family of Danish and German descent in which five males in three generations presented with a unique syndrome characterized by parkinsonian features and variably penetrant spasticity for which X-linked disease transmission was strongly suggested (XPDS). Autopsy in one individual failed to reveal synucleinopathy; however, there was a significant four-repeat tauopathy in the striatum. Our objective was to identify the locus responsible for this unique parkinsonian disorder. Members of the XPDS family were genotyped for markers spanning the X chromosome. Two-point and multipoint linkage analyses were performed and the candidate region refined by analyzing additional markers. A multipoint LOD(max) score of 2.068 was obtained between markers DXS991 and DXS993. Haplotype examination revealed an approximately 20 cM region bounded by markers DXS8042 and DXS1216 that segregated with disease in all affected males and obligate carrier females and was not carried by unaffected at-risk males. To reduce the possibility of a false-positive linkage result, multiple loci and genes associated with other parkinsonian or spasticity syndromes were excluded. In conclusion, we have identified a unique X-linked parkinsonian syndrome with variable spasticity and four-repeat tau pathology, and defined a novel candidate gene locus spanning approximately 28 Mb from Xp11.2-Xq13.3.


[Molecular aspects of anthrax pathogenesis].
A model of anthrax infection with the role determined for main pathogenicity factors of Bacillus anthracis exotoxin and capsule is presented. After spore phagocytosis by macrophages, synthesis of the main exotoxin component begins - a protective antigen that in oligomeric form disrupts phagosome membrane. This accelerates the transition of the pathogen from phagosome into the macrophage cytoplasm. Poly-D-glutamine capsule synthesized by the pathogen triggers the exit (exocytosis) of vegetative cells from macrophages and protects them from re-phagocytosis in lymphatic node lumen. The vegetative cells, that actively and freely replicate in lymphatic node, secret an exotoxin that disrupts endothelial septum between lymph and blood due to cytotoxic activity. As a result the vegetative cells get into blood and bacteremia develops. Pathogenetic pattern during anthrax (multiple hemorrhages in various organs etc.) is associated with local microcirculation disorders of various organs caused by the effect of bacterial exoproteases via activation of Willebrand factor. This results in a rapid local increase of microbial mass and consequent powerful cytotoxic effect of exotoxin on the tissue cells of the affected organ. Death of the infected organism takes place at the final stage of infec- tion due to toxic shock caused by the exotoxin. A reduction of body temperature takes place after death and the process of spore formation begins in the dead animal: capsule depolymerization, chain shortening, peptidoglycan cortex formation. Spores in this form are the prolonged source of infectious agent conservation and spread of infection in nature.


Genome resolved analysis of a premature infant gut microbial community reveals a Varibaculum cambriense genome and a shift towards fermentation-based metabolism during the third week of life.
The premature infant gut has low individual but high inter-individual microbial diversity compared with adults. Based on prior 16S rRNA gene surveys, many species from this environment are expected to be similar to those previously detected in the human microbiota. However, the level of genomic novelty and metabolic variation of strains found in the infant gut remains relatively unexplored. To study the stability and function of early microbial colonizers of the premature infant gut, nine stool samples were taken during the third week of life of a premature male infant delivered via Caesarean section. Metagenomic sequences were assembled and binned into near-complete and partial genomes, enabling strain-level genomic analysis of the microbial community.We reconstructed eleven near-complete and six partial bacterial genomes representative of the key members of the microbial community. Twelve of these genomes share >90% putative ortholog amino acid identity with reference genomes. Manual curation of the assembly of one particularly novel genome resulted in the first essentially complete genome sequence (in three pieces, the order of which could not be determined due to a repeat) for Varibaculum cambriense (strain Dora), a medically relevant species that has been implicated in abscess formation.During the period studied, the microbial community undergoes a compositional shift, in which obligate anaerobes (fermenters) overtake Escherichia coli as the most abundant species. Other species remain stable, probably due to their ability to either respire anaerobically or grow by fermentation, and their capacity to tolerate fluctuating levels of oxygen. Metabolic predictions for V. cambriense suggest that, like other members of the microbial community, this organism is able to process various sugar substrates and make use of multiple different electron acceptors during anaerobic respiration. Genome comparisons within the family Actinomycetaceae reveal important differences related to respiratory metabolism and motility. Genome-based analysis provided direct insight into strain-specific potential for anaerobic respiration and yielded the first genome for the genus Varibaculum. Importantly, comparison of these de novo assembled genomes with closely related isolate genomes supported the accuracy of the metagenomic methodology. Over a one-week period, the early gut microbial community transitioned to a community with a higher representation of obligate anaerobes, emphasizing both taxonomic and metabolic instability during colonization.


Birth parameters are associated with late-life white matter integrity in community-dwelling older people.
Lower birth weight is associated with increased risk of stroke, but little is known about the mechanism for this association or influence in addition to vascular risk factors. We investigated whether there was an association between birth parameters and imaging markers of white matter integrity in community-dwelling older people. One hundred seven volunteers, age 75 to 81 years, had birth parameters (weight, length, placental weight, gestational age) extracted from archives. Neuroimaging included assessment of white matter lesions and diffusion tensor-magnetic resonance imaging parameters in normal-appearing white matter. Lower placental weight was correlated with increased white matter lesion load (P<0.05) and diffusion tensor-magnetic resonance imaging parameters (P<0.05). Birth weight and frontal white matter fractional anisotropy were significantly correlated (P<0.05). These associations were only slightly attenuated when corrected for gestational age, sex, age at scan, and vascular risk factors. Lower placental and possibly lower birth weight were associated with sensitive neuroimaging measures of white matter lesions in this cohort, independent of vascular risk factors later in life. Further studies are required to confirm these findings to explore life-long risk factors for age-related white matter changes.


Toll-like receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with type 2 diabetes and diabetic foot.
Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus (DM). The aim of this study is to evaluate the association of TLR2 and TLR9 gene polymorphism in patients with type 2 DM (T2DM) and diabetic foot (DF).The study included 90 subjects divided into group I (30 patients with T2DM and DF), group II (30 patients with T2DM and no evidence of DF), and group III (normal control subjects). TLR2 (1350 T/C, rs3804100) and TLR9 (1237 T/C, rs5743836) genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for all subjects.There was a statistically significant difference in the distribution of TLR9-1237 T/C genotypes between groups I and II (P < .029) as well as between groups I and III (P < .001). Calculated risk estimation revealed that TLR9-1237 polymorphism conferred almost 20 times increased risk of DF disorders in T2DM (OR = 20, 95% CI = 5.38-74.30). There was no statistical difference in the distribution of TLR2-1350T/C genotypes between the 3 groups.TLR9-1237 T/C gene polymorphism may be considered as a molecular risk for DF among patients with T2DM.


Detection and typing of human papillomavirus in cervical specimens of Turkish women.
The DNA in situ hybridization (DISH) and conventional solution phase polymerase chain reaction (PCR) were applied to identify human papillomavirus (HPV) DNA in cervical specimens of Turkish women. Samples consisted of 21 cervical brushings from pregnant women and 20 paraffin-embedded biopsies from women with condylomatous or dysplasic lesions. It was found that two out of 21 (9.5%) pregnant women were harbouring HPV-DNA detected by PCR. One woman was infected with HPV 16/30's and the other with an unidentified type. As for the biopsy specimens, the rate of HPV-DNA positivity was 30% and 45% by DISH and PCR, respectively. A double infection was observed in more than 50% of the positive cases. Moreover, HPV 18 was never detected. The results indicated that HPV-DNA is rarely present in cytomorphologically normal smears from pregnant women. The PCR method was successfully adapted for HPV typing in clinical lesions which simultaneously contained different HPV sequences.


Somatostatin receptor distribution and function in immune system.
Somatostatin and cortistatin, a recently discovered endogenous neuropeptide relative of somatostatin, have multiple modulatory effects on the immune system. The specific somatostatin receptor distribution might in part explain the heterogeneity of effects of somatostatin or its analogs on immunocytes. In fact, somatostatin receptor subtypes are differentially expressed on specific cell subsets within the organs of the immune system and the expression is dynamically regulated and seems to depend on the traffic of these cells through and within lymphoid structure and homing in tissues. Somatostatin effects on immune cells are mainly based on autocrine and paracrine modes of action. In fact, activated cells producing somatostatin (or cortistatin) may interact with other cells expressing the receptors. Here, we review the postulated modes of action of somatostatin and somatostatin-like peptides, including the currently available synthetic somatostatin analogs, in cells of the immune system. We also discuss the wide distribution of somatostatin and its specific five receptor subtypes in immune cell lines, as well as throughout animal and human lymphoid organs, in both normal and pathological conditions.


Neural ITD Sensitivity and Temporal Coding with Cochlear Implants in an Animal Model of Early-Onset Deafness.
Users of cochlear implant (CI) face challenges in everyday situations such as understanding conversations in noise, even with CIs in both ears. These challenges are related to difficulties with tasks that require fine temporal processing such as discrimination of pulse rates or interaural time differences (ITD), a major cue for sound localization. The degradation in temporal processing and ITD sensitivity are especially acute in those who lost hearing in early childhood. Here, we characterized temporal coding and ITD sensitivity of single neurons in a novel animal model of early-onset deafness. Rabbits were deafened as neonates and deprived of auditory stimulation until they reached adult age when single-unit recordings from the auditory midbrain were made chronically using an unanesthetized preparation. The results are compared to measurements from adult-deafened rabbits with normal auditory development to understand the effect of early-onset deafness on neural temporal coding and ITD sensitivity. Neurons in the inferior colliculus (IC) of early-deafened rabbits were less likely to show sustained, excitatory responses to pulse train stimulation and more likely to show suppressive responses compared to neurons in adult-deaf animals. Fewer neurons showed synchronized responses to pulse trains at any rate in the early-deaf group. In addition, fewer neurons showed significant ITD sensitivity in their overall firing rate in the early-deaf group compared to adult-deaf animals. Neural ITD discrimination thresholds in the early-deaf group were poorer than thresholds in adult-deaf group, especially at high pulse rates. The overall degradation in neural ITD sensitivity is consistent with the difficulties encountered by human CI users with early-onset hearing loss. These results lay the groundwork for investigating whether the degradations in temporal coding and ITD sensitivity observed in early-deaf animals can be reversed by appropriate CI stimulation during development.


SAMMate: a GUI tool for processing short read alignments in SAM/BAM format.
Next Generation Sequencing (NGS) technology generates tens of millions of short reads for each DNA/RNA sample. A key step in NGS data analysis is the short read alignment of the generated sequences to a reference genome. Although storing alignment information in the Sequence Alignment/Map (SAM) or Binary SAM (BAM) format is now standard, biomedical researchers still have difficulty accessing this information. We have developed a Graphical User Interface (GUI) software tool named SAMMate. SAMMate allows biomedical researchers to quickly process SAM/BAM files and is compatible with both single-end and paired-end sequencing technologies. SAMMate also automates some standard procedures in DNA-seq and RNA-seq data analysis. Using either standard or customized annotation files, SAMMate allows users to accurately calculate the short read coverage of genomic intervals. In particular, for RNA-seq data SAMMate can accurately calculate the gene expression abundance scores for customized genomic intervals using short reads originating from both exons and exon-exon junctions. Furthermore, SAMMate can quickly calculate a whole-genome signal map at base-wise resolution allowing researchers to solve an array of bioinformatics problems. Finally, SAMMate can export both a wiggle file for alignment visualization in the UCSC genome browser and an alignment statistics report. The biological impact of these features is demonstrated via several case studies that predict miRNA targets using short read alignment information files. With just a few mouse clicks, SAMMate will provide biomedical researchers easy access to important alignment information stored in SAM/BAM files. Our software is constantly updated and will greatly facilitate the downstream analysis of NGS data. Both the source code and the GUI executable are freely available under the GNU General Public License at http://sammate.sourceforge.net.


Hippocratic Oath and Heart Failure Journey: An Update on Therapies.
The innovation that has taken place in medicine, combined with state-of-the-art technological developments, provides therapeutic options for patients in conditions that were previously considered incurable. This promotion at the same time presents us with new ethical challenges. In this article, we review the journey through life of an advanced heart failure patient, covering a variety of potential clinical and ethics subjects in the field of heart failure treatment. We review the ethical principles of the Hippocratic Oath against the background of the realities of practicing medicine and of the enormous advances in therapeutics.


Enhancement of hole mobility in InSe monolayer via an InSe and black phosphorus heterostructure.
To enhance the low hole mobility (∼40 cm2 V-1 s-1) of InSe monolayer, a novel two-dimensional (2D) van der Waals heterostructure made of InSe and black phosphorus (BP) monolayers with high hole mobility (∼103 cm2 V-1 s-1) has been constructed and its structural and electronic properties are investigated using first-principles calculations. We find that the InSe/BP heterostructure exhibits a direct band gap of 1.39 eV and type-II band alignment with electrons (holes) located in the InSe (BP) layer. The band offsets of InSe and BP are 0.78 eV for the conduction band minimum and 0.86 eV for the valence band maximum, respectively. Surprisingly, the hole mobility in the InSe/BP heterostructure exceeds 104 cm2 V-1 s-1, which is one order of magnitude larger than the hole mobility of BP and three orders larger than that of the InSe monolayer. The electron mobility is also increased to 3 × 103 cm2 V-1 s-1. The physical reason has been analyzed deeply, and a universal method is proposed to improve the carrier mobility of 2D materials by forming heterostructures with them and other 2D materials with complementary properties. The InSe/BP heterostructure can thus be widely used in nanoscale InSe-based field-effect transistors, photodetectors and photovoltaic devices due to its type-II band alignment and high carrier mobility.


First experience with the ultra compact mobile extracorporeal membrane oxygenation system Cardiohelp in interhospital transport.
In patients with severe cardiopulmonary failure extracorporeal assist devices are to support patients during resuscitation, for transportation, until organ recovery, and as bridge to further therapeutic modalities. We report on our first experience with the new Cardiohelp system for interhospital transfer of cardiopulmonarily compromised patients. The Cardiohelp system was used for transportation and in-house treatment in six male patients with a mean age of 41±17 years. Five patients suffered respiratory failure; one patient with acute myocardial infarction was in profound cardiogenic shock. Accordingly, the Cardiohelp system was implanted as a venovenous extracorporeal membrane oxygenation (ECMO) in five patients and as a venoarterial system in one patient. The preECMO ventilation time was 0.5-4 days. The patients were transported to our institution by car (n=1) or helicopter (n=5) over a distance of 80-5850 km. The subsequent in-house ECMO support was continued with the Cardiohelp and lasted for 5-13 days. PostECMO ventilation was one to 25 days. A 100% survival was achieved. The portable Cardiohelp system allows location-independent stabilization of cardiopulmonary compromised patients with consecutive interhospital transfer and in-house treatment. The integrated sensors, which register arterial and venous line pressure, blood temperature, hemoglobin as well as SvO(2), greatly alleviate its management and considerably increase safety.


Distribution of body fat and its influence on esophageal inflammation and dysplasia in patients with Barrett's esophagus.
Increased waist circumference and visceral fat are associated with increased risk of Barrett's esophagus (BE) and esophageal adenocarcinoma. This association might be mediated by mechanical and endocrine mechanisms. We investigated the distribution of fat in subjects with BE and its association with esophageal inflammation and dysplasia. We collected data from 50 BE cases and 50 controls (matched for age and sex, identified from a radiology trauma database) seen at the Mayo Clinic in 2009. Abdominal (subcutaneous and visceral) and gastroesophageal junction (GEJ) fat area was measured using computed tomography with standard techniques. Esophageal inflammation (based on a histologic score) and dysplasia grade were assessed from esophageal biopsies of BE cases by a gastrointestinal pathologist. Conditional logistic regression was used to assess the association of body fat depot area with BE status, esophageal inflammation, and dysplasia. All BE subjects had controlled reflux symptoms without esophagitis, based on endoscopy. The GEJ fat area (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.3-27.7; P = .02), visceral fat area (OR, 4.9; 95% CI, 1.0-22.8; P = .04), and abdominal circumference (OR, 9.1; 95% CI, 1.4-57.2; P = 0.02) were associated with BE, independent of body mass index (BMI). The subcutaneous fat area was not associated with BE. Visceral and GEJ fat were significantly greater in BE subjects with esophageal inflammation (compared with those without, P = .02) and high-grade dysplasia (compared with those without, P = .01), independent of BMI. GEJ and visceral fat are associated with BE, and with increased esophageal inflammation and high-grade dysplasia in BE subjects, independent of BMI. Visceral fat therefore might promote esophageal metaplasia and dysplasia.


Technology-based interventions in health care.
There are several converging forces that create a particularly opportune time for technological solutions to enhance cost efficiency in healthcare. Health care costs are unsustainable, yet many patients do not have adequate access to state-of-the-art treatments or to ongoing disease management. Consumerism is an increasingly powerful force in healthcare and the emphasis on personalised medicine will help to define future research and clinical treatment strategies. At the same time, the phenomenal advances in internet utilisation and mobile device applications provide possibilities that have never before existed. We have reason to be very optimistic about these opportunities, but appropriate research will be required to develop scalable and sustainable methods as well as determine expected outcomes.


The Relative Operating Characteristic in Psychology: A technique for isolating effects of response bias finds wide use in the study of perception and cognition.
The clinician looking, listening, or feeling for signs of a disease may far prefer a false alarm to a miss, particularly if the disease is serious and contagious. On the other hand, he may believe that the available therapy is marginally effective, expensive, and debilitating. The pilot seeing the landing lights only when they are a few yards away may decide that his plane is adequately aligned with the runway if he is alone and familiar with that plight. He may be more inclined to circle the field before another try at landing if he has many passengers and recent memory of another plane crashing under those circumstances. The Food and Drug administrator suspecting botulism in a canned food may not want to accept even a remote threat to the public health. But he may be less clearly biased if a recent false alarm has cost a canning company millions of dollars and left some damaged reputations. The making of almost any fine discrimination is beset with such considerations of probability and utility, which are extraneous and potentially confounding when one is attempting to measure the acuity of discrimination per se. The ROC is an analytical technique, with origins in statistical decision theory and electronic detection theory, that quite effectively isolates the effects of the observer's response bias, or decision criterion, in the study of discrimination behavior. This capability, pursued through a century of psychological testing, provides a relatively pure measure of the discriminability of different stimuli and of the capacity of organisms to discriminate. The ROC also treats quantitatively the response, or decision, aspects of choice behavior. The decision parameter can then be functionally related to the probabilities of the stimulus alternatives and to the utilities of the various stimulus-response pairs, or to the observer's expectations and motivations. In separating and quantifying discrimination and decision processes, the ROC promises a more reliable and valid solution to some practical problems and enhances our understanding of the perceptual and cognitive phenomena that depend directly on these fundamental processes. In several problem areas in psychology, effects that were supposed to reflect properties of the discrimination process have been shown by the ROC analysis to reflect instead properties of the decision process.


Physical mapping of temperature-sensitive mutations of herpes simplex virus type 2 by marker rescue.
The physical mapping of six ts mutations of herpes simplex virus type 2 (HSV-2) is presented. The results were obtained from 14 separate intratypic marker rescue experiments and the analysis of 20 HSV-1/HSV-2 intertypic recombinants. The order of these mutations on the physical map of HSV-2 is unambiguous and correlates almost exactly with the previously published genetic map of Timbury & Calder (1976). One of the mutants studied (HSV-2 ts12) has apparently two distinct conditionally lethal ts mutations, one in the long and the other in the short region of the HSV genome.


Infantile experience with suckling odors determines adult sexual behavior in male rats.
Because infant rats learn about odors that elicit suckling, and because certain chemosensory cues that help elicit mating behavior in adults are similar to those that elicit suckling, an experiment was undertaken to assess the influence of suckling-associated odors experienced during infancy on adult sexual behavior. Rat pups lived with and suckled dams whose nipple and vaginal odors were altered with citral, a lemon scent. The rats were weaned and never exposed again, until testing, to citral or females. At about 100 days of age, the males were paired in mating tests with a normal sexually receptive female or with a sexually receptive female that had been treated perivaginally with citral immediately before testing. The males ejaculated readily when paired with citral-treated females but were slow to achieve ejaculation when paired with normal females. These findings implicate an infantile experience as a determinant of adult sexual behavior in a mammal.


[Treatment of cutaneous human papilloma virus, poxvirus and herpes simplex virus infections with topical cidofovir in HIV positive patients].
Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100. Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes. Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially. In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.


Evidence for the emergence of leg sympathetic vasoconstrictor tone with age in healthy women.
While muscle sympathetic nerve activity (MSNA) is elevated with advancing age, correlational evidence suggests that, in contrast to men, basal MSNA is not related to resting lower limb hemodynamics in women. However, limited data exists in women that have attempted to directly assess the degree of limb sympathetic vasoconstrictor tone, and whether it is altered with age. To address this issue, we measured changes in femoral artery vascular conductance (FVC) during an acute sympatho-inhibitory stimulus (-60 mm Hg neck suction, NS) in groups of healthy younger (n = 8, 23 ± 1 years) and older (n = 7, 66 ± 1 years) women. The percent change in FVC in response to NS was significantly augmented in the older (P = 0.006 vs. young) women. Although NS caused no significant change (3 ± 3%, P = 0.33) in FVC in the young women, there was a robust increase in FVC (21 ± 5%, P = 0.003) in the old women. Collectively, these findings provide evidence that in women, leg sympathetic vasoconstrictor tone emerges with age.


Disseminated intravascular coagulation.
Disseminated intravascular coagulation (DIC) is a clinico-pathological syndrome of variable expression, resulting from uncontrolled simultaneous activation of the coagulation and fibrinolytic systems. DIC can be initiated in a variety of different ways. Additional studies are needed to determine the importance of vascular endothelial damage, hemodynamic alterations and the role of naturally occurring inhibitors of hemostasis. Progressive increase in our understanding of the mechanisms involved in triggering DIC will improve our therapeutic measures in the rational management of these patients. Absolutely essential in the successful management of patients with DIC is identification and control of the underlying illness.


The direct and indirect economic costs incurred by living kidney donors-a systematic review.
Despite the many benefits of living donor kidney transplantation, economic consequences can result for donors. We reviewed studies which quantified the direct and indirect costs incurred by living kidney donors, in order to understand the strengths and limitations of existing literature. We identified relevant studies in MEDLINE, EMBASE and ECONOLIT bibliographic databases, in the Science Citation Index and study reference lists. Any study which reported at least one cost relevant to donors was included. The accuracy of abstracted data was verified by two reviewers and reported in year 2004 US dollars. Thirty-five studies from 12 countries described costs incurred by individuals who donated between the years 1964 and 2003. No study comprehensively quantified all relevant expenses-the sum of select costs considered in one US study averaged Dollars 837 per donor and ranged from Dollars 0 to 28,906. Travel and/or accommodation costs were incurred by 9-99% of donors, and were higher in countries with a larger land mass. Post-discharge analgesics were required by 4-24% of donors, but prescription costs were not reported. Between 14 and 30% of donors incurred costs for lost income, with an average loss of Dollars 3386 in one study from the UK and Dollars 682 in another study from the Netherlands. Costs for dependent care were incurred by 9-44% of donors, while costs for domestic help were incurred by 8% of donors. Donors incur many types of costs attributable to kidney donation and the total costs are certainly higher than previously reported. To guide informed consent and fair reimbursement policies, further data on all relevant costs, preferably from a detailed prospective multi-centre cohort study, are required.


Multivariate analyses of patient financial systems and oral health-related quality of life.
Since 1999, the public dental health service (PDHS) in the county of Värmland, Sweden, has two co-existing patient financial systems, i.e. ways for the patient to pay for dental care services. Alongside the traditional system of fee-for-service payment, i.e. paying afterwards for provided services, a new system of contract care is offered. In this system, dental care is covered by a contractual agreement, for which the patient pays an annual fee and receives care covered by the contract without additional costs. The aim of this article was to study whether patient financial system was associated with oral health-related quality of life (OHRQoL). A questionnaire was answered by 1324 randomly selected patients, 52% from contract care and 48% from fee-for-service. The questionnaire contained questions about how much one was prepared to pay for dental care, how much one paid for dental care the previous year, OHIP-14 (measured OHRQoL), dental anxiety, humanism of caregiver, SF-36 (measured general health), multidimensional health locus of control, sense of coherence (SOC), self-esteem and demographics. Data on patient financial system, gender and age were obtained from the sampling frame. The material was analysed with a hierarchical block method of multiple regression analysis. When controlling for all other variables, patient financial system was one of the strongest associations with OHRQoL: patients in fee-for-service had worse OHRQoL than those in contract care. OHRQoL was also associated with general health, SOC and to some extent also with psychological and economic factors. Of the social variables, only being foreign born was significant: it was associated with worse OHRQoL. Patient financial system was associated with OHRQoL when controlling for confounding factors: patients in contract care had better OHRQoL than those in fee-for-service care.


Regulation of S100G Expression in the Uterine Endometrium during Early Pregnancy in Pigs.
Calcium ions play an important role in the establishment and maintenance of pregnancy, but molecular and cellular regulatory mechanisms of calcium ion action in the uterine endometrium are not fully understood in pigs. Previously, we have shown that calcium regulatory molecules, transient receptor potential vanilloid type 5 (TRPV6) and calbindin-D9k (S100G), are expressed in the uterine endometrium during the estrous cycle and pregnancy in a pregnancy status- and stage-specific manner, and that estrogen of conceptus origin increases endometrial TRPV6 expression. However, regulation of S100G expression in the uterine endometrium and conceptus expression of S100G has been not determined during early pregnancy. Thus, we investigated regulation of S100G expression by estrogen and interleukin-1β (IL1B) in the uterine endometrium and conceptus expression of S100G during early pregnancy in pigs. We obtained uterine endometrial tissues from day (D) 12 of the estrous cycle and treated with combinations of steroid hormones, estradiol-17β (E2) and progesterone (P4), and increasing doses of IL1B. Real-time RT-PCR analysis showed that E2 and IL1B increased S100G mRNA levels in the uterine endometrium, and conceptuses expressed S100G mRNA during early pregnancy, as determined by RT-PCR analysis. To determine if endometrial expression of S100G mRNA during the implantation period was affected by the somatic cell nuclear transfer (SCNT) procedure, we compared S100G mRNA levels in the uterine endometrium from gilts with SCNT-derived conceptuses with those from gilts with conceptuses derived from natural mating on D12 of pregnancy. Real-time RT-PCR analysis showed that levels of S100G mRNA in the uterine endometrium from gilts carrying SCNT-derived conceptuses was significantly lower than those from gilts carrying conceptuses derived from natural mating. These results showed that S100G expression in the uterine endometrium was regulated by estrogen and IL1B of conceptus origin, and affected by the SCNT procedure during early pregnancy. These suggest that conceptus signals regulate S100G, an intracellular calcium transport protein, for the establishment of pregnancy in pigs.


Process evaluation of a store-based environmental obesity intervention on two American Indian Reservations.
Obesity and other diet-related chronic diseases are widespread in American Indian communities. Inadequate access to healthy food on many reservations has led to a high-fat, high-sugar diet. The purpose of this paper is to report on the results of the process evaluation of a food store-based program to improve diet on two American Indian reservations. Process data were collected from 11 intervention stores to document the implementation of the Apache Healthy Stores (AHS) program. Process evaluation instruments recorded the stocking of promoted foods, presence of in-store communication materials, implementation of and participation in the cooking demonstrations and taste tests, and the transmission of mass-media messages. At the store level, the program was implemented with a high level of dose and reach, and a moderate to high level of fidelity. At the community level, the AHS program was implemented with a moderate degree of fidelity and dose. At the individual level, the cooking demonstrations and taste tests reached a large number of community members with a high dose. Implementing the AHS program on multiple levels (store, community, individual) was challenging, and differed between levels. Overall, improvements were seen from start to finish as program staff monitored, documented and responded to barriers to implementation. Process data will be tied to outcomes and will be useful for the planning of future store-based programs.


Enzyme-linked immunoassay of somatostatin.
An enzyme-linked immunoassay for somatostatin using somatostatin-alkaline phosphatase conjugate as "labeled" antigen was developed. Minimal detectable dose at present was 40 pg per tube. Serial dilutions of rat hypothalamic extract gave a gradual change of antibody-bound alkaline phosphatase activity which was parallel to that with standard somatostatin. Precision and accuracy of the method were comparable to those in radioimmunoassay reported by others. This method will be a useful tool for the determination of somatostatin, especially in tissues.


Conserved glycine residues in the fusion peptide of the paramyxovirus fusion protein regulate activation of the native state.
Hydrophobic fusion peptides (FPs) are the most highly conserved regions of class I viral fusion-mediating glycoproteins (vFGPs). FPs often contain conserved glycine residues thought to be critical for forming structures that destabilize target membranes. Unexpectedly, a mutation of glycine residues in the FP of the fusion (F) protein from the paramyxovirus simian parainfluenza virus 5 (SV5) resulted in mutant F proteins with hyperactive fusion phenotypes (C. M. Horvath and R. A. Lamb, J. Virol. 66:2443-2455, 1992). Here, we constructed G3A and G7A mutations into the F proteins of SV5 (W3A and WR isolates), Newcastle disease virus (NDV), and human parainfluenza virus type 3 (HPIV3). All of the mutant F proteins, except NDV G7A, caused increased cell-cell fusion despite having slight to moderate reductions in cell surface expression compared to those of wild-type F proteins. The G3A and G7A mutations cause SV5 WR F, but not NDV F or HPIV3 F, to be triggered to cause fusion in the absence of coexpression of its homotypic receptor-binding protein hemagglutinin-neuraminidase (HN), suggesting that NDV and HPIV3 F have stricter requirements for homotypic HN for fusion activation. Dye transfer assays show that the G3A and G7A mutations decrease the energy required to activate F at a step in the fusion cascade preceding prehairpin intermediate formation and hemifusion. Conserved glycine residues in the FP of paramyxovirus F appear to have a primary role in regulating the activation of the metastable native form of F. Glycine residues in the FPs of other class I vFGPs may also regulate fusion activation.


Optical assessment of tumor resection margins in the breast.
Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 women annually. Of these nearly 200,000 patients who undergo this surgical procedure, between 20-70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intra-operative tools which can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes which may make them useful tools for intra-operative assessment of breast tumor resection margins. In this manuscript, we discuss clinical design criteria for intra-operative breast tumor margin assessment, and review optical techniques appied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool which has been applied to 56 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins.


Lipid Droplets Embedded in a Model Cell Membrane Create a Phospholipid Diffusion Barrier.
Lipid droplets (LDs) are ubiquitous, cytoplasmic fat storage organelles that originate from the endoplasmic reticulum (ER) membrane. They are composed of a core of neutral lipids surrounded by a phospholipid monolayer. Proteins embedded into this monolayer membrane adopt a monotopic topology and are crucial for regulated lipid storage and consumption. A key question is, which collective properties of protein-intrinsic and lipid-mediated features determine spatio-temporal protein partitioning between phospholipid bilayer and LD monolayer membranes. To address this question, a freestanding phospholipid bilayer with physiological lipidic composition is produced using microfluidics and micrometer-sized LDs are dispersed around the bilayer that spontaneously insert into the bilayer. Using confocal microscopy, the 3D geometry of the reconstituted LDs is determined with high spatial resolution. The micrometer-sized bilayer-embedded LDs present a characteristic lens shape that obeys predictions from equilibrium wetting theory. Fluorescence recovery after photobleaching measurements reveals the existence of a phospholipid diffusion barrier at the monolayer-bilayer interface. Coarse-grained molecular dynamics simulation reveals lipid specific density distributions along the pore rim, which may rationalize the diffusion barrier. The lipid diffusion barrier between the LD covering monolayer and the bilayer may be a key phenomenon influencing protein partitioning between the ER membrane and LDs in living cells.


Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study.
Intravenous alteplase is approved for use within 3 h of ischaemic stroke onset, although a meta-analysis of randomised controlled trials suggests treatment benefit up to 4.5 h. We compared outcome in patients treated between 3 h and 4.5 h versus those treated within 3 h, who were recorded in the in the Safe Implementation of Treatments in Stroke (SITS), a prospective internet-based audit of the International Stroke Thrombolysis Registry (ISTR). We compared 664 patients presenting with ischaemic stroke and given intravenous altepase (0.9 mg/kg total dose) between 3 h and 4.5 h with 11 865 patients treated within 3 h. All patients were otherwise compliant with European summary of product characteristics criteria and had been documented in the international stroke treatment registry between Dec 25, 2002, and Nov 15, 2007. Outcome measures were symptomatic intracerebral haemorrhage within 24 h (haemorrhage type 2 associated with National Institutes of Health Stroke Scale [NIHSS] > or = 4 points deterioration), and mortality and independence (modified Rankin scale of 0-2) at 3 months. In the 3-4.5-h cohort, treatment was started at a median of 55 min later after symptom onset (195 min [IQR 187-210] vs 140 min [115-165], p<0.0001), median age was 3 years younger (65 years [55-73] vs 68 years [58-74], p<0.0001), and stroke severity was lower (NIHSS score 11 [7-16] vs 12 [8-17], p<0.0001) than in the 3-h cohort. We recorded no significant differences between the 3-4.5-h cohort and the within 3-h cohort for any outcome measure--rate of symptomatic intracerebral haemorrhage: 2.2% (14 of 649) versus 1.6% (183 of 11 681) (odds ratio [OR] 1.18 [95% CI 0.89-1.55], p=0.24; adjusted OR 1.32 [1.00-1.75], p=0.052); mortality: 12.7% (70 of 551) versus 12.2% (1263 of 10 368) (OR 1.02 [0.90-1.17]; p=0.72; adjusted OR 1.15 [1.00-1.33]; p=0.053); and independence: 58.0% (314 of 541) versus 56.3% (5756 of 10231) (OR 1.04 [0.95-1.13], p=0.42; adjusted OR 0.93 [0.84-1.03], p=0.18). Alteplase remains safe when given at 3-4.5 h after ischaemic stroke, offering an opportunity for patients who cannot be treated within the standard 3-h timeframe. Boehringer-Ingelheim, European Union Public Health Executive Authority.


Hindered Rotations of Protein Asparagine/Glutamine Side-Chain NH2 Groups: Impact of Hydrogen Bonding with DNA.
Hindered rotation about an sp2 C-N bond is known to occur in arginine (Arg), asparagine (Asn), and glutamine (Gln) side chains of proteins. However, very little is known about the rotational dynamics of Asn and Gln side-chain NH2 groups. Here, using a unique NMR method, we quantitatively characterized the hindered rotations of protein Asn/Gln side-chain NH2 groups. This NMR method yields simple NH2-selective spectra that allow for an accurate determination of the kinetic rate constants for the hindered rotations. Through the NMR measurements at different temperatures, we investigated the energy barriers that restrict the C-N bond rotations of protein side-chain NH2 groups. Through a comparison of the kinetic data for the free and DNA-bound states of the Antp homeodomain, we also examined the impact of hydrogen bonding on the hindered rotations of the side-chain NH2 groups. Our data suggest that the hydrogen bonding increases the energy barriers by 1-6 kJ/mol.


Ontogeny and polarization of macrophages in inflammation: blood monocytes versus tissue macrophages.
The explosion of new information in recent years on the origin of macrophages in the steady-state and in the context of inflammation has opened up numerous new avenues of investigation and possibilities for therapeutic intervention. In contrast to the classical model of macrophage development, it is clear that tissue-resident macrophages can develop from yolk sac-derived erythro-myeloid progenitors, fetal liver progenitors, and bone marrow-derived monocytes. Under both homeostatic conditions and in response to pathophysiological insult, the contribution of these distinct sources of macrophages varies significantly between tissues. Furthermore, while all of these populations of macrophages appear to be capable of adopting the polarized M1/M2 phenotypes, their respective contribution to inflammation, resolution of inflammation, and tissue repair remains poorly understood and is likely to be tissue- and disease-dependent. A better understanding of the ontology and polarization capacity of macrophages in homeostasis and disease will be essential for the development of novel therapies that target the inherent plasticity of macrophages in the treatment of acute and chronic inflammatory disease.


A comparison of genotype and markers of disease severity of chronic hepatitis C in patients with and without end-stage renal disease.
This study was conducted to compare the genotype and markers of disease severity of chronic hepatitis C (CHC), namely viral load, alanine transaminase (ALT) levels and histopathological findings on liver biopsy, in patients with and without end-stage renal disease (ESRD). This was a cross-sectional retrospective comparative study that included ESRD patients on haemodialysis and non-ESRD patients with CHC who underwent liver biopsy between January 2004 and December 2006. Blood tests for viral load (VL) (hepatitis C virus, ribonucleic acid, polymerase chain reaction), genotyping and ALT were administered. VL was grouped into low (less than 5 log10) and high (more than or equal to 5 log10) VL, genotype into G1 and 2, 3, 4, and ALT into normal and elevated ALT. Necroinflammatory activity was grouped into mild (G0-6) and moderate/severe (G7-18) activity, and fibrosis into mild (S0-2) and moderate/severe (S3-6) fibrosis. These variables were compared between the two groups. Genotype 1 was significantly higher in ESRD patients than in non-ESRD patients, in whom genotypes 2, 3 and 4 were higher. Although the proportion of patients with high VL was greater and the duration of CHC was longer in the ESRD group, the ALT levels were lower and the histopathological grading of necroinflammatory activity and stages of fibrosis were less severe in ESRD compared to non-ESRD patients. The lower levels of ALT observed in CHC patients with ESRD translate to histopathological benefits.


Poisson-distributed active fusion complexes underlie the control of the rate and extent of exocytosis by calcium.
We have investigated the consequences of having multiple fusion complexes on exocytotic granules, and have identified a new principle for interpreting the calcium dependence of calcium-triggered exocytosis. Strikingly different physiological responses to calcium are expected when active fusion complexes are distributed between granules in a deterministic or probabilistic manner. We have modeled these differences, and compared them with the calcium dependence of sea urchin egg cortical granule exocytosis. From the calcium dependence of cortical granule exocytosis, and from the exposure time and concentration dependence of N-ethylmaleimide inhibition, we determined that cortical granules do have spare active fusion complexes that are randomly distributed as a Poisson process among the population of granules. At high calcium concentrations, docking sites have on average nine active fusion complexes.


Effect of ketoconazole on isolated mitochondria from Candida albicans.
Ketoconazole, an oral antimycotic imidazole drug, blocked the transport of electrons in the respiratory chain of Candida albicans under aerobic conditions with different substrates, such as NADH and succinate. This effect was a nonspecific inhibition of NADH oxidases and succinate oxidases. The addition of ketoconazole to C. albicans mitochondria without a substrate resulted in strong reduction of cytochrome a3, as revealed by difference spectra (reduced versus oxidized). This indicated that there was a specific interaction between ketoconazole and cytochrome c oxidase. A spectrophotometric analysis confirmed that the cytochrome oxidases other than cytochrome c oxidase were not inhibited because subsequent addition of any substrate caused an increased level of reduction of all of the other respiratory chain components compared with the control. Consequently, our data strongly suggested that the primary site of ketoconazole inhibition on isolated mitochondria from C. albicans is the most distal portion of the respiratory chain.


Effect of Metal Ions on Oxidation of Micropollutants by Ferrate(VI): Enhancing Role of FeIV Species.
This paper investigated the oxidation of recalcitrant micropollutants [i.e., atenolol (ATL), flumequine, aspartame, and diatrizoic acid] by combining ferrate(VI) (FeVIO42-, FeVI) with a series of metal ions [i.e., Fe(III), Ca(II), Al(III), Sc(III), Co(II), and Ni(II)]. An addition of Fe(III) to FeVI enhanced the oxidation of micropollutants compared solely to FeVI. The enhanced oxidation of studied micropollutants increased with increasing [Fe(III)]/[FeVI] to 2.0. The complete conversion of phenyl methyl sulfoxide (PMSO), as a probe agent, to phenyl methyl sulfone (PMSO2) by the FeVI-Fe(III) system suggested that the highly reactive intermediate FeIV/FeV species causes the increased oxidation of all four micropollutants. A kinetic modeling of the oxidation of ATL demonstrated that the major species causing the increase in ATL removal was FeIV, which had an estimated rate constant as (6.3 ± 0.2) × 104 M-1 s-1, much higher than that of FeVI [(5.0 ± 0.4) × 10-1 M-1 s-1]. Mechanisms of the formed oxidation products of ATL by FeIV, which included aromatic and/or benzylic oxidation, are delineated. The presence of natural organic matter significantly inhibited the removal of four pollutants by the FeVI-Fe(III) system. The enhanced effect of the FeVI-Fe(III) system was also seen in the oxidation of the micropollutants in river water and lake water.


Century-scale trends and seasonality in pH and temperature for shallow zones of the Bering Sea.
No records exist to evaluate long-term pH dynamics in high-latitude oceans, which have the greatest probability of rapid acidification from anthropogenic CO2 emissions. We reconstructed both seasonal variability and anthropogenic change in seawater pH and temperature by using laser ablation high-resolution 2D images of stable boron isotopes (δ(11)B) on a long-lived coralline alga that grew continuously through the 20th century. Analyses focused on four multiannual growth segments. We show a long-term decline of 0.08 ± 0.01 pH units between the end of the 19th and 20th century, which is consistent with atmospheric CO2 records. Additionally, a strong seasonal cycle (∼ 0.22 pH units) is observed and interpreted as episodic annual pH increases caused by the consumption of CO2 during strong algal (kelp) growth in spring and summer. The rate of acidification intensifies from -0.006 ± 0.007 pH units per decade (between 1920s and 1960s) to -0.019 ± 0.009 pH units per decade (between 1960s and 1990s), and the episodic pH increases show a continuous shift to earlier times of the year throughout the centennial record. This is indicative of ecosystem shifts in shallow water algal productivity in this high-latitude habitat resulting from warming and acidification.


Influence of temperature on the iron metabolism of a fluorescent pseudomonad.
The iron requirement for maximal cell yields of a fluorescent pseudomonad increases as the temperature of incubation is increased. On a succinate salts medium, maximal cell yields are attained at iron concentrations of 0.10 mug/ml of added iron at 20 C and at 3.0 mug/ml of added iron at 28 C. This bacterium does not grow in the basal medium at 31 C even in the presence of 0.01 to 10 mug/ml of added iron. The inability to grow at the higher temperature is due to the loss, by this organism, of its ability to biosynthesize hydroxamate iron transport compounds at temperatures of 28 C and above, since supplementation with such compounds produced by this organism at lower temperatures promoted growth at 31 C. The biosynthesis of these compounds at lower temperatures contributes to the efficient utilization of iron by the bacterium.


Propagation of partially coherent beams with convex-shaped spatial coherence modulation in vertical turbulent links.
The convex partially coherent beam (CPCB) is a special type of nonuniformly correlated beam with a convex-shaped complex degree of coherence (DoC) distributions. Previously our research has illustrated the potential of CPCBs with super-Gaussian DoCs in free-space optical communications (FSOC), mainly manifested as self-focusing which can be transferred into extra scintillation reduction and SNR gain. In this study, the effects of the DoC transition slopes are analyzed and more details about the turbulence propagation of CPCBs with super-Gaussian shaped DoC are revealed. By means of wave optics simulation, the longitudinal intensity evolution of the CPCB is explored, showing that the DoC slope has a profound influence on the self-focusing features such as the focusing plane and the peak intensity. Aperture scintillation and mean SNR at the receiver end of some short-range vertical turbulent links are numerically computed. The obtained results show that, with CPCBs, an ~2 dB SNR gain can be achieved as compared to conventional Gaussian Schell-modal (GSM) beams. However, CPCBs are preferred only in shorter links, which is found to be relevant to the power-in-the-bucket of the receiving aperture. Furthermore, the impacts of the ratio of the source coherence time to the detector integration time are investigated, implying that the CPCB is less susceptible than the GSM. We have also examined the off-axis scintillation of the CPCB. Due to its convex-shaped DoC, the CPCB has significantly reduced off-axis scintillation, which can be beneficial in the presence of pointing errors.