Missed Care from the Patient's Perspective - A Scoping Review.
Missed care, defined as any aspect of patient care that is omitted or delayed, is receiving increasing attention. It is primarily caused by the imbalance between patients' nursing care needs and the resources available, making it an ethical issue that challenges nurses' professional and moral values. In this scoping review, conducted using the five-stage approach by Arksey and O'Malley, our aim is to analyze the patients' perspective to missed care, as the topic has been mainly examined from nurses' perspective. The search was conducted in April 2019 in PubMed, CINAHL, PsycINFO, Web of Science, ProQuest and Philosophers Index databases using the following terms: omitted care, unfinished nursing care, care undone, care unfinished, missed care, care left undone, task undone and implicit rationing with no time limitation. The English-language studies where missed care was examined in the nursing context and had patients as informants on patient-reported missed care or patients' perceptions on nurse-reported missed care were selected for the review. Thirteen studies were included and analyzed with thematic content analysis. Twelve studies were quantitative in nature. Patients were able to report missed care, and mostly reported missed basic care, followed by missed communication with staff and problems with timeliness when they had to wait to get the help they needed. In statistical analysis, missed care was associated with patient-reported adverse events and patients' perceptions of staffing adequacy, and in patients' perception, it was mainly caused by lack of staff and insufficient experience. Furthermore, patients' health status, as opposed to gender, predicted missed care. The results concerning patients' age and education level were conflicting. Patients are able to identify missed care. However, further research is needed to examine patient-perceived missed care as well as to examine how patients identify missed care, and to get a clear definition of missed care.


Mechanisms of sodium and chloride transport across equine tracheal epithelium.
Equine tracheal epithelium, stripped of serosal muscle, mounted in Ussing chambers, and bathed in plasmalike Ringer solution generates a serosa-positive transepithelial potential of 10-22 mV and a short-circuit current (Isc) of 70-200 microA/cm2. Mucosal amiloride (10 microM) causes a 40-60% decrease in Isc and inhibits the net transepithelial Na flux by 95%. Substitution of Cl with gluconate resulted in a 30% decrease in basal Isc. Bicarbonate substitution with 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid decreased the Isc by 21%. The Cl-dependent Isc was inhibited by serosal addition of 1 mM amiloride. Bicarbonate replacement or serosal amiloride (1 mM) inhibits the net Cl flux by 72 and 69%, respectively. Bicarbonate replacement significantly reduces the effects of serosal amiloride (1 mM) on Isc, indicating its effect is HCO3 dependent. Addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP; 100 microM) causes a 40% increase in Isc. This effect is inhibited by subsequent addition of 10 microM serosal bumetanide. Bumetanide (10 microM) reduces net Cl secretion following stimulation with 8-BrcAMP (100 microM). Serosal addition of BaCl2 (1 mM) causes a reduction in Isc equal to that following Cl replacement in the presence or absence of 100 microM cAMP. These results suggest that 1) Na absorption depends on amiloride-inhibitable Na channels in the apical membrane, 2) Cl influx across the basolateral membrane occurs by both a Na-H/Cl-HCO3 parallel exchange mechanism under basal conditions and by a bumetanide-sensitive Na-(K?)-Cl cotransport system under cAMP-stimulated conditions, and 3) basal and cAMP-stimulated Cl secretion depends on Ba-sensitive K channels in the basolateral membrane.


Probabilistic secretion of quanta in the central nervous system: granule cell synaptic control of pattern separation and activity regulation.
The implications of probabilistic secretion of quanta for the functioning of neural networks in the central nervous system have been explored. A model of stochastic secretion at synapses in simple networks, consisting of large numbers of granule cells and a relatively small number of inhibitory interneurons, has been analysed. Such networks occur in the input to the cerebellum Purkinje cells as well as to hippocampal CA3 pyramidal cells and to pyramidal cells in the visual cortex. In this model the input axons terminate on granule cells as well as on an inhibitory interneuron that projects to the granule cells. Stochastic secretion at these synapses involves both temporal variability in secretion at single synapses in the network as well as spatial variability in the secretion at different synapses. The role of this stochastic variability in controlling the size of the granule cell output to a level independent of the size of the input and in separating overlapping inputs has been determined analytically as well as by simulation. The regulation of granule-cell output activity to a reasonably constant value for different size inputs does not occur in the absence of an inhibitory interneuron when both spatial and temporal stochastic variability occurs at the remaining synapses; it is still very poor in the presence of such an interneuron but in the absence of stochastic variability. However, quite good regulation is achieved when the inhibitory interneuron is present with spatial and temporal stochastic variability of secretion at synapses in the network. Excellent regulation is achieved if, in addition, allowance is made for the nonlinear behaviour of the input-output characteristics of inhibitory interneurons. The capacity of granule-cell networks to separate overlapping patterns of activity on their inputs is adequate, with spatial variability in the secretion at synapses, but is improved if there is also temporal variability in the stochastic secretion at individual synapses, although this is at the expense of reliability in the network. Other factors which improve pattern separation are control of the output to very low activity levels, and a restriction on the cumulative size of the excitatory input terminals of each granule cell. Application of the theory to the input neural networks of the cerebellum and the hippocampus shows the role of stochastic variability in quantal transmission in determining the capacity of these networks for pattern separation and activity regulation.


Quasistatic to inertial transition in granular materials and the role of fluctuations.
On the basis of discrete element numerical simulations of a Couette cell, we revisit the rheology of granular materials in the quasistatic and inertial regimes, and discuss the origin of the transition between these two regimes. We show that quasistatic zones are the seat of a creep process whose rate is directly related to the existence and magnitude of velocity fluctuations. The mechanical behavior in the quasistatic regime is characterized by a three-variable constitutive law relating the friction coefficient (normalized stress), the inertial number (normalized shear rate), and the normalized velocity fluctuations. Importantly, this constitutive law appears to remain also valid in the inertial regime, where it can account for the one-to-one relationship observed between the friction coefficient and the inertial number. The abrupt transition between the quasistatic and inertial regimes is then related to the mode of production of the fluctuations within the material, from nonlocal and artificially sustained by the boundary conditions in the quasistatic regime, to purely local and self-sustained in the inertial regime. This quasistatic-to-inertial transition occurs at a critical inertial number or, equivalently, at a critical level of fluctuations.


[Aortoarteritis in HBV-associated liver cirrhosis: diagnostics, therapeutic strategy, and prognosis].
A case of decompensated liver cirrhosis in a women with a long silent period of HBV infection is presented. The first manifestation was generalized vasculitis involving small and medium-size vessels and elastic-type arteries with the development of aortoarteritis. Proper interpretation of manifestations of viral liver cirrhosis allowed for immunosuppressive treatment in combination with effective antiviral drugs. As a result, aviremia, regression of vasculitis and portal hypertension along with considerable improvement of the prognosis were achieved.


5-HT1A receptor agonist properties of the antipsychotic, nemonapride: comparison with bromerguride and clozapine.
5-HT1A receptor agonists are thought to enhance the antipsychotic-like effects of dopamine D2 receptor antagonists while reducing their potential to produce extrapyramidal side effects. Thus, 5-HT1A receptor agonist properties of mixed 5-HT1A receptor agonists/D2 receptor antagonists might be of clinical importance. The antipsychotics, clozapine and nemonapride, and the putative antipsychotic, bromerguride, have intermediate to high affinity for 5-HT1A receptors. The present study examined the 5-HT1A receptor agonist activity of nemonapride and bromerguride, in comparison with clozapine, which has partial 5-HT1A receptor agonist properties in vitro. Here, 5-HT1A receptor activation was examined in vitro, by measuring forskolin-stimulated cAMP accumulation in HeLa cells expressing human 5-HT1A receptors, and in vivo, by using microdialysis to measure the extracellular concentration of hippocampal 5-hydroxytryptamine (5-HT) in rats. Nemonapride markedly decreased both forskolin-stimulated cAMP accumulation and the extracellular concentration of 5-HT; both effects were antagonized by the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY100635). In contrast, clozapine only partially decreased forskolin-stimulated cAMP accumulation and extracellular 5-HT, and only its effects on cAMP accumulation were attenuated by WAY100635. Bromerguride decreased neither forskolin-stimulated cAMP accumulation nor extracellular 5-HT; instead, it antagonized the decrease of cAMP accumulation produced by 5-HT and the decrease of extracellular 5-HT produced by the 5-HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The selective D2 receptor antagonist, raclopride, affected neither forskolin-stimulated cAMP in vitro nor extracellular 5-HT in vivo. Thus, in contrast with clozapine and bromerguride, only the novel antipsychotic, nemonapride, exhibited marked 5-HT1A receptor agonist properties both in vitro and in vivo; conceivably, these properties may play a role in its preclinical and clinical effects.


Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor.
Bone marrow stromal cells (BMSCs) strongly contribute to multiple myeloma (MM) progression, promoting the survival and growth of malignant plasma cells (PCs). However, the possible impact of these cells on the immune-mediated recognition of MM cells remains largely unknown. DNAM-1 activating receptor plays a prominent role in NK cell anti-MM response engaging the ligands poliovirus receptor (PVR) and nectin-2 on malignant PCs. Here, we analysed the role of MM patient-derived BMSCs in the regulation of PVR expression. We found that BMSCs enhance PVR surface expression on MM cells and promote their NK cell-mediated recognition. PVR upregulation occurs at transcriptional level and involves NF-kB transcription factor activation by BMSC-derived soluble factors. Indeed, overexpression of a dominant-negative mutant of IKBα blocked PVR upregulation. IL-8 plays a prominent role in these mechanisms since blockade of CXCR1/2 receptors as well as depletion of the cytokine via RNA interference prevents the enhancement of PVR expression by BMSC-derived conditioned medium. Interestingly, IL-8 is associated with stromal microvesicles which are also required for PVR upregulation via CXCR1/CXCR2 signaling activation. Our findings identify BMSCs as regulators of NK cell anti-MM response and contribute to define novel molecular pathways involved in the regulation of PVR expression in cancer cells.


Suppression effect of soy isoflavones on nitric oxide production in RAW 264.7 macrophages.
Genistein, daidzein, and glycitein, as primary isoflavones in soybeans, are reported to have beneficial effects on atherosclerosis, chronic inflammatory diseases, and cancers that are conducted by nitric oxide (NO) injury. The objectives of this study were to investigate the effects and mechanisms of these soy isoflavones on the inducible nitric oxide synthase (iNOS) system in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Genistein, daidzein, and glycitein dose-dependently suppress NO production (IC(50) = 50 microM) in supernatants of LPS-activated macrophages as measured on the basis of nitrite accumulation. In addition, direct inhibition of iNOS activity, determined by means of the conversion of L-[(3)H]arginine to L-[(3)H]citrulline, and markedly reduced iNOS protein and mRNA levels, evaluated by means of Western blot and RT-PCR, respectively, were found in homogenates of LPS-activated cells treated with each isoflavone. Moreover, genistein was found to have a greater inhibitory effect on NO production but no significant effect on iNOS activity or protein and gene expression to daidzein and glycitein. These observations reveal that the suppression of NO production by genistein, daidzein, and glycitein might be due to the inhibition of both the activity and expression of iNOS in LPS-activated macrophages. The result suggests that soy isoflavones might attenuate excessive NO generation at inflammatory sites.


Damage to Candida albicans hyphae and pseudohyphae by the myeloperoxidase system and oxidative products of neutrophil metabolism in vitro.
In previous studies, we noted that Candida hyphae and pseudohyphae could be damaged and probably killed by neutrophils, primarily by oxygen-dependent nonphagocytic mechanisms. In extending these studies, amount of damage to hyphae again was measured by inhibition of [(14)C]cytosine uptake. Neutrophils from only one of four patients with chronic granulomatous disease damaged hyphae at all, and neutrophils from this single patient damaged hyphae far less efficiently than simultaneously tested neutrophils from normal control subjects. Neutrophils from neither of two subjects with hereditary myeloperoxidase deficiency damaged the hyphae. This confirmed the importance of oxidative mechanisms in general and myeloperoxidase-mediated systems in particular in damaging Candida hyphae. Several potentially fungicidal oxidative intermediates are produced by metabolic pathways of normal neutrophils, but their relative toxicity for Candida hyphae was previously unknown. To help determine this, cell-free in vitro systems were used to generate these potentially microbicidal products. Myeloperoxidase with hydrogen peroxide, iodide, and chloride resulted in 91.2% damage to hyphal inocula in 11 experiments. There was less damage when either chloride or iodide was omitted, and no damage when myeloperoxidase was omitted or inactivated by heating. Azide, cyanide, and catalase (but not heated catalase) inhibited the damage. Systems for generation of hydrogen peroxide could replace reagent hydrogen peroxide in the myeloperoxidase system. These included glucose oxidase, in the presence of glucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence of myeloperoxidase and a halide, the toxicity of the xanthine oxidase system was not inhibited by superoxide dismutase and, under some conditions, was marginally increased by this enzyme. This suggested that superoxide radical did not damage hyphae directly but served primarily as an intermediate in the production of hydrogen peroxide. The possible damage to hyphae by singlet oxygen was examined using photoactivation of rose bengal. This dye damaged hyphae in the presence of light and oxygen. The effect was almost completely inhibited by putative quenchers of singlet oxygen: histidine, tryptophan, and 1,4-diazobicyclo[2.2.2]octane. These agents also inhibited damage to hyphae by myeloperoxidase, halide, and either hydrogen peroxide or a peroxide source (xanthine oxidase plus acetaldehyde). Myeloperoxidase-mediated damage to hyphae was also inhibited by dimethyl sulfoxide, an antioxidant and scavenger of the hydroxyl radical. These data support the involvement of oxidative mechanisms and the myeloperoxidase-H(2)O(2)-halide system, in particular in damaging hyphae in vitro and perhaps in vivo as well.


Indications for the use of MemoryShape breast implants in aesthetic and reconstructive breast surgery: long-term clinical outcomes of shaped versus round silicone breast implants.
The availability of different styles of silicone gel implants-including traditional round devices and shaped, form-stable implants-offers a variety of choices for women undergoing breast augmentation and reconstruction. The purpose of this analysis was to characterize clinical outcomes associated with the Mentor MemoryGel (round) MemoryShape/Contour Profile Gel (shaped) devices through 9 years of use in women undergoing breast augmentation or reconstruction. The Mentor Core studies are nonrandomized, open-label clinical trials designed to assess the long-term safety and efficacy of silicone gel breast implants. The cumulative incidence of selected complications and reoperations was estimated using the Kaplan-Meier method. Patient satisfaction was assessed by asking the patient if she would decide to have breast implant surgery again. Shaped implants were associated with lower cumulative incidence rates of Baker Grade III/IV capsular contracture compared with round implants (3.4% vs 11.3%, respectively, in primary augmentation, P < 0.0001; 15.6% vs 24.4% in revision-augmentation, P < 0.05). Reoperation, explantation, and infection rates were comparable between devices across cohorts, except for lower incidence of infection with shaped than round implants in primary reconstruction (1.6% vs 6.2%, P < 0.05). Rupture rates were lower with shaped implants, with significance reached in primary augmentation patients at 8 years (3.1% vs 10.3%, P < 0.05). High levels of patient satisfaction (exceeding 94%) with both devices were reported at 9 years across cohorts. Prospective data through 9 years support comparable safety of round and shaped breast implants, and high levels of patient satisfaction, in patients undergoing primary and revision breast augmentation and reconstruction.


Stress-reducing interventions in pregnancy for the prevention of preterm birth: a systematic review and meta-analysis.
Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Maternal stress during pregnancy is an established risk factor for PTB. We aimed to review the effects of stress-reducing interventions during pregnancy on PTB. Studies reporting on stress-reducing interventions during pregnancy and PTB rates in general low-risk obstetric populations were included. PTB rates, low birth weight (LBW) rates, mean gestational age and birth weight, maternal anxiety and stress, and adverse perinatal outcomes were investigated. Data were extracted using a standardized extraction form, pooled effect sizes were calculated with the random effects model. Ten studies with a total of 4.816 women were included. The interventions included Pilates, yoga, a multidisciplinary stress reduction program, combination therapy (combining mindfulness, yoga, music, baby bonding, and education), and hypnosis. The incidence of PTB was significantly lower in the intervention group (RR 0.50, 95% CI 0.35 - 0.71). The overall quality of the included studies was low, and the risk of bias was high. In conclusion, this study provides evidence supporting the potential efficacy of stress-reducing interventions in reducing the incidence of PTB in low-risk women. We propose a RCT of high quality to determine the effectiveness of stress-reducing interventions in reducing PTB risk.


Nurses' knowledge of blood transfusion in medical training centers of Shahrekord University of Medical Science in 2004.
Using blood and blood components is a common therapeutic procedure in hospitals. Nurses have an important role in a safe blood transfusion. Therefore, it is crucial for nurses to have sufficient knowledge of situations, amount and methods of using blood components, possible side effects and necessary cares. This study investigated nurses' knowledge of blood transfusion. This was a cross-sectional descriptive study on 117 nurses in medical training hospitals of Shahrekord University of Medical Sciences in 2004, aiming to evaluate their knowledge of blood transfusion. Data were collected using a questionnaire including 4 sections and 29 questions. Sections included demographic data, nurses' knowledge of blood components, nurses' knowledge of blood components infusion techniques, and nurses' knowledge of indication and side effects of blood components infusion. Knowledge scores were first coded and then categorized in three levels of good, average, and poor. Data were analyzed using SPSS software. The nurses' knowledge of blood and blood component, techniques of blood components infusion, and its indication and side effects was average (66.7%, 65.8% and 59%, respectively). The findings showed that the nurses' knowledge of blood and blood component was average and insufficient. Therefore, it is recommended to activate the blood transfusion committees in hospitals to increase the quality of this common procedure and prevent side effects by in-service trainings of nurses.


Where and how does physical therapy fit? Integrating physical therapy into interprofessional HIV care.
Purpose: To investigate the role of physical therapy in HIV care from the perspective of people living with HIV and health care professionals with expertise in HIV care. Methods: We conducted a qualitative descriptive study using semistructured interviews (with health care professionals) and focus groups (with people living with HIV). We purposively sampled health care professionals and recruited people living with HIV in collaboration with an HIV-specialty hospital. We asked participants about their knowledge of and experiences with physical therapy, and perceptions of the physical therapy role in interprofessional HIV care. We analyzed data using content analytical techniques. Results: Thirteen people living with HIV and 12 health care professionals conceptualized physical therapy as positively influencing independence and social participation, and as a valuable ally in interprofessional collaboration. The Framework of Physical Therapy Role in HIV Care consists of two components: (1) multidimensional and client-centered roles of physical therapy addressing physical, psychological and social health domains; and (2) contextual factors important to consider for the role of physical therapy: aging, episodic nature of HIV, multimorbidity, competing priorities, continuity of care, stigma, resource security and social isolation. The interaction between contextual factors and health domains can influence the role of physical therapy. Conclusion: The role of physical therapy in HIV is multidimensional and client-centered. This Framework can be used by rehabilitation professionals working with people living with HIV. Implications for Rehabilitation Participants living with HIV in this study experienced physical therapy as a means of addressing rehabilitation goals that positively influenced physical health and social participation. The role of physical therapy in HIV care is multidimensional and client-centered and can address health challenges in physical, social and psychological health domains. The presence and interaction of contextual factors including aging, episodic nature of HIV, multimorbidity, competing priorities, continuity of care, stigma, resource security and social isolation are important for clinicians to consider in order to optimize healthcare for people living with HIV. The Framework describing the role of physical therapy in HIV care can be used by rehabilitation professionals to help inform their approach for providing client-centered HIV care.


Emergency physician versus cardiologist-initiated thrombolysis for acute myocardial infarction: a Singapore experience.
To compare the door-to-needle time between thrombolysis administration for patients with ST elevation myocardial infarction (STEMI) in the emergency department (EMD) by emergency physicians and those administered in the coronary care unit (CCU) by cardiologists. The data was collected prospectively for all patients with STEMI who received thrombolysis in the emergency department over a one-year period from January 2001 to December 2001. We recorded the time of arrival in the EMD as well as the time thrombolytic therapy was commenced. This data was compared to those from the previous year, obtained retrospectively, where the patients received thrombolysis in the CCU. 118 patients were thrombolysed in the CCU and 78 patients were thrombolysed in the EMD. The median door-to-needle time was significantly shorter in patients who are thrombolysed in the emergency department by emergency physicians than in the coronary care unit by cardiologists (29 minutes versus 60 minutes, p value is less than 0.001). There was no incident of inappropriate thrombolysis nor was there intracranial or gastrointestinal bleed in the patients who were thrombolysed in the EMD. There was one case of medication dose error but it was of no consequence to the patient. Emergency physicians can administer thrombolytic treatment appropriately, quickly and safely in patients with STEMI.


Rapid synthesis of long-chain deoxyribooligonucleotides by the N-methylimidazolide phosphotriester method.
A modified phosphotriester method has been employed for the efficient chemical synthesis of long-chain deoxyribooligonucleotides. During the course of this work, a general and rapid procedure was developed for the preparation of 24-62-mers in solution. Preparative reversed phase column chromatography on silanized silica gel was used to purify triester intermediates starting from 10-mers. The rapid synthesis of 32-mer and 42-mer on glass and silica gel supports using suitably protected 2-8-mer blocks as coupling units has been also accomplished. In particular, a convenient procedure for the solid-phase synthesis of oligonucleotide blocks bearing 3'-terminal phosphodiester groups is described.


Chromatin maintenance and dynamics in senescence: a spotlight on SAHF formation and the epigenome of senescent cells.
Senescence is a stable proliferation arrest characterized by profound changes in cellular morphology and metabolism as well as by extensive chromatin reorganization in the nucleus. One particular hallmark of chromatin changes during senescence is the formation of punctate DNA foci in DAPI-stained senescent cells that have been called senescence-associated heterochromatin foci (SAHF). While many advances have been made concerning our understanding of the effectors of senescence, how chromatin is reorganized and maintained in senescent cells has remained largely elusive. Because chromatin structure is inherently dynamic, senescent cells face the challenge of developing chromatin maintenance mechanisms in the absence of DNA replication in order to maintain the senescent phenotype. Here, we summarize and review recent findings shedding light on SAHF composition and formation via spatial repositioning of chromatin, with a specific focus on the role of lamin B1 for this process. In addition, we discuss the physiological implication of SAHF formation, the role of histone variants, and histone chaperones during senescence and also elaborate on the more general changes observed in the epigenome of the senescent cells.


SUGAR-DEPENDENT6 encodes a mitochondrial flavin adenine dinucleotide-dependent glycerol-3-p dehydrogenase, which is required for glycerol catabolism and post germinative seedling growth in Arabidopsis.
The aim of this study was to clone and characterize the SUGAR-DEPENDENT6 (SDP6) gene, which is essential for postgerminative growth in Arabidopsis (Arabidopsis thaliana). Mutant alleles of sdp6 were able to break down triacylglycerol following seed germination but failed to accumulate soluble sugars, suggesting that they had a defect in gluconeogenesis. Map-based cloning of SDP6 revealed that it encodes a mitochondrial flavin adenine dinucleotide (FAD)-dependent glycerol-3-P (G3P) dehydrogenase:ubiquinone oxidoreductase called FAD-GPDH. This gene has previously been proposed to play a role both in the break down of glycerol (derived from triacylglycerol) and in NAD(+)/NADH homeostasis. Germinated seeds of sdp6 were severely impaired in the metabolism of [U-(14)C]glycerol to CO(2) and accumulated high levels of G3P. These data suggest that SDP6 is essential for glycerol catabolism. The activity of the glycolytic enzyme phosphoglucose isomerase is competitively inhibited by G3P in vitro. We show that phosphoglucose isomerase is likely to be inhibited in vivo because there is a 6-fold reduction in the transfer of (14)C-label into the opposing hexosyl moiety of sucrose when [U-(14)C]glucose or [U-(14)C]fructose is fed to sdp6 seedlings. A block in gluconeogenesis, at the level of hexose phosphate isomerization, would account for the arrested seedling growth phenotype of sdp6 and explain its rescue by sucrose and glucose but not by fructose. Measurements of NAD(+) and NADH levels in sdp6 seedlings also suggest that NAD(+)/NADH homeostasis is altered, and this observation is consistent with the hypothesis that SDP6 participates in a mitochondrial G3P shuttle by cooperating with the cytosolic NAD-dependent GPDH protein GPDHC1.


Understanding the magnitude of emergent contaminant releases through target screening and metabolite identification using high resolution mass spectrometry: Illicit drugs in raw sewage influents.
A QExactive Orbitrap was used for the identification of phase I and II transformation products (TPs) of illicit drugs in raw sewage influents. Two operating modes (targeted MS(2) and Data-dependent screening) were used for data acquisition. Even though, data-dependent scan is a faster route towards the potential identification of metabolites, it suffered from its limitation to provide enough data points across the chromatographic peak during the MS(2) cycle in contrast to targeted MS(2). Therefore, the later technique was implemented as the method of choice in this study for the positive confirmation and quantitation of TPs (n=54). The vast majority of the identified TPs were products of phase I transformation reactions, with the latter being more prevalent in the nature. Estimated mole fractions showed that for a large number of the analytes, TPs must also be monitored in order to fully understand their environmental fate and calculate potential consumption.


Distortion product otoacoustic emission test performance when both 2f1-f2 and 2f2-f1 are used to predict auditory status.
The objective of this study was to determine whether distortion product otoacoustic emission (DPOAE) test performance, defined as its ability to distinguish normal-hearing ears from those with hearing loss, can be improved by examining response and noise amplitudes at 2 f1-f2 and 2f2-f1 simultaneously. In addition, there was interest in knowing whether measurements at both DPs and for several primary frequency pairs can be used in a multivariate analysis to further optimize test performance. DPOAE and noise amplitudes were measured at 2f1-f2 and 2 f2-f1 for 12 primary levels (L2 from 10 to 65 dB SPL in 5-dB steps) and 9 pairs of primary frequencies (0.5 to 8 kHz in 1/2-octave steps). All data were collected in a sound-treated room from 70 subjects with normal hearing and 80 subjects with hearing loss. Subjects had normal middle-ear function at the time of the DPOAE test, based on standard tympanometric measurements. Measurement-based stopping rules were used such that the test terminated when the noise floor around the 2 f1-f2 DP was < or = -30 dB SPL or after 32 s of artifact-free averaging, whichever occurred first. Data were analyzed using clinical decision theory in which relative operating characteristics (ROC) curves were constructed and areas under the ROC curves were estimated. In addition, test performance was assessed by selecting the criterion value that resulted in a sensitivity of 90% and determining the specificity at that criterion value. Data were analyzed using traditional univariate comparisons, in which predictions about auditory status were based only on data obtained when f2 = audiometric frequency. In addition, multivariate analysis techniques were used to determine whether test performance can be optimized by using many variables to predict auditory status. As expected, DPOAEs were larger for 2f1-f2 compared to 2 f2-f1 in subjects with normal hearing. However, noise amplitudes were smaller for 2f2-f1, but this effect was restricted to the lowest f2 frequencies. A comparison of signal-to-noise ratios (SNR) within normal-hearing ears showed that the 2f1-f2 DP was more frequently characterized by larger SNRs compared to 2f2-f1. However, there were several subjects in whom 2f2-f1 produced a larger SNR. ROC curve areas and specificities for a fixed sensitivity increased only slightly when data from both DPs were used to predict auditory status. Multivariate analyses, in which the inputs included both DPs for several primary frequency pairs surrounding each audiometric frequency, produced the highest areas and specificities. Thus, DPOAE test performance was improved slightly by examining data at two DP frequencies simultaneously. This improvement was achieved at no additional cost in terms of test time. When measurements at both DPs were combined with data obtained for several primary frequency pairs and then analyzed in a multivariate context, the best test performance was achieved. Excellent test performance (ROC) curve areas >0.95% and specificities >92% at all frequencies, including 500 Hz, were achieved for these conditions. Although the results described should be validated on an independent set of data, they suggest that the accuracy with which DPOAE measurements identify auditory status can be improved with multivariate analyses and measurements at multiple DPs.


Effect of inversion recovery fat suppression on hepatic R2* quantitation in transfusional siderosis.
OBJECTIVE. The purpose of this study is to evaluate whether the application of spectral pre-saturation inversion recovery (SPIR) fat suppression in standard multiecho gradient-echo sequences has a significant effect on hepatic R2* quantitation in patients with iron overload syndromes. MATERIALS AND METHODS. Eighty patients were scanned with a multiecho gradient-echo sequence without and with the application of SPIR. Six different postprocessing approaches were used to extract R2* values for maximum generality. RESULTS. SPIR fat suppression lowered R2* values by 3.9-7.0% (p < 0.0001 in all pairwise comparisons), independently of the postprocessing algorithm. Coefficients of variation for R2* ranged from 4.5% to 10.0%. Regardless of the size of the ROI (area of homogeneous tissue or entire liver profile in the slice), pixelwise approaches combined with an exponential-plus-constant fitting model yielded the lowest coefficients of variation (4.5% and 5.1%), whereas truncated exponential fits of the averaged signals produced the highest coefficients of variation (7.8% and 10%). For R2* values exceeding 200 Hz, a Bland-Altman analysis showed a bias that grew linearly for all postprocessing methods. CONCLUSION. SPIR fat suppression resulted in systematically lower hepatic R2* estimates. Because calibration curves were derived using images without fat suppression, these biases should be corrected when reporting liver iron concentrations estimated from fat-suppressed multiecho T2*-weighted images.


The use of the latissimus dorsi myocutaneous flap in the reconstruction of complex head and neck defects.
To compare and contrast the use of the latissimus dorsi myocutaneous flap in complex head and neck defects requiring major reconstructive surgery with respect to the other reconstruction techniques, and to emphasize the importance of this flap as an life and surgeon-saving reconstruction modality. In this study, 20 cases (17 males, 3 females; mean age 58.5 years; range 48 to 72 years) of major head and neck operations reconstructed with a latissimus dorsi myocutaneous flap in Istanbul University, Istanbul Medical Faculty, Ear, Nose and Throat Clinic between October 2004 and November 2006 were retrospectively examined. The latissimus dorsi myocutaneous flap was preferred as a primary reconstructive modality in eight of the cases and a secondary reconstructive modality in the remaining 12 cases. The reasons for choosing the latissimus dorsi myocutaneous flap as the reconstructive modality were examined in this study and compared with other reconstruction techniques. Partial flap necrosis was observed in four of the 20 cases. In two of these unsuccessful cases, minor intervention was sufficient to achieve functionally satisfactory results. However, one case with partial flap necrosis was lost due to the uncontrollable primary disease. In the one remaining case who had undergone cranioplasty, partial necrosis of the flap developed after the completion of radiotherapy in the 4th postoperative month. No total flap necrosis was encountered in any of the cases. The latissimus dorsi myocutaneous flap is a reconstructive modality with a high success rate and should be considered among reconstruction alternatives.


Conjugative Mating Assays for Sequence-specific Analysis of Transfer Proteins Involved in Bacterial Conjugation.
The transfer of genetic material by bacterial conjugation is a process that takes place via complexes formed by specific transfer proteins. In Escherichia coli, these transfer proteins make up a DNA transfer machinery known as the mating pair formation, or DNA transfer complex, which facilitates conjugative plasmid transfer. The objective of this paper is to provide a method that can be used to determine the role of a specific transfer protein that is involved in conjugation using a series of deletions and/or point mutations in combination with mating assays. The target gene is knocked out on the conjugative plasmid and is then provided in trans through the use of a small recovery plasmid harboring the target gene. Mutations affecting the target gene on the recovery plasmid can reveal information about functional aspects of the target protein that result in the alteration of mating efficiency of donor cells harboring the mutated gene. Alterations in mating efficiency provide insight into the role and importance of the particular transfer protein, or a region therein, in facilitating conjugative DNA transfer. Coupling this mating assay with detailed three-dimensional structural studies will provide a comprehensive understanding of the function of the conjugative transfer protein as well as provide a means for identifying and characterizing regions of protein-protein interaction.


Cervical proprioceptive impairment in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) involving the cervical spine can lead to various neurologic defects and impairment of proprioception is just one of them. The aim of this study was the assessment of cervical proprioception and its relation with radiographic, clinical, and functional characteristics of patients with RA. One hundred and six rheumatoid arthritis patients who diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and age, gender, educational status matched one hundred and six healthy volunteers were enrolled in this study. Cervical joint position error test (CJPET) was applied to healthy volunteers and RA patients for cervical proprioception assessment. Fatigue, depression, balance, quality of life and balance scales were administered to all patients. Cervical radiography was used to assess cervical subluxations. Regression analysis was used for grading the factors which had relations with cervical proprioception. Mean age of patients and healthy volunteers was 51 ± 11.1 and 48.9 ± 9.2, respectively. Scores of CJPET were statistically significantly higher in RA group than healthy volunteers (p = 0.001). CJPET scores were negatively correlated with Berg balance scale findings in right rotation, left rotation, flexion and extension (rho = - 0.421,- 0.473,- 0.448,- 0.515). There was weak or not significant correlation between the scores of CJPET and fatigue, depression, and quality of life scales. Scores of CJPET in patients with atlantoaxial subluxations (AAS) were statistically significantly higher than those without AAS (p < 0.05). Regression analysis results showed that the AAS was related to impaired cervical proprioception on right and left rotations. There was no correlation between CJPET scores and functional parameters. Cervical proprioception impaired in RA patients. This impairment was related to the existence of AAS and balance problems.


Elective non-therapeutic intensive care and the four principles of medical ethics.
The chronic worldwide lack of organs for transplantation and the continuing improvement of strategies for in situ organ preservation have led to renewed interest in elective non-therapeutic ventilation of potential organ donors. Two types of situation may be eligible for elective intensive care: patients definitely evolving towards brain death and patients suitable as controlled non-heart beating organ donors after life-supporting therapies have been assessed as futile and withdrawn. Assessment of the ethical acceptability and the risks of these strategies is essential. We here offer such an ethical assessment using the four principles of medical ethics of Beauchamp and Childress applying them in their broadest sense so as to include patients and their families, their caregivers, other potential recipients of intensive care, and indeed society as a whole. The main ethical problems emerging are the definition of beneficence for the potential organ donor, the dilemma between the duty to respect a dying patient's autonomy and the duty not to harm him/her, and the possible psychological and social harm for families, caregivers other potential recipients of therapeutic intensive care, and society more generally. Caution is expressed about the ethical acceptability of elective non-therapeutic ventilation, along with some proposals for precautionary measures to be taken if it is to be implemented.


Characteristics of interactive communication between Pepper robot, patients with schizophrenia, and healthy persons.
Expressing enjoyment when conversing with healthcare robots is an opportunity to enhance the value of human robots with interactive capabilities. In clinical practice, it is common to find verbal dysfunctions in patients with schizophrenia. Thus, interactive communication characteristics may vary between Pepper robot, persons with schizophrenia, and healthy persons. Two case studies aimed to describe the characteristics of interactive communications, 1) between Pepper as a healthcare robot and two patients with schizophrenia, and 2) between Pepper as a healthcare robot and two healthy persons. The "Intentional Observational Clinical Research Design" was used to collect data. Using audio-video technology, the conversational interactions between the four participants with the Pepper healthcare robot were recorded. Their interactions were observed, with significant events noted. After their interactions, the four participants were interviewed regarding their experience and impressions of interacting with the Pepper healthcare robot. Audio-video recordings were analyzed following the analysis and interpretation protocol, and the interview data were transcribed, analyzed, and interpreted. There were similarities and differences in the interactive communication characteristics between the Pepper robot and the two participants with schizophrenia and between Pepper and the two healthy participants. The similarities were experiences of human enjoyment while interacting with the Pepper robot. This enjoyment was enhanced with the expectancy of the Pepper robot as able to entertain, and possessing interactive capabilities, indicating two-way conversational abilities. However, different communicating characteristics were found between the healthy participants' impressions of the Pepper robot and the participants with schizophrenia. Healthy participants understood Pepper to be an automaton, with responses to questions often constrained and, on many occasions, displaying inaccurate gaze. Pepper robot showed capabilities for effective communication pertaining to expressing enjoyment. The accuracy and appropriateness of gaze remained a critical characteristic regardless of the situation or occasion with interactions between persons with schizophrenia, and between healthy persons. It is important to consider that in the future, for effective use of healthcare robots with multiple users, improvements in the areas of the appropriateness of gaze, response time during the conversation, and entertaining functions are critically observed.


HAP score as prognostic factor of hepatocellular carcinoma treated with transarterial chemoembolization in a Latin American center.
Hepatocellular carcinoma (HCC) in cirrhosis is diagnosed, most of times, when it is not susceptible to curative treatment. Transarterial chemoembolization (TACE) is a palliative therapeutic option with heterogeneous results. The HAP score stratifies patients who will benefit from the first TACE. To evaluate if the HAP score is a prognostic factor of HCC treated with TACE. Retrospective cohort study in cirrhotic patients with HCC and first TACE at the Edgardo Rebagliati Martins National Hospital, Lima-Peru, from June 2011 to June 20139. The HAP score was applied, mortality and survival were observed with a follow-up of 36 months. We included 54 patients with age of 67.7±9.9 years, 59.3% Child-Pugh A and 40.7% Child-Pugh B, MELD score of 11±2.7; 51.9 and 40.7% were BCLC A and B, respectively; 66.7% had a single tumor and 70.4% had a predominant tumor <5cm. The HAP score classified 8, 14, 26 and 6 patients as HAP A, B, C and D, respectively. The overall survival was 19.5±11.2 months and 32.8±6.5 months for HAP A, 24.9±14.8 months for HAP B, 13.9±5.2 months for HAP C and 14±6.6 months for HAP D. There were no deaths at 12 months in HAP A. At 24 months, mortality for HAP C and D was 100%. At 36 months, the survival rate for HAP A and B was 75 and 42.9%, respectively. The HAP score is a useful tool to guide the management decisions of cirrhotic patients with HCC requiring TACE due to its value in predicting mortality and survival.


Pigeon control by chemosterilization: population model from laboratory results.
Reproductivity of pigeons is inhibited with mestranol incorporated in a synthetic grit; continual erosion releases daily doses. Young squabs may be permanently sterilized when fed crop milk by treated birds. A theoretical model of pigeon population dynamics using laboratory-obtained data shows the advantages of chemosterilization over killing as a means of pigeon control.


Third-harmonic generation via nonlinear Raman-Nath diffraction in nonlinear photonic crystal.
We report on the observation of multiple third-harmonic conical waves generated in an annular periodically poled nonlinear photonic crystal. We show that the conical beams are formed as a result of the cascading effect involving two parametric processes that satisfy either the transverse and/or longitudinal phase-patching conditions. This is the first experimental observation of third-harmonic generation based on nonlinear Raman-Nath diffraction.


Pharmacological intervention with oxidative burst in human neutrophils.
In this study we investigated the effect of five therapeutically used drugs and four natural polyphenolic compounds on the mechanism of oxidative burst of human neutrophils concerning their participation in the generation of reactive oxygen species (ROS). The compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin > quercetin > curcumin > arbutin > dithiaden > carvedilol. The generation of intracellular reactive oxygen species in isolated neutrophils decreased in the same rank order, while carvedilol was ineffective. Scavenging of extracellular oxygen radicals followed the rank order of potency: N-feruloylserotonin > curcumin > quercetin > dithiaden. Arbutin and carvedilol had no effect. All compounds tested increased the activity of caspase-3 in cell-free system indicating a positive effect on apoptosis of neutrophils. Activation of protein kinase C was significantly decreased by dithiaden, curcumin, quercetin and N-feruloylserotonin. Carvedilol, dithiaden, quercetin and arbutin reduced activated neutrophil myeloperoxidase release more significantly compared with their less pronounced effect on superoxide generation The presented results are indicative of pharmacological intervention with neutrophils in pathological processes. Of particular interest was the effect of natural compounds. Intracellular inhibition of oxidative burst in isolated neutrophils by the drugs tested and natural antioxidants has to be further analysed since ROS play an important role in immunological responses of neutrophils.


[Next-Generation Sequencing: A Quantum Leap in Ophthalmology Research and Diagnostics].
Many eye diseases have a genetic basis, and most can be caused by mutations in many different genes (extensive genetic heterogeneity). The retinal dystrophies are a good example: More than 200 genes have been identified for the isolated forms (Leber's congenital amaurosis, retinitis pigmentosa, cone-rod dystrophy, congenital stationary night blindness), and for syndromes that comprise additional dysfunctions or malformations of extraocular tissues and organs. Selecting genes for diagnostic testing has been difficult, and their analysis with the hitherto predominant DNA sequencing method (Sanger sequencing) has been extremely laborious: The phenotype rarely indicates the affected gene, and the contributions of the particular genes to the disease (e.g., to LCA) were largely unknown. Consequently, comprehensive genetic analyses were impossible in most cases. In the recent years, high-throughput sequencing technologies, summarized as next-generation sequencing (NGS), have revolutionized genetic research and, subsequently, genetic diagnostics. The latter has far-reaching implications for the individual management of patients with genetic eye diseases and their families.


Constitutively-active FGFR3 disrupts primary cilium length and IFT20 trafficking in various chondrocyte models of achondroplasia.
Fibroblast growth factor receptor 3 (FGFR3) gain-of-function mutations cause dwarfisms, including achondroplasia (ACH) and thanatophoric dysplasia (TD). The constitutive activation of FGFR3 disrupts the normal process of skeletal growth. Bone-growth anomalies have been identified in skeletal ciliopathies, in which primary cilia (PC) function is disrupted. In human ACH and TD, the impact of FGFR3 mutations on PC in growth plate cartilage remains unknown. Here we showed that in chondrocytes from human (ACH, TD) and mouse Fgfr3Y367C/+ cartilage, the constitutively active FGFR3 perturbed PC length and the sorting and trafficking of intraflagellar transport (IFT) 20 to the PC. We demonstrated that inhibiting FGFR3 with FGFR inhibitor, PD173074, rescued both PC length and IFT20 trafficking. We also studied the impact of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) pathway. Interestingly, mTOR inhibition also rescued PC length and IFT20 trafficking. Together, we provide evidence that the growth plate defects ascribed to FGFR3-related dwarfisms are potentially due to loss of PC function, and these dwarfisms may represent a novel type of skeletal disorders with defective ciliogenesis.


Assessment of cytotoxic lymphocyte gene expression in the peripheral blood of human islet allograft recipients: elevation precedes clinical evidence of rejection.
Studies in nonhuman primates have demonstrated that elevation of the cytotoxic lymphocyte (CL) genes granzyme B, perforin, and Fas ligand in peripheral blood precedes islet allograft rejection. The purpose of this study was to determine whether this approach has utility for prediction of human islet allograft loss. We studied 13 patients who had long-term type 1 diabetes and were treated with steroid-free immunosuppression and given sequential islet cell infusions. All recipients became insulin independent, and eight of them experienced deterioration in glycemic control, followed by reinitiation of insulin therapy. Frequent peripheral blood samples were collected to monitor CL gene mRNA levels with real-time PCR. For the eight back-to-insulin patients, there was a clear elevation of CL gene mRNA levels 25-203 days before the onset of frequent hyperglycemia. Granzyme B was the most reliable indicator of ongoing graft loss. Additional correlations with infection were noted; however, evidence of sensitization in antidonor mixed lymphocyte reaction was observed in seven of eight patients who experienced partial graft loss, whereas this was not seen when upregulated CL gene expression was associated with infection. The results suggest that, when taken into consideration with other clinical parameters, elevated CL gene levels may enable prediction of islet allograft loss.


TreeVector: scalable, interactive, phylogenetic trees for the web.
Phylogenetic trees are complex data forms that need to be graphically displayed to be human-readable. Traditional techniques of plotting phylogenetic trees focus on rendering a single static image, but increases in the production of biological data and large-scale analyses demand scalable, browsable, and interactive trees. We introduce TreeVector, a Scalable Vector Graphics-and Java-based method that allows trees to be integrated and viewed seamlessly in standard web browsers with no extra software required, and can be modified and linked using standard web technologies. There are now many bioinformatics servers and databases with a range of dynamic processes and updates to cope with the increasing volume of data. TreeVector is designed as a framework to integrate with these processes and produce user-customized phylogenies automatically. We also address the strengths of phylogenetic trees as part of a linked-in browsing process rather than an end graphic for print. TreeVector is fast and easy to use and is available to download precompiled, but is also open source. It can also be run from the web server listed below or the user's own web server. It has already been deployed on two recognized and widely used database Web sites.


The impact of senior doctor assessment at triage on emergency department performance measures: systematic review and meta-analysis of comparative studies.
To determine if placing a senior doctor at triage versus standard single nurse in a hospital emergency department (ED) improves ED performance by reviewing evidence from comparative design studies using several quality indicators. Systematic review. Cochrane Library, MEDLINE, EMBASE, CINAHL, Cochrane Effective Practice and Organisation of Care (EPOC), Web of Science, Clinical Trials Registry website. In addition, references from included studies and citation searches were used to identify relevant studies. Databases were searched for comparative studies examining the role of senior doctor triage (SDT), published from 1994 to 2014. Senior doctor was defined as a qualified medical doctor who completed high specialty training in emergency medicine. Articles with a primary aim to investigate the effect of SDT on ED quality indicators such as waiting time (WT), length of stay (LOS), left without being seen (LWBS) and left without treatment complete (LWTC) were included. Articles examining the adverse events and cost associated with SDT were also included. Only studies with a control group, either in a randomised controlled trial (RCT) or in an observational study with historical controls, were included. The systematic literature search was followed by assessment of relevance and risk of bias in each individual study fulfilling the inclusion criteria using the Effective Public Health Practice Project (EPHPP) bias tool. Data extraction was based on a form designed and piloted by the authors for dichotomous and continuous data. Narrative synthesis and meta-analysis of homogenous data were performed. Of 4506 articles identified, 25 relevant studies were retrieved; 12 were of the weak pre-post study design, 9 were of moderate quality and 4 were of strong quality. The majority of the studies revealed improvements in ED performance measures favouring SDT. Pooled results from two Canadian RCTs showed a significant reduction in LOS of medium acuity patients (weighted means difference (WMD) -26.26 min, 95% CI -38.50 to -14.01). Another two RCTs revealed a significant reduction in WT (WMD -26.17 min, 95% CI -31.68 to -20.65). LWBS was reduced in two Canadian RCTs (risk ratio (RR)=0.79, 95% CI 0.66 to 0.94). This was echoed by the majority of pre-post study designs. SDT did not change the occurrence of adverse events. No clear benefit of SDT in terms of patient satisfaction or cost effectiveness could be identified. This review demonstrates that SDT can be an effective measure to enhance ED performance, although cost versus benefit analysis is needed. The potential high risk of bias in the evidence identified, however, mandates more robust multicentred studies to confirm these findings.


[Cohort study on the association between alcohol consumption and the risk of colorectal cancer in the Korean elderly].
We examined the association between alcohol consumption and incidence of colorectal cancer in elderly Koreans. The cohort members (n=14,304) consisted of 4,834 males and 9,470 females derived from the Korea Elderly Pharmacoepidemiologic Cohort (KEPEC), a population-based dynamic cohort. They were aged 65 years old or older and lived in Busan between 1993-1998; they were beneficiaries of the Korean Medical Insurance Corporation (KMIC). Baseline information was surveyed by a self-administered, mailed questionnaire. This study population was restricted to 14,304 participants who reported alcohol drinking habits on the questionnaire and had not been diagnosed with colorectal cancer at baseline. The adjusted hazard ratios (aHR) of status, type, frequency and daily average amount of alcohol consumption were computed with Cox's proportional hazard model, with the never-drinkers as a reference group and controlling for age and gender. After 4.82 person-years of mean follow-up 112 cases of colorectal cancer occurred. The incidence densities of colorectal cancer were 161 (95% CI=123-200) for never-drinkers, 219 (95% CI=125-339) for ex-drinkers, and 137 (95% CI=84-189) for current-drinkers per 100,000 person-year. The status, type, frequency, and daily average amount of alcohol consumption were not significantly related to the incidence of colorectal cancer after controlling for age and gender. There was no significant association between alcohol consumption and colorectal cancer among elderly people after controlling for age and gender.


Friend virus-specific cytotoxic T lymphocytes recognize both gag and env gene-encoded specificities.
We have constructed a series of "synthetic" target cell lines for an analysis of the specificity of anti-Friend virus (FV) CTL. Our results show that murine H-2 genes and individual retroviral genes can be stable expressed in Fisher rat embryo (FRE) cells, and that their products have the potential to form target structures recognized by mouse CTL. Cells expressing H-2Db and either the env or gag genes of one component of FV, helper Friend murine leukemia virus (FMuLV), were lysed by anti-FV CTL and by CTL generated against FMuLV alone. Experiments with Db-transfected FRE clones infected only with the replication-defective spleen focus-forming virus (SFFV) component of FV indicate that the SFFV genome also provides specificities recognized by both anti-FV and anti-FMuLV CTL, thus demonstrating the existence of a crossreactive CTL population. An unexpected finding was that anti-FMuLV CTL, but not anti-FV CTL were also able to lyse FRE clones that expressed H-2Kb in either the presence or absence of FV. The use of heterologous cell lines for the construction of synthetic target cells thus offers a useful approach for the analysis of T cell specificity.


Bacillus piliformis infection (Tyzzer's disease) in foals in northwestern United States: a retrospective study of 21 cases.
From Jan 1, 1967 through June 1980, 21 cases of Bacillus piliformis infection (Tyzzer's disease) in foals were diagnosed at the Washington Animal Disease Diagnostic Laboratory. Affected foals died between 7 and 35 days of age. Of 4 Arabian foals with the disease, 2 also had combined immunodeficiency.


Nutrients, neurogenesis and brain ageing: From disease mechanisms to therapeutic opportunities.
Appreciation of the physiological relevance of mammalian adult neurogenesis has in recent years rapidly expanded from a phenomenon of homeostatic cell replacement and brain repair to the current view of a complex process involved in high order cognitive functions. In parallel, an array of endogenous or exogenous triggers of neurogenesis has also been identified, among which metabolic and nutritional cues have drawn significant attention. Converging evidence from animal and in vitro studies points to nutrient sensing and energy metabolism as major physiological determinants of neural stem cell fate, and modulators of the whole neurogenic process. While the cellular and molecular circuitries underlying metabolic regulation of neurogenesis are still incompletely understood, the key role of mitochondrial activity and dynamics, and the importance of autophagy have begun to be fully appreciated; moreover, nutrient-sensitive pathways and transducers such as the insulin-IGF cascade, the AMPK/mTOR axis and the transcription regulators CREB and Sirt-1 have been included, beside more established "developmental" signals like Notch and Wnt, in the molecular networks that dictate neural-stem-cell self-renewal, migration and differentiation in response to local and systemic inputs. Many of these nutrient-related cascades are deregulated in the contest of metabolic diseases and in ageing, and may contribute to impaired neurogenesis and thus to cognition defects observed in these conditions. Importantly, accumulating knowledge on the metabolic control of neurogenesis provides a theoretical framework for the trial of new or repurposed drugs capable of interfering with nutrient sensing as enhancers of neurogenesis in the context of neurodegeneration and brain senescence.


Estimation of 24-hour urine phosphate excretion from spot urine collection: development of a predictive equation.
The management of hyperphosphatemia in patients with moderate to severe chronic kidney disease (CKD) includes dietary phosphate restriction and/or prescription of phosphate binders. Measuring phosphate intake in CKD is important for monitoring dietary adherence and for the effectiveness of therapeutic interventions. The 24-hour urine collection is the gold standard method for determining phosphate intake; however, timed urine collections are cumbersome and prone to error. We investigated the precision and accuracy of spot urine phosphate measurements, compared to 24-hour urine phosphate (24hUrP) collection. We evaluated simultaneous spot and 24hUrP measurements, collected on multiple occasions, from 143 participants in the Phosphate Normalization Trial, a randomized trial of phosphate binders versus placebo among persons with an estimated glomerular filtration rate between 20-45 mL/minute per 1.73 m2. We used residual analyses and graphical methods to model the functional relationship of spot urine phosphate and creatinine measurements with 24hUrP. We used multiple linear regression to test whether additional covariates improved model prediction, including treatment assignment, age, sex, height, weight, urine collection time, and last meal time. We internally validated results using leave-one-out cross-validation, and externally validated in an independent replication cohort. A log-log relation between the spot urine phosphate-to-creatinine ratio and 24hUrP excretion yielded the best model fit. In addition to spot urine phosphate and creatinine concentrations, inclusion of age, sex, and weight significantly improved prediction of 24hUrP. Compared with a spot urine phosphate-to-creatinine ratio alone (r2 = 0.12, P < .001), the new equation more accurately predicted 24hUrP (leave-one-out validation r2 = 0.43, P < .001, independent validation r2 = 0.39, P < .001). We describe a novel equation to predict 24hUrP excretion using spot urine phosphate and creatinine, age, sex, and weight. The equation is more accurate and precise than the urine phosphate-to-creatinine ratio alone, and it provides a simple method for estimating 24hUrP excretion in patients with nondialysis-requiring CKD.


Radiobiologic comparison of helical tomotherapy, intensity modulated radiotherapy, and conformal radiotherapy in treating lung cancer accounting for secondary malignancy risks.
The aim of the present study is to examine the importance of using measures to predict the risk of inducing secondary malignancies in association with the clinical effectiveness of treatment plans in terms of tumor control and normal tissue complication probabilities. This is achieved by using radiobiologic parameters and measures, which may provide a closer association between clinical outcome and treatment delivery. Overall, 4 patients having been treated for lung cancer were examined. For each of them, 3 treatment plans were developed based on the helical tomotherapy (HT), multileaf collimator-based intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (CRT) modalities. The different plans were evaluated using the complication-free tumor control probability (p+), the overall probability of injury (pI), the overall probability of control/benefit (pB), and the biologically effective uniform dose (D¯¯). These radiobiologic measures were used to develop dose-response curves (p-D¯¯ diagram), which can help to evaluate different treatment plans when used in conjunction with standard dosimetric criteria. The risks for secondary malignancies in the heart and the contralateral lung were calculated for the 3 radiation modalities based on the corresponding dose-volume histograms (DVHs) of each patient. Regarding the overall evaluation of the different radiation modalities based on the p+ index, the average values of the HT, IMRT, and CRT are 67.3%, 61.2%, and 68.2%, respectively. The corresponding average values of pB are 75.6%, 70.5%, and 71.0%, respectively, whereas the average values of pI are 8.3%, 9.3%, and 2.8%, respectively. Among the organs at risk (OARs), lungs show the highest probabilities for complications, which are 7.1%, 8.0%, and 1.3% for the HT, IMRT, and CRT modalities, respectively. Similarly, the biologically effective prescription doses (DB¯¯) for the HT, IMRT, and CRT modalities are 64.0, 60.9, and 60.8Gy, respectively. Regarding the risk for secondary cancer, for the heart, the lowest average risk is produced by IMRT (0.10%) compared with the HT (0.17%) and CRT (0.12%) modalities, whereas the 3 radiation modalities show almost equivalent results regarding the contralateral lung (0.8% for HT, 0.9% for IMRT, and 0.9% for CRT). The use of radiobiologic parameters in the evaluation of different treatment plans and estimation of their expected clinical outcome is shown to provide very useful clinical information. The radiobiologic analysis of the response probabilities showed that different radiation modalities appear to be more effective in different patient geometries and target sizes and locations. Furthermore, there is not a clear pattern between the plans that appear to be more effective for the treatment and the risk of secondary malignancy. It seems that radiobiologically based treatment planning taking into account the risk of secondary cancer can be established as an effective clinical tool for a more clinically relevant treatment optimization.


Nation-wide hypertension screening in Italy: data from May Measurements Month 2017-Europe.
Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative organized by the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programs worldwide. A similar approach has been used in Italy since 2012, showing inadequate awareness of the consequences of hypertension, a generally increased cardiovascular risk and unsatisfactory BP control in 36% of interviewed individuals. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017, during the joint MMM and World Hypertension Day events. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screenings were conducted both in cities and villages, indoor and outdoor, by health personnel. Eighty-five sites, involving approximately 300 investigators, took part in MMM17/World Hypertension Day in Italy, screening 10 076 individuals during a month-long period. After multiple imputation, 3099 participants were found (30.8%) to have high BP levels. This was the biggest opportunistic BP screening in a single time-point ever reported in Italy. A significant proportion of individuals had high BP, although it was not possible to differentiate between known treated hypertensive patients with inadequate BP control and as yet undiagnosed hypertensive individuals. Opportunistic screening can reach a significant number of individuals, being a powerful tool for raising awareness and carrying out BP screening.


[Coronary lithotripsy in calcified lesions: fragmented calcium].
Complex calcified coronary lesions are a frequent finding during percutaneous coronary intervention, representing for decades a challenge and limitation in patients with indication of revascularization, due to suboptimal angiographic results, high incidence of perioperative complications and long-term adverse events despite the multiple strategies employed, such as the use of cutting balloon, high-pressure balloons or rotational or orbital atherectomy, interventions with limitations that have hindered its routine use, recently a new plaque modification technique known as coronary intravascular lithotripsy has burst into the treatment of this complex entity, which consists in the use of a specially modified balloon for the emission of pulsatile mechanical energy (sonic pressure waves) that allows modifying the calcified plate. By presenting a series of clinical cases and reviewing the literature, our initial experience is presented, key elements are summarized and discussed in the understanding of this new intervention technique necessary for decision making. Coronary intravascular lithotripsy is projected as a promising technique for the modification and preparation of superficial and deep calcified coronary lesions, through microfractures that allow the apposition and effective expansion of the stent, strategy that according to different trials (Disrupt CAD series, SOLSTICE assay) and records presents a high efficiency and good safety profile, data consistent with our initial experience.


The Pathophysiology, Diagnosis, and Management of Wolff-Parkinson-White Syndrome in the Neonate.
Wolff-Parkinson-White (WPW) is a congenital defect of the cardiac conduction system (CCS), with proliferation of extra embryologic conduction pathways and rapid conduction of electrical impulses. The estimated neonatal incidence of 0.1% to 0.2% may be misrepresented secondary to missed or misdiagnosis. Undiagnosed WPW can result in sudden cardiac death. To discuss the pathogenesis, manifestations, diagnosis, management, and lifespan implications of WPW in the prenatal and postnatal periods. A literature review was conducted using PubMed, CINAHL, and Google Scholar (2013-2019). Search terms included (newborn OR infant), wolff parkinson white, pathogenesis, management, and ventricular preexcitation. After removal of duplicates, 267 references were identified, abstracts reviewed, and 30 publications fully evaluated. Separation of the heart chambers begins around 7 weeks' gestation with formation of the annulus fibrosis complete after term. The unknown external environmental influence on the development of the preterm infant's CCS places neonates at risk for persistent atrioventricular reentrant tachycardia with WPW development. Ensuring an appropriate diagnosis is crucial, as an incorrect diagnosis could mean death. Due to the rarity of WPW, any fetal or neonatal supraventricular tachycardia requires further evaluation with an electrocardiogram and involvement of an experienced cardiologist for diagnosis. One episode of supraventricular tachycardia warrants evaluation for WPW, as recurring episodes may result in irreversible damage. The recommendations for treatment of WPW in the prenatal and immediate postnatal periods are based heavily on standards of care for the adult population. A paucity of evidenced-based literature exists and future research is crucial to understand the true incidence, physiologic effects, and lifespan implications of WPW on neonates.


Why 'knowledge transfer' is misconceived for applied social research.
'Knowledge transfer' has become established as shorthand for a wide variety of activities linking the production of academic knowledge to the potential use of such knowledge in non-academic environments. While welcoming the attention now being paid to non-academic applications of social research, we contend that terms such as knowledge transfer (and its subordinate sibling, knowledge translation) misrepresent the tasks that they seek to support. By articulating the complex and contested nature of applied social research, and then highlighting the social and contextual complexities of its use, we can see that other terms may serve us better. Following from this analysis, we suggest that 'knowledge interaction' might more appropriately describe the messy engagement of multiple players with diverse sources of knowledge, and that 'knowledge intermediation' might begin to articulate some of the managed processes by which knowledge interaction can be promoted. While it might be hard to shift the terminology of knowledge transfer in the short term, awareness of its shortcomings can enhance understanding about how social research can have wider impacts.


Emergency preparedness: What is the future?
Emergency preparedness programs have evolved over the last several decades as communities have responded to natural, intentional, and accidental disasters. This evolution has resulted in a comprehensive all-hazards approach centered around 4 fundamental phases spanning the entire disaster life cycle: mitigation, preparedness, response, and recovery. Increasing frequency of outbreaks and epidemics of emerging and reemerging infectious diseases in the last decade has emphasized the significance of healthcare emergency preparedness programs, but the coronavirus disease 2019 (COVID-19) pandemic has tested healthcare facilities' emergency plans and exposed vulnerabilities in healthcare emergency preparedness on a scale unexperienced in recent history. We review the 4 phases of emergency management and explore the lessons to be learned from recent events in enhancing health systems capabilities and capacities to mitigate, prepare for, respond to, and recover from biological threats or events, whether it be a pandemic or a single case of an unknown infectious disease. A recurring cycle of assessing, planning, training, exercising, and revising is vital to maintaining healthcare system preparedness, even in absence of an immediate, high probability threat. Healthcare epidemiologists and infection preventionists must play a pivotal role in incorporating lessons learned from the pandemic into emergency preparedness programs and building more robust preparedness plans.


Differences among states in the identification of autistic spectrum disorders.
To explore variation among the 50 US states in the administrative prevalence of autistic spectrum disorders (ASDs) and factors associated with that variation. This survey study used secondary data from all 50 states obtained from the US Department of Education, Washington, DC, and the American Board of Pediatrics, Chapel Hill, NC. The outcome of interest was the proportion of children identified with ASD in the academic year 2000-2001. Linear regression was used to examine its association with education and health system characteristics. States ranged in the proportion of children diagnosed with ASD from 0.6 per 1000 to 4.6 per 1000 in 2000-2001. In adjusted analyses, education-related spending, the number of pediatricians in the state, and the number of school-based health centers in the state were positively associated with the administrative prevalence of ASD. Variation in the administrative prevalence of ASD is associated with education-related spending, which may be associated with better-trained educational staff who can recognize the problem, and more and better trained in-school specialists who can provide screening. It is also associated with the availability of health care resources. Increased access to pediatricians and school-based health centers may lead to improved recognition of ASD. Interstate variability in the identification of ASD should be taken into account when interpreting the results of prevalence studies based on administrative data and the associated system characteristics taken into account by policy makers working to improve the recognition of ASD.


The brain knows the difference: two types of grammatical violations.
The brain has been shown to honor the fundamental linguistic difference between semantic and syntactic information. Here we demonstrate that it even further indicates the necessity to distinguish between two differential syntactic processes: that is to say between the processing of phrase structure information necessary to build up syntactic structures on-line and verb argument structure information crucial to build up representations of who is doing what to whom. The former process is reflected in the event-related brain potentials (ERPs) as an anterior negativity followed by a late centro-parietal positivity, whereas the latter process is reflected as a centro-parietal negativity-positivity pattern. The different ERP patterns clearly suggest that the theoretically assumed difference between local syntactic structure building and argument structure processing is neurophysiologically real.


A hybrid augmented ant colony optimization for the multi-trip capacitated arc routing problem under fuzzy demands for urban solid waste management.
Nowadays, urban solid waste management is one of the most crucial activities in municipalities and their affiliated organizations. It includes the processes of collection, transportation and disposal. These major operations require a large amount of resources and investments, which will always be subject to limitations. In this paper, a chance-constrained programming model based on fuzzy credibility theory is proposed for the multi-trip capacitated arc routing problem to cope with the uncertain nature of waste amount generated in urban areas with the aim of total cost minimization. To deal with the complexity of the problem and solve it efficiently, a hybrid augmented ant colony optimization algorithm is developed based on an improved max-min ant system with an innovative probability function and a simulated annealing algorithm. The performance of hybrid augmented ant colony optimization is enhanced by using the Taguchi parameter design method to adjust the parameters' values optimally. The overall efficiency of the algorithm is evaluated against other similar algorithms using well-known benchmarks. Finally, the applicability of the suggested methodology is tested on a real case study with a sensitivity analysis to evolve the managerial insights and decision aids.


Involvement of zinc in intracellular oxidant/antioxidant balance.
The effect of zinc (Zn) on cellular oxidative metabolism is complex and could be explained by multiple complementary interactions. In this study, we evaluated the impact of Zn on the pro-oxidant/antioxidant balance of HaCaT keratinocytes. Cells were submitted to a diffusible metal chelator able to induce intracellular Zn deprivation, TPEN, in combination or not with Zn chloride (ZnCl2), in the culture medium. The intracellular amount of Zn, copper (Cu), and iron (Fe) was determined, as well as CuZnSOD and MnSOD activities and glutathione reserves. The consequence of the modulation of Zn concentration on lipid peroxidation was also evaluated. TPEN induced a significant dose-dependent decrease in intracellular Zn and Cu (from 394-181 and 43-21 microg/g protein, respectively, after 6 h of TPEN 50 microM). No significant change in intracellular Fe concentration was found following TPEN exposure. The SOD activities were unchanged after 6 h of TPEN 50 microM application, either CuZnSOD or MnSOD. Cells exposure to TPEN induced a deep time- and dose-dependent decrease in their glutathione content (from 65-8 microM/g protein after 6 h of TPEN 50 microM), and a concomitant increase in glutathione in the cell-culture supernatants. No significant change in lipid peroxidation products was detected.


Z-Ligustilide Combined with Cisplatin Reduces PLPP1-Mediated Phospholipid Synthesis to Impair Cisplatin Resistance in Lung Cancer.
Lung cancer is a malignant tumor with one of the highest morbidity and mortality rates in the world. Approximately 80-85% of lung cancer is diagnosed as non-small lung cancer (NSCLC), and its 5-year survival rate is only 21%. Cisplatin is a commonly used chemotherapy drug for the treatment of NSCLC. Its efficacy is often limited by the development of drug resistance after long-term treatment. Therefore, determining how to overcome cisplatin resistance, enhancing the sensitivity of cancer cells to cisplatin, and developing new therapeutic strategies are urgent clinical problems. Z-ligustilide is the main active ingredient of the Chinese medicine Angelica sinensis, and has anti-tumor activity. In the present study, we investigated the effect of the combination of Z-ligustilide and cisplatin (Z-ligustilide+cisplatin) on the resistance of cisplatin-resistant lung cancer cells and its mechanism of action. We found that Z-ligustilide+cisplatin decreased the cell viability, induced cell cycle arrest, and promoted the cell apoptosis of cisplatin-resistant lung cancer cells. Metabolomics combined with transcriptomics revealed that Z-ligustilide+cisplatin inhibited phospholipid synthesis by upregulating the expression of phospholipid phosphatase 1 (PLPP1). A further study showed that PLPP1 expression was positively correlated with good prognosis, whereas the knockdown of PLPP1 abolished the effects of Z-ligustilide+cisplatin on cell cycle and apoptosis. Specifically, Z-ligustilide+cisplatin inhibited the activation of protein kinase B (AKT) by reducing the levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3). Z-ligustilide+cisplatin induced cell cycle arrest and promoted the cell apoptosis of cisplatin-resistant lung cancer cells by inhibiting PLPP1-mediated phospholipid synthesis. Our findings demonstrate that the combination of Z-Ligustilide and cisplatin is a promising approach to the chemotherapy of malignant tumors that are resistant to cisplatin.


An extremely high-altitude plume seen at Mars' morning terminator.
The Martian limb (that is, the observed 'edge' of the planet) represents a unique window into the complex atmospheric phenomena occurring there. Clouds of ice crystals (CO2 ice or H2O ice) have been observed numerous times by spacecraft and ground-based telescopes, showing that clouds are typically layered and always confined below an altitude of 100 kilometres; suspended dust has also been detected at altitudes up to 60 kilometres during major dust storms. Highly concentrated and localized patches of auroral emission controlled by magnetic field anomalies in the crust have been observed at an altitude of 130 kilometres. Here we report the occurrence in March and April 2012 of two bright, extremely high-altitude plumes at the Martian terminator (the day-night boundary) at 200 to 250 kilometres or more above the surface, and thus well into the ionosphere and the exosphere. They were spotted at a longitude of about 195° west, a latitude of about -45° (at Terra Cimmeria), extended about 500 to 1,000 kilometres in both the north-south and east-west directions, and lasted for about 10 days. The features exhibited day-to-day variability, and were seen at the morning terminator but not at the evening limb, which indicates rapid evolution in less than 10 hours and a cyclic behaviour. We used photometric measurements to explore two possible scenarios and investigate their nature. For particles reflecting solar radiation, clouds of CO2-ice or H2O-ice particles with an effective radius of 0.1 micrometres are favoured over dust. Alternatively, the plume could arise from auroral emission, of a brightness more than 1,000 times that of the Earth's aurora, over a region with a strong magnetic anomaly where aurorae have previously been detected. Importantly, both explanations defy our current understanding of Mars' upper atmosphere.


Cold and hunger induce diurnality in a nocturnal mammal.
The mammalian circadian system synchronizes daily timing of activity and rest with the environmental light-dark cycle. Although the underlying molecular oscillatory mechanism is well studied, factors that influence phenotypic plasticity in daily activity patterns (temporal niche switching, chronotype) are presently unknown. Molecular evidence suggests that metabolism may influence the circadian molecular clock, but evidence at the level of the organism is lacking. Here we show that a metabolic challenge by cold and hunger induces diurnality in otherwise nocturnal mice. Lowering ambient temperature changes the phase of circadian light-dark entrainment in mice by increasing daytime and decreasing nighttime activity. This effect is further enhanced by simulated food shortage, which identifies metabolic balance as the underlying common factor influencing circadian organization. Clock gene expression analysis shows that the underlying neuronal mechanism is downstream from or parallel to the main circadian pacemaker (the hypothalamic suprachiasmatic nucleus) and that the behavioral phenotype is accompanied by phase adjustment of peripheral tissues. These findings indicate that nocturnal mammals can display considerable plasticity in circadian organization and may adopt a diurnal phenotype when energetically challenged. Our previously defined circadian thermoenergetics hypothesis proposes that such circadian plasticity, which naturally occurs in nocturnal mammals, reflects adaptive maintenance of energy balance. Quantification of energy expenditure shows that diurnality under natural conditions reduces thermoregulatory costs in small burrowing mammals like mice. Metabolic feedback on circadian organization thus provides functional benefits by reducing energy expenditure. Our findings may help to clarify relationships between sleep-wake patterns and metabolic phenotypes in humans.


Prenatal mercury contamination: relationship with maternal seafood consumption during pregnancy and fetal growth in the 'EDEN mother-child' cohort.
Maternal seafood intake is of great health interest since it constitutes an important source of n-3 fatty acids, but provides also an important pathway for fetal exposure to Hg. The objective of the present study was to determine associations between Hg contamination and both maternal seafood consumption and fetal growth in French pregnant women. Pregnant women included in the 'EDEN mother-child' cohort study answered FFQ on their usual diet in the year before and during the last 3 months of pregnancy, from which frequencies of seafood intake were evaluated. Total hair-Hg level was determined for the first 691 included women. Associations between Hg level, seafood intake and several neonatal measurements were studied using linear regressions adjusted for confounding variables. The median Hg level for mothers was 0.52 μg/g. Maternal seafood intake was associated with Hg level (r 0.33; P < 0.0001). There was no association between Hg level and fetal growth in the whole sample of women, except for an early negative relationship with biparietal diameter. A positive association was found between seafood intake and fetal growth in overweight women only which remained unchanged after adjustment for Hg level (birth weight: +101 g for a difference of 1 sd in seafood consumption; P = 0.008). Although seafood intake was associated with Hg contamination in French pregnant women, the contamination level was low. There was no consistent association between Hg level and fetal growth. Taking into account Hg level did not modify associations between seafood intake and fetal growth.


gltBDF operon of Escherichia coli.
A 2.0-kilobase DNA fragment carrying antibiotic resistance markers was inserted into the gltB gene of Escherichia coli previously cloned in a multicopy plasmid. Replacement of the chromosomal gltB+ gene by the gltB225::omega mutation led to cells unable to synthesize glutamate synthase, utilize growth rate-limiting nitrogen sources, or derepress their glutamine synthetase. The existence of a gltBDF operon encoding the large (gltB) and small (gltD) subunits of glutamate synthase and a regulatory peptide (gltF) at 69 min of the E. coli linkage map was deduced from complementation analysis. A plasmid carrying the entire gltB+D+F+ operon complemented cells for all three of the mutant phenotypes associated with the polar gltB225::omega mutation in the chromosome. By contrast, plasmids carrying gltB+ only complemented cells for glutamate synthase activity. A major tricistronic mRNA molecule was detected from Northern (RNA blot) DNA-RNA hybridization experiments with DNA probes containing single genes of the operon. A 30,200-dalton polypeptide was identified as the gltF product, the lack of which was responsible for the inability of cells to use nitrogen-limiting sources associated with gltB225::omega.


The quantitative genetics of sexually selected traits, preferred traits and preference: a review and analysis of the data.
The maintenance of variation in sexually selected traits is a puzzle that has received increasing attention in the past several decades. Traits that are related to fitness, such as life-history or sexually selected traits, are expected to have low additive genetic variance (and hence, heritability) due to the rapid fixation of advantageous alleles. However, previous analyses have suggested that the heritabilities of sexually selected traits are on average higher than nonsexually selected traits. We show that the heritabilities of sexually selected traits are not significantly different from those of nonsexually selected traits overall or when separated into the three trait categories: behavioural, morphological and physiological. In contrast with previous findings, the heritability of preference is quite low (h(2) = 0.25 ± 0.06) and is in the same range as life-history traits. We distinguish preferred traits as a category of sexually selected traits and find that the heritability of the former is not significantly different than sexually selected traits overall (0.48 ± 0.04 vs. 0.46 ± 0.03). We test the hypothesis that the heritability of sexually selected traits is negatively correlated with the strength of sexual selection. As predicted, there is a significant negative correlation between the heritabilities of sexually selected traits and the strength of selection. This suggests that heritabilities do indeed decrease as sexual selection increases but sexual selection is not strong enough to cause heritabilities of sexually selected traits to deviate from the same type of nonsexually selected traits.


Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?
To determine the frequency and predictors of pause dependent torsade de pointes among patients with the congenital long QT syndrome and spontaneous ventricular tachyarrhythmias. The literature on the "congenital long QT" was reviewed. Articles with illustrations demonstrating the onset of spontaneous polymorphic ventricular arrhythmias in the absence of arrhythmogenic drugs were included. Illustrations of 62 spontaneous episodes of torsade de pointes among patients with congenital long QT syndrome were found in the literature. The majority (74%) of documented arrhythmias were "pause dependent"; 82% of these pauses were longer than the basic cycle length by > 100 ms. Age and sex correlated with the mode of arrhythmia initiation. Arrhythmias in infants (</= 3 years old) were not pause dependent, while female sex correlated with pause dependent torsade. Using multivariate analysis, age was the only independent predictor of the mode of onset of torsade de pointes. Available data suggest that the majority of spontaneous arrhythmias in the congenital long QT syndrome are pause dependent. Torsade de pointes that is not preceded by pauses appears to be limited to patient subgroups with severe forms of the disease, like symptomatic infants. These findings have important implications regarding the use of cardiac pacing for arrhythmia prevention.


Teratogenicity of carbamazepine-10, 11-epoxide and oxcarbazepine in the SWV mouse.
The mechanism of carbamazepine (CBZ)-related teratogenicity was investigated in the SWV mouse by contrasting the effects of CBZ-10, 11-epoxide (CBZE) and oxcarbazepine (OXC) treatments. Dietary CBZE administration was initiated 2 weeks before mating and continued through day 18 of gestation. OXC was administered to pregnant dams by gavage on day 6 of gestation and continued through day 18 of gestation. Maternal plasma concentrations of CBZE ranged from 1.4 to 17.7 micrograms/ml and OXC ranged from 6.1 to 15.9 micrograms/ml. In comparison, clinical plasma concentrations of CBZE ranged from 1 to 2 micrograms/ml and OXC plasma concentrations were 1 microgram/ml or less. The incidence of malformation were 14%, 27% and 26% after daily CBZE doses of 300, 600 and 1000 mg/kg, respectively, compared with a 6% incidence in no-drug control mice, P < .05. The incidence of malformation was 8% after exposure at the highest tolerable dose of OXC (1100 mg/kg/day), compared with a 5% incidence in no-drug controls, P > .05. Phenobarbital cotreatment (45 mg/kg/day) with OXC (1100 mg/kg/day) did not lead to changes in the incidence of malformation when compared with OXC (1100 mg/kg/day) dosed alone. These data are consistent with a teratogenic CBZ metabolite, possibly CBZE, or with oxidation of CBZE or CBZ at positions on the aromatic ring leading to the formation of reactive intermediates such as arene oxides or quinones.


NEUROLOGICAL FACTORS IN READING DISABILITY.
An overview is presented of that portion of the literature on reading disability wherein neurological defect is seen as causal or correlative. From the publication of Hinshelwood's "Congenital Word Blindness" (1917) to the present, investigators have considered the possible association of reading difficulty with genetically determined neurological defect, with cerebral damage, with biochemical imbalance inhibiting synaptic transmission, and with some form of maturational lag.


2D-1D structural phase transformation of Co(II) 3,5-pyridinedicarboxylate frameworks with chromotropism.
Two new metal-organic frameworks [Co(pydc)(H(2)O)(2)](n) (1) and [Co(pydc)(H(2)O)(4)](n)(H(2)O)(n) (2), (pydc = 3,5-pyridinedicarboxylate) have been synthesized by a diffusion method and characterized by single-crystal X-ray diffraction. The structure of 1 reveals an infinite 2D layer with honeycomb-like cavities in which each pydc ligand bridges three Co(II) ions. The adjacent 2D layers are orderly packed in an ABAB-type array via intermolecular interactions of the combined π-π stacking and hydrogen bonds to form a 3D supramolecular architecture. Interestingly, compound 1 exhibits a water induced crystal-to-amorphous transformation with chromotropism confirmed by spectroscopic techniques, elemental analysis, TGA and XRPD. When this amorphous phase (1A) was exposed to water vapor, it was readily converted into the second crystalline phase 1B with a color change. Moreover, a reversible process between 1A and 1B was performed. In the case of compound 2, pydc acts as didentate bridging ligand connecting two Co(II) ions, leading to a 1D zig-zag chain. Guest water molecules fill the gaps in between chains and form hydrogen bonds with the host chains stabilizing the 3D network of 2. Additionally, compound 2 also exhibits a water induced crystal-to-amorphous transformation with chromotropism and the reversible process was also performed between the dehydrated (2A) and rehydrated (2') forms. Surprisingly, the IR and UV-vis spectra, elemental analysis, TGA curve and XRPD pattern of the rehydrated second phase 1B are found to be identical to that of 2 and 2', these results confirm that 2, 2' and 1B are the same compound.