Establishment of a three-dimensional finite element model of severe kyphotic deformity secondary to ankylosing spondylitis.
Objective To establish a three-dimensional (3D) finite element (FE) model of ankylosing spondylitis (AS) kyphosis that is a digital platform for further studies. Methods A 30-year-old man with AS kyphosis underwent computed tomography transverse scanning from T1 to the sacrococcyx. The images were imported into Mimics® 17.0 software to establish a 3D model of the posterior spine, which was then imported into Studio Geomagic 2013 software. Posterior spine convex geometry was established on the 3D geometric model for subsequent optimization of image processing. Unigraphics NX 8.5 produced the spinal kyphosis surface model. Modeled calcification of ligaments and partial resection of useless sacral bone were added. The model was imported into ANSYS 15.0 FE analysis software. Ligaments were added. Parameters were set to generate a 3D FE model of AS. Results and Conclusion A 3D FE model of AS was successfully established, providing a reliable digital platform for subsequent biomechanical analysis.


NMR Crystallography: Evaluation of Hydrogen Positions in Hydromagnesite by 13 C{1 H} REDOR Solid-State NMR and Density Functional Theory Calculation of Chemical Shielding Tensors.
Solid-state NMR measurements coupled with density functional theory (DFT) calculations demonstrate how hydrogen positions can be refined in a crystalline system. The precision afforded by rotational-echo double-resonance (REDOR) NMR to interrogate 13 C-1 H distances is exploited along with DFT determinations of the 13 C tensor of carbonates (CO3 2- ). Nearby 1 H nuclei perturb the axial symmetry of the carbonate sites in the hydrated carbonate mineral, hydromagnesite [4 MgCO3 ⋅Mg(OH)2 ⋅4 H2 O]. A match between the calculated structure and solid-state NMR was found by testing multiple semi-local and dispersion-corrected DFT functionals and applying them to optimize atom positions, starting from X-ray diffraction (XRD)-determined atomic coordinates. This was validated by comparing calculated to experimental 13 C{1 H} REDOR and 13 C chemical shift anisotropy (CSA) tensor values. The results show that the combination of solid-state NMR, XRD, and DFT can improve structure refinement for hydrated materials.


Development of the New Zealand White Rabbit Eye: I. Pre- and Postnatal Development of Eye Tunics.
The New Zealand white (NZW) rabbit has been and is right now regularly utilized in ophthalmic surgery evaluation. Inside NZW rabbit eye, the visibility of ocular structures throughout surgical procedure is fantastic. Younger rabbits are used in different ages for the evaluation of ophthalmic surgery. Complete studies of ocular development in the NZW rabbits have not been reported previously. The aim of the present investigation was to describe the major landmarks and the time course of the pre- and post-natal development of the complete eye tunics of the NZW rabbit to give a superb model as well as a fruitful area for further ophthalmological investigations. Serial histological sections of NZW rabbit prenatal (E13-E28) and post-natal (P1-P14) stages were examined, respectively. The eye of the NZW rabbit developed in a similar manner to that of the human and domestic animals eyes; the principal differences were at the time of occurrence of certain developmental events, absence of pigmentation which represent an exploited benefit for ophthalmic surgery, remarkable Bowman's membrane at E25, poor developed ciliary stroma and juvenile retinal layer until P9. In human, the basic morphogenetic processes of the development of eye tunics are completed towards the end of the first half of gestation period. However, the latter represents the beginning stage of the development of eye tunics in the rabbit. Thus, allowing various extensive ophthalmic researches to be performed.


Antithyroid medications and psychosis.
Antithyroid drugs (ATDs) are used in the treatment of hyperthyroidism. Very rarely ATDs were reported to trigger acute psychosis in patients with no history of psychiatric disturbances. Our aim is to review the literature on psychosis as a side effect of ATD and to give a personal opinion on this issue. The cases of acute psychosis elicited by ATD are few and most were reported many years ago, before radioimmunoassay for thyroid-stimulating hormone (TSH) and thyroid hormones was introduced. Most of those cases lack a description of serum thyroid hormone profile before, during and after the appearance of the psychiatric disorder; hence, an abrupt shift from hyperthyroidism to euthyroidism or hypothyroidism cannot be excluded. In addition, patients underwent specific psychiatric therapy, so that it is difficult to attribute the disappearance of the mental disorders to the withdrawal of ATD per se. Patients who develop mental disorders while under ATD should be followed by an accurate evaluation of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) levels throughout the course of the psychiatric disease. The use of new imaging techniques could be helpful in ruling out the encephalopathy associated with autoimmune thyroid diseases and other cerebral pathologies that might be possible causes of these mental disorders.


Amniotic fluid lamellar body count and its sensitivity and specificity in evaluating of fetal lung maturity.
This prospective study was designed to perform lamellar body count of amniotic fluid to evaluate fetal lung maturity. Lamellar body counts of 80 amniotic fluid samples from 80 pregnant women (28-40 weeks of gestation) were evaluated. After delivery, each infant was evaluated for any evidence of respiratory distress syndrome. Standard clinical and radiographic criteria were used to diagnose respiratory distress syndrome, and the diagnosis was confirmed by reviewing newborn records. Twenty (25%) infants delivered within 24 hours of sample collection developed RDS. Lamellar body count more than 50,000/microl predicted pulmonary maturity. Seventeen out of 20 respiratory distress syndrome cases had been predicted correctly. The negative predictive value of lamellar body count>50,000/microl was 93% and positive predictive value was 48% and the sensitivity for prediction of RDS was 85% and specificity was 70%. Lamellar body count can be used as a favourable predictor of fetal lung maturity because it is quick, simple and universally available. Also it can be used as an extremely inexpensive, reliable screening test for evaluating fetal lung maturity.


Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia.
HIF-1alpha is the regulated subunit of the HIF-1 transcription factor, which induces transcription of a number of genes involved in the cellular response to hypoxia. The HIF-1alpha protein is rapidly degraded in cells supplied with adequate oxygen but is stabilized in hypoxic cells. Using polysome profile analysis, we found that translation of HIF-1alpha mRNA in NIH3T3 cells is spared the general reduction in translation rate that occurs during hypoxia. To assess whether the 5'UTR of the HIF-1alpha mRNA contains an internal ribosome entry site (IRES), we constructed a dicistronic reporter with the HIF-1alpha 5'UTR inserted between two reporter coding regions. We found that the HIF-1alpha 5'UTR promoted translation of the downstream reporter, indicating the presence of an IRES. The IRES had activity comparable to that of the well-characterized c-myc IRES. IRES activity was not affected by hypoxic conditions that caused a reduction in cap-dependent translation, and IRES activity was less affected by serum-starvation than was cap-dependent translation. These data indicate that the presence of an IRES in the HIF-1alpha 5'UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation.


Perceived heaviness in the context of Newton's Second Law: Combined effects of muscle activity and lifting kinematics.
Researchers generally agree that perceived heaviness is based on the actions associated with unsupported holding. Psychophysical research has supported this idea, as has psychophysiological research connecting muscle activity to the perceptions of heaviness and effort. However, the role of muscle activity in the context of the resulting motions has not been investigated. In the present study, perceptions of heaviness were recorded along with the electromyogram (EMG) of the lifting muscle and peak acceleration of the lift. Consistent with predictions derived from Newton's Second Law of motion (Force=Mass × Acceleration), normal and illusory perceptions of heaviness were a function of the ratio of muscle activity to lifting acceleration. These results identify a psychophysiological mechanism for heaviness perception based on the forces and motions associated with unsupported holding.


circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis.
Circular RNA (circRNA) THBS1 has been shown to exist as an oncogene in non-small-cell lung cancer, but its role in cervical cancer is still unclear. Our experiment aimed to uncover the functions and specific mechanism of circRNA THBS1 in cervical cancer cells. Levels of circRNA THBS1 and miR-543 in cervical cancer tissues and cell lines were assessed by RT-qPCR. starBase and dual luciferase reporter gene assay were applied for investigating the correlation between miR-543 and circRNA THBS1/HMGB2. Cell proliferation and apoptosis were evaluated by MTT and flow cytometry, respectively. Furthermore, the levels of HMGB2, E-cadherin, and N-cadherin in HeLa cells were determined by RT-qPCR and western blot analysis. Our data revealed that circRNA THBS1 was significantly upregulated and miR-543 was low expressed in cervical cancer tissues and cell lines. circRNA THBS1 interacted with miR-543 and negatively regulated miR-543 expression in HeLa cells. Silencing of circRNA THBS1 remarkably suppressed HeLa cells' viability, accelerated cells' apoptosis, and inhibited the EMT of HeLa cells, while these changes were reversed by miR-543 inhibitor. Moreover, miR-543 affected HeLa cells by targeting HMGB2. In conclusion, circRNA THBS1 silencing inhibited the malignant biological behaviors of cervical cancer cells via the regulation of miR-543/HMGB2 axis.


Feasibility of detecting aflatoxin B1 on inoculated maize kernels surface using Vis/NIR hyperspectral imaging.
The feasibility of using a visible/near-infrared hyperspectral imaging system with a wavelength range between 400 and 1000 nm to detect and differentiate different levels of aflatoxin B1 (AFB1 ) artificially titrated on maize kernel surface was examined. To reduce the color effects of maize kernels, image analysis was limited to a subset of original spectra (600 to 1000 nm). Residual staining from the AFB1 on the kernels surface was selected as regions of interest for analysis. Principal components analysis (PCA) was applied to reduce the dimensionality of hyperspectral image data, and then a stepwise factorial discriminant analysis (FDA) was performed on latent PCA variables. The results indicated that discriminant factors F2 can be used to separate control samples from all of the other groups of kernels with AFB1 inoculated, whereas the discriminant factors F1 can be used to identify maize kernels with levels of AFB1 as low as 10 ppb. An overall classification accuracy of 98% was achieved. Finally, the peaks of β coefficients of the discrimination factors F1 and F2 were analyzed and several key wavelengths identified for differentiating maize kernels with and without AFB1 , as well as those with differing levels of AFB1 inoculation. Results indicated that Vis/NIR hyperspectral imaging technology combined with the PCA-FDA was a practical method to detect and differentiate different levels of AFB1 artificially inoculated on the maize kernels surface. However, indicated the potential to detect and differentiate naturally occurring toxins in maize kernel.


Further evaluation of the factor structure, prevalence, and concurrent validity of DSM-5 criteria for Persistent Complex Bereavement Disorder and ICD-11 criteria for Prolonged Grief Disorder.
Persistent complex bereavement disorder (PCBD) is a disorder of grief included in DSM-5. Prolonged grief disorder (PGD) is included in ICD-11. Few studies have evaluated and compared criteria sets for DSM-5 PCBD and ICD-11 PGD. The current study explored and compared the dimensionality, prevalence rates, diagnostic agreement, concurrent validity, and socio-demographic and loss-related correlates of both criteria sets. Self-reported data were available from 551 bereaved individuals. Confirmatory factor analysis showed that for DSM-5 PCBD-symptoms, a three-factor model with distinct but correlated factors fit the data well; for ICD-11 PGD-symptoms a one-factor model yielded adequate fit. The prevalence of probable DSM-5 PCBD (8.2%) was significantly lower than ICD-11 PGD (19.2%). Both DSM-5 PCBD and ICD-11 PGD were significantly associated with concurrent overall grief and depression, and varied as a function of education and time since loss. ICD-11 PGD prevalence rates went down and agreement with PCBD-caseness went up, when heightening the number of symptoms required for an ICD-11 PGD diagnosis. This study was limited by its reliance on self-reported data and grief symptoms were derived from two scales. That notwithstanding, findings provide further evidence that differences exist between disturbed grief criteria in DSM-5 and ICD-11 that may negatively impact research and care.


A single-base deletion in soybean flavonol synthase gene is associated with magenta flower color.
The Wm locus of soybean [Glycine max (L.) Merr.] controls flower color. Dominant Wm and recessive wm allele of the locus produce purple and magenta flower, respectively. A putative full-length cDNA of flavonol synthase (FLS), gmfls1 was isolated by 5' RACE and end-to-end PCR from a cultivar Harosoy with purple flower (WmWm). Sequence analysis revealed that gmfls1 consisted of 1,208 nucleotides encoding 334 amino acids. It had 59-72% homology with FLS proteins of other plant species. Conserved dioxygenase domains A and B were found in the deduced polypeptide. Sequence comparison between Harosoy and Harosoy-wm (magenta flower mutant of Harosoy; wmwm) revealed that they differed by a single G deletion in the coding region of Harosoy-wm. The deletion changed the subsequent reading frame resulting in a truncated polypeptide consisting of 37 amino acids that lacked the dioxygenase domains A and B. Extracts of E. coli cells expressing gmfls1 of Harosoy catalyzed the formation of quercetin from dihydroquercetin, whereas cell extracts expressing gmfls1 of Harosoy-wm had no FLS activity. Genomic Southern analysis suggested the existence of three to four copies of the FLS gene in the soybean genome. CAPS analysis was performed to detect the single-base deletion. Harosoy and Clark (WmWm) exhibited longer fragments, while Harosoy-wm had shorter fragments due to the single-base deletion. The CAPS marker co-segregated with genotypes at Wm locus in a F(2) population segregating for the locus. Linkage mapping using SSR markers revealed that the Wm and gmfls1 were mapped at similar position in the molecular linkage group F. The above results strongly suggest that gmfls1 represents the Wm gene and that the single-base deletion may be responsible for magenta flower color.


Similarities and differences between atrial flutter and atrial fibrillation.
Atrial flutter and atrial fibrillation have a complex relationship that has mechanistic, diagnostic, therapeutic and prognostic components. While thromboembolic risk management and pharmacological strategies share many similarities, there are important differences. Radiofrequency ablation should be considered to be an early, first-line alternative to pharmacological strategies for many patients with atrial flutter.


CD4+CD25+FoxP3+PD1- regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy.
The intracellular expression of the programmed death receptor 1 (PD1) identifies a subset of naive T(reg) cells with enhanced suppressive ability; antigen stimulation results in the surface expression of PD1. Because the role of T(reg) impairments in multiple sclerosis (MS) is still contradictory, we analyzed naive PD1- and PD1+ T(reg) cells in peripheral blood and cerebrospinal fluid (CSF) of relapsing-remitting multiple sclerosis (RR-MS) patients and of healthy control subjects. Results showed that 1) CSF PD1- T(reg) cells were significantly augmented in MS patients; 2) PD1- T(reg) cells were significantly increased in the peripheral blood of patients with stable disease (SMS) compared to those with acute (AMS) disease, and in patients responding to glatiramer acetate (COPA) compared to AMS- and COPA-unresponsive patients; and 3) PD1+ T(reg) cells were similar in CSF and peripheral blood of all groups analyzed. PD1- T(reg) cells were not increased in the peripheral blood of interferon-beta (IFNbeta) -responsive patients, but the suppressive ability of T(reg) cells was significantly higher in SMS and in COPA- or IFNbeta-responsive compared to AMS- and COPA-unresponsive individuals. The data herein suggest that PD1- T(reg) cells play a pivotal role in MS and offer a biological explanation for disease relapse and for the mechanism associated with response to COPA and IFNbeta.


Phosphorylation of calmodulin alters its potency as an activator of target enzymes.
Previous work has shown that calmodulin (CaM) is constitutively phosphorylated in rat liver, probably by casein kinase II [Quadroni, M., James, P., and Carafoli, E. (1994) J. Biol. Chem. 269, 16116-16122]. A procedure is now described for the isolation of the phosphorylated forms of calmodulin (PCaM) free from CaM, since in vitro phosphorylation experiments yield a 50:50 mixture of 3-4 times phosphorylated CaM and native CaM. The activation of six target enzymes by PCaM was tested: myosin light chain kinase, 3',5'-cyclic nucleotide phosphodiesterase, plasma membrane Ca2+-ATPase, Ca2+-CaM-dependent protein phosphatase 2B (calcineurin), neuronal nitric oxide synthase, and CaM-kinase II. In general, the phosphorylation of CaM caused a decrease in enzyme binding affinity, increasing the Kact by 2-4-fold for MLCK, PDE, PM Ca2+-ATPase, and calcineurin. The Vmax at saturating concentrations of PCaM was less affected, with the exception of CaM-kinase II, which was only minimally activated by PCaM and NOS whose Vmax was increased 2.6 times by PCaM with respect to CaM. Phosphorylation of calmodulin had very little effect on the binding of calcium to the enzyme despite the fact that Ser 101 which is phosphorylated is located in the third calcium binding loop. CD measurements performed on CaM and PCaM indicated that phosphorylation causes a marked decrease in the alpha-helical content of the protein. Phosphorylated CaM is very prone to dephosphorylation and was thus tested as a substrate for several phosphatases. It was unaffected by calcineurin (PP2B), but was a reasonable substrate for the pleiotropic phosphatases PP1gamma and PP2A.


Interstitial pneumonia; a pathologic concept.
Interstitial pneumonias present a pulmonary inflammatory reaction pattern that is common to a wide variety of noxious agents and disease processes. These include viruses, Rickettsiae, hypersensitivity reactions, the "collagen disease," x-irradiation, uremia, certain chemicals, early histoplasmosis, toxoplasmosis and possibly unknown substances and diseases. Interstitial pneumonia is characterized histologically by interalveolar exudate, hyaline membranes, epithelialization of alveolar walls and lack of polymorphonuclear response. Histologic features that aid in differentiating among cases of varying etiology are few. It is postulated that the basic pathogenic mechanism of the interstitial inflammatory reaction is primary damage to pulmonary capillary endothelium that brings about increased capillary permeability.


Cost-effectiveness of Catheter Ablation Versus Antiarrhythmic Drug Therapy for the Treatment of Atrial Fibrillation: A Canadian Perspective.
Background: Atrial fibrillation (AF) affects approximately 350,000 Canadians and has an estimated annual economic burden exceeding $800 million dollars. Anti-arrhythmic drug (AAD) therapy and catheter ablation (CA) are the two common treatments for paroxysmal AF. However, the upfront costs of CA are quite substantial. Objective: The objective of this study was to assess the cost-effectiveness of CA compared to AAD for AF based on community practice. Methods: A Markov simulation model was developed for a hypothetical cohort of 55-year-old patients with paroxysmal AF and a low stroke risk. Patients received either CA or AAD. Costs and quality-adjusted life years (QALYs) were computed over lifetime, 10-year, and 5-year time horizons. Model inputs were obtained from a large, prospectively collected, single-center Canadian registry and augmented with the published literature, using Canadian cost estimates for disease states. Threshold values of $25,000, $50,000, and $100,000 per QALY, respectively, were used to determine cost-effectiveness. All costs were expressed in 2012 Canadian dollars. Results: The incremental cost-effectiveness ratio for CA versus AAD therapy was $1,228, $22,879, and $63,647 for the lifetime, 10-year, and 5-year time horizons, respectively. Over a lifetime horizon, the probability of achieving cost-effectiveness was 100% for all 3 cost per QALY thresholds. The 10-year probability of achieving cost-effectiveness was 74%, 100%, and 100% at the $25,000, $50,000, and $100,000 thresholds, respectively. The 5-year probability of achieving cost-effectiveness was 0%, 0.9%, and 100% at the 3 cost per QALY thresholds. Results were most sensitive to time horizon, probability of repeat AF ablation, and stroke rate. Conclusions: From the perspective of the Canadian Healthcare system, CA is a potentially cost-effective treatment compared to AAD therapy in a low stroke risk population using real-world data when examining a time horizon of greater than 5 years.


Thermal therapies in interventional MR imaging. Focused ultrasound.
MR image-guided focused ultrasound (FUS) provides an entirely noninvasive approach for local thermal therapies. MR imaging allows target definition and continuous temperature mapping. Therefore, the heating procedure can be controlled spatially and temporally based on automatic feedback to the FUS apparatus. Phased-array ultrasound technology will further help the development. MR imaging/FUS may be applied not only for tissue ablation, but also for local drug delivery, gene therapy, and drug activation.


Using the microbiology laboratory in the diagnosis of pneumonia.
Pneumonia/influenza is one of the top ten leading causes of mortality in the United States each year. The identification of the etiologic agent responsible for lower respiratory tract infection plays an important role in the proper management of this clinical problem. The specimens submitted for evaluation are obtained in diverse ways and include expectorated sputum, material from transtracheal and bronchoscopic procedures, pleural fluid and lung aspirates, and biopsy of actual lung tissue. Processing of material can include stained smears, aerobic and anaerobic cultures, and special processing techniques for fungal, viral, Pneumocystis carinii, Legionella, mycobacterial, and mycoplasma identification. Modifications of smear preparation techniques and application of the new DNA probe technology are providing the opportunity for rapid microbiologic testing of clinical specimens with increased sensitivity and specificity, often obviating the need for invasive diagnostic procedures. Laboratory methodology is continually undergoing technological change, and optimal care of the patient with pneumonia requires close cooperation between the attending physician and the clinical laboratory.


Impaired social behaviors and minimized oxytocin signaling of the adult mice deficient in the N-methyl-d-aspartate receptor GluN3A subunit.
The N-methyl-d-aspartate receptor (NMDAR) has been implicated in the pathophysiology of neurological diseases, such as schizophrenia, autism spectrum disorders (ASD), and Alzheimer's disease (AD), whose unique clinical hallmark is a constellation of impaired social and/or cognitive behaviors. GluN3A (NR3A) is a unique inhibitory subunit in the NMDAR complex. The role of GluN3A in social behavioral activities is obscure. In this study, we sought to evaluate altered social activities in adult GluN3A knockout (KO) mice. GluN3A KO mice spent less time in reciprocal social interaction in the social interaction test compared to wild-type (WT) mice. A social approach test using a three-chamber system confirmed that mice lacking GluN3A had lower sociability and did not exhibit a preference for social novelty. GluN3A KO mice displayed abnormal food preference in the social transmission of food preference task and low social interaction activity in the five-trial social memory test, but without social memory deficits. Using a home cage monitoring system, we observed reduced social grooming behavior in GluN3A KO mice. Signaling genes that might mediate the altered social behaviors were examined in the prefrontal cortex, hippocampus, and thalamus. Among nine genes examined, the expression of the oxytocin receptor was significantly lower in the prefrontal cortex of GluN3A KO mice than that in WT mice. Oxytocin treatment rescued social activity deficits in GluN3A KO mice. These findings support a novel idea that a chronic state of moderate increases in NMDAR activities may lead to downregulation of the oxytocin signaling and impaired behavioral activities that are seen in psychiatric/neurodegenerative disorders.


Evidence-Based Care of Older Adults With Metastatic Colorectal Cancer: Insights From Landmark Clinical Trials.
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States with more than half of the patients diagnosed being older than 65 years, and an expected further increase in older adults (OA) diagnosed with this cancer in the coming years as the population ages. Prospective data guiding the management of older patients with metastatic CRC (mCRC) have been limited and treatment decisions for these patients are often guided by chronologic age, crude evaluation of performance status, and extrapolation from trials conducted in younger individuals. Recent evidence from randomized clinical trials specifically designed for OA supports treatment deintensification and dose modification to increase tolerability without compromising efficacy in older, frailer patients with mCRC. Additional studies support the incorporation of geriatric assessment (GA)-driven care to further improve the outcomes of OA with mCRC. Although the use of GA has not been validated in guiding specific treatment selection or modification for OA with mCRC, it provides a comprehensive and objective evaluation of a patient's functional status, comorbidities, risk of potential toxicities, effect on the quality of life, goals of care, and assists with personalizing therapy. With the increase in the number of OA we care for in our practices, it is time to stop extrapolating and define an evidence-based approach for this population that is based on data from prospective elderly specific clinical trials.


[Effects of copper mine tailings on seed germination and seedling growth of five legumes species].
Through solution culture and soil culture experiments, effects of Tongling copper mine tailings on seed germination and seeding growth of five legumes species were studied in this paper. The results showed that the seeds of five legumes species could germinate in the normal and acidified tailings extracted solution, but germination percentage was lower than that under control. It indicated that tailings extracted solution had inhibition effect on seed germination, however, acidified tailings extracted solution promoted absorbing water of the seeds in early stage. In five amelioration substrates between tailings and soils, the tailings also inhibited seed germination of the five species. No dead seedlings of Glycine max, Phaseolus angularis, P. calacaratus were found within 70 days.


A mouse model for evaluation of efficacy and concomitant toxicity of anti-human CXCR4 therapeutics.
The development of therapeutic monoclonal antibodies through mouse immunization often originates drug candidates that are not cross-reactive to the mouse ortholog. In such cases, and particularly in oncology, drug efficacy studies are performed on human tumor xenografts or with "surrogate" anti-mouse ortholog antibodies if targeting tumor host cells. Safety assessment of drug candidate(s) is performed at a later development stage in healthy non-human primates. While the latter remains necessary before a drug advances into human subjects, it precludes evaluation of safety in disease conditions and drug de-risking during early development. Therefore, mouse models that allow concomitant evaluation of drug efficacy and safety are highly desirable. The C-X-C motif chemokine receptor 4 (CXCR4) is an attractive target for tumor-targeted and immuno-oncology therapeutics, with multiple mouse immunization-derived antibodies undergoing clinical trials. Given the pleiotropic role of CXCR4 in cancer biology, we anticipate continuous interest in this target, particularly in the testing of therapeutic combinations for immuno-oncology. Here, we describe the generation and validation of the first mouse knock-in of the whole coding region of human CXCR4. Homozygous human CXCR4 knock-in (hereafter designated as HuCXCR4KI) mice were viable and outwardly healthy, reproduced normally and nursed their young. The expression pattern of human CXCR4 in this model was similar to that of CXCR4 expression in normal human tissues. The human CXCR4 knock-in gene was expressed as a biologically active protein, thereby allowing normal animal development and adequate"homing" of leukocytes to the bone marrow. To further validate our model, we used an in vivo functional assay of leukocyte mobilization from bone marrow to peripheral blood by blocking CXCR4 signaling. Both an anti-human CXCR4 -specific blocking antibody and the small molecule CXCR4 inhibitor AMD3100 induced increased leukocyte counts in peripheral blood, whereas an anti-mouse CXCR4 -specific blocking antibody had no effect. This new mouse model is useful to evaluate efficacy and safety of anti-human CXCR4 -specific drugs as single agents or in combination therapies, particularly in the oncology, immuno-oncology, wound healing and chronic inflammation therapeutic areas.


Characterization of viral inhibitory substance released from fused splenocyte.
The D variant of the encephalomyocarditis (EMC-D) virus is diabetogenic in mice by infecting and destroying pancreatic beta cells, but the EMC-B and EMC-DV viruses are not diabetogenic. We have presumed that the nondiabetogenicity of EMC-B and EMC-DV is mainly caused by release of some viral inhibitory factors from lymphocytes or phagocytic cells. Mice were infected with EMC-B and their splenocytes were fused with myeloma cells. The splenocyte hybridoma 12D8 releases the viral inhibitory substance (VIS) which is neither immunoglobulin nor interferon. VIS has inhibitory effects against EMC-D in several kinds of cell lines, and against EMC-D, EMC-B, coxsackie B4, reovirus and the vesicular stomatitis virus in the L cell. VIS has a strong preventive effect (100%) against EMC-D induced diabetes in SJL/J mice and DBN/2N mice. In both pre- and post-treatment studies, VIS remarkably decreased the incidence of both illness and death in SJL/J mice infected with the EMC-D virus. VIS, culture supernate itself of hybridoma, had viral inhibitory activities equivalent to 10(6)-10(7) IU/ml of interferon. VIS was very labile to heat (75% loss of activities at 37 degrees C for 18 h), stable only at pH 5-9, and precipitated at 50% (NH4)2SO4 solution. VIS activities existed in supernatant and pellet prepared from ultracentrifugation, but the properties of their activities could be differentiated quantitatively and qualitatively. It is speculated that VIS may be composed of at least two factors even though interferon may partially participate in one component of supernatant. The prevention and treatment effect of VIS on EMC-D infection in SJL/J mice might be due to the inhibition of the virus replication by VIS.


Effect of Postoperative Specific Immunotherapy Combined with Nasal Irrigation on Chronic Rhinosinusitis with Allergic Rhinitis.
Patients with chronic rhinosinusitis (CRS) and allergic rhinitis (AR) (CRSwAR) have a more severe condition with a higher rate of recurrence after endoscopic sinus surgery (ESS). This study aimed to explore the effect of specific subcutaneous immunotherapy (SCIT) and nasal irrigation on CRSwAR after ESS. Sixty-four patients who were diagnosed as CRSwAR and received ESS were enrolled and divided into groups A, B, and C to receive different postoperative treatment strategies (conventional medication, medication with nasal irrigation, and medication with nasal irrigation and SCIT), and their prognosis was evaluated by scoring, electron microscopy, and inflammatory factors. One year after ESS, the recurrence rate of group C was significantly reduced; and the scoring from baseline was significantly different among the three groups, which of group C were the best. The epithelium arrangement, cilia morphology, and inflammation of nasal mucosa in each group were better than those in the preoperative state; and those in group C were the best. After one year, the expression levels of eosinophil cationic protein (ECP), interleukin (IL)-8, and IL-17 in group B were lower than those of group A; and the expression levels of ECP, IL-8, IL-25, IL-33, IL-17 in group C were lower than those in group A. SCIT combined with nasal irrigation can improve the patients' symptoms and quality of life, promote the epithelialization of the mucosa in the surgical cavity, regulate the local immune response of the nasal cavity; thus improve the prognosis of patients with ESS after 1 year.


Controlled Ni-catalyzed mono- and double-decarbonylations of α-ketothioesters.
A method for Ni-catalyzed controlled decarbonylation of α-ketothioesters is described. Mono- and double-decarbonylations, which gave thioesters and thioethers, respectively, were selectively achieved by changing the ligand. A fundamental study of Ni-catalyzed decarbonylation of α-ketothioesters is presented.


Induced changes in the antioxidative compounds of Vigna mungo genotypes due to infestation by Bemisia tabaci (Gennadius).
Antioxidative compounds were quantified from the leaves of nine black gram (Vigna mungo (L.) Hepper) genotypes over a period of two years, for potential whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleryrodidae) resistance. Oviposition preference, nymphal and adult development were evaluated under screen-house conditions. Biochemical analysis revealed that higher per cent increase in the total phenol and o-dihydroxy phenol contents both at 30 and 50 days after sowing was evident in moderately resistant genotypes NDU 5-7 (49.6 and 50.8%, respectively) and KU 99-20 (47.8 and 50.8%, respectively) under whitefly stress conditions as compared to non-stressed plants. Tannin and flavonol contents in leaves increased to varying degrees (up to 11.1 and 7.1%, respectively) in resistant plants after whitefly infestation, indicating that the changes in tannin and flavonol contents were closely associated with the resistance to whitefly. Correlation studies relating leaf content of black gram antioxidative compounds from different genotypes with whitefly population were also worked out. Total phenols (r = -0.71 & -0.88), o- dihydroxy phenols (r = -0.56 & -0.76), flavonols (r = -0.80 & -0.81) and tannins (r= -0.16 & -0.26) showed significant negative correlation with whitefly population (nymphs and adults) suggesting that enhanced level of these biochemicals may contribute to bioprotection of black gram plants against B. tabaci infestation. Comparatively higher level of resistance in genotype NDU 5-7 and KU 99-20 can serve as base for genetic improvement of black gram, focusing on the development of resistant varieties to B. tabaci.


Temporal discounting in children and adolescents with and without attention-deficit/hyperactivity disorder: a comparison of four scoring methods.
Temporal discounting (TD) tasks measure the preference for immediate rewards over larger delayed rewards and have been widely used to study impulsivity in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Relatively impulsive individuals tend to show high inconsistency in their choices, which makes it difficult to determine commonly used TD outcome measures (e.g., area under the curve, AUC). In this study, we leveraged two published datasets to compare four methods to compute TD outcome measures in children and adolescents (8-17 years) with (n = 107) and without ADHD (n = 128): two predetermined rules methods, a proportion method, and logistic regression. In both datasets, when using the two predetermined rules methods and the proportion method, TD outcomes were highly correlated and group differences in TD were similar. When using logistic regression, a large proportion of AUCs (95% in dataset 1; 33% in dataset 2) could not be computed due to inconsistent choice patterns. These findings indicate that predetermined rules methods (for studies with small sample sizes and experienced raters) and a proportion method (for studies with larger sample sizes or less experienced raters) are recommended over logistic regression when determining subjective reward values for participants with inconsistent choice patterns.


Regular exercise modulates cardiac mast cell activation in ovariectomized rats.
It is well accepted that regular exercise is a significant factor in the prevention of cardiac dysfunction; however, the cardioprotective mechanism is as yet not well defined. We have examined whether regular exercise can modulate the activity of cardiac mast cells (CMC) after deprivation of female sex hormones, as well as the density and percentage degranulation of mast cells, in ventricular tissue of ovariectomized (OVX) rats after an 11-week running program. A significant increase in CMC density with a greater percentage degranulation was induced after ovarian sex hormone deprivation. Increased CMC density was prevented by estrogen supplements, but not by regular training. To the contrary, increased CMC degranulation in the OVX rat heart was attenuated by exercise training, but not by estrogen supplement. These findings indicate a significant correlation between the degree of CMC degranulation and myocyte cross-section area. However, no change in the expression of inflammatory mediators, including chymase, interleukin-6, and interleukin-10, was detected. Taken together, these results clearly indicate one of the cardioprotective mechanisms of regular aerobic exercise is the modulation of CMC activation.


Interaction of strong DNA-intercalating bioreductive compounds with topoisomerases I and II.
Nitro(imidazole/triazole)-linked acridines (NLAs) have been previously developed in our laboratory as DNA-intercalating bioreductive drugs. Such compounds demonstrate toxicity through the formation of bulky monoadducts with cellular macromolecules upon activation and reductive metabolism under hypoxic conditions. However, NLAs also demonstrate considerable aerobic toxicity. Based on the ability of NLAs to bind strongly to DNA through intercalation, we investigated whether their relatively high aerobic cytotoxicity and their relatively low hypoxic selectivity in vitro are associated with topoisomerases I and II (Topo I and II) inhibition. DNA Topo I or II-mediated activity studies have been performed using supercoiled or kinetoplast DNA plasmids. Calf thymus or human Topo I and human Topo II purified enzymes were used. All NLA derivatives strongly inhibited relaxation of supercoiled DNA catalyzed by either Topo I or II, in a concentration-dependent manner, without stabilization of a cleavable complex. Aerobic toxicity correlated well with the inhibition of Topo II-mediated decatenation of kinetoplast DNA, whereas the intracellular concentrations of NLAs were 27-152-fold greater than those needed for 50% inhibition of Topo-II mediated decatenation of DNA. These results suggest that topoisomerase inhibition accounts for NLAs aerobic toxicity.


Alterations in circulating human chorionic gonadotropin free alpha-subunit in insulin-dependent diabetic pregnancy: correlation with maternal characteristics.
Circulating concentrations of hCG free alpha-subunit (alpha hCG) increase throughout pregnancy. To address the hypothesis that maternal plasma alpha hCG may reflect placental dysfunction and/or adverse perinatal outcome during insulin-dependent diabetic pregnancy, alpha hCG was measured serially throughout gestation, beginning before week 12, with a specific RIA using a monoclonal antibody in 54 insulin-dependent diabetic (randomly assigned to strict and customary glycemic control) and 25 nondiabetic pregnancies. alpha hCG was significantly lower in pregnant insulin-dependent diabetic subjects than in nondiabetics subjects until 24 weeks gestation, after which it was higher until delivery. Plasma alpha hCG stabilized in nondiabetics at 32 weeks, whereas it continued to increase in diabetics until delivery, at which time it was 37% greater than that in nondiabetics (mean +/- SE, 1441 +/- 90 vs. 1052 +/- 78 micrograms/L; P less than 0.002). Values in diabetic subjects assigned to strict control were intermediate between those in diabetic subjects assigned to customary control and nondiabetic subjects. alpha hCG was greater in diabetic subjects with pregestational hypertension or microvascular disease, but not in those with pregnancy-induced hypertension. These findings were independent of the assigned goals of glycemic control. alpha hCG was not correlated with the duration of diabetes or related to premature delivery, fetal distress, birth asphyxia, or macrosomia. Thus, alpha hCG is increased during the third trimester of the type I diabetic pregnancy and is associated with preexisting hypertension and maternal microangiopathy, but is not a predictor of adverse perinatal outcome. Excessive alpha hCG secretion in diabetes may share pathophysiological mechanisms in common with those underlying diabetic microangiopathy.


[Metabolism of calcium in sarcoidosis].
Sarcoidosis is a multisystemic disease of unknown etiology with characteristic picture of immunological disorders. As an unfavourable course of the disease both fibrosis and abnormal calcium metabolism may occur. The last one is reflected by hypercalcemia and/or hypercalcuria. In this paper the recent advances in the explanation of pathogenesis of impaired calcium homeostasis in patients with sarcoidosis have been reviewed. The evaluation of calcium concentration in urine and plasma, production rate of vitamin D metabolites, isolation and structural identification of 1,25 dihydroxy vitamin D3 as well as regulation of its synthesis by pulmonary alveolar macrophages from patients with sarcoidosis have been discussed. Subsequently, vitamin D metabolism by sarcoid lymph node and application of steroids and chloroquine for the treatment of disturbed calcium metabolism has been presented.


The future of Catholic health care: observations from an Orthodox Christian perspective.
The author reflects on the future of Catholic health care by looking at the essays in this volume by Dennis Brodeur, Clarke E. Cochran, and Christopher J. Kauffman. The author argues that (1) Roman Catholic teaching on the Trinity is defective, yielding an inadequate model of society, (2) Roman Catholic teaching on the Incarnation is defective, yielding an impoverished understanding of the "sacramental," and (3) the institutional orientation of Roman Catholicism combined with the lack of true sacramental vision makes it nearly impossible for Roman Catholic theory to criticize the current structure of health care financing.


Multivariate autoregressive model constrained by anatomical connectivity to reconstruct focal sources.
In this paper, we present a framework to reconstruct spatially localized sources from Magnetoencephalography (MEG)/Electroencephalography (EEG) using spatiotemporal constraint. The source dynamics are represented by a Multivariate Autoregressive (MAR) model whose matrix elements are constrained by the anatomical connectivity obtained from diffusion Magnetic Resonance Imaging (dMRI). The framework assumes that the whole brain dynamic follows a constant MAR model in a time window of interest. The source activations and the MAR model parameters are estimated iteratively. We could confirm the accuracy of the framework using simulation experiments in both high and low noise levels. The proposed framework outperforms the two-stage approach.


Do fibrin sealants impact negative outcomes after robot-assisted partial nephrectomy?
Contemporary rates of postoperative hemorrhage after partial nephrectomy (PN) are low. Commercially available hemostatic agents are commonly used during this surgery to reduce this risk despite a paucity of data supporting the practice. We assessed the impact of fibrin sealant hemostatic agents, a costly addition to surgeries, during robot-assisted partial nephrectomy (RAPN). Between 2007 and 2011, 114 consecutive patients underwent RAPN by a single surgeon (MEA). Evicel fibrin sealant was used in the first 74 patients during renorraphy. The last 40 patients had renorraphy performed without the use of any hemostatic agents. Clinicopathologic, operative, and complication data were compared between groups. Multivariate and univariate logistic regression analysis was performed to test the association between the use of fibrin sealants and operative outcomes. Patient demographic data and clinical tumor characteristics were similar between groups. The use of fibrin sealant did not increase operative time (166.3 vs 176.1 minutes, P=0.28), warm ischemia time (WIT) (14.4 vs 16.1 minutes, P=0.18), or length of hospital stay (2.6 vs 2.4 days, P=0.35). The omission of these agents did not increase estimated blood loss (116.6 vs 176.1 mL, P=0.8) or postoperative blood transfusion (0% vs 2.5%, P=0.17). Univariate analysis demonstrated no association between use of fibrin sealants and increased complications (P>0.05). Multivariable logistic regression showed no statistically significant predictive value of omission of hemostatic agents for perioperative outcomes (P>0.05). Perioperative hemorrhage and other major complications after contemporary RAPN are rare in experienced hands. In our study, the use of fibrin sealants during RAPN does not decrease the rate of complications, blood loss, or hospital stay. Furthermore, no impact is seen on operative time, WIT, or other negative outcomes. Omitting these agents during RAPN could be a safe, effective, cost-saving measure.


Understanding HIV infection for the design of a therapeutic vaccine. Part II: Vaccination strategies for HIV.
HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies.


Significance of the Fanconi anemia FANCD2 protein in sporadic and metastatic human breast cancer.
FANCD2, a pivotal protein in the Fanconi anemia and BRCA pathway/network, is monoubiquitylated in the nucleus in response to DNA damage. This study examines the subcellular location and relationship with prognostic factors and patient survival of FANCD2 in breast cancer. Antibodies to FANCD2 were used to immunocytochemically stain 16 benign and 20 malignant breast specimens as well as 314 primary breast carcinomas to assess its association with subcellular compartment and prognostic factors using Fisher's Exact test or with patient survival over 20 years using Wilcoxon-Gehan statistics. Immunoreactive FANCD2 was found in the nucleus and cytoplasm of all 16 benign tissues, but nuclear staining was lost from a significant 19/20 malignant carcinomas (P < 0.0001). Antibodies to FANCD2 stained the cytoplasm of 196 primary carcinomas, leaving 118 as negatively stained. Negative cytoplasmic staining was significantly associated with positive staining for the metastasis-inducing proteins S100A4, S100P, osteopontin, and AGR2 (P < or = 0.002). Survival of patients with FANCD2-negative carcinomas was significantly worse (P < 0.0001) than those with positively stained carcinomas, and only 4% were alive at the census date. Multivariate regression analysis identified negative staining for cytoplasmic FANCD2 as the most significant indicator of patient death (P = 0.001). Thus FANCD2's cytoplasmic loss in the primary carcinomas may allow the selection of cells overexpressing proteins that can induce metastases before surgery.


[Hypereosinophilia in premature newborn infants].
Eosinophilia is a common finding in premature babies during the neonatal period (75%). It has a variable correlation with several factors that may influence it: gestational age, birth weight, time required to regain birthweight, neonatal stress, caesarean birth, formula feeding, endotracheal intubation, positive pressure ventilation, parenteral nutrition, umbilical catheterization, blood transfusions, antibiotics, phototherapy, sex, neutropenia and sepsis. The possible mechanisms are discussed: resolution of a stress, anabolic state, reaction to antigens, normal granulopoietic maturation, transplacental transfer of a factor stimulating the eosinophil synthesis.


Acute daily exposure to ambient air pollution impairs endothelium-dependent vasodilator responses in young, healthy individuals.
Exposure to ambient air pollution influences cardiovascular (CV) morbidity and mortality. The differential effects of changing particulate or gaseous air pollution on endothelial function in young healthy individuals remain unclear. The aim of this study was to evaluate the relationships between exposures to different pollutants and vascular function in a group of 39 young (33±11 years old) subjects with low CV risk. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were performed, when air pollution reached highest levels (heating period) and repeated in a subgroup of 18 participants a few months later (just before the heating period starts). Daily mean concentrations of PM2.5 and PM10 were inversely correlated with FMD, and this relationship remained significant after adjusting for factors known to affect vascular dysfunction. Endothelial function did not differ between the two time points studied. However, we observed a strong inverse association between the change in the concentration of particulate matter (deltaPM2.5 and deltaPM10) and the change in FMD (deltaFMD) between the two visits (R= -0.65, p= 0.02; R= -0.64, p= 0.02, respectively). In summary, we provide evidence that the concentration of PM2.5 and PM10, but not SO2, NO, NO2, CO, or O3 is associated with impaired endothelial function in young, healthy individuals.


Reaction mechanisms of Li(0.30)La(0.57)TiO3 powder with ambient air: H+/Li+ exchange with water and Li2CO3 formation.
The proton/lithium exchange property of the lithium lanthanum titanate Li(0.30)La(0.57)TiO(3) (named LLTO) is shown to occur at room temperature under ambient air. The (1)H and (7)Li MAS NMR, TGA analysis and IR spectroscopy techniques are used to probe reaction mechanisms. XRPD analysis gives evidence of the topotactic character of this exchange reaction. As for exchange in aqueous solution, it is shown that Li(0.30)La(0.57)TiO(3) is able to dissociate water on the grain surface and then to exchange H(+) for Li(+) into the perovskite structure. Lithium hydroxide is then formed on the grain surface and afterwards reacts with CO(2) contained in air to form Li(2)CO(3). It is shown that this mechanism is reversible. When the aged sample (aging in air for 5 months at room temperature) is annealed at 400 degrees C for two hours, the initial LLTO sample is totally recovered, a mass loss is observed and the carbonate signal in IR spectra disappears, demonstrating the reversibility of the carbonation reaction process.


Transmissible drug resistance of Escherichia coli and Salmonella from humans, animals, and their rural environments.
Isolates of Escherichia coli and Salmonella species obtained from humans, animals, and their rural environments were tested for their ability to transfer multiple drug resistance to competent recipients. In all, 125 (52.9%) of 242 isolates of E.coli transferred all or part of their resistance to E.coli CSH-2, and 103 (44.4%) of 232 isolates of E.coli transferred all or part of their resistance to Salmonella choleraesuis var. kuzendorf 214. The data suggest that the multiple drug resistance of E.coli transferred all or part of their resistance to Salmonella choleraesuis var kuzendorf 214. The data suggest that the multiple drug resistance of E. coli in the gut of humans who work with livestock may be due to the transfer of resistance determinants from animal strains to the resident flora of the human gut. Such transfer could occur during transient passage through the digestive tract. Multiple drug-resistant Salmonella were isolated from all sources. In all, 48 (80%) of 60 isolates of Salmonella transferred all or part of their resistance to E. coli CSH-2, and isolates of Salmonella transferred all or part of their resistance to E.coli CSH-2, and 42 (82.4%) of 51 isolates of Salmonella transferred all or part of their resistance to S. choleraesuis var, kuzendorf 214. Fifty-three (46.9%) of 113 antibiotic-sensitive isolates of E.coli possessed resistance transfer factor, and six (23.1%) of 26 isolates with resistance transfer factor mobilized resistance determinants in isolates unable to transfer drug resistance during conjugation experiments.


[Multidisciplinar approach to the management of gliomas].
Gliomas represent two thirds of all primary brain tumors. Their prognosis depends directly upon their level of differentiation. On MRI, tumoral aggressivity is highlighted by contrast uptake and the infiltrative nature of the lesion. Clinical suspicion must however be confirmed by histology and molecular markers become essential to refine the diagnosis and tailor the treatment. Isocytrate dehydrogenase (IDH) mutations, codeletion of 1p and 19q and the presence of methylation of the MGMT promoter identify a subgroup of gliomas with better prognosis and may help predict response to treatment. Management of patients with primary brain tumors should always be defined in multidisciplinar tumor boards involving neurosurgeons, oncologists, radiation oncologists, neuropathologists and neuroradiologists.


Loss of vacuolar H+-ATPase (V-ATPase) activity in yeast generates an iron deprivation signal that is moderated by induction of the peroxiredoxin TSA2.
Vacuolar H(+)-ATPases (V-ATPases) acidify intracellular organelles and help to regulate overall cellular pH. Yeast vma mutants lack V-ATPase activity and allow exploration of connections between cellular pH, iron, and redox homeostasis common to all eukaryotes. A previous microarray study in a vma mutant demonstrated up-regulation of multiple iron uptake genes under control of Aft1p (the iron regulon) and only one antioxidant gene, the peroxiredoxin TSA2 (Milgrom, E., Diab, H., Middleton, F., and Kane, P. M. (2007) Loss of vacuolar proton-translocating ATPase activity in yeast results in chronic oxidative stress. J. Biol. Chem. 282, 7125-7136). Fluorescent biosensors placing GFP under transcriptional control of either an Aft1-dependent promoter (P(FIT2)-GFP) or the TSA2 promoter (P(TSA2)-GFP) were constructed to monitor transcriptional signaling. Both biosensors were up-regulated in the vma2Δ mutant, and acute V-ATPase inhibition with concanamycin A induced coordinate up-regulation from both promoters. PTSA2-GFP induction was Yap1p-dependent, indicating an oxidative stress signal. Total cell iron measurements indicate that the vma2Δ mutant is iron-replete, despite up-regulation of the iron regulon. Acetic acid up-regulated P(FIT2)-GFP expression in wild-type cells, suggesting that loss of pH control contributes to an iron deficiency signal in the mutant. Iron supplementation significantly decreased P(FIT2)-GFP expression and, surprisingly, restored P(TSA2)-GFP to wild-type levels. A tsa2Δ mutation induced both nuclear localization of Aft1p and P(FIT2)-GFP expression. The data suggest a novel function for Tsa2p as a negative regulator of Aft1p-driven transcription, which is induced in V-ATPase mutants to limit transcription of the iron regulon. This represents a new mechanism bridging the antioxidant and iron-regulatory pathways that is intimately linked to pH homeostasis.


Mice from lines selectively bred for high voluntary wheel running exhibit lower blood pressure during withdrawal from wheel access.
Exercise is known to be rewarding and have positive effects on mental and physical health. Excessive exercise, however, can be the result of an underlying behavioral/physiological addiction. Both humans who exercise regularly and rodent models of exercise addiction sometimes display behavioral withdrawal symptoms, including depression and anxiety, when exercise is denied. However, few studies have examined the physiological state that occurs during this withdrawal period. Alterations in blood pressure (BP) are common physiological indicators of withdrawal in a variety of addictions. In this study, we examined exercise withdrawal in four replicate lines of mice selectively bred for high voluntary wheel running (HR lines). Mice from the HR lines run almost 3-fold greater distances on wheels than those from non-selected control lines, and have altered brain activity as well as increased behavioral despair when wheel access is removed. We tested the hypothesis that male HR mice have an altered cardiovascular response (heart rate, systolic, diastolic, and mean arterial pressure [MAP]) during exercise withdrawal. Measurements using an occlusion tail-cuff system were taken during 8 days of baseline, 6 days of wheel access, and 2 days of withdrawal (wheel access blocked). During withdrawal, HR mice had significantly lower systolic BP, diastolic BP, and MAP than controls, potentially indicating a differential dependence on voluntary wheel running in HR mice. This is the first characterization of a cardiovascular withdrawal response in an animal model of high voluntary exercise.


A Bifunctional Spray Coating Reduces Contamination on Surfaces by Repelling and Killing Pathogens.
Surface-mediated transmission of pathogens is a major concern with regard to the spread of infectious diseases. Current pathogen prevention methods on surfaces rely on the use of biocides, which aggravate the emergence of antimicrobial resistance and pose harmful health effects. In response, a bifunctional and substrate-independent spray coating is presented herein. The bifunctional coating relies on wrinkled polydimethylsiloxane microparticles, decorated with biocidal gold nanoparticles to induce a "repel and kill" effect against pathogens. Pathogen repellency is provided by the structural hierarchy of the microparticles and their surface chemistry, whereas the kill mechanism is achieved using functionalized gold nanoparticles embedded on the microparticles. Bacterial tests with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa reveal a 99.9% reduction in bacterial load on spray-coated surfaces, while antiviral tests with Phi6─a bacterial virus often used as a surrogate to SARS-CoV-2─demonstrate a 98% reduction in virus load on coated surfaces. The newly developed spray coating is versatile, easily applicable to various surfaces, and effective against various pathogens, making it suitable for reducing surface contamination in frequently touched, heavy traffic, and high-risk surfaces.


The Unexplored Role of Intra-articular Adipose Tissue in the Homeostasis and Pathology of Articular Joints.
Intra-articular adipose tissue deposits known as articular fat pads (AFPs) are described to exist within synovial joints. Their assumed role in normal joint biomechanics is increasingly objectivized by means of advanced methods of functional imaging. AFPs possess structural similarity with body subcutaneous white adipose tissue (WAT), however, seems to be regulated by independent metabolic loops. AFP dimension are conserved during extreme WAT states: obesity, metabolic syndrome, lipodystrophy, and cachexia. Hoffa fat pad (HFP) in the knee is increasingly recognized as a major player in pathological joint states such as anterior knee pain and osteoarthritis. HFP contains numerous population of mesenchymal and endothelial progenitors; however, the possible role of mature adipocytes in the maintenance of stem cell niche is unknown. We propose that AFP is an active component of the joint organ with multifunctional roles in the maintenance of joint homeostasis. Endowed with a rich network of sensitive nervous fibbers, AFPs may act as a proprioceptive organ. Adipokines and growth factors released by AFP-resident mature adipocytes could participate in the maintenance of progenitor stem cell niche as well as in local immune regulation. AFP metabolism may be locally controlled, correlated with but independent of WAT homeostasis. The identification of AFP role in normal joint turnover and its possible implication in pathological states could deliver diagnostic and therapeutic targets. Drug and/or cell therapies that restore AFP structure and function could become the next step in the design of disease modifying therapies for disabling joint conditions such as osteoarthritis and inflammatory arthritis.


Ocular manifestations of leukaemia in Ethiopians.
A prospective ophthalmic evaluation of 74 newly diagnosed and 34 old (on follow-up) leukaemic patients, carried out from March 1990 to December 1995 is described. Primary ocular involvement, that is leukaemic retinal infiltrates, were detected in 32% of the newly diagnosed. In contrast, none of the old leukaemic patients had this lesion. In 69% of the new and 21% of the old cases, secondary ocular manifestations of leukaemia were observed. The major secondary ocular manifestation of leukaemia in both groups was intra-retinal haemorrhage. A variety of miscellaneous ocular findings, such as cataract, pterygium, pingeculae, etc. were detected in 36% of all leukemics. These findings indicate the importance of a complete ophthalmologic evaluation in the diagnosis, follow-up and management of leukaemic patients.


[Cardiological aspects of fatigue states in athletes].
The physical load increase during training can lead to the development of clinical patterns of intolerance differing according to their severity, prognosis and reversibility. However, they always include fatigue as a key symptom. The aim of this paper is to review recent data on fatigue states in sportsmen, their clinical presentation and diagnostic orientations. A continuum exists, from acute fatigue states after one or several highly-intensive training sessions, to overreaching, associated to performances alteration which can be easily reversed, and to overtraining, representing a severe clinical pattern which can hardly be reversed. Overreaching and overtraining are characterized by a persisting fatigue state, associated to performances alteration and mood disorders. In an athlete with unexplained alteration of performances associated to physical fatigue, the medical interrogation is critical, in order to check the durable character of sportive performances alteration, to describe the fatigue and identify risk factors of occurrence of overtraining (training program intensity, mental stress, diet factors, hypoxic training, etc.). The use of a validated and adapted questionnaire as the one proposed by the French Society of Sports Medicine is valuable. In majority, in athletes and those doing sports regularly, the cardiological alert signs are rare, and the clinical examination by a specialist is poorly contributive, except for eliminating an organic cause of fatigue.


Enhancing a Person, Enhancing a Civilization: A Research Program at the Intersection of Bioethics, Future Studies, and Astrobiology.
There are manifold intriguing issues located within largely unexplored borderlands of bioethics, future studies (including global risk analysis), and astrobiology. Human enhancement has for quite some time been among the foci of bioethical debates, but the same cannot be said about its global, transgenerational, and even cosmological consequences. In recent years, discussions of posthuman and, in general terms, postbiological civilization(s) have slowly gained a measure of academic respect, in parallel with the renewed interest in the entire field of future studies and the great strides made in understanding of the origin and evolution of life and intelligence in their widest, cosmic context. These developments promise much deeper synergic answers to questions regarding the long-term future of enhancement: how far can it go? Is human enhancement a further step toward building a true postbiological civilization? Should we actively participate and help shape this process? Is the future of humanity "typical" in the same Copernican sense as our location in space and time is typical in the galaxy, and if so, can we derive important insights about the evolutionary pathways of postbiological evolution from astrobiological and Search for ExtraTerrestrial Intelligence (SETI) studies? These and similar questions could be understood as parts of a possible unifying research program attempting to connect cultural and moral evolution with what we know and understand about their cosmological and biological counterparts.


Single-shot (short-term) prophylaxis with ceftriaxone in biliary surgery.
A short-term prophylaxis based on a one-shot injection 30 min before operation of 2 g ceftriaxone has been used in 20 cases, in patients undergoing elective cholecystectomy or biliary tract surgery for gall-stones. The prophylaxis with ceftriaxone proved to be successful in all patients.


Geoengineering, climate change scepticism and the 'moral hazard' argument: an experimental study of UK public perceptions.
Many commentators have expressed concerns that researching and/or developing geoengineering technologies may undermine support for existing climate policies-the so-called moral hazard argument. This argument plays a central role in policy debates about geoengineering. However, there has not yet been a systematic investigation of how members of the public view the moral hazard argument, or whether it impacts on people's beliefs about geoengineering and climate change. In this paper, we describe an online experiment with a representative sample of the UK public, in which participants read one of two arguments (either endorsing or rejecting the idea that geoengineering poses a moral hazard). The argument endorsing the idea of geoengineering as a moral hazard was perceived as more convincing overall. However, people with more sceptical views and those who endorsed 'self-enhancing' values were more likely to agree that the prospect of geoengineering would reduce their motivation to make changes in their own behaviour in response to climate change. The findings suggest that geoengineering is likely to pose a moral hazard for some people more than others, and the implications for engaging the public are discussed.


Computerised analysis of facial emotion expression in eating disorders.
Problems with social-emotional processing are known to be an important contributor to the development and maintenance of eating disorders (EDs). Diminished facial communication of emotion has been frequently reported in individuals with anorexia nervosa (AN). Less is known about facial expressivity in bulimia nervosa (BN) and in people who have recovered from AN (RecAN). This study aimed to pilot the use of computerised facial expression analysis software to investigate emotion expression across the ED spectrum and recovery in a large sample of participants. 297 participants with AN, BN, RecAN, and healthy controls were recruited. Participants watched film clips designed to elicit happy or sad emotions, and facial expressions were then analysed using FaceReader. The finding mirrored those from previous work showing that healthy control and RecAN participants expressed significantly more positive emotions during the positive clip compared to the AN group. There were no differences in emotion expression during the sad film clip. These findings support the use of computerised methods to analyse emotion expression in EDs. The findings also demonstrate that reduced positive emotion expression is likely to be associated with the acute stage of AN illness, with individuals with BN showing an intermediate profile.


Mesenchymal stromal cells can be derived from bone marrow CD133+ cells: implications for therapy.
It is known that the bone marrow (BM) CD133(+) cells play an important role in the hematopoietic compartment, but this is not their only role. The cells indeed can take part in vascular reconstitution when they become endothelial cells (EC), in skeletal muscle fiber regeneration when there is a switch in muscle precursors, and to cardiomyocyte phenotypic conversion when differentiating in cardiomyocytes-like cells. While the role in hematopoiesis and vasculogenesis of the selected cells is well established, their ability to differentiate along multiple non-EC lineages has not yet been fully elucidated. The goal of this study is to assert whether human CD133(+)BM-derived cells are able to differentiate in vitro, besides to blood cells, cell lineages pertinent to the mesoderm germ layers. To this end, we isolated CD133(+) cells using a clinically approved methodology and compared their differentiation potential to that of hematopoietic progenitor cells (HPCs) and mesenchymal stem cells (MSCs) obtained from the same BM samples. In our culture conditions, CD133 expression was consistently decreased after passage 2, as well as the expression of the stemness markers c-kit and OCT4, whereas expression of Stage Specific Embryonic Antigen 4 (SSEA4) remained consistent in all different conditions. Expanded CD133 were also positive for HLA-ABC, but negative for HLA-DR, in accordance with what has been previously reported for MSCs. Moreover, CD133(+) cells from human BM demonstrated a wide range of differentiation potential, encompassing not only mesodermal but also ectodermal (neurogenic) cell lineages. CD133 antigen could be potentially used to select a cell population with similar characteristics as MSCs for therapeutic applications.


Coordinated incorporation of skeletal muscle dihydropyridine receptors and ryanodine receptors in peripheral couplings of BC3H1 cells.
Rapid release of calcium from the sarcoplasmic reticulum (SR) of skeletal muscle fibers during excitation-contraction (e-c) coupling is initiated by the interaction of surface membrane calcium channels (dihydropyridine receptors; DHPRs) with the calcium release channels of the SR (ryanodine receptors; RyRs, or feet). We studied the early differentiation of calcium release units, which mediate this interaction, in BC3H1 cells. Immunofluorescence labelings of differentiating myocytes with antibodies against alpha1 and alpha2 subunits of DHPRs, RyRs, and triadin show that the skeletal isoforms of all four proteins are abundantly expressed upon differentiation, they appear concomitantly, and they are colocalized. The transverse tubular system is poorly organized, and thus clusters of e-c coupling proteins are predominantly located at the cell periphery. Freeze fracture analysis of the surface membrane reveals tetrads of large intramembrane particles, arranged in orderly arrays. These appear concomitantly with arrays of feet (RyRs) and with the appearance of DHPR/RyS clusters, confirming that the four components of the tetrads correspond to skeletal muscle DHPRs. The arrangement of tetrads and feet in developing junctions indicates that incorporation of DHPRs in junctional domains of the surface membrane proceeds gradually and is highly coordinated with the formation of RyR arrays. Within the arrays, tetrads are positioned at a spacing of twice the distance between the feet. The incorporation of individual DHPRs into tetrads occurs exclusively at positions corresponding to alternate feet, suggesting that the assembly of RyR arrays not only guides the assembly of tetrads but also determines their characteristic spacing in the junction.


County-Level Radon and Incidence of Female Thyroid Cancer in Iowa, New Jersey, and Wisconsin, USA.
Few studies have investigated the association between radon and thyroid cancer despite the sensitivity of the thyroid gland to radiation. Our goal is to investigate the association between county-level radon and incidence of female thyroid cancer in the US States of Iowa, New Jersey, and Wisconsin. Thyroid cancer incidence data were provided by individual state cancer registries and span 1990-2013. Radon data come from a publicly available third-party database, AirChek, accessed in 2017. We tabulated the percent of radon above four picocuries per liter and the female thyroid cancer incidence rate in each county. Quantile maps were constructed, and an ordinary least-squares regression model was run using Geoda 22.214.171.124 (Chicago, IL, USA). No association was observed between county-level radon and incidence of female thyroid cancer in any of the States: New Jersey (β = 0.06, p = 0.23); Iowa (β = -0.07, p = 0.07); or Wisconsin (β = -0.01, p = 0.78). A spatial regression model was considered, but the Moran's I of the residuals from each of the models was not significant, so no spatial term was required. In this county-level ecological study across three different States in the US, we did not find an association between elevated radon and thyroid cancer incidence in women. While this ecologic study reports null findings, due to the ecologic fallacy, individual-level studies of this association may still be warranted.


Couple-Oriented Interventions for Mental Health: A Scoping Review.
The purpose of this research was to systematically examine and collate evidence on couple-oriented interventions for mental health to identify trends in the literature, review research strategies, and suggest directions for future research. A systematic search included studies relating to couple-oriented interventions for preventing mental disorders and/or promoting mental health. We identified a total of 52 studies, which included 55 articles. Our findings revealed that interventions were delivered through various modes, including face-to-face, telephone, and online, with the majority of couple-oriented interventions operating in conjoint sessions. The most common intervention was for selective prevention targeting patients with cancer and their partners. This review provided evidence of the applicability of theoretical frameworks, dyad analysis, and measurements associated with couple-oriented interventions. Findings can help family nurse practitioners and health care professionals advance strategies to develop and implement evidence-based, couple-oriented interventions for primary prevention of mental disorders and the promotion of mental health.


[Elastase-alpha 1-proteinase inhibitor in diseases of the neonatal period].
Elastase, a neutral protease stored in the azurophilic granules of neutrophils, is immediately released during the process of phagocytosis and rapidly bound and inactivated by alpha 1-proteinase inhibitor. This complex (E-alpha 1-PI) is highly stable and can be identified by ELISA-technique. In our study 95% of all infants with neonatal septicemia and/or meningitis had significantly increased plasma levels of E-alpha 1-PI at the time of diagnosis (n = 37). After initiation of therapy normalization of E-alpha 1-PI levels was observed in all neonates who recovered from infection. These data suggest that E-alpha 1-PI is a sensitive and rapidly responsive indicator of neonatal septicemia. In addition E-alpha 1-PI may be helpful in monitoring the course of the disease. However, the specificity of E-alpha 1-PI is rather low: in patients with local infections and inflammatory processes such as neonatal pneumonia, enterocolitis and meconium aspiration E-alpha 1-PI levels were also shown to be increased. In contrast, all patients with hyaline membrane disease had E-alpha 1-PI levels within the normal range.


Cardioprotective effect of endogenous pituitary adenylate cyclase-activating polypeptide on Doxorubicin-induced cardiomyopathy in mice.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is known as a cytoprotective polypeptide. PACAP and its receptors are expressed in the heart, but it is unclear whether PACAP exerts its protective effect on the myocardium in vivo. The aim of the present study was to investigate whether endogenous PACAP has a cardioprotective effect on Doxorubicin (Dox)-induced cardiomyopathy. Dox was intraperitoneally injected to induce cardiomyopathy in wild type (WT) and PACAP knockout (ie, PACAP+/- and PACAP-/-) mice. The survival rates up to 15 days of PACAP+/- mice and PACAP-/- mice were significantly less than that of WT mice. Cardiac function, measured by echocardiography, was significantly lower in PACAP+/- mice than in WT mice at day 10. Morphological examination of sections of myocardium showed degenerative change and fibrosis in PACAP+/- mice at day 10. Serum reactive oxygen metabolites (a marker of oxidative stress), the number of 8-hydroxy-deoxyguanosine-positive nuclei and TdT-mediated dUTP nick end-labeling (TUNEL) positive nuclei in the myocardium were higher in PACAP+/- mice than WT mice. However, continuous subcutaneous administration of PACAP38 was able to prevent the myocardial damage typically caused by Dox injection in PACAP+/-. These results suggest that endogenous PACAP might attenuate Dox-induced myocardial damage and that its mechanism of action is likely to be associated with the reduction of oxidative stress and mediated via anti-apoptotic effects.


[Clinical staging and course evaluation of patients with multiple myeloma and benign monoclonal hyperglobulinemia using the Salmon-Wampler total tumor cell mass calculation].
The calculation of tumor cell mass according to Salmon and Wampler was applied in a retrospective study comprising 79 unselected patients with multiple myeloma. The method proved to be a useful parameter for judging prognosis and course of the disease. IgG myelomas showed a better and prolonged regression of tumor cell mass than IgA myelomas. The average reduction of tumor cell mass under chemotherapy amounted to approximately 0.5 log. 38.5% of all patients went into a plateau phase after an initial decrease of their tumor cell mass, 30.8% showed varying values, whereas in 7.7% the reduction of the tumor cell mass occurred in a protracted fashion. The investigation of those patients in whom the first chemotherapy regimen was exchanged for another one showed, however, that the tumor cell mass calculation could not replace other controls, particularly X-ray controls pertaining to the progression of bone destruction. In benign monoclonal hyperglobulinemia, the calculation of the "tumor cell mass" can be applied as a sensitive parameter for judging the transition into multiple myeloma.


Knowledge Gaps Regarding Indigenous Health in Occupational Therapy: A National Survey.
Background. There is a need for the occupational therapy profession to respond to the Truth and Reconciliation Commission of Canada Calls to Action and work towards supporting the health and well-being of Indigenous Peoples. Purpose. (1) To determine the knowledge gaps of occupational therapists about Indigenous health and (2) to create recommendations to address identified gaps and inform responses from the profession. Method. A national needs survey was created and distributed to occupational therapists across Canada to determine the knowledge of occupational therapists about Indigenous health. Survey results were analyzed using thematic analysis and descriptive statistics. Findings. Data collected from 364 survey responses informed six distinct themes representing knowledge gaps of occupational therapists related to Indigenous health as follows: lack of foundational knowledge, power relations, lifelong learner, need for appropriate tools/approaches, respectful collaboration, and environmental influences. Implications. The project offers insight into the role of the occupational therapy profession in the process of reconciliation. Insights are focused on decolonizing occupational therapy practice, building trusting relationships with Indigenous Peoples, and the provision of appropriate training for occupational therapists to engage in culturally safer practices.


'You have to be a certain sort of person': An interpretative phenomenological analysis of mental health support workers' experiences of physical restraint in inpatient settings.
Physical restraint is a controversial practice in psychiatric inpatient settings. Research has clearly demonstrated its physical and psychological risks, but few studies investigate how mental health support workers understand their experiences of restraint use. This study uses interpretative phenomenological analysis to explore support workers' understanding of these experiences. The COREQ checklist was used to ensure explicit reporting of the study. Semi-structured interviews were conducted with three participants and were then analysed using an interpretative phenomenological process. One superordinate theme emerged: 'You have to be a certain sort of person'. Restraints require not only the ability to overcome one's emotions, but also the ability to connect with the person being restrained. The implications of these findings for psychiatric care provision and for further research are discussed.


Key role of proline L209 in connecting the distant quinone pockets in the reaction center of Rhodobacter sphaeroides.
Photosynthetic bacterial reaction centers convert light excitation into chemical free energy. The initial electron transfer leads to the consecutive semireductions of the primary (Q(A)) and secondary (Q(B)) quinone acceptors. The Q(A)(-) and Q(B)(-) formations induce proton uptake from the bulk. Their magnitudes (H(+)/Q(A)(-) and H(+)/Q(B)(-), respectively) probe the electrostatic interactions within the complex. The pH dependence of H(+)/Q(A)(-) and H(+)/Q(B)(-) were studied in five single mutants modified at the L209 site (L209P-->F,Y,W,E,T). This residue is situated at the border of a continuous chain of water molecules connecting Q(B) to the bulk. In the wild type (WT), a proton uptake band is present at high pH in the H(+)/Q(A)(-) and H(+)/Q(B)(-) curves and is commonly attributed to a cluster of acidic groups situated nearby Q(B). In the H(+)/Q(A)(-) curves of the L209 variants, this band is systematically absent but remains in the H(+)/Q(B)(-) curves. Moreover, notable increase of H(+)/Q(B)(-) is observed in the L209 mutants at neutral pH as compared with the WT. The large effects observed in all L209 mutants are not associated with significant structural changes (Kuglstatter, A., Ermler, U., Michel, H., Baciou, L. & Fritzsch, G. Biochemistry (2001) 40, 4253-4260). Our data suggest that, in the L209 mutants, the Q(B) cluster does not respond to the Q(A)(-) formation as observed in the WT. We propose that, in the mutants, removal of the rigid proline L209 breaks a necessary hydrogen bonding connection between the quinone sites. These findings suggest an important role for structural rigidity in ensuring a functional interaction between quinone binding sites.


Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in blunt chest trauma patients.
After blunt chest trauma, life-threatening arrhythmias may occur in the early post-injury period, as well as a few days after the injury. This study aimed to evaluate the risk of arrhythmias in blunt chest trauma patients using Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio. In this study, patients who applied to the emergency department due to blunt chest trauma were examined prospectively. The 12-lead ECG was performed to both blunt chest trauma and control group. ECG measurements of QT and Tp-e intervals were performed from both groups. A total of 81 participants; 41 blunt chest trauma patients and 40 healthy volunteers were included in this study. Tpe, Tpe/QT, Tpe/QTc values were statistically significant in the trauma group compared to the control group (p<0.001). Although Tpe/QTc, max QT and min QT were statistically significant (p<0.05) in patients with a rib fracture, no difference was detected concerning Tpe, Tpe/QT compared to no-rib fracture group (p>0.05). Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in ECG predict the arrhythmias that may occur in blunt cardiac trauma, especially in blunt chest trauma patients.


Assessing adherence and exploring barriers to provision of prescribed texture modifications for dysphagia in a residential aged care facility in rural Australia.
Purpose: Between 55-65% of residents living in residential aged care facilities (RACFs) experience dysphagia and are prescribed texture-modified diets by a speech-language pathologist (SLP). The aim of this study was to assess current adherence to prescribed texture modification for people with dysphagia; and explore barriers to implementation in a rural aged care setting. Method: Meal texture audits (N = 42) were completed with residents with dysphagia in a rural RACF who were prescribed texture-modified diets or fluids by a SLP. Semi-structured focus groups were conducted with nursing and food preparation staff (N = 11) to identify barriers to implementation. Result: Mealtime texture audits identified that 54.8% (n = 23) of residents' food modification requirements were incorrectly documented in the manual entry database (kitchen form) and 64.3% (n = 27) of meal trays contained foods that did not meet residents' dysphagia management plans. Focus group data revealed seven main themes impacting on the ability of staff to implement prescribed texture-modified diets. Complicated processes and communication between nursing, food services and SLP staff were identified as major barriers. These were complicated further by time pressures experienced by staff as well as staffing issues, resourcing of the kitchen, accommodating individual dietary preferences and the variety/presentation of dietary options at the aged care facility.Conclusion: There was low adherence to SLP prescribed texture-modified diets and fluids in the participating rural RACF. This study identified major barriers to implementing SLP prescribed texture-modified diets including complicated processes, communication breakdowns, time pressures and limited staffing. Implementation of an online menu management system and regular dysphagia-specific training may address barriers to communication and complicated paper-based menu systems and should be a priority for health services to ensure adequate dysphagia management.


Supporting decision making and action selection under time pressure and uncertainty: the case of in-flight icing.
Operators in high-risk domains such as aviation often need to make decisions under time pressure and uncertainty. One way to support them in this task is through the introduction of decision support systems (DSSs). The present study examined the effectiveness of two different DSS implementations: status and command displays. Twenty-seven pilots (9 pilots each in a baseline, status, and command group) flew 20 simulated approaches involving icing encounters. Accuracy of the decision aid (a smart icing system), familiarity with the icing condition, timing of icing onset, and autopilot usage were varied within subjects. Accurate information from either decision aid led to improved handling of the icing encounter. However, when inaccurate information was presented, performance dropped below that of the baseline condition. The cost of inaccurate information was particularly high for command displays and in the case of unfamiliar icing conditions. Our findings suggest that unless perfect reliability of a decision aid can be assumed, status displays may be preferable to command displays in high-risk domains (e.g., space flight, medicine, and process control), as the former yield more robust performance benefits and appear less vulnerable to automation biases.


Does Routine Bioimpedance-Guided Fluid Management Provide Additional Benefit to Non-Anuric Peritoneal Dialysis Patients? Results from COMPASS Clinical Trial.
In peritoneal dialysis (PD) patients, volume overload is related to cardiac dysfunction and mortality, while intravascular volume depletion is associated with a rapid decline in the residual renal function (RRF). This study sought to determine the clinical usefulness of bioimpedance spectroscopy (BIS)-guided fluid management for preserving RRF and cardiac function in PD patients. This is a multicenter, prospective, open-label study that was conducted over a 1-year period (NCT01887262). Non-anuric (urine volume > 500 mL/day) subjects on PD were enrolled. Subjects in the control group received fluid management based on the clinical information alone. Those in the BIS group received BIS-guided fluid management along with clinical information. The subjects (N = 137, mean age 51.3 ± 12.8 years, 54% male) were randomly assigned to the BIS group (n = 67) or to the control group (n = 70). There were no significant differences between the 2 groups with regard to age, sex ratio, cause of kidney failure, duration of PD, baseline comorbidity, RRF, PD method, or peritoneal transport type. At baseline, the 2 groups were not different in terms of RRF (glomerular filtration rate [GFR], 5.1 ± 2.9 vs 5.5 ± 3.7 mL/min/1.73 m2). After follow-up, changes in the GFR between the 2 groups were not different (-1.5 ± 2.4 vs -1.3 ± 2.6 mL/min/1.73 m2, p = 0.593). Over the 1-year study period, both groups maintained stability of various fluid status parameters. Between the 2 groups, there were no differences in the net change of various fluid status parameters such as overhydration (OH) and extracellular water/total body water (ECW/TBW). A net change in ECW over 1 year was slightly but significantly higher in the control group (net increase, 0.57 ± 1.27 vs 0.05 ± 1.63 L, p = 0.047). However, this difference was not translated into an improvement in RRF in the BIS group. There were no differences in echocardiographic parameters or arterial stiffness at the end of follow-up. Routine BIS-guided fluid management in non-anuric PD patients did not provide additional benefit in volume control, RRF preservation, or cardiovascular (CV) parameters. However, our study cannot be generalized to the whole PD population. Further research is warranted in order to investigate the subpopulation of PD patients who may benefit from routine BIS-guided fluid management.


Upgrading syngas fermentation effluent using Clostridium kluyveri in a continuous fermentation.
The product of current syngas fermentation systems is an ethanol/acetic acid mixture and the goal is to maximize ethanol recovery. However, ethanol currently has a relatively low market value and its separation from the fermentation broth is energy intensive. We can circumvent these disadvantages of ethanol production by converting the dilute ethanol/acetic acid mixture into products with longer carbon backbones, which are of higher value and are more easily extracted than ethanol. Chain elongation, which is the bioprocess in which ethanol is used to elongate short-chain carboxylic acids to medium-chain carboxylic acids (MCCAs), has been studied with pure cultures and open cultures of microbial consortia (microbiomes) with several different substrates. While upgrading syngas fermentation effluent has been studied with open cultures, to our knowledge, no study exists that has performed this with pure cultures. Here, pure cultures of Clostridium kluyveri were used in continuous bioreactors to convert ethanol/acetic acid mixtures into MCCAs. Besides changing the operating conditions in regards to substrate loading rates and composition, the effect of in-line product extraction, pH, and the use of real syngas fermentation effluent on production rates were tested. Increasing the organic loading rates resulted in proportionally higher production rates of n-caproic acid, which were up to 40 mM day-1 (4.64 g L-1 day-1) at carbon conversion efficiencies of 90% or higher. The production rates were similar for bioreactors with and without in-line product extraction. Furthermore, a lower ethanol/acetic acid ratio (3:1 instead of 10:1) enabled faster and more efficient n-caproic acid production. In addition, n-caprylic acid production was observed for the first time with C. kluyveri (up to 2.19 ± 0.34 mM in batch). Finally, the use of real effluent from syngas fermentation, without added yeast extract, but with added defined growth factors, did maintain similar production rates. Throughout the operating period, we observed that the metabolism of C. kluyveri was inhibited at a mildly acidic pH value of 5.5 compared to a pH value of 7.0, while reactor microbiomes perform successfully at mildly acidic conditions. Clostridium kluyveri can be used as a biocatalyst to upgrade syngas fermentation effluent into MCCAs at pH values above 5.5.


Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.
The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.