Mentalization, session-to-session negative emotion expression, symbolic play, and affect regulation in psychodynamic child psychotherapy.
Internalizing and externalizing problems have been related to negative emotionality, and affect regulation deficits in several studies. Certain psychodynamic models of treatment use children's symbolic play activity as a medium to mentalize negative emotions in order to develop children's affect regulation. However, the complex associations among these constructs and their associations with outcome have not been examined. This study aimed to investigate, first, whether average mentalization practices in treatment, as well as session-to-session expression of negative emotions and symbolic play predict gains in affect regulation and, second, whether changes in these variables are associated with clinically significant change in symptoms and global function. The sample included 40 outpatient children, who underwent long-term psychodynamic treatment. Nine hundred seventy-five sessions were coded for children's symbolic play, affect expression (anger and dysphoric affect), and affect regulation characteristics, and each treatment was scored for average adherence to mentalizing principles. Time Series Panel Analyses (TSPA) indicated session-to session use of symbolic play predicted gains in affect regulation. A significant 2-way interaction indicated that dysphoric affect expression in high mentalization adherent treatments was associated with higher affect regulation than in low adherent treatments. Partial correlation analyses indicated that mentalization adherence in treatment was associated with symptomatic improvement at trend level of significance, and changes in affect regulation and symbolic play were significantly associated with gains in global function. Findings point to the importance of use of symbolic play, and dysphoric affect expression in the context of mentalization practices for gains in affect regulation and outcome. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Biomechanics and Microstructural Analysis of the Mouse Knee and Ligaments.
The purpose of this study is to determine the feasibility of using murine models for translational study of knee ligament injury, repair, and reconstruction. To achieve this aim, we provide objective, quantitative data detailing the gross anatomy, biomechanical characteristics, and microscopic structure of knee ligaments of 44 male mice (C57BL6, 12 weeks of age). Biomechanical testing determined the load-to-failure force, stiffness, and the site of ligament failure for the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and the medial and lateral collateral ligaments (MCL and LCL). These data are complemented by histological characterization of each of the knee ligaments. In addition, the osseous morphology of the mouse knee was examined using high-resolution nanofocus computed tomography (CT), while standard micro-CT was employed to measure bone morphometrics of the distal femur and proximal tibia. Collectively, our findings suggest that the gross anatomy of the mouse knee is similar to the human knee despite some minor differences and features unique to the murine knee. The ACL had the highest load to failure (5.60 ± 0.75 N), the MCL (3.33 ± 1.45 N), and the PCL (3.45 ± 0.84 N) were similar, and the LCL (1.44 ± 0.37 N) had the lowest load to failure and stiffness. Murine models provide a unique opportunity to focus on biological processes that impact ligament pathology and healing due to the availability of transgenic strains. Our data support their use as a translational platform for the in vivo study of ligament injury, repair, and reconstruction.


Binding characteristics of Hoechst 33258 with calf thymus DNA, poly[d(A-T)], and d(CCGGAATTCCGG): multiple stoichiometries and determination of tight binding with a wide spectrum of site affinities.
Equilibrium binding experiments using fluorescence and absorption techniques have been performed throughout a wide concentration range (1 nM to 30 microM) of the dye Hoechst 33258 and several DNAs. The most stable complexes found with calf thymus DNA, poly[d(A-T)], d(CCGGAATTCCGG), and d(CGCGAATTCGCG) all have dissociation constants in the range (1-3) X 10(-9) M-1. Such complexes on calf thymus DNA occur with a frequency of about 1 binding site per 100 base pairs, and evidence is presented indicating a spectrum of sequence-dependent affinities with dissociation constants extending into the micromolar range. In addition to these sequence-specific binding sites on the DNA, the continuous-variation method of Job reveals distinct stoichiometries of dye-poly[d(A-T)] complexes corresponding to 1, 2, 3, 4, and 6 dyes per 5 A-T base pairs and even up to 1 and 2 (and possibly more) dyes per backbone phosphate. Models are suggested to account for these stoichiometries. With poly[d(G-C)] the stoichiometries are 1-2 dyes per 5 G-C pairs in addition to 1 and 2 dyes per backbone phosphate. Thermodynamic parameters for formation of the tightest binding complex between Hoechst 33258 and poly[d(A-T)] or d-(CCGGAATTCCGG) are determined. Hoechst 33258 binding to calf thymus DNA, chicken erythrocyte DNA, and poly[d(A-T)] exhibits an ionic strength dependence similar to that expected for a singly-charged positive ion. This ionic strength dependence remains unchanged in the presence of 25% ethanol, which decreases the affinity by 2 orders of magnitude. In addition, due to its strong binding, Hoechst 33258 easily displaces several intercalators from DNA.


RECK inhibits stemness gene expression and tumorigenicity of gastric cancer cells by suppressing ADAM-mediated Notch1 activation.
The Reversion-inducing Cysteine-rich Protein with Kazal Motifs (RECK) gene encodes a membrane-anchored glycoprotein that exhibits strong inhibitory activity against various matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase 10 (ADAM10). RECK functions as a tumor suppressor by inhibiting migration, invasion, and angiogenesis. However, whether RECK can modulate the stem-like phenotypes of cancer cells is not known. In this study, we demonstrate that RECK is down-regulated in gastric cancer cells and is further reduced in CD133-positive cancer stem-like cells. Ectopic expression of RECK induces down-regulation of the expression of stemness genes including Sox2, Oct4, and Nanog and the cancer stem cell marker CD133. Treatment of DAPT (a γ-secretase inhibitor) or TAPI-2 (a hydroxamate-based inhibitor of MMPs, tumor necrosis factor α converting enzyme and ADAM17) reduces Notch1 shedding and activation which results in attenuation of stemness genes and CD133. Our data show that ADAM10 and ADAM17 are co-pulled down by RECK suggesting a physical interaction between RECK and ADAMs on cell surface. In addition, RECK suppresses sphere formation and sphere size of CD133-positive gastric cancer cells. Overexpression of Notch intracellular domain (NICD) or ADAM17 effectively reverse the inhibitory effect of RECK in CD133-positive cells. More importantly, RECK reduces tumorigenic activity of CD133-positive cells in vivo. Conversely, knockdown of RECK in non-tumorigenic GI2 cells increases stemness and CD133 expression and sphere forming ability. Collectively, these results indicate that RECK represses stemness gene expression and stem-like properties by inhibiting ADAM-mediated Notch1 shedding and activation.


Proteomics analysis of major royal jelly protein changes under different storage conditions.
Protein changes in fresh royal jelly (RJ) were compared when stored at -20, 4 degrees C, and room temperature (RT) for 12 months. Protein was partially identified using combinations of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF/MS), gel filtration chromatography, nanoLC MS/MS, and a protein engine identification tool applied to the honeybee genome. Significantly more protein spots were found in fresh (85 spots) and -20 degrees C (81 spots) stored RJ than in samples stored at 4 degrees C (73 spots) and at RT (70 spots) for 1 year. Most identified spots, 56, 57, 51, 46, corresponding to RJ sample of the fresh, -20 degrees C, 4 degrees C, and RT, were assigned to major royal jelly proteins (MRJPs). Marked differences were found in the heterogeneity of the MRJPs, in particular, MRJP3. The quantity of MRJP1 decreased significantly following the temperature trend in all images, but MRJP 2 and -3 did not increase or decrease following the temperature trend, thus, suggesting that MRJP 1-3 are sensitive to temperature. However, MRJP4, 5, glucose oxidase (GOD), peroxiredoxin (PRDX), and glutathione S-transferase (GST) S1 were clearly absent in all images in samples held at RT for 1 year. This indicates that they are the proteins most sensitive to storage temperature and protein markers for freshness of RJ. Combining chromatography and nanoLC MS/MS results, we tentatively conclude that MRJP5 is a reliable freshness marker and that the best way to maintain quality of RJ is under freezing conditions.


Measuring Concentrations of Dissolved Methane and Ethane and the 13 C of Methane in Shale and Till.
Baseline characterization of concentrations and isotopic values of dissolved natural gases is needed to identify contamination caused by the leakage of fugitive gases from oil and gas activities. Methods to collect and analyze baseline concentration-depth profiles of dissolved CH4 and C2 H6 and δ13 C-CH4 in shales and Quaternary clayey tills were assessed at two sites in the Williston Basin, Canada. Core and cuttings samples were stored in Isojars® in a low O2 headspace prior to analysis. Measurements and multiphase diffusion modeling show that the gas concentrations in core samples yield well-defined and reproducible depth profiles after 31-d equilibration. No measurable oxidative loss or production during core sample storage was observed. Concentrations from cuttings and mud gas logging (including IsoTubes® ) were much lower than from cores, but correlated well. Simulations suggest the lower concentrations from cuttings can be attributed to drilling time, and therefore their use to define gas concentration profiles may have inherent limitations. Calculations based on mud gas logging show the method can provide estimates of core concentrations if operational parameters for the mud gas capture cylinder are quantified. The δ13 C-CH4 measured from mud gas, IsoTubes® , cuttings, and core samples are consistent, exhibiting slight variations that should not alter the implications of the results in identifying the sources of the gases. This study shows core and mud gas techniques and, to a lesser extent, cuttings, can generate high-resolution depth profiles of dissolved hydrocarbon gas concentrations and their isotopes.


Incremental effects of reward on creativity.
The authors examined 2 ways reward might increase creativity. First, reward contingent on creativity might increase extrinsic motivation. Studies 1 and 2 found that repeatedly giving preadolescent students reward for creative performance in 1 task increased their creativity in subsequent tasks. Study 3 reported that reward promised for creativity increased college students' creative task performance. Second, expected reward for high performance might increase creativity by enhancing perceived self-determination and, therefore, intrinsic task interest. Study 4 found that employees' intrinsic job interest mediated a positive relationship between expected reward for high performance and creative suggestions offered at work. Study 5 found that employees' perceived self-determination mediated a positive relationship between expected reward for high performance and the creativity of anonymous suggestions for helping the organization.


Contact allergens in shoe leather among patients with foot eczema.
Some patients with relapsing foot eczema and a shoe leather allergy, who fail to show positive results with standard series and shoe wear screening tray patch testing, do not respond to the use of hypoallergenic shoe leather. We assume that relevant allergens are present in hypoallergenic shoe leather. We described an experiment to demonstrate the presence of these allergens. Alcoholic extracts were made of green, black and undyed hypoallergenic shoe leather, and the extracts were fractioned by paper chromatography. The resulting chromatograms were cut into 16 equal paper disks and patch tests were performed with extracts and the paper chromatography fractions. Positive reactions were seen to all extracts and to fractions of all types of leather. From analysis of the pattern of positive patch tests we concluded that leather-related allergens (e.g. tanning agent) and dyes were present in hypoallergenic shoe leather. In these cases, alternatives to shoe leather should be sought, for instance wooden or plastic shoes.


MRP2 (ABCC2) and cisplatin sensitivity in hepatocytes and human ovarian carcinoma.
The ABC transporter MRP2 (ABCC2) can mediate cisplatin efflux, and over-expression of MRP2 has been associated with cisplatin resistance in cancer cell lines. The aim of this study was to determine the role of MRP2 in modulating cisplatin cytotoxicity in normal cells as well as the relationship between MRP2 expression and clinical response to platinum-based agents in ovarian cancer. The effect of absence of MRP2 expression on cisplatin sensitivity was investigated using primary hepatocyte cultures from the TR- rat strain, which is deficient in Mrp2. We also examined MRP2 expression immunohistochemically in human ovarian tumors exhibiting extremes of clinical response to platinum-based chemotherapy, either absolute platin resistance or patients with residual disease after surgery who experienced extremely long complete response to primary platinum-based chemotherapy. Primary hepatocyte cultures from Mrp2-deficient TR- rats were over threefold more sensitive to cisplatin and accumulated a twofold greater amount of platinum on DNA that wild-type rat hepatocytes. In human ovarian carcinomas, MRP2 was detected by immunohistochemistry in 3/13 (23%) tumors from patients with absolute platin resistance compared with 5/9 (56%) tumors from patients with prolonged survival following treatment including a platinum-based agent. These studies indicate that MRP2 may play an important role in modulating normal tissue response to cisplatin. However, MRP2 expression occurred only in a subset of primary ovarian cancers, was frequently aberrant in location and was not correlated with clinical response to platinum-based chemotherapy.


A rare case of primary ovarian mesonephric adenocarcinoma and a review of the literature.
Are reported in the cervix in the female genital tract, has been reported in very few studies in the literature. In this report, we aimed to present a case with mesonephric carcinoma, which was detected in the ovary and is very rarely seen. In a case since the frozen section results of the left adnexal mass were reported as malignant. Ovarian mesonephric carcinoma is very rare and exhibits very different morphological patterns. Therefore, immunohistochemical and morphological findings should be evaluated together. If the pathological picture does not fit the common carcinomas of ovarian origin and this entity must be brought to mind, because, if these tumors with different molecular developmental pathways are diagnosed correctly, treatment schemes will change and targeted therapies will be developed too. Mesonephric carcinoma, Mesonephric like carcinoma, Ovarian carcinoma.


Vitamin D in patients with kidney disease: cautiously optimistic.
Nephrologists are well aware of the therapeutic effects of activated vitamin D in managing secondary hyperparathyroidism. Beyond bone and mineral metabolism, however, we are now beginning to appreciate the effects of activating the vitamin D receptor (VDR) in other cell types. Our group and others recently found a survival advantage associated with injectable vitamin D therapy in hemodialysis populations. The observational nature of these studies, however, subjects them to the possibility that confounding and bias may have accounted for their results. Therefore, it is unclear if indeed a survival benefit exists, if harm is incurred with this therapy or if activation of the VDR in cell types other than bone, intestine, and the parathyroid gland are applicable to our patients with kidney disease. The range of studies being planned include those targeting the cardiovascular effects of VDR activation, further understanding of the prevalence and consequences of vitamin D deficiency in patients with kidney disease, trials to examine the effects of VDR activation on intermediate cardiovascular and noncardiovascular endpoints, and trials targeting mortality endpoints. If consistent with the recent observations, these studies may provide nephrologists with an intervention to alter the otherwise poor outcomes in patients with kidney disease.


Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions.
Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis. RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility. Here we propose and analyze a mathematical model representing core interactions involved in the spatial localization of junctional RhoA signaling. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. This dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behavior of the system when contractility is inhibited are in qualitative agreement with the predictions of the model.


Effects of hypoxia on ventilation during postnatal development in conscious kittens.
Effects of steady-state hypoxia (inspired O2 fraction = 0.11) on ventilation and breathing pattern were studied during postnatal development in unanesthetized kittens. Studies were done from 2 days to 8 mo of age, every week during the first month and every month thereafter. During the first 2 months, states of consciousness were determined. In the first month, minute ventilation (VE) was depressed in hypoxia compared with control values in air, whereas in the older kittens VE was increased in hypoxia, as in adult cats. The inhibitory effect of hypoxia was observed in all three states of consciousness in 7- and 14-day-old kittens. In the 21- and 28-day-old kittens, VE could not be reliably related to the state of consciousness. In the 2-mo-old kittens, VE increased in all states. Tidal volume (VT) was markedly decreased in kittens up to 14 days of age, and respiratory frequency increased. In the 21- and 28-day-old kittens, changes in breathing pattern were variable. In the oldest, the increase of VE was mainly due to an increase of VT. We conclude that in unanesthetized kittens, the ventilatory response to hypoxia is mature at 2 mo of age. The hypoxic tachypnea observed at 7 and 14 days resembles that previously seen in adult carotid-denervated cats, and may be due to a low level of carotid chemoreceptor drive and to a central excitatory effect of hypoxia on respiratory frequency. The complex response observed during the first month of life must reflect the development of peripheral and central mechanisms and their interactions.


Inhibition by insulin of ethanol-induced hyperglycaemia in perfused livers from fed rats.
Livers from fed male rats were perfused with homologous whole blood and infused with ethanol and insulin. Ethanol raised hepatic glucose output by enhancing gluconeogenesis from perfusate lactate and amino acids. Ketogenesis and the ratio [3-hydroxy butyrate]/[acetoacetate] were also raised. Insulin, infused alone, lowered blood glucose, ketogenesis and total serum amino acids and when added with ethanol opposed the metabolic effects of the latter. Ethanol did not affect serum fatty acids but their concentrations were raised by insulin.


Hemoglobin and adult height loss among Japanese workers: A retrospective study.
Height loss starting in middle age is reported to be associated with increased all-cause and cardiovascular mortality later in life. However, the mechanisms underlying this association are unclear. Hypoxia and oxidative stress, which are known causes of cardiovascular disease, could be reduced by hemoglobin. Therefore, hemoglobin could be inversely associated with height loss. However, high body mass index (BMI) is a known risk factor for intervertebral disc disorder, a known cause of height loss in adults. High BMI might confound the association between hemoglobin and height loss. Therefore, we performed analyses stratified by BMI status. To clarify the association between hemoglobin and height loss, we conducted a retrospective study of Japanese workers (6,471 men and 3,180 women) aged 40-74 years. Height loss was defined as being in the highest quintile of height decrease per year. In men overall and men with BMI <25 kg/m2, hemoglobin was significantly inversely associated with height loss; but no association was observed for men with high BMI (BMI ≥25 kg/m2) and for women. For men, after adjusting for known cardiovascular risk factors, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for height loss with each 1 standard deviation (SD) increase in hemoglobin (1.0 g/dL for men and 0.8g/dL for women) were 0.89 (0.83, 0.95) for men overall, 0.82 (0.75, 0.89) for men who do not have high BMI, and 1.01 (0.92, 1.12) for men with high BMI. For women, the corresponding values were 0.97 (0.89, 1.06), 0.98 (0.89, 1.09), and 0.93 (0.75, 1.15) respectively. Hemoglobin is significantly inversely associated with height loss in men who do not have high BMI, but not in men with high BMI or women. These results help clarify the mechanisms underlying height loss, which has been reported to be associated with a higher risk of mortality in adults.


Ethyl 4-oxo-2,3,4,9-tetra-hydro-1H-carbazole-3-carboxyl-ate.
In the title compound, C(15)H(15)NO(3), the carbazole skeleton includes an eth-oxy-carbonyl group at the 3-position. In the indole ring system, the benzene and pyrrole rings are nearly coplanar, forming a dihedral angle of 0.89 (4)°. The cyclo-hexenone ring has an envelope conformation. In the crystal, inter-molecular N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into a three dimensional network. A weak C-H⋯π inter-action is also observed.


Three-dimensional atomic force microscopy - taking surface imaging to the next level.
Materials properties are ultimately determined by the nature of the interactions between the atoms that form the material. On surfaces, the site-specific spatial distribution of force and energy fields governs the phenomena encountered. This article reviews recent progress in the development of a measurement mode called three-dimensional atomic force microscopy (3D-AFM) that allows the dense, three-dimensional mapping of these surface fields with atomic resolution. Based on noncontact atomic force microscopy, 3D-AFM is able to provide more detailed information on surface properties than ever before, thanks to the simultaneous multi-channel acquisition of complementary spatial data such as local energy dissipation and tunneling currents. By illustrating the results of experiments performed on graphite and pentacene, we explain how 3D-AFM data acquisition works, what challenges have to be addressed in its realization, and what type of data can be extracted from the experiments. Finally, a multitude of potential applications are discussed, with special emphasis on chemical imaging, heterogeneous catalysis, and nanotribology.


[Gastric acid and parotid secretion in obesity [greater than 55%] (author's transl)].
In order to investigate exocrine secretory activity in obesity we studied gastric acid and parotid secretion in 22 massively obese patients (greater than 55% overweight); 15 normal persons were taken as controls. Basal and stimulated secretory values were determined. Basal acid output (BAO) in the obese (4,10 +/- 3,8 mval/h) was higher compared to normal (1,98 +/- 1,59 mval/h); the amylase activity in parotid saliva was reduced in the obese means = 195 U/ml (93,8-406) compared to normal means = 307 U/ml (145-652). These differences were not statistically significant. Maximal acid output (MAO) in the obese was within the normal range 17,6 +/- 8,98 mval/h (norm 16-25) despite it was expected, in a weight related manner, to be in a strongly hypersecretory range.


Medicare payment data for spine reimbursement; important but flawed data for evaluating utilization of resources.
Medicare data showing physician-specific reimbursement for 2012 were recently made public in the mainstream media. Given the ongoing interest in containing healthcare costs, we analyze these data in the context of the delivery of spinal surgery. Demographics of 206 leading surgeons were extracted including state, geographic area, residency training program, fellowship training, and academic affiliation. Using current procedural terminology (CPT) codes, information was evaluated regarding the number of lumbar laminectomies, lumbar fusions, add-on laminectomy levels, and anterior cervical fusions reimbursed by Medicare in 2012. In 2012 Medicare reimbursed the average neurosurgeon slightly more than an orthopedic surgeon for all procedures ($142,075 vs. $110,920), but this was not found to be statistically significant (P = 0.218). Orthopedic surgeons had a statistical trend illustrating increased reimbursement for lumbar fusions specifically, $1187 versus $1073 (P = 0.07). Fellowship trained spinal surgeons also, on average, received more from Medicare ($125,407 vs. $76,551), but again this was not statistically significant (P = 0.112). A surgeon in private practice, on average, was reimbursed $137,495 while their academic counterparts were reimbursed $103,144 (P = 0.127). Surgeons performing cervical fusions in the Centers for Disease Control West Region did receive statistically significantly less reimbursement for that procedure then those surgeons in other parts of the country (P = 0.015). Surgeons in the West were reimbursed on average $849 for CPT code 22,551 while those in the Midwest received $1475 per procedure. Medicare reimbursement data are fundamentally flawed in determining healthcare expenditure as it shows a bias toward delivery of care in specific patient demographics. However, neurosurgeons, not just policy makers, must take ownership to analyze, investigate, and interpret these data as it will affect healthcare reimbursement and delivery moving forward.


Discrimination and characterization of the volatile profiles of five Fu brick teas from different manufacturing regions by using HS-SPME/GC-MS and HS-GC-IMS.
Although aroma is one of the most essential factors determining the quality of Fu brick tea (FBT), the aroma profiles of FBTs from different manufacturing areas are rarely investigated. The aroma profiles of FBTs manufactured in five typical provinces of China were comprehensively analyzed on the basis of headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), sensory evaluation, odor activity value (OAV), and relative odor activity value (ROAV). HS-GC-IMS and HS-SPME-GC-MS identified 63 and 93 volatile organic compounds (VOCs), respectively. Multivariate statistical analysis indicated that the FBTs from different production regions had remarkably varied aromas. HS-SPME-GC-MS revealed that 27 VOCs (OAV >1) contributed to the overall aroma of the samples, of which 15 key differential compounds can effectively distinguish the aroma profiles of different FBTs. FBT from Shaanxi manifested a strong floral and fruity aroma; that from Hunan had a floral, grassy, and pine-woody aroma; that from Guizhou presented a grassy and herbal aroma; that from Guangxi exhibited a sweet, floral, and minty aroma; and that from Zhejiang possessed various fruit flavors and floral fragrance. OAV analysis identified the biomarkers responsible for the variation in the aroma characteristics of diverse FBTs. These biomarkers included linalool, 6-methyl-5-hepten-2-one, α-ionone, hexanal, and ethyl hexanoate. Sensory evaluation demonstrated that the infusion color and aroma of FBT samples from different provinces also greatly varied. Network correlation analysis revealed that Aspergillus and Eurotium were the crucial microorganisms for the metabolism and formation of VOCs. These findings provide new insight into the VOCs and fragrance features of FBTs produced in different regions of China.


NOD-Like Receptor P3 Inflammasome Controls Protective Th1/Th17 Immunity against Pulmonary Paracoccidioidomycosis.
The NOD-like receptor P3 (NLRP3) inflammasome is an intracellular multimeric complex that triggers the activation of inflammatory caspases and the maturation of IL-1β and IL-18, important cytokines for the innate immune response against pathogens. The functional NLRP3 inflammasome complex consists of NLRP3, the adaptor protein apoptosis-associated speck-like protein, and caspase-1. Various molecular mechanisms were associated with NLRP3 activation including the presence of extracellular ATP, recognized by the cell surface P2X7 receptor (P2X7R). Several pattern recognition receptors on innate immune cells recognize Paracoccidioides brasiliensis components resulting in diverse responses that influence adaptive immunity and disease outcome. However, the role of NLRP3 inflammasome was scantily investigated in pulmonary paracoccidioidomycosis (PCM), leading us to use an intratracheal (i.t.) model of infection to study the influence of this receptor in anti-fungal immunity and severity of infection. For in vivo studies, C57BL/6 mice deficient for several NLRP3 inflammasome components (Nlrp3-/-, Casp1/11-/-, Asc-/-) as well as deficient for ATP receptor (P2x7r-/-) were infected via i.t. with P. brasiliensis and several parameters of immunity and disease severity analyzed at the acute and chronic periods of infection. Pulmonary PCM was more severe in Nlrp3-/-, Casp1/11-/-, Asc-/-, and P2x7r-/- mice as demonstrated by the increased fungal burdens, mortality rates and tissue pathology developed. The more severe disease developed by NLRP3, ASC, and Caspase-1/11 deficient mice was associated with decreased production of IL-1β and IL-18 and reduced inflammatory reactions mediated by PMN leukocytes and activated CD4+ and CD8+ T cells. The decreased T cell immunity was concomitant with increased expansion of CD4+CD25+Foxp3 regulatory T (Treg) cells. Characterization of intracellular cytokines showed a persistent reduction of CD4+ and CD8+ T cells expressing IFN-γ and IL-17 whereas those producing IL-4 and TGF-β appeared in increased frequencies. Histopathological studies showed that all deficient mouse strains developed more severe lesions containing elevated numbers of budding yeast cells resulting in increased mortality rates. Altogether, these findings led us to conclude that the activation of the NLRP3 inflammasome has a crucial role in the immunoprotection against pulmonary PCM by promoting the expansion of Th1/Th17 immunity and reducing the suppressive control mediated by Treg cells.


[Kulturelle Aspekte (in) der Seelsorge - ein Essay].
Work in the field of intercultural communication initially assumed negotiations between 'culturally homogeneous' delegations. In the clinical field, it became apparent that 'cultural homogeneity' cannot be assumed, especially in the 'party' of patients or relatives. Thus, the approach of transculturality was developed for the clinical field. The service of (hospital) pastoral care, if it wants to be understood correctly, must subject itself to a transcultural analysis. It is characterized by a constantly changing, individually shaped 'culture'. This proves to be an opportunity in the clinical field.


Blood Biochemical Reference Intervals for Wild Ornate Box Turtles ( Terrapene ornata) during the Active Season.
Blood biochemical and hematology analyses are helpful indicators of the physiologic health of animals, particularly when making conservation and management decisions for threatened species. In this study, we 1) established blood biochemical reference intervals for two populations of threatened, free-ranging ornate box turtles ( Terrapene ornata) in northern Illinois during their active season and 2) examined the effects of individual carapace temperature ( Tc) on blood biochemical variables by using a Bayesian hierarchical framework. Individual blood variables differed throughout the active season (May-September 2015), but there were few distinct patterns in concentrations over time. When controlling for individual variability, blood biochemical variables potassium, sodium, chloride, ionized calcium, hematocrit (percentage of packed cell volume), and osmolality showed no effect of Tc (i.e., slope estimates for these variables were not credibly different from zero) and had little individual variation. Glucose and urea nitrogen were found to have slopes credibly different from zero, with glucose having an estimated positive slope and urea nitrogen having an estimated negative slope, suggesting different relationships in response to Tc when controlling for individual variability. These physiologic blood data will serve as important baseline reference values for the clinical evaluation of wild ornate box turtles presented for veterinary care or for comparison to other studies of wild populations. Further, this study highlights the importance of considering individual-level effects (e.g., Tc) on physiologic health variables.


Herpes simplex thymidine kinase gene-transduced donor lymphocyte infusions.
Donor lymphocytes mediate both a beneficial graft-vs-leukemia/lymphoma (GVL) effect as well as graft-vs-host disease (GVHD), the most dreaded complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transduction of donor lymphocytes with a herpes simplex thymidine kinase (HSVtk) gene prior to infusion confers lethal sensitivity to the anti-herpes drug, ganciclovir (GCV). HSVtk-transduced donor lymphocyte infusions (DLI) have already been used and significant problems have limited the clinical experience to very few patients. To this end, we also report on a study of whether HSVtk-DLI induces GVHD/GVL and if infusion of GCV allows abrogation of GVHD by selective killing of donor lymphocytes. Nine patients with relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT) were infused with HSVtk gene-modified donor lymphocytes. In brief, transgeneic lymphocytes were prepared by 3 days of activation, 1 day of transduction, 6 days of selection with G418, and 2 to 4 weeks of expansion. From 5.0 to 199 x 10(6) CD3(+) DLI were infused. There were no toxicities and no correlation between CD3(+) cell dose and either GVHD or GVL was observed. Only one patient who had cutaneous T-cell lymphoma (CTCL) developed GVHD and that same patient is the only patient to have an anti-tumor response. The patient was infused with 23 x 10(6) CD4(+) and 9.7 x 10(6) CD8(+) HSVtk DLI. Following discontinuation of immune suppression and infusion of GCV, GVHD promptly resolved. Although the CTCL relapsed, it has been easily controlled with intermittent topical therapy. One patient with acute myelogenous leukemia (AML) had a remission inversion of undetermined significance. Two patients with AML, one patient with lymphoma, and four patients with chronic myelogenous leukemia (CML) did not respond. HSVtk-DLI may provide an anti-tumor effect in vivo and may induce GVHD that is abrogated by GCV treatment. While technical aspects to improve response need to be perfected, HSVtk-DLI infusion to induce a transient GVL/GVHD may become an effective future therapy to minimize complications of allogeneic HSCT.


The cortical dementias.
A striking accumulation of new technologies and recent diverse research developments open new insight into the nature of primary dementias. The gene of the familial form of Alzheimer's disease was located in the chromosome 21. By further study of the amyloid protein precursor gene, laboratory diagnosis and eventual treatment of Alzheimer's disease may become a reality. This paper reviews and adds perspective to old and new data on the cortical dementias: Alzheimer's disease and Pick's disease.


Growth inhibition of seven strains of bovine mycoplasma on solid and semisolid media.
Using the growth inhibition test on semisolid media, the inhibition of mycoplasma growth could be demonstrated even with those antisera that failed to give clear inhibition on solid media under suboptimal growth conditions. The test requires no elaborate equipment and can prove useful as an alternative of , or a supplement to, the growth inhibition test on solid media.


All-in-One Engineering Multifunctional Nanoplatforms for Sensitizing Tumor Low-Temperature Photothermal Therapy In Vivo.
Low-temperature photothermal therapy (PTT) is a noninvasive method that harnesses the photothermal effect at low temperatures to selectively eliminate tumor cells, while safeguarding normal tissues, minimizing thermal damage, and enhancing treatment safety. First we evaluated the transcriptome of tumor cells at the gene level following low-temperature treatment and observed significant enrichment of genes involved in cell cycle and heat response-related signaling pathways. To address this challenge, we have developed an engineering multifunctional nanoplatform that offered an all-in-one strategy for efficient sensitization of low-temperature PTT. Specifically, we utilized MoS2 nanoparticles as the photothermal core to generate low temperature (40-48 °C). The nanoplatform was coated with DPA to load CPT-11 and Fe2+ and was further modified with PEG and iRGD to enhance tumor specificity (MoS2/Fe@CPT-11-PEG-iRGD). Laser- and acid-triggered release of CPT-11 can significantly increase intracellular H2O2 content, cooperate with Fe2+ ions to increase intracellular lipid ROS content, and activate ferroptosis. Furthermore, CPT-11 induced cell cycle arrest in the temperature-sensitive S-phase, and increased lipid ROS levels contributed to the degradation of HSPs protein expression. This synergistic approach could effectively induce tumor cell death by the sensitized low-temperature PTT and the combination of ferroptosis and chemotherapy. Our nanoplatform can also maximize tumor cell eradication and prolong the survival time of tumor-bearing mice in vivo. The multifunctional approach will provide more possibilities for clinical applications of low-temperature PTT and potential avenues for the development of multiple tumor treatments.


Methods of testing and analyzing excito-repellency responses of malaria vectors to insecticides.
A new test system that includes an excito-repellency test box, test procedures, and statistical treatment of data is described. The method consists of enclosing 25 mosquitoes in an exposure chamber lined with insecticide-treated or untreated (control) test papers. Each chamber has a single portal for mosquitoes to escape to a receiving cage, and numbers escaping are manually recorded at 1-min intervals. The exposure chamber accommodates a screened, 2nd chamber that, when placed in the exposure chamber, prevents the mosquitoes from making physical contact with test papers. A full assay utilized one exposure chamber that permits physical contact with insecticide-treated papers, one chamber that permits physical contact with control papers, one chamber that prevents physical contact with insecticide-treated papers, and a 4th chamber that prevents contact with control papers. After insecticide exposure, test populations are held for observations on 24-h mortalities. A survival analysis approach is described for estimating mosquito escape rates and for comparing differences in mosquito escape rates, with or without physical contact with insecticide, among populations, insecticides, and doses of insecticide.


Kinetic analysis in mixed micelles of partially purified rat brain phospholipase D activity and its activation by phosphatidylinositol 4,5-bisphosphate.
A partially purified rat brain membrane phospholipase D (PLD) activity was characterized in a mixed micellar system consisting of 1-palmitoyl-2-[6-N-(7-nitrobenzo-2-oxa-1,3-diazol-4-yl)-amino]capr oyl-phosphatidylcholine (NBD-PC) and Triton X-100, under conditions where Triton X-100 has a surface dilution effect on PLD activity and the catalytic rate is dependent on the surface concentration (expressed in terms of molar ratio) of NBD-PC. PLD activity was specifically activated by phosphatidylinositol 4,5-bisphosphate (PIP2), and the curve of activation versus PIP2 molar ratio fitted a Michaelis-Menten equation with a K(act) value between molar ratios of 0.001-0.002. Maximal activation was observed at a PIP2 molar ratio of 0.01. Similar values were obtained when activities of partially purified PLD as well as membrane-bound PLD were determined towards pure NBD-PC micelles. In the mixed micellar system PIP2 was shown to elevate by 6-22 fold the specificity constant of PLD towards NBD-PC (K(A), which is proportional to Vmax/Km). Kinetic analysis of PLD trans-phosphatidylation activity towards ethanol, 1-propanol and 1-butanol revealed a Michaelis-Menten type dependence on alcohol concentration up to 1000, 200 and 80 mM, respectively. While Vmax values were similar towards all three alcohols, enzyme affinity increased as the alcohol was longer, and Km values for ethanol, 1-propanol and 1-butanol were 291, 75 and 16 mM (respectively). PLD specificity constants (K(A)) towards ethanol, 1-propanol and 1-butanol were shown to be respectively 260, 940 and 5,920 times higher than to water, the competing substrate. 1-Propanol and 1-butanol inhibited PLD activity above 400 and 100 mM, respectively. The present results indicate that partially purified PLD obeys surface dilution kinetics with regard to its phospholipid substrate PC and its cofactor PIP2, and that in the presence of alcohols, its transphosphatidylation activity may be analyzed as a competitive reaction to the hydrolysis reaction.


Immunologic alterations following excisional wounding and immediate repair with syngeneic or allogeneic skin grafts.
Immunosuppression and its associated infectious complications have long been recognized as consequences of major thermal trauma, though the factors that mediate this suppression remain unclear. A murine split-thickness skin graft model was developed to investigate the role of a large surface area wound in the initiation of immunosuppression in the absence of burn injury. Significant T cell-mediated immunosuppression was demonstrated following wounding and immediate repair with either syngeneic or allogeneic split-thickness skin grafts. These results are consistent with previous experiments in a murine burn model treated by escharectomy and resurfacing with syngeneic composite full-thickness skin. Data also supports the concept that mediators of inflammation at the wound site play an important role in postburn immunosuppression. Furthermore, these results suggest that the use of skin allografts during the early postburn period does not adversely affect cell-mediated immunity in any way that could be abrogated by primary autografting.


Oxidative damage mediates the association between polycyclic aromatic hydrocarbon exposure and lung function.
Exposure to polycyclic aromatic hydrocarbons (PAHs) is related to decreased lung function. However, whether oxidative damage is involved in this relationship remains unclear. This study was aimed to explore the potential mediating role of oxidative DNA or lipid damage in the association between PAH exposure and lung function. The urinary levels of monohydroxy polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and lung function parameters were measured among 3367 participants from the baseline of the Wuhan-Zhuhai cohort. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-iso-PGF2α) were determined to evaluate the individuals' oxidative DNA and lipid damage degrees, respectively. Linear mixed models were used to investigate the associations of urinary OH-PAHs, 8-OHdG and 8-iso-PGF2α with lung function parameters. Mediation analysis was further conducted to assess the potential role of oxidative damage in the association between urinary OH-PAHs and lung function. Each one-percentage increase in the sum of urinary OH-PAHs, high-molecular-weight or low-molecular-weight OH-PAHs (ƩOH-PAHs, ƩHMW OH-PAH or ƩLMW OH-PAHs, respectively) was associated with a 0.2152-, 0.2076- or 0.1985- ml decrease in FEV1, and a 0.1891-, 0.2195- or 0.1634- ml decrease in FVC, respectively. Additionally, significantly positive dose-response relationships of ƩOH-PAHs, ƩHMW OH-PAH and ƩLMW OH-PAHs with urinary 8-OHdG or 8-iso-PGF2α, as well as an inverse dose-response relationship between urinary 8-OHdG and FVC, were observed (all P for trend < 0.05). Mediation analysis indicated that urinary 8-OHdG mediated 14.22% of the association between ƩHMW OH-PAH and FVC. Higher levels of oxidative DNA damage might be involved in the decreased levels of FVC caused by high-molecular-weight PAH exposure.


Peptide Transporter CstA Imports Pyruvate in Escherichia coli K-12.
Pyruvate is an important intermediate of central carbon metabolism and connects a variety of metabolic pathways in Escherichia coli Although the intracellular pyruvate concentration is dynamically altered and tightly balanced during cell growth, the pyruvate transport system remains unclear. Here, we identified a pyruvate transporter in E. coli using high-throughput transposon sequencing. The transposon mutant library (a total of 5 × 105 mutants) was serially grown with a toxic pyruvate analog (3-fluoropyruvate [3FP]) to enrich for transposon mutants lacking pyruvate transport function. A total of 52 candidates were selected on the basis of a stringent enrichment level of transposon insertion frequency in response to 3FP treatment. Subsequently, their pyruvate transporter function was examined by conventional functional assays, such as those measuring growth inhibition by the toxic pyruvate analog and pyruvate uptake activity. The pyruvate transporter system comprises CstA and YbdD, which are known as a peptide transporter and a conserved protein, respectively, whose functions are associated with carbon starvation conditions. In addition to the presence of more than one endogenous pyruvate importer, it has been suggested that the E. coli genome encodes constitutive and inducible pyruvate transporters. Our results demonstrated that CstA and YbdD comprise the constitutive pyruvate transporter system in E. coli, which is consistent with the tentative genomic locus previously suggested and the functional relationship with the extracellular pyruvate sensing system. The identification of this pyruvate transporter system provides valuable genetic information for understanding the complex process of pyruvate metabolism in E. coliIMPORTANCE Pyruvate is an important metabolite as a central node in bacterial metabolism, and its intracellular levels are tightly regulated to maintain its functional roles in highly interconnected metabolic pathways. However, an understanding of the mechanism of how bacterial cells excrete and transport pyruvate remains elusive. Using high-throughput transposon sequencing followed by pyruvate uptake activity testing of the selected candidate genes, we found that a pyruvate transporter system comprising CstA and YbdD, currently annotated as a peptide transporter and a conserved protein, respectively, constitutively transports pyruvate. The identification of the physiological role of the pyruvate transporter system provides valuable genetic information for understanding the complex pyruvate metabolism in Escherichia coli.


Nutrition and osteoporosis prevention for the orthopaedic surgeon: A wholefoods approach.
Osteoporosis is a prevalent and debilitating condition with no signs of subsiding. Rising numbers of people consuming nutrient-poor diets coupled with ageing populations and sedentary lifestyles appear to be the main drivers behind this.While the nutrients calcium and vitamin D have received most attention, there is growing evidence that wholefoods and other micronutrients have roles to play in primary and potentially secondary osteoporosis prevention.Until recently, calcium and vitamin D were regarded as the main nutrients essential to bone health but now there are emerging roles for iron, copper and selenium, among others.Fruit and vegetables are still not being eaten in adequate amounts and yet contain micronutrients and phytochemicals useful for bone remodelling (bone formation and resorption) and are essential for reducing inflammation and oxidative stress.There is emerging evidence that dried fruits, such as prunes, provide significant amounts of vitamin K, manganese, boron, copper and potassium which could help to support bone health.Just 50 g of prunes daily have been found to reduce bone resorption after six months when eaten by osteopaenic, postmenopausal women.Dairy foods have an important role in bone health. Carbonated drinks should not replace milk in the diet.A balanced diet containing food groups and nutrients needed for bone health across the whole lifecycle may help to prevent osteoporosis.Greater efforts are needed to employ preventative strategies which involve dietary and physical activity modifications, if the current situation is to improve. Cite this article: EFORT Open Rev 2017;2:300-308. DOI: 10.1302/2058-5241.2.160079.


Quality Assurance of Teleconsultations in a Store-and-Forward Telemedicine Network - Obtaining Patient Follow-up Data and User Feedback.
User surveys in telemedicine networks confirm that follow-up data are essential, both for the specialists who provide advice and for those running the system. We have examined the feasibility of a method for obtaining follow-up data automatically in a store-and-forward network. We distinguish between follow-up, which is information about the progress of a patient and is based on outcomes, and user feedback, which is more general information about the telemedicine system itself, including user satisfaction and the benefits resulting from the use of telemedicine. In the present study, we were able to obtain both kinds of information using a single questionnaire. During a 9-month pilot trial in the Médecins Sans Frontières telemedicine network, an email request for information was sent automatically by the telemedicine system to each referrer exactly 21 days after the initial submission of the case. A total of 201 requests for information were issued by the system and these elicited 41 responses from referrers (a response rate of 20%). The responses were largely positive. For example, 95% of referrers found the advice helpful, 90% said that it clarified their diagnosis, 94% said that it assisted with management of the patient, and 95% said that the telemedicine response was of educational benefit to them. Analysis of the characteristics of the referrers who did not respond, and their cases, did not suggest anything different about them in comparison with referrers who did respond. We were not able to identify obvious factors associated with a failure to respond. Obtaining data by automatic request is feasible. It provides useful information for specialists and for those running the network. Since obtaining follow-up data is essential to best practice, one proposal to improve the response rate is to simplify the automatic requests so that only patient follow-up information is asked for, and to restrict user feedback requests to the cases being assessed each month by the quality assurance panel.


Production of high-titer RCAS retrovirus.
RCAS (B/P) is a replication-competent avian retrovirus engineered by Hughes et al. (J Virol 61:3004-3012, 1987) and is referred to in this chapter as RCAS for simplicity. The RCAS retrovirus has been widely used as a vehicle for stable transduction of a gene into cells both in the developing chick embryo and tissue/cell culture. It can be used for both gain- and loss-function experiments. The ability of this virus to spread among proliferating cells makes it possible to achieve widespread gene transduction in the developing retina. The transduction efficiency of RCAS is highly depending on the titer of the viral stock, particularly for experiments involving solid tissues such as the developing retina. Here, we describe the procedure that we have used for 15 years to generate RCAS viral stocks with a titer of 1-5 × 10(8) pfu/ml.


Tolypocladium terricola sp. N., a new mosquito-killing species of the genus Tolypocladium Gams (Hyphomycetes).
A new entomopathogenic species of the genus Tolypocladium, T. terricola is described from a soil sample from Finalnd. From other known Tolypocladium species, T. terricola differs in morphology, production of secondary metabolites and possession of relatively strong mosquitocidal activity. The fungus is characterized by broad oval conidia (2.5 x 2 microns) with one pointed end which are produced in grape-like clusters, and are not firmly adherent. When treated with T. terricola, mosquito larvae show typical features of intoxication characterized by the concentration of larvae in the centre of cup, hanging by their siphons on the surface.


Cost-effective strategies for the management of vascular disease.
Cardiovascular disease accounts for over 950,000 deaths and an estimated $151 billion in direct and indirect costs. Because of this escalating clinical and financial burden, economic analysis has become essential for the evaluation of preventative therapies for vascular disease. Economic analysis compares competing interventions or management strategies for costs and benefits; more specifically, cost-effectiveness analysis compares cost in financial terms like dollars to measures of effectiveness like years of life saved. Important concepts in the creation of a valid cost-effectiveness analysis include perspective, time horizon, measurement of costs and effectiveness and sensitivity analysis. In patients with peripheral arterial occlusive disease, most morbidity and mortality arises from complications of coronary artery disease. Because coronary artery disease and peripheral arterial occlusive disease commonly occur together and share risk factors, pathophysiology and response to preventative therapy, economic evaluations of preventative therapies for coronary artery disease have relevance for patients with vascular disease. Cost-effectiveness analysis reveals that modification of vascular risk factors like tobacco use, hypertension and hypercholesterolemia improve clinical outcomes at acceptable cost-effectiveness ratios, usually less than $20,000 per year of life saved. More importantly, interventions like smoking cessation or lipid modification in high-risk groups may be cost saving, with treatment costs outweighed by financial benefits. From the patient, clinician and societal perspective, cost-effectiveness analysis supports the aggressive modification of cardiovascular risk factors in patients with peripheral arterial occlusive disease.


Seashore Rhythm Test performance in patients with unilateral temporal lobe damage.
The Seashore Rhythm Test has been reported to be sensitive to right hemisphere dysfunction and, in particular, right temporal lobe integrity. However, several reports have appeared that have failed to support these earlier findings. In the latter studies, the confounding effects of possible bilateral or extratemporal lobe dysfunction in the patient groups could not be ruled out. The present study investigated the Seashore Rhythm Test performance of 38 right-handed seizure patients with evidence of glucose hypometabolism restricted to the right (n = 23) or left (n = 15) temporal lobe on positron computed tomography. Patients were studied prior to and subsequent to unilateral anterior temporal lobectomy for control of medically intractable seizures. No significant difference was found between right and left temporal lobe dysfunctional patients, either pre- or post-lobectomy, which further corroborates that the Seashore Rhythm Test does not discriminate between patients with right vs. left temporal lobe damage.


Correlation between the Severity of Adhesions and Desmoid Disease in Patients with Familial Adenomatous Polyposis: A Prospective Cohort Study.
Clinical experience teaches that intraperitoneal adhesions are more severe in patients with familial adenomatous polyposis than in patients without it. This impression may come from the common association of familial adenomatous polyposis with desmoid disease. To determine whether patients with familial adenomatous polyposis and desmoid disease develop more severe adhesions than those without desmoid disease. Prospectively collected data study. Hereditary colorectal cancer center in a tertiary referral hospital. Patients undergoing first reoperative intra-abdominal surgery for familial adenomatous polyposis: controls were those having their initial abdominal surgery. Surgery and adhesiolysis. Presence and type of desmoid disease; presence and severity of non-desmoid intraperitoneal adhesions. Where patients had multiple operations, only the first reoperative surgery was chosen. Desmoid disease was noted as reaction (sheet) or mass. Adhesions were graded as none, mild (<10 minutes for mobilization), average (10 to 30 minutes) and severe (>30 minutes or significant bowel damage). Patients having first abdominal surgery for familial adenomatous polyposis were used as a control group. A total of 221 patients had no prior surgery: 5% had desmoids and 1% had adhesions. 137 patients underwent reoperative surgery: 39% had desmoid disease (p < 0.05 vs no prior surgery), the highest rate being in patients after ileal pouch anal anastomosis (57%), and 45% had severe adhesions (p < 0.01 vs no prior surgery), worst after Koch pouch (89%) and total proctocolectomy with ileostomy (82%). 36% of patients without desmoid disease had severe adhesions. Desmoid reaction was associated with severe adhesions in 47% of cases, and desmoid tumors were associated with severe adhesions in 66% of cases. Possible limitations include the potential overlap between desmoid adhesions and non-desmoid adhesions as well as the potential for inaccuracy in defining time of adhesiolyses. Familial adenomatous polyposis is associated with severe postoperative adhesions after reoperative abdominal surgery, especially in patients who develop desmoid disease.


Experimental assessment of selected antimotion drugs.
Space motion sickness (SMS) has been a perplexing problem in both the Soviet and U.S. manned space programs. Both the sensory conflict theory (neuronal signal mismatch) and the cephalad fluid shift concept explain the mechanism. This paper reviews the mechanism of action of various drugs that primarily affect brain blood flow or brain metabolism. In particular, Cavinton (apovincamic acid ethyl ester) has been used successfully in offsetting SMS in experimental test subjects.


Anaerobic exercise testing in rehabilitation: A systematic review of available tests and protocols.
Anaerobic capacity assessment in rehabilitation has received increasing scientific attention in recent years. However, anaerobic capacity is not tested consistently in clinical rehabilitation practice. This study reviews tests and protocols for anaerobic capacity in adults with various disabilities (spinal cord injury, cerebral palsy, cerebral vascular accident, lower-limb amputation(s)) and (able-bodied) wheelchair users. PubMed, CINAHL and Web of Science. Papers were screened by 2 independent assessors, and were included when anaerobic exercise tests were performed on the above-selected subject groups. Included articles were checked for methodological quality. A total of 57 papers was included. Upper-body testing [56 protocols] was conducted with arm crank [16] and wheelchair tests [40]. With a few [2] exceptions, modified Wingate (Wingate) protocols and wheelchair sprint tests dominated upper-body anaerobic testing. In lower-body anaerobic work [11], bicycle [3] and recumbent [1], and overground tests [7] were used, in which Wingate, sprint or jump protocols were employed. When equipment is available a Wingate protocol is advised for assessment of anaerobic capacity in rehabilitation. When equipment is not avail-able a 20-45 s sprint test is a good alternative. Future research should focus on standardized tests and protocols specific to different disability groups.


Different patterns of HIV-1 DNA after therapy discontinuation.
By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16-24 weeks to study the possible relationship between DNA and RNA viral load. The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load). Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA. Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects.


Congestive heart failure and axonal polyneuropathy induced by alfacalcidol in a patient with systemic lupus erythematosus.
Abstract We describe the case of a 29-year-old woman with systemic lupus erythematosus (SLE), who developed congestive heart failure and severe axonal polyneuropathy after 9 months of treatment with alfacalcidol for the prevention of corticosteroid-induced osteoporosis. There was no evidence for the exacerbation of SLE. Moreover, both congestive heart failure and axonal polyneuropathy improved after discontinuation of the alfacalcidol without increasing the dose of corticosteroid. Since alfacalcidol is commonly used in the prevention of corticosteroid-induced osteoporosis, rheumatologists should be aware of the presence of this life-threatening adverse effect.


Shunt failure without ventriculomegaly proclaimed by ophthalmic findings.
Four patients who developed increased intracranial pressure from ventricular shunt failure suffered a delay in diagnosis because magnetic resonance imaging of the brain did not show ventriculomegaly and because ophthalmic findings were initially overlooked or misinterpreted. None of the patients had the conventional manifestations of shunt failure: severe headache, nausea, vomiting, and depressed consciousness. Three patients suffered marked, permanent vision loss from chronic papilledema. These cases affirm that increased intracranial pressure may occur in shunt dependency without producing either conventional clinical symptoms or signs on imaging of the brain. Because ophthalmic manifestations may be the major clues to diagnosis, and because irreversible loss of vision is possible if these clues are overlooked, consideration should be given to periodic ophthalmological examination of shunt-dependent patients.


Obstructive sleep apnea: effect of comorbidities and positive airway pressure on all-cause mortality.
Most studies have used cardiovascular and cerebrovascular disease (CVD) end-points to measure the effect of continuous positive airway pressure (CPAP), but pre-diagnostic morbidities involve a range of comorbidities that may influence the consequences of obstructive sleep apnea (OSA). We therefore aimed to evaluate all-cause total mortality after a diagnosis of OSA, the effect of CPAP in women and men, and the potential effect of major comorbidities. We used national registry data as a historical cohort and included 22,135 OSA patients aged 20 years or more with comorbidity data three years before diagnosis and follow-up morbidity and mortality over a period of 17 years. A total of 8129 (37%) accepted CPAP for more than six months; 14,006 (63%) were CPAP non-user/non-compliant. Those treated with CPAP tended to have higher mortality rates. Patients treated with CPAP were more likely to be male, elderly, suffer from diabetes, and present with more cardiovascular diseases than those not treated with CPAP. After a diagnosis of OSA, more patients in the CPAP-treated group developed cardiovascular complications. Female gender was associated with lower mortality, whereas age, diabetes type 2, and hypertension prior to OSA diagnosis were associated with negative effects on outcome. After an OSA diagnosis, male gender, age, diabetes (types 1 and 2), hypertension, and heart failure were all associated with greater mortality. CPAP treatment had a positive effect in middle-aged and elderly people, whereas CPAP in females had no effect on all-cause mortality. CPAP-treated patients present more comorbidities before and after diagnosis compared with non-treated/non-compliant patients, which explains the higher mortality in this group. CPAP treatment is associated with lower mortality rates in middle-aged and elderly (aged 60+ years) males, but only after adjustment for multiple comorbidities. No effect of CPAP treatment on all-cause mortality in female OSA patients was found. Males with OSA, older than 40 years, with comorbidities and a low educational level presented a particularly high mortality risk.


Diabetes mellitus: is it protective against aortic root dilatation?
There is evidence of a negative association between diabetes and both abdominal aortic aneurysm and aortic diameter. However, little information is available on the relation between diabetes and aortic root diameter. We studied 109 patients with type 2 diabetes. Two-dimensional echocardiography was used to measure the aortic root at the aortic annulus, the sinus of Valsalva, the sinotubular junction and the proximal part of the ascending aorta. Measured mean values were compared with 218 age- and sex-matched patients without diabetes. A comparison of the prevalence of aortic regurgitation between the 2 groups was also performed. In patients with diabetes, the mean aortic root dimensions were significantly smaller than in nondiabetic patients (p < 0.05). The prevalence of aortic root dilatation was significantly higher in nondiabetic subjects than in patients with diabetes (9.63 vs. 2.75%; p = 0.025). In the multivariable regression model, diabetes was a significant negative determinant of aortic root size at all measured sites. The prevalence of aortic regurgitation tended to be higher in nondiabetic subjects than in diabetic participants (11 vs. 18.8%); however, the difference did not achieve statistical significance (p = 0.071). In patients with diabetes, the aortic root dimension is significantly smaller than in patients without diabetes.


Characterisation of Phosphate Accumulating Organisms and Techniques for Polyphosphate Detection: A Review.
Phosphate minerals have long been used for the production of phosphorus-based chemicals used in many economic sectors. However, these resources are not renewable and the natural phosphate stocks are decreasing. In this context, the research of new phosphate sources has become necessary. Many types of wastes contain non-negligible phosphate concentrations, such as wastewater. In wastewater treatment plants, phosphorus is eliminated by physicochemical and/or biological techniques. In this latter case, a specific microbiota, phosphate accumulating organisms (PAOs), accumulates phosphate as polyphosphate. This molecule can be considered as an alternative phosphate source, and is directly extracted from wastewater generated by human activities. This review focuses on the techniques which can be applied to enrich and try to isolate these PAOs, and to detect the presence of polyphosphate in microbial cells.


On the use of tert-butanol/water cosolvent systems in production and freeze-drying of poly-ε-caprolactone nanoparticles.
This work deals with the use of a water/tert-butyl alcohol (TBA) system in the manufacturing process of poly-ε-caprolactone (PCL) nanoparticles, namely in the synthesis stage, using the solvent displacement method in a confined impinging jet mixer (CIJM), and in the following freeze-drying stage. The experimental investigation evidenced that the nanoparticles size is significantly reduced with respect to the case where acetone is the solvent. Besides, the solvent evaporation step is not required before freeze-drying as TBA is fully compatible with the freeze-drying process. The effect of initial polymer concentration, flow rate, water to TBA flow rate ratio, and quench volumetric ratio on the mean nanoparticles size was investigated, and a simple equation was proposed to relate the mean nanoparticles size to these operating parameters. Then, freeze-drying of the nanoparticles suspensions was studied. Lyoprotectants (sucrose and mannitol) and steric stabilizers (Cremophor EL and Poloxamer 388) have to be used to avoid nanoparticles aggregation, thus preserving particle size distribution and mean nanoparticles size. Their effect, as well as that of the heating shelf temperature, has been investigated by means of statistical techniques, with the goal to identify which of these factors, or combination of factors, plays the key role in the nanoparticles size preservation at the end of the freeze-drying process.


Effortful control among low-income preschoolers in three cities: Stability, change, and individual differences.
Existing developmental models of effortful control focus more on the roles of child characteristics and parenting and focus less on the contributions of poverty-related stressors to individual differences in children's self-regulatory competence. Using a representative sample of low-income, predominantly African American and Latino children (n = 439), the author examined effortful control at ages 2-4 and again 16 months later. Delayed gratification showed moderate stability and improvement over time. Risk factors were associated with individual differences in these developmental patterns, net of child age, gender, temperament, and child-mother connectedness. Low birth weight compromised preschoolers' delayed gratification and executive control. Exposure to more sociodemographic and residential stressors jeopardized children's executive control but did not jeopardize delayed gratification.


Ambient air levels and trends of polychlorinated biphenyls at four different sites.
In this study, samples were collected in order to determine atmospheric levels of polychlorinated biphenyls (PCBs) in four different sites by using a high-volume air sampler (HVAS). Eighty-three congeners of gas and particle- phase PCBs were investigated in air samples. The total (gas + particle) concentrations for Mudanya (coastal), Butal (traffic/urban), the Uludag University Campus (semirural), and Yavuz Selim (residential) were determined as 570, 394, 412, and 316 pg/m(3), respectively. These levels coincide with the values reported for the sites having similar characteristics. In terms of homolog groups, 3-chlorinated biphenyls (3-CBs) and 4-CBs constituted at least 47% of the total PCB concentration. PCBs in all sites were determined mostly in the gas phase, with a percentage from 85 to 95%. Obtained atmospheric PCB data were correlated with meteorological parameters and a significant relationship was obtained between coastal and semirural sites (p < 0.05). With the movements of air transportation and wind rose possible data sources of PCBs were enlightened. Partitioning of gas/particle was examined with available models; significant relationships were determined for coastal and semirural sites especially.


Fractal dynamics in dexterous tool use: the case of hammering behavior of bead craftsmen.
Dexterous behavior exhibits exquisite context sensitivity, implying the efficacy of exploration to detect the task-relevant information. Inspired by the recent finding that fractal scaling of exploratory movements predicts how well the movements sample available perceptual information, we investigate the possibility that dexterity of craftsmen would be characterized by fractal (long-range) temporal correlation properties of fluctuations in their movement wielding a tool. A reanalysis of hammering behavior involved in stone beads production in India (Nonaka & Bril, 2012) revealed the presence of long-range, power-law correlations, as part of multiplicative cascades operating over a wide range of time scales. In the unfamiliar condition using unusual material, the wielding behavior of highly skilled experts displayed a significant increase of long-range temporal correlations, whereas that of less experts exhibited a significant loss of long-range correlations and reduced heterogeneity of scaling properties over time, which robustly discriminated the groups with different skill levels. Alterations in long-range correlation properties of movement fluctuations are apparently associated with changes in the situation differently depending on the level of expertise.


A dialog on common morality in medical ethics in a pluralist setting in Iran: a qualitative content analysis.
The concept of common morality is fundamental in medical ethics, and lack of universal content and characteristics of common morality is a product of its multifaceted nature. This study aimed to identify the ideas and experiences of academic faculties regarding common morality in a pluralistic setting to promote conceptual knowledge and strengthen moral reasoning and ethical decision-making. The study was conducted using a qualitative method, employing semi-structured in-depth interviews with thirteen faculty members who were selected purposively. In order to assess their ideas and experiences, the transcripts of the interviews were analyzed using the content analysis method through directed and conventional approaches. The interviews were coded manually. Two themes were reflected in the interviews: ontology and epistemology of common morality. The study indicates that the debate about the subjective or objective dependence of common morality questions the coherence of Beauchamp and Childress' common morality (CM) theory, as common morality is the result of various individual and social factor that influence moral and decision -making in pluralistic environments. Additional studies are needed in order to investigate the effect of cultural, social, theoretical, ideological and individual factors on promoting clinical ethical reasoning and decision-making skills.


The experience of nursing women with breastfeeding support: a qualitative inquiry.
Breastfeeding difficulties are a common occurrence, are highly personal and can vary from one infant to the next for any mother. Multiple sources of support, help and advice for breastfeeding are available to nursing mothers. Evidence suggests that the experience of the quality of breastfeeding supports may play an important role in maternal mental health and well-being in the postpartum period. We sought to explore the experiences of nursing mothers with support they received for breastfeeding in order to better inform and optimize existing breastfeeding supports and interventions. We conducted a qualitative inquiry of nursing mothers' experiences with help, advice and support for breastfeeding. Participants were asked to provide open-ended, written accounts of their experiences with all sources of breastfeeding support received in the 6 months following the delivery of a healthy full-term infant in Calgary. We conducted qualitative thematic analysis, using constant comparison techniques. The sample included 86 mothers. Our analyses uncovered 4 emergent themes that contributed to the perceived quality of breastfeeding support: knowledge, effectiveness, sensitivity/emotional support and accessible when sought. Our study provides a greater understanding of how mothers perceive the quality of the breastfeeding support that they receive, as well as what qualities of breastfeeding support are seen as beneficial or negative. The qualities contributing to the perception of breastfeeding support are important to inform and optimize perinatal care, and potentially reduce the risk of negative mental health outcomes for mothers.


Gingipains from Porphyromonas gingivalis W83 synergistically disrupt endothelial cell adhesion and can induce caspase-independent apoptosis.
We have shown previously that gingipains from Porphyromonas gingivalis W83 can induce cell detachment, cell adhesion molecule (CAM) cleavage, and apoptosis in endothelial cells; however, the specific roles of the individual gingipains are unclear. Using purified gingipains, we determined that each of the gingipains can cleave CAMs to varying degrees with differing kinetics. Kgp and HRgpA work together to quickly detach endothelial cells. Interestingly, in the absence of active caspases, both gingipain-active W83 extracts and purified HRgpA and RgpB induce apoptotic morphology, suggesting that the gingipains can induce both caspase-dependent and caspase-independent apoptosis. Using z-VAD-FMK to inhibit Kgp activity and leupeptin to inhibit Rgp activity in gingipain-active W83 extracts, we investigated the relative significance of the synergistic role of the gingipains. z-VAD-FMK or leupeptin delayed, but did not inhibit, cell detachment induced by gingipain-active W83 extracts or purified gingipains. There was partial cleavage of N-cadherin and cleavage of VE-cadherin was not inhibited. Degradation of integrin beta1 was inhibited only in the presence of z-VAD-FMK. These results further clarify the role P. gingivalis plays in tissue destruction occurring in the periodontal pocket.


Concentration of antipneumococcal antibodies as a serological correlate of protection: an application to acute otitis media.
For the licensing of new pneumococcal vaccines, it is vital to be able to predict their protective efficacy on the basis of immunogenicity. However, the serological correlates of protection have not been established for pneumococcal diseases. A total of 1666 children were immunized with the pneumococcal conjugate vaccine. Acute otitis media (AOM) events were identified, and middle-ear fluid was cultured for pneumococci. The association between the concentration of antibodies against serotypes 6B, 19F, and 23F and the risk of AOM caused by the homologous serotypes or by the cross-reactive serotype 6A was assessed. An association model was used to predict efficacy at different geometric mean concentrations (GMCs). An association between antibody concentration and risk of AOM was found, but with large differences between serotypes. On the basis of the association, the predicted efficacy for 19F was negligible up to the highest GMC tested. In contrast, 6B was found to be highly efficacious (>65%) at a GMC of 0.5 microg/mL. The results challenge the view that a new vaccine candidate should always induce antibody concentrations that are not inferior to those produced by the licensed vaccine. Furthermore, the differences between serotypes caution against defining a common correlate of protection that is applicable to all serotypes.


Immigration and the New Racial Diversity in Rural America.
This article highlights the new racial and ethnic diversity in rural America, which may be the most important but least anticipated population shift in recent demographic history. Ethnoracial change is central to virtually every aspect of rural America over the foreseeable future: agro-food systems, community life, labor force change, economic development, schools and schooling, demographic change, intergroup relations, and politics. The goal here is to plainly illustrate how America's racial and ethnic transformation has emerged as an important dimension of ongoing U.S. urbanization and urbanism, growing cultural and economic heterogeneity, and a putative "decline in community" in rural America. Rural communities provide a natural laboratory for better understanding the implications of uneven settlement and racial diversity, acculturation, and economic and political incorporation among Hispanic newcomers. This article raises the prospect of a new racial balkanization and outlines key impediments to full incorporation of Hispanics into rural and small town community life. Immigration and the new ethnoracial diversity will be at the leading edge of major changes in rural community life as the nation moves toward becoming a majority-minority society by 2042.


Response of Escherichia coli hypermutators to selection pressure with antimicrobial agents from different classes.
The responses of hypermutable Escherichia coli strains to selection with antibiotics having different endogenous resistance potentials were determined. Selections with rifampicin or ciprofloxacin at 4 x MIC, i.e. conditions where they act as single target agents against RpoB and GyrA, respectively, demonstrated that some hypermutators generated resistant mutants with frequencies up to 1000-fold higher than normal strains. Furthermore, individual mutants recovered from hypermutable hosts often exhibited higher levels of resistance to the drugs than mutants arising in normal hosts. Exposure to ciprofloxacin at 16 x MIC, i.e. conditions where it has low endogenous resistance potential, failed to select resistant mutants in hypermutable or normal hosts (mutation frequency <10(-11)). Consistent with these findings, the highest estimated mutation frequency for selection at 16 x MIC in a hypermutable host would be 4.4 x 10(-15) (mutT), calculated by determining the individual mutation frequencies for first-step ciprofloxacin resistance and second-step resistance arising in hosts already harbouring single first-step mutations in gyrA at codons 83 or 87. The frequency with which second-step ciprofloxacin resistance mutations arose was suppressed in hypermutators and demonstrated at most a 10-fold increase in mutation rate compared with non-hypermutator hosts. Second-step mutants may contain mutations in mar, since a survey of 170 second-step ciprofloxacin-resistant mutants derived from both hypermutator and non-hypermutator parents demonstrated that they all possessed increased resistance to chloramphenicol, a phenotype associated with mar mutations. Exposure to 4 x MIC of D-cycloserine, cefotaxime or polymyxin B (agents with multiple targets or membrane activity) failed to select resistant mutants in normal or hypermutator hosts (mutation frequency <10(-11)); however, continuous culture in the presence of sub-lethal concentrations of D-cycloserine (0.25 x MIC) selected resistant mutants in hypermutators after c. 33 generations, compared with c. 44 generations in normal hosts. Since hypermutable bacteria occur naturally, our data emphasize that successful new drugs will need to possess low endogenous resistance potentials.


Driver Movement Patterns Indicate Distraction and Engagement.
Objective This research considers how driver movements in video clips of naturalistic driving are related to observer subjective ratings of distraction and engagement behaviors. Background Naturalistic driving video provides a unique window into driver behavior unmatched by crash data, roadside observations, or driving simulator experiments. However, manually coding many thousands of hours of video is impractical. An objective method is needed to identify driver behaviors suggestive of distracted or disengaged driving for automated computer vision analysis to access this rich source of data. Method Visual analog scales ranging from 0 to 10 were created, and observers rated their perception of driver distraction and engagement behaviors from selected naturalistic driving videos. Driver kinematics time series were extracted from frame-by-frame coding of driver motions, including head rotation, head flexion/extension, and hands on/off the steering wheel. Results The ratings were consistent among participants. A statistical model predicting average ratings from the kinematic features accounted for 54% of distraction rating variance and 50% of engagement rating variance. Conclusion Rated distraction behavior was positively related to the magnitude of head rotation and fraction of time the hands were off the wheel. Rated engagement behavior was positively related to the variation of head rotation and negatively related to the fraction of time the hands were off the wheel. Application If automated computer vision can code simple kinematic features, such as driver head and hand movements, then large-volume naturalistic driving videos could be automatically analyzed to identify instances when drivers were distracted or disengaged.


Tropisetron suppresses collagen synthesis in skin fibroblasts via α7 nicotinic acetylcholine receptor and attenuates fibrosis in a scleroderma mouse model.
There is increasing evidence that serotonin (5-hydroxytryptamine [5-HT]) and distinct 5-HT receptors are involved in the pathogenesis of systemic sclerosis. The aim of this study was to test the hypothesis that tropisetron, a routinely used antiemetic agent previously characterized as a 5-HT(3/4) receptor-modulating agent, can directly affect collagen synthesis in vitro and attenuate experimentally induced fibrosis in vivo. Functional in vitro studies were performed using human dermal fibroblasts (HDFs). Signal transduction studies included immunofluorescence analysis, Western immunoblotting, promoter reporter assays, cAMP/Ca(2+) measurements, and use of pharmacologic activators and inhibitors. Gene silencing was performed using small interfering RNA. Putative receptors of tropisetron were detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. The murine model of bleomycin-induced scleroderma was used to assess the antifibrogenic and antifibrotic effects of tropisetron in vivo. Collagen expression in vitro, ex vivo, and in situ was determined by real-time RT-PCR analysis, Western immunoblotting, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunohistochemical analysis. Tropisetron suppressed collagen synthesis induced by transforming growth factor β1 (TGFβ1). This effect was independent of 5-HT(3/4) receptor but was mediated via α7 nicotinic acetylcholine receptor (α7nAChR). Suppression of TGFβ1-induced collagen synthesis occurred via an unknown molecular mechanism not involving modulation of the Smad, cAMP, Akt, c-Jun, or MAPK pathway. In vivo, tropisetron not only prevented skin fibrosis but also reduced the collagen content in established dermal fibrosis induced by bleomycin. Tropisetron directly reduces collagen synthesis in HDFs via an α7nAChR-dependent mechanism. The antifibrogenic and antifibrotic effects of this agent observed in a mouse model of bleomycin- induced scleroderma indicate the future potential of tropisetron in the treatment of fibrotic diseases such as scleroderma.


Diffuse diseases of the myocardium: MRI-pathologic review of nondilated cardiomyopathies.
This article will present correlation of the key radiologic findings with gross and microscopic pathology for the characterization of diffuse myocardial diseases using advanced imaging techniques. Our goal is to provide a focused and in-depth review of the pathophysiology underlying each entity and to emphasize the structural basis for the corresponding imaging characteristics. This article is limited to those disorders characterized by ventricular wall thickening without chamber dilatation, including hypertrophic cardiomyopathy, hypertensive cardiomyopathy, and cardiac amyloidosis. For the characterization of diffuse myocardial diseases using advanced imaging techniques, it is essential to understand the underlying pathologic changes in the heart. With these techniques, such as cardiac MRI, the various cardiomyopathies can be differentiated accurately, which may potentially obviate invasive testing and endomyocardial biopsy.


Optimization of iron-doped Ni3S2 nanosheets by disorder engineering for oxygen evolution reaction.
Nowadays, disorder engineering of catalytic materials has attracted significant attention because it can increase catalytic active sites and thus enhance their catalytic activity for electrocatalytic reactions. However, it is extremely important to uncover the relationship between disorder engineering and catalytic activity. Particularly, deep exploration of the relationship is very important for fabricating excellent highly active catalysts for oxygen evolution reaction (OER), which is one of the promising technologies in energy transition. In this study, we prepared Fe-doped Ni3S2 materials and simultaneously controlled the disorder degree by regulating the ion concentration to improve the activity for OER. By investigating the as-prepared catalysts with various disorder degrees for OER, we also explored the relationship between the disordered structure and OER catalytic performance. In particular, the optimized electrocatalyst with an appropriate disorder degree showed excellent activity and stability. We hope that this study provides a feasible direction to fabricate and optimize transition metal chalcogenide (TMC) electrocatalysts as efficient and stable electrocatalysts for OER.


Mitochondrial intermembrane junctional complexes and their involvement in cell death.
Mitochondria establish contact sites between the inner and outer membranes. The contact sites are held together by junctional complexes of the adenine nucleotide translocase (ANT; inner membrane) and the voltage-dependent anion channel (VDAC; outer membrane). The junctional complexes act as multifunctional recruitment centres, binding a range of proteins according to the function to be executed. Some of these, involving kinases and enzymes of lipid transfer, are readily understood as ongoing functions in energy and lipid metabolism. But the roles of other proteins recruited to the junctional complexes are less well defined. Here, we focus on the complexes formed with Bax and with cyclophilin-D, and their possible roles in apoptotic and necrotic cell death. We have isolated both types of complexes using glutathione-S-transferase fusion proteins of Bax and of cyclophilin-D. The VDAC/ANT/cyclophilin-D complex reconstitutes Ca(2+)- and cyclosporin A-sensitive permeability transition pore activity when incorporated into proteoliposomes. The complex forms readily in the absence of factors required for pore opening in isolated mitochondria, suggesting that these factors act on the preexisting complex, rather than drive its assembly, and that the complex is a physiological entity in healthy cells.


[Complete reconstruction of the nose using a prefabricated free forearm graft].
The aim of prefabricated free transplants is to create a composite graft including a vascular pedicle with artery and vein, a muscle and its nerve, cellular tissue, bony tissue, cartilage, periosteum, and skin with its sensory nerve. This composite transplant is entirely constructed and modelled around the chosen vascular pedicle beforehand. Once the various materials of the future graft are removed and put in contact with the vascular pedicle, the subsequent neovascularisation should nourish the different elements. The vasculonervous pedicle, with the graft, are transplanted five weeks after preconstruction, revascularized and reinnervated. With these free prefabricated transplants, graft tissue which does not exist in the organism can be created. Cosmetic sequellae can be avoided since the vascular pedicle is chosen beforehand. Ear-nose-throat and plastic surgeons have used local structural preconstruction for many years, especially for ear reconstruction. The work presented here has the original feature of revascularized free transplant. From 1988, we have performed two complete reconstructions of the nose using a free forearm transplant modelled into a nasal pyramid. The classical techniques could not be used. In the first case a radius strut was used to form the nasal crest. In the second a chondrocostal cartilage was used. Transplantation was performed five weeks after preconstruction. In both cases, transplant viability was excellent but the cosmetic and functional results were less than satisfactory and required reoperation.


Evaluating the Financial Vulnerability of a Major Electric Utility in the Southeastern U.S. to Drought under Climate Change and an Evolving Generation Mix.
There is increasing recognition of the vulnerability of electric power systems to drought and the potential for both climate change and a shifting generation mix to alter this vulnerability. Nonetheless, the considerable research in this area has not been synthesized to inform electric utilities with respect to a key factor that influences their decisions about critical infrastructure: financial risk for shareholders. This study addresses this gap in knowledge by developing a systems framework for assessing the financial exposure of utilities to drought, with further consideration of the effects of climate change and a shifting generation mix. We then apply this framework to a major utility in the Southeastern U.S. Results suggest that extreme drought could cause profit shortfalls of more than $100 million if water temperature regulations are strictly enforced. However, even losses of this magnitude would not significantly impact returns for shareholders. This may inadvertently reduce pressure internally at utilities to incorporate drought vulnerability into long-term strategic planning, potentially leaving utilities and their customers at greater risk in the future.


[The needs of mothers of children affected by skin diseases].
The needs assessment of mothers with children affected by dermatitis is as crucial as technical interventions. The child's disease may modify mothers' priorities of needs. Aim of the study is to identify priority of needs in mothers of children admitted to a dermatological hospital (IDI-IRCSS) in Rome. Data were collected between May and June 2007. The Needs Assessment Questionnaire and the Patient Global Assessment (PGA) were distributed to 160 mothers to assess the perceived severity of the disease. The main needs were to receive more information about diagnosis (59%), more care after discharge (48%), more information about treatments (36%) a better symptoms control (36%) and to receive informational material (33%). Mothers who perceived very severe the illness of their children expressed an higher need to receive more care after discharge (63%) and a better symptoms control (56%) compared to those with lower severity scores. The need of information about diagnosis is the first priority irrespective of the perceived severity of the illness. Information and education are crucial to involve mothers in the caring process. Nurses can improve critical areas of dermatological care through identification of needs.


MK801 impairs thermoregulation in the heat.
The effects of MK801 (dizocilpine), a glutamate NMDA receptor antagonist, on thermoregulation in the heat were studied in awake rats exposed to 40 degrees C ambient temperature until their body core temperature reached 43 degrees C. Under these conditions, MK801-treated rats exhibited enhanced locomotor activity and a steady rise in body core temperature, which reduced the heat exposure duration required to reach 43 degrees C. Since MK801-treated rats also showed increased striatal dopaminergic metabolism at thermoneutrality, the role of dopamine in the MK801-induced impairment of thermoregulation in the heat was determined using co-treatment with SCH23390, a dopamine D1 receptor antagonist. SCH23390 normalized the locomotor activity in the heat without any effect on the heat exposure duration. These results suggest that the MK801-induced impairment of thermoregulation in the heat is related to neither a dopamine metabolism alteration nor a locomotor activity enhancement.


Photoresistance switching of plasmonic nanopores.
Fast and reversible modulation of ion flow through nanosized apertures is important for many nanofluidic applications, including sensing and separation systems. Here, we present the first demonstration of a reversible plasmon-controlled nanofluidic valve. We show that plasmonic nanopores (solid-state nanopores integrated with metal nanocavities) can be used as a fluidic switch upon optical excitation. We systematically investigate the effects of laser illumination of single plasmonic nanopores and experimentally demonstrate photoresistance switching where fluidic transport and ion flow are switched on or off. This is manifested as a large (∼ 1-2 orders of magnitude) increase in the ionic nanopore resistance and an accompanying current rectification upon illumination at high laser powers (tens of milliwatts). At lower laser powers, the resistance decreases monotonically with increasing power, followed by an abrupt transition to high resistances at a certain threshold power. A similar rapid transition, although at a lower threshold power, is observed when the power is instead swept from high to low power. This hysteretic behavior is found to be dependent on the rate of the power sweep. The photoresistance switching effect is attributed to plasmon-induced formation and growth of nanobubbles that reversibly block the ionic current through the nanopore from one side of the membrane. This explanation is corroborated by finite-element simulations of a nanobubble in the nanopore that show the switching and the rectification.