Comparison of different analytical techniques for the analysis of carotenoids in tamarillo (Solanum betaceum Cav.).
An on-line method based on the coupling of supercritical fluid extraction and supercritical fluid chromatography with triple quadrupole mass spectrometry detection (SFE-SFC-QqQ/MS) for the native carotenoids characterization and apocarotenoids detection in yellow tamarillo was developed for the first time; this is the first work reporting the application of this methodology for the apocarotenoids analysis in any matrix. An off-line liquid extraction (LE) and analysis by LC-PDA-MS, using both a conventional C30 (3 μm I.D. particles) and a novel C30 column with sub-2 micron particles were also performed. 31 compounds were extracted and identified by the developed SFE-SFC-QqQ/MS methodology in less than 18 min, including free carotenoids, carotenoids monoesters, carotenoids diesters and apocarotenoids in a very fast, and efficient way; moreover among those 31 compounds, 3 antheraxanthin monoesters and 9 apocarotenoids were detected in yellow tamarillo for the first time, namely apo-8'-zeaxanthinal, apo-10'-zeaxanthinal, apo-12'-zeaxanthinal, apo-14'-zeaxanthinal, apo-15'-zeaxanthinal, apo-12'-carotenal, apo-14'-carotenal and the two apocarotenoids esters apo-10'-zeaxanthinal-C4:0 and apo-8'-zeaxanthinal-C12:0. Further, the novel sub-2 micron particles C30 column, showed a better performance compared to the conventional C30 one. Finally a quantitative comparison of two selected carotenoids was performed by using SFE-SFC-QqQ/MS, SFC-QqQ/MS, and LC-PDA, which showed overall comparable results.


CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis.
The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (±0.034) vs HD 0.039 Giga/L (±0.030), p < 0.01, and dSSc 0.071 Giga/L (±0.034) vs lSSc 0.048 Giga/L (±0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.


Managing symptoms and maximizing quality of life after preventive interventions for cancer risk reduction.
The prevention of breast, ovarian and endometrial cancer frequently involves hormonal or surgical interventions. Each of these may have noncancerous sequelae and can affect quality of life in women with hereditary cancer syndromes. The purpose of this review is to discuss the medical management of hormonal suppression and surgical menopause in hereditary breast and ovarian cancer syndromes and in Lynch syndrome. As we gain a better understanding of genetic cancer risk, we are able to reduce the development of cancer with risk-reducing surgery. Understanding the significance of noncancer outcomes helps improve surveillance and treatment strategies and improves our understanding of the interaction between our interventions and their effects on quality of life. Advances in our understanding of the pathogenesis of hereditary breast and ovarian cancer, as well as the difference in ovarian ageing in these high-risk women, allow us to improve our counselling and interventions for family planning and risk-reducing surgery. Studies are ongoing regarding the optimal surveillance of cardiovascular and bone health after risk-reducing salpingo-oophorectomy, although more studies are needed regarding the optimal management of sexual health and other quality of life measures.


When Less Is More - Discrete Tactile Feedback Dominates Continuous Audio Biofeedback in the Integrated Percept While Controlling a Myoelectric Prosthetic Hand.
State of the art myoelectric hand prostheses can restore some feedforward motor function to their users, but they cannot yet restore sensory feedback. It has been shown, using psychophysical tests, that multi-modal sensory feedback is readily used in the formation of the users' representation of the control task in their central nervous system - their internal model. Hence, to fully describe the effect of providing feedback to prosthesis users, not only should functional outcomes be assessed, but so should the internal model. In this study, we compare the complex interactions between two different feedback types, as well as a combination of the two, on the internal model, and the functional performance of naïve participants without limb difference. We show that adding complementary audio biofeedback to visual feedback enables the development of a significantly stronger internal model for controlling a myoelectric hand compared to visual feedback alone, but adding discrete vibrotactile feedback to vision does not. Both types of feedback, however, improved the functional grasping abilities to a similar degree. Contrary to our expectations, when both types of feedback are combined, the discrete vibrotactile feedback seems to dominate the continuous audio feedback. This finding indicates that simply adding sensory information may not necessarily enhance the formation of the internal model in the short term. In fact, it could even degrade it. These results support our argument that assessment of the internal model is crucial to understanding the effects of any type of feedback, although we cannot be sure that the metrics used here describe the internal model exhaustively. Furthermore, all the feedback types tested herein have been proven to provide significant functional benefits to the participants using a myoelectrically controlled robotic hand. This article, therefore, proposes a crucial conceptual and methodological addition to the evaluation of sensory feedback for upper limb prostheses - the internal model - as well as new types of feedback that promise to significantly and considerably improve functional prosthesis control.


The effect of image enhancements and dual observers on proximal caries detection.
The aim of this study was to determine if the use of certain image enhancements and dual observers had an effect on the detection of caries, dentin extension, and cavitation. Seven observers viewed unenhanced and enhanced images taken on photostimulable phosphor plates (PSP) and Schick 33 sensors and were asked to determine whether proximal caries lesions, dentin extension, and cavitation were present. Pairs of observers also evaluated the unenhanced PSP images and recorded their confidence. Micro-computed tomography was used as the gold standard. For caries lesion detection, PSP outperformed Schick sensors, although the differences are most likely not clinically significant. Observers (single and dual) and filters had no effect on any of the diagnostic tasks. Schick sensors and unfiltered images were more specific for dentin extension. Caries detection was statistically greater with the PSP plate, but both detectors allowed for high accuracy. Expensive software or time-consuming consultations did not improve outcomes.


[Aliskiren (Rasilez), direct renin inhibitor].
Aliskiren (Rasilez) is the first oral renin inhibitor. Its present indication is essential hypertension, as monotherapy or in combination with other antihypertensive agents (diuretic, calcium antagonist, ...). It may also be associated with an angiotensin converting enzyme inhibitor (or an AT1 angiotensin receptor antagonist) in order to benefit of a dual blockade of the renin-angiotensin-aldosterone system. The usual daily dose is 150 mg, to be increased up to 300 mg if necessary. New clinical trials are ongoing to validate this novel therapeutic approach in other indications such as congestive heart failure and diabetic nephropathy.


Interstitial Pneumonitis Secondary to Trastuzumab: A Case Report and Literature Review.
Interstitial lung disease is a rare complication of trastuzumab-based breast cancer treatment with few case reports published. Herein, we report the case of a 67-year-old female with early-stage HER2-postitive breast cancer who developed interstitial pneumonitis during cycle 5 of treatment with trastuzumab combined with carboplatin and docetaxel. After supportive care and treatment with prednisone, the patient showed rapid improvement of respiratory symptoms. Retreatment with trastuzumab as a single agent led to worsening of symptoms and required a second course of treatment with prednisone combined with cyclophosphamide, which was followed by improvement of symptoms. In conclusion, interstitial pneumonitis is a rare but life-threatening adverse event from trastuzumab breast cancer treatment.


Children's theories of intelligence: beliefs, goals, and motivation in the elementary years.
The authors tested a developmental model of children's theories about intelligence in kindergarten, second grade, and fourth grade children by using paper-and-pencil maze tasks. Older children were more likely than younger children to espouse learning goals (e.g., that they preferred difficult mazes to improve their skill), and less likely to espouse performance goals (e.g., that they preferred easy mazes to be successful). Children in all 3 age groups reported stronger beliefs in the malleability of intelligence than the stability of intelligence. In general, the results supported the authors' hypotheses about developmental change in children's theory-like conceptions of intelligence: Beliefs, goals, and motivation were related in expected ways for second and fourth graders more than for kindergartners. The authors discussed contextual influences on children's beliefs and the development of children's conceptualizations of intelligence.


Characterisation of the metal-ion-GDP complex at the active sites of transforming and nontransforming p21 proteins by observation of the 17O-Mn superhyperfine coupling and by kinetic methods.
Kinetic studies on the interaction of three Ha-ras-encoded p21 proteins with GDP and MgGDP have yielded values for the association (10(6)-10(7) M-1 s-1) and dissociation (10(-3)-10(-5) s-1) rate constants at 0 degrees C. Dramatic differences in the rate constants were not observed for the three proteins. Under non-physiological conditions (absence of Mg2+), the rate constant for GDP release was an order of magnitude faster for the viral protein p21v than for the cellular form p21c or the T24 mutant p21t, but this was reduced to a factor of about 3 in the presence of Mg2+. In all cases, there was an increase of about one order of magnitude in the rate of GDP release on removing magnesium. The binding affinities ranged from 5.7 X 10(10) M-1 for p21c to 1.3 X 10(11) M-1 for p21v. Electron paramagnetic resonance (EPR) measurements on Mn2+ bound together with stereospecifically 17O-labelled GDP showed direct coordination of a beta-phosphate oxygen to the metal ion with a superhyperfine coupling constant of 0.16-0.22 mT, but no interaction with the alpha-phosphate oxygens at the active site of all three proteins. The association constant of Mn(II) to p21 proteins in the absence of nucleotides was estimated to be greater than 10(5) M-1. In agreement with the EPR results, experiments on the metal ion dependence of the binding of thiophosphate analogs of GDP provided further evidence for the absence of direct coordination of the metal ion to the alpha-phosphate group. These results have been used to construct a model for the interactions of Mg X GDP with the active site of p21 proteins.


Analysis of farmers' willingness to participate in pasture grazing programs: Results from a discrete choice experiment with German dairy farmers.
Over the last decades, the usage of pasture for grazing of dairy cows has decreased considerably. Pasture grazing programs initiated by dairy companies try to counteract this trend. The present paper investigates farmers' willingness to participate in such grazing programs. A special aim was to quantify the price premiums farmers require for program participation and to identify determinants influencing the premium level. The empirical analysis is based on a discrete choice experiment with 293 German dairy farmers. Models are estimated in terms of willingness to accept. It was found that farmers have no substantial preference for whether the pasture grazing program is financed by the food industry, a governmental scheme, or the dairy company. However, an extension of the annual or daily grazing period results in a decreasing willingness of farmers to participate in a pasture grazing program. In addition, farmers decline the option of a feeding standard prescribing the use of only green fodder when offered an alternative program that merely reduces the amount of concentrated feed or maize silage in the diet. Farmers' with an aversion toward program participation have a significant higher price demand for fulfilling the program requirements. Furthermore, the required price premiums increase with growing milk yields and a greater number of cows kept on the farm. However, if the availability of pasture is high, farmers are more likely to participate. The estimated price premiums and factors influencing farmers' willingness to participate found by this study should be considered by dairies and policymakers to gain insights into the design of possible pasture grazing programs from the perspective of farmers. Thereby, paying price premiums to farmers may increase the attractiveness of pasture grazing, which could finally result in an extended usage of pasture grazing.


Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals.
A deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO synthesis and increases superoxide production. Supplementation of BH4 has been postulated to improve endothelial function in atherosclerotic patients. The purpose of this study was to determine whether BH4 restores endothelium-dependent vasodilation in patients with essential hypertension. We evaluated the effects of BH4 on forearm vascular responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, both in patients with essential hypertension and in age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using strain gauge plethysmography. The response of FBF to ACh was less in hypertensive patients (n = 8) than in normal control subjects (n = 8). There was no significant difference in FBF response to ISDN in the two groups. During coinfusion of BH4 (500 mg/min), the FBF response to ACh in hypertensive patients increased significantly (14.8 +/- 4.6 to 25.6 +/- 7.3 mL/min/100 mL tissue, P < .05) to the level of normal control subjects. In the control subjects, also, BH4 augmented the FBF response to ACh (27.8 +/- 8.7 to 36.1 +/- 9.6 mL/min/100 mL tissue, P < .05). The increase in FBF after ISDN was not altered by BH4 in either group (each group, n = 6). Supplementation of BH4 augments endothelium-dependent vasodilation in both normotensive and hypertensive individuals.


Pathologic Characterization of Coinfection with Histomonas meleagridis, Marek's Disease Virus, and Subtype J Avian Leukosis Virus in Chickens.
Histomonas meleagridis is a trichomonad protozoan parasite that can cause an important poultry disease known as histomoniasis; Marek's disease virus (MDV) and subtype J avian leukosis virus (ALV-J) usually cause avian oncogenic diseases. Although these diseases have been reported in a single pathogen infection, information about their coinfection is scarce. This study reports a naturally occurring case of coinfection with H. meleagridis, MDV, and ALV-J in a local chicken flock at the age of 150 days. Necropsy revealed necrosis and swelling in the liver and spleen. Histologic analysis showed large areas of mild to severe necrosis of hepatocytes, with numerous intralesional trophozoites of H. meleagridis by H&E and periodic acid-Schiff staining; H&E staining showed pleomorphic and neoplastic lymphoid tumor cells in the liver and myeloid cells with eosinophilic cytoplasmic granules in the spleen. Coexpression of MDV and ALV-J antigens was detected in the liver by fluorescence multiplex immunohistochemistry staining. The 18S rRNA gene of H. meleagridis, meq gene of MDV, and gp85 gene of ALV-J were identified in mixed liver and spleen tissues by PCR and sequencing, respectively.


Glutamine synthetase and heteroresistance in methicillin-resistant Staphylococcus aureus.
Inactivation of femC in methicillin-resistant Staphylococcus aureus (MRSA) results in lowered methicillin resistance and a reduction in the amidation of the iso-D-glutamate of the peptidoglycan stem peptide. The femC phenotype is due to insertional inactivation of the glutamine synthetase repressor gene glnR by Tn551, which has a polar effect on glutamine synthetase (glnA) transcription. The complete glutamine synthetase operon (glnRA) of S. aureus was cloned and sequenced, and its transcriptional start was determined. The deduced amino acid sequence of the staphylococcal glutamine synthetase showed 76% identity and 87% similarity to the Bacillus subtilis glutamine synthetase. The staphylococcal glnRA operon was shown to complement an Escherichia coli glutamine synthetase-negative mutant and to restore methicillin resistance in femC mutants. femC mutants revert to resistance in the presence of high concentrations of methicillin. These revertants, which still carried the femC lesion, were shown to retain the lowered amidation of the iso-D-glutamate peptidoglycan stem peptide. A new chromosomal locus hmrC was postulated to have mutated to allow expression of high methicillin resistance in these femC revertants. Although the highly resistant hmrC revertant resembled phenotypically the highly methicillin-resistant subclones occurring in heterogeneously resistant MRSA, we could show by transduction that the locus hmrC was distinct from chr*, a chromosomal site postulated to confer high methicillin resistance in heterogeneous MRSA. This suggests that S. aureus can adopt multiple ways to achieve high methicillin resistance.


Health-relevant personality is associated with sensitivity to sound (hyperacusis).
Hyperacusis, over-sensitivity to sounds, causes distress and disability and the etiology is not fully understood. The study aims to explore possible associations between health-relevant personality traits and hyperacusis. Hyperacusis was assessed using the Hyperacusis Questionnaire (HQ), and clinical uncomfortable loudness levels (ULL). Personality was measured with the Health-relevant Personality (HP5i) Inventory. The study sample was 348 (140 men and 208 women; age 23-71 years). Moderate correlations were found between the personality trait negative affectivity (NA; a facet of neuroticism) and dimensions of the HQ and weak correlations were found with the ULLs. Hedonic capacity (a facet of extraversion) was significantly correlated with the HQ but not with the ULLs. Impulsivity (a facet of conscientiousness) was correlated with the HQ and the ULLs. A significant difference in mean values was found in all hyperacusis measures and different levels of NA - those with higher levels displayed more severe signs of hyperacusis. A multiple logistic regression analysis showed that higher levels of NA increases the odds of having hyperacusis on average 4.6 times for men and 2.4 times for women. These findings imply that health-relevant personality traits should be considered in the diagnosis and treatment of hyperacusis.


HORSE SPECIES SYMPOSIUM: Can the microbiome of the horse be altered to improve digestion?
Intensive management practices in the horse industry present a unique challenge to the microbiome of the large intestine. Common management practices such as high-concentrate diets, low forage quality, meal feeding, and confinement housing have an impact on intestinal function, specifically large intestinal fermentation. The microbiome of the equine large intestine is a complex and diverse ecosystem, and disruption of microbiota and their environment can lead to increased incidence of gastrointestinal disorder. Digestion in the horse can be improved through a variety of approaches such as feedstuff selection, forage quality, feeding management, and inclusion of digestive aids. These digestive aids, such as prebiotics and probiotics, have been used to improve digestibility of equine diets and stabilize the microbiome of the large intestine. Probiotics, or direct-fed microbials, have been widely used in horses for treatment and prevention of gastrointestinal disease. The introduction of these live, beneficial microorganisms orally into the intestinal tract has yielded variable results. However, it is difficult to compare data due to variations in choice of organism, dosage, and basal diet. Although there are still many unanswered questions about the mode of action of successful probiotics, evidence indicates competitive inhibition and enhanced immunity. Lactic acid bacteria such as , and and yeast have all successfully been used in the horse. Use of these products has resulted in improved fiber digestibility in horses offered both high-starch and high-fiber diets. When high-concentrate diets were fed, probiotic supplementation helped maintain cecal pH, decreased lactic acid concentrations, and enhanced populations of cellulolytic bacteria. Similarly, use of prebiotic preparations containing fructooligosaccharide (FOS) or mannanoligosaccharides have improved DM, CP, and NDF digestibility when added to high-fiber diets. Furthermore, use of FOS in horses reduced disruptions in colonic microbial populations after an abrupt change in diet and altered fecal VFA concentrations toward propionate and butyrate. Potential use of prebiotics and probiotics to create greater stability in the equine microbiome impacts not only the digestibility of feed but also the health of the horse.


Localization of epitopes and functional effects of two novel monoclonal antibodies against skeletal muscle myosin.
Two skeletal myosin monoclonal antibodies, raised against human skeletal myosin, were used to study the correlation between function, primary and tertiary structure of S-1 prepared from rabbit skeletal myosin. The heavy chain of S-1 is cleaved into three fragments by trypsin--27 kDa, 50 kDa and 20 kDa--aligned in this order from the N-terminus. The epitope of the first antibody was assigned to the N-terminal 1-23 amino acid stretch of S-1, since it reacted with the 27 kDa N-terminal tryptic fragment of S-1 but not with a derivative of the 27 kDa fragment, which lacks the above amino acid stretch. The epitope of the second antibody was assigned to the 3 kDa N-terminal region of the central 50 kDa domain of S-1. This assignment was based on proteolytic and photochemical cleavage of S-1 and on the labelling of its N-terminus by a specific antibody. The antibodies were visualized binding to the myosin head on electron micrographs of rotary-shadowed complexes of antibodies with myosin. Measurements on the micrographs indicated that the distances between the head-tail junction of myosin and the 'anti-27 K' and 'anti-50 K' epitopes are 14 nm and 17 nm, respectively. Both antibodies have a high affinity to S-1. The affinity of the 'anti-50 K' to S-1 decreased upon actin binding, while that of the 'anti-27 K' was not affected by binding of S-1 to F-actin. The 'anti-50 K' antibody inhibited the K+ (EDTA) and the actin-activated ATPase activity of S-1, while the 'anti-27 K' had no effect. The results indicate that either the epitope of the 'anti-50 K' is near to the actin or to the ATP-binding sites of S-1, or that there is communication, expressed as propagated conformational changes, between these sites and the epitope.


Chronic experimental autoimmune myasthenia gravis induced by monoclonal antibody to acetylcholine receptor: biochemical and electrophysiologic criteria.
To determine whether the chronic presence of antibody to acetylcholine receptor (AChR) can account for the neuromuscular abnormalities in myasthenia gravis (MG), rats injected repeatedly with monoclonal antibody (mAb) to AChR were compared with those injected with control mAb. In a previous report, those receiving anti-AChR mAb, studied ultrastructurally, had grossly simplified endplates when compared with normal controls. In this report, animals injected once or chronically for 9 to 12 wk had reduced content of muscle AChR. The chronically injected animals also had diminished miniature endplate potential amplitudes, but to a lesser extent than the reduction in AChR content. These studies establish the pathogenetic role of antibody to AChR in the induction of the ultrastructural, biochemical, and electrophysiologic hallmarks of MG.


Molecular Dynamics and Diffusion in Amorphous Solid Dispersions Containing Imidacloprid.
The main goal of this study is to develop an experimental toolbox to estimate the self-diffusion coefficient of active ingredients (AI) in single-phase amorphous solid dispersions (ASD) close to the glass transition of the mixture using dielectric spectroscopy (DS) and oscillatory rheology. The proposed methodology is tested for a model system containing the insecticide imidacloprid (IMI) and the copolymer copovidone (PVP/VA) prepared via hot-melt extrusion. For this purpose, reorientational and the viscoelastic structural (α-)relaxation time constants of hot-melt-extruded ASDs were obtained via DS and shear rheology, respectively. These were then utilized to extract the viscosity as well as the fragility index of the dispersions as input parameters to the fractional Stokes-Einstein (F-SE) relation. Furthermore, a modified version of Almond-West (AW) formalism, originally developed to describe charge diffusion in ionic conductors, was exercised on the present model system for the estimation of the AI diffusion coefficients based on shear modulus relaxation times. Our results revealed that, at the calorimetric glass-transition temperature (Tg), the self-diffusion coefficients of the AI in the compositional range from infinite dilution up to 60 wt % IMI content lied in the narrow range of 10-18-10-20 m2 s-1, while the viscosity values of the dispersions at Tg varied between 108 Pa s and 1010 Pa s. In addition, the phase diagram of the IMI-PVP/VA system was determined using the melting point depression method via differential scanning calorimetry (DSC), while mid-infrared (IR) spectroscopy was employed to investigate the intermolecular interactions within the solid dispersions. In this respect, the findings of a modest variation in melting point at different compositions stayed in agreement with the observations of weak hydrogen bonding interactions between the AI and the polymer. Moreover, IR spectroscopy showed the intermolecular IMI-IMI hydrogen bonding to have been considerably suppressed, as a result of the spatial separation of the AI molecules within the ASDs. In summary, this study provides experimental approaches to study diffusivity in ASDs using DS and oscillatory rheology, in addition to contributing to an enhanced understanding of the interactions and phase behavior in these systems.


Anti-cancer Effect of a Planar Catechin Analog through the Decrease in Mitochondrial Membrane Potential.
Catechin is one of the best-known antioxidants and is reported to have some favorable physiological activities, including anti-cancer effects. We previously synthesized a catechin analog, planar catechin, which showed a 10-fold larger radical scavenging activity than (+)-catechin. However, the physiological effects of the planar catechin have remained unclear. In this study, we examined cytotoxicity and mitochondrial membrane potential after planar catechin treatment using a rat normal gastric mucosal cell line, RGM1, and its chemically induced cancer-like cell line, RGK1. Interestingly, the planar catechin showed remarkable cytotoxicity compared to (+)-catechin, with cancer cell specificity. Furthermore, the decrease in the mitochondrial membrane potential of cancer cells was observed at specific concentrations of the planar catechin. These results indicate that the planar catechin, possessing higher antioxidant activity, induces its anti-cancer effect through a decrease in the mitochondrial membrane potential and thus can be a promising agent for cancer treatment.


Benign neonatal sleep myoclonus. Relationship to sleep states.
Neonatal sleep myoclonus is a benign syndrome characterized by myoclonic jerks occurring only during sleep and presenting in the first month of life. There are no associations with abnormal development, neurologic deficits, or seizures. The electroencephalogram is normal and has no correlation with the myoclonic jerks. The myoclonus is present in all sleep states although its frequency is state dependent and greatest during quiet sleep. It is not associated with an arousal response as previously thought. Transient serotonin imbalance and genetic factors might play a role in the pathogenesis of this disorder.


Induction of CD25 expression in human B lymphocytes by pharmacological activators of cellular signalling pathways.
IL-4 promotes simultaneous expression of both the CD23 and CD25 antigens in resting human B lymphocytes in a dose-dependent manner. Simultaneous three-colour flow cytometric analysis revealed that CD19+/CD23+/CD25+ triple-positive cells were derived from a CD19+/CD23-/CD25- pool, and that induction of CD23 required lower doses of IL-4 than did induction of CD25. Although the concentrations of IL-4 required for half-maximal up-regulation of CD23 (35 pM) and CD25 (150 pM) expression were different, the capacity of IL-4 to promote expression of the two markers could be mimicked by the same combination of pharmacological agents. Thus, maximal expression of CD23 and CD25 was obtained with a 30 (or 120) second pulse with phorbol ester and/or ionomycin followed by a sustained (20 minute) treatment with forskolin. Use of BAPTA to chelate intracellular calcium suggested that IL-4 driven CD25 expression required mobilization of intracellular Ca2+. Finally, down-regulation of cellular protein kinase C by chronic treatment of resting B lymphocytes with phorbol ester abolished the ability of IL-4 to elevate CD23 and CD25 expression; phorbol ester treatment similarly abrogated the ability of anti-CD40 and anti-Ig reagents to promote expression of CD25. The data are consistent with the proposal that IL-4 influences CD23 and CD25 expression via a similar signal transduction pathway which involves both protein kinase C activation and elevation of intracellular cAMP levels.


Vitamin D metabolism and anticonvulsant therapy: effect of sunshine on incidence of osteomalacia.
To study the association between anticonvulsant therapy and osteomalacia or rickets, we evaluated 450 epileptic patients receiving anticonvulsants and residing in an institution for the mentally retarded in Florida. Fifty-five of them with increased mean serum alkaline phosphatase and mildly depressed mean serum calcium levels were identified as being at risk for having osteomalacia. None of them, however, had low serum levels of vitamin D (25[OH]D) or radiologic evidence of osteomalacia or rickets. In contrast to reports from northern climates, we found minimal evidence of anticonvulsant-induced bone disease. The study suggests that exposure to sunshine in our patients probably prevented the development of anticonvulsant-induced osteomalacia or rickets.


Spiritual support for families of patients with cancer: a pilot study of nursing staff assessments.
The results reported in this article are drawn from a larger study aimed at describing and explaining the support provided by nursing staff to the families of patients with cancer. The purpose of this component of the study was to explore the views of nursing staff on the importance of spiritual support as well as their readiness and willingness to provide that support. A further concern was with the provision of spiritual support, obstacles to providing support, and related factors. A total of 166 nurses (registered nurses and licensed practical nurses) from 5 central hospitals in Finland participated. The data were collected using a structured questionnaire in which spiritual support was measured by multiple-choice items and one open-ended question. Analysis of the multiple-choice items was based on SPSS statistical software, and interpretation of the responses to the open-ended question relied on the method of content analysis. There was broad agreement on the importance of providing spiritual support to family members, however, 58% of the nurses believed they were poorly equipped to provide support and 53% were less or not at all willing to provide spiritual support. Willingness to provide support was lowest among licensed practical nurses. Willingness and readiness to provide support were related to on another. Overall, nursing staff rarely discussed spiritual issues with or offered spiritual support to family members. The study also revealed many obstacles to the provision of spiritual support. The age of nursing staff and the type of ward were associated with the provision of spiritual support.


Mapping the MMPI-2-RF Specific Problems Scales Onto Extant Psychopathology Structures.
A main objective in developing the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008 ) was to link the hierarchical structure of the instrument's scales to contemporary psychopathology and personality models for greater enhancement of construct validity. Initial evidence published with the Restructured Clinical scales has indicated promising results in that the higher order structure of these measures maps onto those reported in the extant psychopathology literature. This study focused on evaluating the internal structure of the Specific Problems and Interest scales, which have not yet been examined in this manner. Two large, mixed-gender outpatient and correctional samples were used. Exploratory factor analyses revealed consistent evidence for a 4-factor structure representing somatization, negative affect, externalizing, and social detachment. Convergent and discriminant validity analyses in the outpatient sample yielded a pattern of results consistent with expectations. These findings add further evidence to indicate that the MMPI-2-RF hierarchy of scales map onto extant psychopathology literature, and also add support to the notion that somatization and detachment should be considered important higher order domains in the psychopathology literature.


Trends in anthropogenic mercury emissions in China from 1995 to 2003.
We have developed multiple-year inventories of anthropogenic mercury emissions in China for 1995 through 2003. We estimate that total Hg emissions from all anthropogenic sources increased at an average annual rate of 2.9% during the period 1995-2003, reaching 696 (+/- 307) t in 2003, with a speciation split of 395 t of Hg0, 230 t of Hg2+, and 70 t of Hg(p). Nonferrous metals smelting and coal combustion continue to be the two leading mercury sources in China, as nonferrous metals production and coal consumption keep increasing. Nonferrous metals smelting and coal combustion together contributed approximately 80% of total Hg emissions during the past decade. Hg emissions from coal combustion increased from 202 t in 1995 to 257 t in 2003 at an average annual rate of 3.0%. Among all of the coal consumption sectors, the power sector is the leading one in Hg emissions growth, up by 5.9% annually. Hg emissions from nonferrous metals smelting increased from 230 t in 1995 to 321 t in 2003 at an average annual rate of 4.2%. Although Hg emissions related to gold smelting decreased since 1996, other nonferrous metals such as zinc, lead, and copper contributed significant Hg growth at annual rates of 8.5%, 13.0%, and 6.9%, respectively. At provincial level, the trends of Hg emissions show significant variation. The uncertainty level decreased from +/- 78% (95% confidence interval) in the estimate of total emissions in 1995, to +/- 44% in 2003. This is primarily attributed to the decreased emissions from those Hg sources with the largest uncertainty in both activity levels and emission factors, such as artisanal gold smelting, mercury mining, and battery/fluorescent lamp production.


A role for stromal autophagy in cancer-associated fibroblast activation.
In the tumor stroma, cancer-associated fibroblasts (CAFs) affect all aspects of tumor evolution. Whereas several programs leading to CAF activation have been elucidated, little is known about the impact of the microenvironment on the turnover of key CAF regulators. RBPJ/CSL is a transcriptional repressor that mediates NOTCH signaling and its down-modulation activates the gene expression program(s) leading to stromal senescence and CAF activation. We overview our evidence that conditions increasing macroautophagy/autophagy, as often found in the stroma of tumors, cause the down-modulation of the RBPJ protein. This event requires the autophagic machinery and is functionally relevant because it is associated with an increase of CAF effector gene expression. The mechanism involves the direct association with the autophagy receptor SQSTM1/p62, which is required for RBPJ down-modulation. As a reflection of increased autophagy in the stroma, both the RBPJ and SQSTM1 proteins are down-modulated in Squamous Cell Carcinoma (SCC) patient-derived CAFs. Increasing RBPJ cellular levels stabilizes SQSTM1 and down-modulates the autophagic process. Our findings identify an autophagy-initiated mechanism for RBPJ down-modulation leading to increased CAF gene expression.


Effects of School-Based Educational Program on Backpack Carrying Behavior in Teenage Students.
One of the most serious issues is the growing prevalence of backaches among adolescent students as a result of carrying backpacks. The purpose of this study was to examine the impact of an education program (remedial information) on the school backpack carrying habits of adolescent students. The study sample consisted of 138 adolescent students aged 12 to 16 from 4 schools who were randomly assigned to either the experimental (N = 69) or control (N = 69) groups. The experimental group was subjected to a 6-week education program consisting of 6 sessions, whereas the control group received no educational intervention. During the pre-test and 3 months after the intervention, participants completed a questionnaire. The results (healthy items) were as follows: (1) carry as little as possible, (2) carry a school backpack on both shoulders, and (3) use lockers or something similar. After a 3-month follow-up, healthy items in the experimental group improved, but no significant changes were observed in the control group. When compared to the baseline, the experimental group's healthy backpack usage habits improved significantly at the post-test (P = .001). The current study's findings show that school-based education interventions on backpack behaviors improve the school-bag carrying habits of adolescent students.


Effects of Orchard Pesticides on Galendromus occidentalis (Acari: Phytoseiidae): Repellency and Irritancy.
The effects of repellency or irritancy in Galendromus occidentalis (Nesbitt) were studied for three rates of 16 pesticides commonly used in apple production. Adult female mites were exposed to residues in a series of choice bioassays (treated and untreated half of bean leaf disks). Novaluron, carbaryl, mancozeb+copper hydroxide, and sulfur were the most repellent materials to G. occidentalis, with females consistently avoiding the treated side of the leaf disk. Spirotetramat, flubendiamide, and cyantriniliprole caused an intermediate or inconsistent degree of repellency; azinphosmethyl, lambda-cyhalothrin, acetamiprid, thiacloprid, imidacloprid, spinetoram, spinosad, and chlorantriniliprole caused little to no repellency. Irritancy (running off of the disk, as opposed to resting on the untreated half) was the most pronounced in the acetamiprid and lambda-cyhalothrin treatments. Acute toxicity (within the 6 h test period) was highest in the lambda-cyhalothrin and spinetoram treatments; in the former case, the mortality at all rates tested was substantial enough to interfere with the measurement of behavioral effects. Although irritancy may be considered the more extreme form of repellency, there were several pesticides (carbaryl, cyantraniliprole, mancozeb+copper hydroxide, novaluron) where a moderate to high degree of repellency did not correspond to a high degree of irritancy. Similarly, repellency was not consistently related to acute toxicity; one of the most repellent materials (novaluron) was not acutely toxic. Behavioral effects may help explain instances where lethal or sublethal bioassays do not fully predict the effects of pesticides seen in orchard use.


The effect of common sclerosing agents on the rabbit pleural space.
New Zealand white rabbits received intrapleural instillations of either tetracycline (7, 20, and 35 mg/kg), HCI (0.01N), quinacrine (10 mg/kg), nitrogen mustard (0.2 mg/kg), bleomycin (1.5 mg/kg), or NaOH (0.5%). All sclerosing agents produced a neutrophil-predominant, exudative pleural effusion within 12 h of instillation. By 48 h the pleural fluid was predominantly mononuclear. Despite the large pH range of the sclerosing agents (tetracycline, 2.0; NaOH, 13.0), the pleural fluid pH was always between 7.40 and 7.49 during the 144-h observation period. There was no difference in protein concentration, leukocyte count, or neutrophil differential with either the 3 different doses of tetracycline or the 5 other sclerosing agents. Autopsies at 30 days showed that only the 35 mg/kg dose of tetracycline produced pleural symphysis. We concluded that the common sclerosing agents produce a similar type of pleural effusion, but only tetracycline leads to pleural fibrosis; this effect appears to be dose-dependent. The pH of the sclerosing agent per se probably has little effect on the development of pleural symphysis.


Kinetic considerations on the electrogenerated luminescence of luminol at platinum electrode in the presence of hydrogen peroxide and oxygen.
The ECL behavior of the luminol/H2O2 and luminol/O2 systems was evaluated at Pt electrode by using different electroanalytical techniques such as chronoamperometry, cyclic and rotating disk electrode (RDE) voltammetry. Diffusive and kinetic parameters such as the diffusion coefficient of luminol, D, the number of exchanged electrons, n, and the apparent heterogeneous rate constant, kap, were determined in the maximum light emission conditions achieved at pH 11, at an electrode potential of 750 mV vs. SCE. The experimental order of reaction were determined from the relation between the reactant concentrations and the emitted light intensity.


Pulp tissue dissolution capacity of QMix 2in1 irrigation solution.
The aim of this study was to evaluate the tissue dissolution efficacy of four root canal irrigation solutions (sodium hypochlorite [NaOCl], chlorhexidine gluconate [CHX], Octenidine [OCT], and QMix 2in1) on bovine pulp tissue. Fifty bovine pulp tissue samples, each weighing 6.55 mg, were prepared and randomly divided into four experimental groups and one control group (n = 10) according to the dissolution irrigants used: (1) 5.25% NaOCl group; (2) 2% CHX group; (3) OCT group; (4) QMix 2in1 group; and (5) control group (saline solution). These samples were then placed into special bovine dentin reservoir models and immersed for 1 h with each test solution (0.1 mL of each) at room temperature. The pulp samples were then blotted dry and weighed again. The percentage of weight loss was calculated. Statistically analyzed with one-way analysis of variance and post-hoc Tukey tests (P = 0.05). Saline solution did not dissolve the bovine pulp tissue. All groups, except OCT, dissolved pulp samples more effectively than the control group (P < 0.05). The highest tissue dissolution was observed in 5.25% NaOCl group (P < 0.05). No statistically significant difference was found between the tissue-dissolving effect between QMix 2in1 and those of 2% CHX. Within the limitations of this in vitro study, NaOCl exhibited the best tissue-dissolving effect out of all solutions tested. CHX and QMix 2in1 were able to dissolve pulp tissue but less than NaOCl. OCT and saline solutions could not exhibit significantly tissue-dissolving effectiveness. This study shown that QMix 2in1 has little capacity to dissolve pulp tissue therefore used alone is not sufficient for this purpose.


EEG-Based Analysis of the Emotional Effect of Music Therapy on Palliative Care Cancer Patients.
Music is known to have the power to induce strong emotions. The present study assessed, based on Electroencephalography (EEG) data, the emotional response of terminally ill cancer patients to a music therapy intervention in a randomized controlled trial. A sample of 40 participants from the palliative care unit in the Hospital del Mar in Barcelona was randomly assigned to two groups of 20. The first group [experimental group (EG)] participated in a session of music therapy (MT), and the second group [control group (CG)] was provided with company. Based on our previous work on EEG-based emotion detection, instantaneous emotional indicators in the form of a coordinate in the arousal-valence plane were extracted from the participants' EEG data. The emotional indicators were analyzed in order to quantify (1) the overall emotional effect of MT on the patients compared to controls, and (2) the relative effect of the different MT techniques applied during each session. During each MT session, five conditions were considered: I (initial patient's state before MT starts), C1 (passive listening), C2 (active listening), R (relaxation), and F (final patient's state). EEG data analysis showed a significant increase in valence (p = 0.0004) and arousal (p = 0.003) between I and F in the EG. No significant changes were found in the CG. This results can be interpreted as a positive emotional effect of MT in advanced cancer patients. In addition, according to pre- and post-intervention questionnaire responses, participants in the EG also showed a significant decrease in tiredness, anxiety and breathing difficulties, as well as an increase in levels of well-being. No equivalent changes were observed in the CG.


Clinical performance of laminate and non-laminate resin composite restorations: a systematic review.
A systematic review was undertaken to determine the clinical outcomes of resin modified glass-ionomer cement or glass-ionomer cement-resin composite (RMGIC/GIC-RC) laminate restorations and flowable resin composite (FRC)-lined RC restorations compared to that of non-laminate RC restorations. Electronic databases were searched and filtered for relevant papers by assessing titles, abstracts and full-text articles. Randomized controlled clinical trials (RCTs) were included, comparing the clinical performance of RMGIC/GIC-RC laminate restorations and FRC-lined restorations with RC restorations as the control. The articles were categorized and critically appraised. Raw data were used for a fixed effects meta-analysis. Thirteen articles were included in the review. Five evaluated FRC-lined restorations, and eight studies evaluated RMGIC/GIC-RC laminate restorations, comparing with non-laminate RC restorations. Three of eight RMGIC/GIC-RC laminate restorations assessed only postoperative sensitivity. A meta-analysis could only be conducted in three studies with the FRC-lined restorations as the intervention. The meta-analysis found no significant difference in clinical failures between FRC-lined RC restorations and RC restorations with no lining (p > 0.05). Based on current clinical evidence, a FRC lining is no more advantageous than RC restorations with no FRC lining. More long-term RCTs are required, particularly for evaluating RMGIC/GIC-RC laminate restorations.


Pituitary and adrenal responses to pulsatile ovine corticotropin-releasing factor administered to fetal sheep.
In fetal sheep a bolus injection of ovine CRF (oCRF) elevates plasma immunoreactive ACTH (IR-ACTH) during the last 5 weeks of gestation. However, the effects of long term administration of oCRF to fetal sheep have not been studied. We examined the effects of pulsatile administration of oCRF (1 microgram every 4 h) for 7 days on fetal pituitary and adrenal responses, as reflected by plasma concentrations of IR-ACTH and cortisol (F). In addition, we examined the effects of oCRF on cAMP accumulation by dispersed pituitary cells in vitro after treatment in vivo with either oCRF or saline. Pulsed oCRF (P-CRF) treatment resulted in a significant (P less than 0.05) increase in basal IR-ACTH and F concentrations on all days of treatment. However, the pituitary response (change in IR-ACTH in response to a pulse of oCRF) decreased, and the adrenal response (change in F in response to endogenously secreted ACTH) increased as treatment progressed. A significant inverse correlation (r = 0.962) between basal F and the IR-ACTH response to oCRF was seen over the 7 days of treatment. Although P-CRF treatment resulted in an increase in fetal adrenal weight, it did not lead to premature parturition. There was a dose-dependent accumulation of cAMP in response to oCRF in vitro by dispersed pituitary cells from both groups of fetuses. However, this response was significantly greater when the fetuses had been pretreated with oCRF in vivo than after saline treatment. We conclude that the P-CRF regimen employed in this study stimulates the fetal pituitary-adrenal axis and the ability of fetal pituitary cells to accumulate cAMP in response to further oCRF in vitro. The reduced plasma IR-ACTH response after continued P-CRF in vivo may be attributed to increasing negative feedback effects of elevated endogenous F.


[Psychometric properties of the Hospital Ethical Climate Survey: a cross-sectional study among Belgian psychiatric nurses].
The task of caring for psychiatric patients is so complex that it often leads to ethical dilemmas. The ethical climate on a ward is a crucial factor. This is the first study about the ethical climate in mental healthcare. To investigate whether the only instrument currently available for measuring the ethical climate in general hospitals, namely the 'Hospital Ethical Climate Survey' (HECS), is a reliable and valid instrument for use on psychiatric wards. A cross-sectional study was performed in a psychiatric hospital in Belgium. All 320 nurses were invited to participate (response rate = 265). The factor structure of the HECS was examined by means of explorative principal component analysis (PCA) and confirmatory factor analysis (CFA). The reliability of the constructed scale and subscales was investigated. Five factors were identified. The structure of these factors in the translated list was almost identical to the structure obtained with the original instrument and its underlying theoretical basis. Items relating to several other allied healthcare professions were added. This addition widened the subscale 'relationship with physician' so that it included 'relationship with other disciplines' (medical and allied healthcare workers). The reliability of the instrument appeared to be good and yielded scores comparable to those obtained as a result of earlier research performed in general hospitals. The setting for our investigation produced a significantly higher main score for the ethical climate than did previous studies.


Connexins in the lens: are they to blame in diabetic cataractogenesis?
The pathohistology of the diabetic lens is an enigma. Under normal conditions the lens behaves as a functional syncitium, whereas the diabetic lens exhibits a localized zone of fibre cell swelling and rupture that is confined to the lens outer cortex. Because the lens fibre cells are extensively coupled by gap junction channels, it is believed that the abnormal closure of these channels is responsible for this phenomenon. New evidence concerning regional differences in gap junction gating supports this contention, and it is used to propose a new hypothesis that may explain the cellular changes observed in the diabetic lens.


The influence of bacterial lipopolysaccharide on the thermoregulation of the box turtle Terrapene carolina.
Ectotherms can adjust their thermoregulatory set points in response to bacterial infection; the result may be similar to endothermic fever. We examined the influence of dose on the set point of body temperature (T(b)) in Terrapene carolina. After acclimating postprandial turtles to 20 degrees C, we injected them with two doses of bacterial endotoxin (LPS; lipopolysaccharide from Escherichia coli), 0.0025 or 0.025 mg LPS/g nonshell body mass, or with reptilian saline (control group). We placed the animals singly in linear thigmothermal gradients and recorded their T(b)'s for 48 h. The turtles showed dose-influenced thermal selection. Turtles injected with the high dose had T(b)'s significantly higher than control turtles, whereas low-dose turtles had T(b)'s significantly lower than control turtles. Also, there was a low daily effect on the T(b) of the turtles injected with the high dose. High-dose turtles had significantly higher T(b)'s than the control turtles during the first day but not during the second. Our results support the prediction of Romanovsky and Székely that an infectious agent may elicit opposite thermoregulatory responses depending on quality and quantity of the agent and the host health status.


Hepatotoxicity mediated by pyrazole (cytochrome P450 2E1) plus tumor necrosis factor alpha treatment occurs in c-Jun N-terminal kinase 2-/- but not in c-Jun N-terminal kinase 1-/- mice.
Cytochrome P450 2E1 (CYP2E1) induction and tumor necrosis factor alpha (TNF-α) production are key risk factors in alcoholic liver injury. Increased oxidative stress from CYP2E1 induction by pyrazole in vivo sensitizes the liver to TNF-α-induced hepatotoxicity by a mechanism involving the activation of c-jun N-terminal kinase (JNK) and mitochondrial damage. The aim of this study was to evaluate whether JNK1 or JNK2 plays a role in this potentiated hepatotoxicity. Wild-type (WT), jnk1(-/-) , and jnk2(-/-) mice were used to identify changes of hepatotoxicity, damage to mitochondria, and production of oxidative stress after pyrazole plus TNF-α treatment. Increased serum alanine aminotransferase, inflammatory infiltration, and central necrosis were observed in the jnk2(-/-) and WT mice treated with pyrazole plus TNF-α, but not in the jnk1(-/-) mice. Pyrazole elevated the activity and protein level of CYP2E1 in all mice. There was a significant increase of malondialdehyde, 4-hydroxynonenal adducts, 3-nitrotyrosine, and inducible nitric oxide synthase in the jnk2(-/-) and WT mice, compared to the jnk1(-/-) mice, upon pyrazole plus TNF-α treatment, or compared to mice treated with either pyrazole alone or TNF-α alone. The antioxidants, catalase, phospholipid hydroperoxide glutathione peroxidase, thioredoxin, and glutathione were lowered, and cytochrome c was released from the mitochondria in the jnk2(-/-) and WT mice. Mitochondrial production of superoxide was increased in the jnk2(-/-) and WT mice, compared to the jnk1(-/-) mice, upon pyrazole plus TNF-α treatment. Electron microscopy showed altered mitochondrial structure in the jnk2(-/-) and WT mice, but not the jnk1(-/-) mice. JNK1 plays a role in the hepatotoxicity, mitochondrial dysfunction, and oxidative stress mediated by pyrazole plus TNF-α treatment. These findings raise the question as to the potential mechanisms of JNK1 activation related to alcoholic liver injury.


Tibial stress injuries - location, severity, and classification in magnetic resonance imaging examination.
To describe and illustrate the spectrum of magnetic resonance imaging (MRI) findings of tibial stress injuries (TSI) and propose a simplified classification system. Retrospective analysis of MRI exams of 44 patients with clinical suspicion of unilateral or bilateral TSI, using a modified classification system to evaluate the intensity and location of soft-tissue changes and bone changes. Most of the patients were young athletic men diagnosed in late stage of TSI. Changes were predominantly found in the middle and distal parts of tibias along medial and posterior borders. TSI may be suspected in young, healthy patients with exertional lower leg pain. MRI is the only diagnostic method to visualise early oedematic signs of TSI. Knowledge of typical locations of TSI can be helpful in proper diagnosis before its evolution to stress fracture.


[Study on a back propogation neural network-based predictive model for prevalence of birth defect].
To evaluate the value of a back propogation (BP) network on prediction of birth defect and to give clues on its prevention. Data of birth defect in Shenyang from 1995 to 2005 were used as a training set to predict the prevalence rate of birth defect. Neural network tools box of Software MATLAB 6.5 was used to train and simulate BP Artificial Neural Network. When using data of the year 1995-2003 to predict the prevalence rate of birth defect in 2004-2005, the results showed that: the fitting average error of prevalence rate was 1.34%, RNL was 0.9874, and the prediction of average error was 1.78%. Using data of the year 1995-2005 to predict the prevalence rate of birth defect in 2006-2007, the results showed that: the fitting average error was 0.33%, RNL was 0.9954, the prevalence rates of birth defect in 2006-2007 were 11.00% and 11.29%. Compared to the conventional statistics method, BP not only showed better prediction precision, but had no limit to the type or distribution of relevant data, thus providing a powerful method in epidemiological prediction.


Elevated immune monitoring early after cardiac transplantation is associated with increased plaque progression by intravascular ultrasound.
Immune monitoring (IM) has not been shown to be associated with cardiac allograft vasculopathy (CAV). Maximal intimal area, average percent stenosis, plaque volume, and maximal intimal thickness (MIT) were measured for matched baseline and one-yr IVUS segments in a blinded fashion. Patients were divided into quartiles by IM scores and outcomes compared. Optimal IM cutoff was determined. IM assays were measured at 63.7 ± 16.4 d after transplantation in fifty patients. Progression of maximal intimal area (p = 0.005), average percent stenosis (p < 0.001), plaque volume (p = 0.005), and MIT (p = 0.001) were increased across the quartiles. An optimal IM assay cutoff of 406.0 ng ATP/mL demonstrated a sensitivity of 66.7% and specificity of 94.3% for predicting rapid progression of MIT ≥ 0.5 mm. Mean IM scores for Group 1 vs. Group 2 were 176.4 ± 102.2 and 616.3 ± 239.5 ngATP/mL, respectively. Rapid progression of MIT ≥ 0.5 mm occurred in 5/38 patients (13.2%) in Group 1 vs. 10/12 patients (83.3%) in Group 2 (p < 0.001). The risk ratio for rapid progression with elevated IM was 11.7 (p < 0.001). Elevated early IM scores are associated with progression of CAV by IVUS. These findings suggest the potential of IM for tailoring of immunosuppressive regimens to minimize the progression of CAV in high-risk patients.


[Inverted papilloma of the nose and paranasal sinuses].
Inverted papilloma is a rare benign tumor of the nose and the paranasal sinuses. There is a controversial discussion concerning the operative approach. The epidemiology, postoperative results, and recurrence rates of endonasally and extranasally operated patients are analysed. Between 1984 and 1995, 25 patients with inverted papilloma were operated upon at the ENT Department St. Gallen, 18 patients by an endonasal microscopic approach, two by midfacial degloving and five through a lateral rhinotomy. After a minimal follow-up of 12 months (mean follow-up 52 months), a recurrence rate of 29% for the external approach and 31% for the endonasal approach was observed. In most cases it is possible to achieve a good result through an endonasal approach. External approaches are recommended in T4-tumors or carcinomas. A longtime follow-up is recommended for each case.


Identification and Characterization of Citrus Chlorotic Spot Virus, a New Dichorhavirus Associated with Citrus Leprosis-Like Symptoms.
Local chlorotic spots resembling early lesions characteristic of citrus leprosis (CL) were observed in leaves of two sweet orange (Citrus sinensis L.) trees in Teresina, State of Piauí, Brazil, in early 2017. However, despite the similarities, these spots were generally larger than those of a typical CL and showed rare or no necrosis symptoms. In symptomatic tissues, transmission electron microscopy revealed the presence of viroplasms in the nuclei of the infected parenchymal cells and rod-shaped particles with an average size of approximately 40 × 100 nm, resembling those typically observed during infection by dichorhaviruses. A bipartite genome of the putative novel virus, tentatively named citrus chlorotic spot virus (CiCSV) (RNA1 = 6,518 nucleotides [nt] and RNA2 = 5,987 nt), revealed the highest nucleotide sequence identity values with the dichorhaviruses coffee ringspot virus strain Lavras (73.8%), citrus leprosis virus N strain Ibi1 (58.6%), and orchid fleck virus strain So (56.9%). In addition to citrus, CiCSV was also found in local chlorotic lesions on leaves of the ornamental plant beach hibiscus (Talipariti tiliaceum (L.) Fryxell). Morphological characterization of mites recovered from the infected plants revealed at least two different types of Brevipalpus. One of them corresponds to Brevipalpus yothersi. The other is slightly different from B. yothersi mites but comprises traits that possibly place it as another species. A mix of the two mite types collected on beach hibiscus successfully transmitted CiCSV to arabidopsis plants but additional work is required to verify whether both types of flat mite may act as viral vectors. The current study reveals a newly described dichorhavirus associated with a citrus disease in the northeastern region of Brazil.


Dramatic improvement in water retention and proton conductivity in electrically aligned functionalized CNT/SPEEK nanohybrid PEM.
Nanohybrid membranes of electrically aligned functionalized carbon nanotube f CNT with sulfonated poly ether ether ketone (SPEEK) have been successfully prepared by solution casting. Functionalization of CNTs was done through a carboxylation and sulfonation route. Further, a constant electric field (500 V·cm(-2)) has been applied to align CNTs in the same direction during the membrane drying process. All the membranes are characterized chemically, thermally, and mechanically by the means of FTIR, DSC, DMA, UTM, SEM, TEM, and AFM techniques. Intermolecular interactions between the components in hybrid membranes are established by FTIR. Physicochemical measurements were done to analyze membrane stability. Membranes are evaluated for proton conductivity (30-90 °C) and methanol crossover resistance to reveal their potential for direct methanol fuel cell application. Incorporation of f CNT reasonably increases the ion-exchange capacity, water retention, and proton conductivity while it reduces the methanol permeability. The maximum proton conductivity has been found in the S-sCNT-5 nanohybrid PEM with higher methanol crossover resistance. The prepared membranes can be also used for electrode material for fuel cells and batteries.


Squamous cell carcinoma of the breast as a clinical diagnostic challenge.
Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice.


Primary cutaneous myxoid spindle cell squamous cell carcinoma: a rare skin cancer.
A 72-year-old woman presented to the plastic surgery outpatient department with a nodular lesion to her shin. This nodule had increased in size, but was slow growing. The patient had a history of sun-damaged skin. On visual examination, the lesion was thought to be a naevus or basal cell carcinoma. The nodule was excised. Histologically, the lesion was classified as a primary cutaneous myxoid spindle cell squamous cell carcinoma. Currently, there is only one other paper that describes this rare skin cancer. As a result of the histological findings, the lesion margin was further excised. The wound failed to heal as expected due to the patient developing a methicillin-resistant Staphylococcus aureus infection. She is currently being closely monitored due to the unknown pathway the carcinoma may take.


Causal relationships between interleukins, interferons and COVID-19 risk: a Mendelian randomization study.
Observational studies have shown close associations between COVID-19 risk and cytokines, especially interleukins (ILs) and interferons (IFNs). However, the causal relationships between ILs, IFNs and COVID-19 were still unclear. To resolve the problem, we conducted a Mendelian randomization analysis between COVID-19 and 47 cytokines, including 35 ILs and 12 IFNs. First, three methods were applied to estimate causal effects by using single nucleotide polymorphisms as instrumental variables (IVs). Subsequently, the MR-Egger method was used to estimate the horizontal pleiotropy of IVs. Finally, sensitivity analyses were applied to assess the robustness of results. As a result, one IFN (IFN-W1) and five ILs (IL-5, IL-6, IL-13, IL-16 and IL-37) were identified to significantly decrease the COVID-19 risk. In contrast, one IFN (IFNG) and five ILs (IL-3, IL-8, IL-27, IL-31 and IL-36β) were found to be significantly associated with an increased risk of COVID-19. In summary, the findings of this study provide insights into potential therapeutic interventions for COVID-19.


Exposure to blood or body fluids: management for health care.
Health care workers are at risk of exposure to blood and body fluids from their patients through needlestick injuries or contamination of mucous membranes - a slash of blood in the eye, for example. Exposure to blood /body fluids is now the second biggest cause of occupational injury among NHS workers (UNISON, 2003). The first example of a case of occupational exposure of a health care worker to human immunodeficiency virus (HIV) and subsequent seroconversion following a needlestick injury was reported in the 1980s. This incident raised awareness of the risk that health care workers face when they are exposed to blood-borne viruses, in particular hepatitis B, hepatitis C and HIV.


Adhesion of cerebral endothelial cells to lymphocytes from patients with multiple sclerosis.
To investigate the factors regulating the entry of lymphocytes into the brain, we assessed the adhesion in vitro of 51Cr labelled lymphocytes from peripheral blood of patients with multiple sclerosis (MS) to human cerebral endothelial cells, and evaluated the effect on the adhesion of endothelium activated by interferon-gamma (IFN-gamma), lipopolysaccharides (LPS), interleukin-1 (IL-1) and tumor necrosis factor (TNF). Patients with acute relapsing MS during an exacerbation showed significant increase in MNC adherence to cerebral endothelial cells as compared with controls (p < 0.001). MNC adherence to cerebral endothelial cells activated by IFN-gamma or LPS, was significantly increased as compared to the controls (p < 0.01). MNC adherence to endothelial cells was not blocked by antibodies against the intercellular adhesion molecule-1 (ICAM-1), but was blocked by lymphocyte function-associated antigen-1 (LFA-1). The increased adherence observed in patients with acute relapsing MS during an exacerbation would modulate the migration of lymphocytes across the blood-brain barrier (BBB).


Using administrative data to evaluate national policy impacts on child and maternal health: a research framework from the Maternal and Child Health Network (MatCHNet).
Reducing health inequalities by addressing the social circumstances in which children are conceived and raised is a societal priority. Early interventions are key to improving outcomes in childhood and long-term into adulthood. Across the UK nations, there is strong political commitment to invest in the early years. National policy interventions aim to tackle health inequalities and deliver health equity for all children. Evidence to determine the effectiveness of socio-structural policies on child health outcomes is especially pressing given the current social and economic challenges facing policy-makers and families with children. As an alternative to clinical trials or evaluating local interventions, we propose a research framework that supports evaluating the impact of whole country policies on child health outcomes. Three key research challenges must be addressed to enable such evaluations and improve policy for child health: (1) policy prioritisation, (2) identification of comparable data and (3) application of robust methods.


Cerebrospinal fluid biomarkers for brain tumor detection: clinical roles and current progress.
Brain tumors include those that originate within the brain (primary tumors) as well as those that arise from other cancers (metastatic tumors). The fragile nature of the brain poses a major challenge to access focal malignancies, which certainly limits both diagnostics and therapeutic approaches. This limitation has been alleviated with the advent of liquid biopsy technologies. Liquid biopsy represents a highly convenient, fast and non-invasive method, which allows multiple sampling and dynamic pathological detection. Biomarkers derived from liquid biopsies can promptly reflect changes on the gene expression profiling of tumors. Biomarkers derived from tumor cells contain abundant genetic information, which may provide a strong basis for the diagnosis and the individualized treatment of brain tumor patients. A series of body fluids can be assessed for liquid biopsy, including peripheral blood, cerebrospinal fluid (CSF), urine or saliva. Interestingly, the sensitivity and specificity of biomarkers from the CSF of patients with brain tumors is typically higher than those detected in the peripheral blood and other sources. Hence, here we describe and properly discuss the clinical roles of distinct classes of CSF biomarkers, isolated from patients with brain tumors, such as circulating tumor DNA (ctDNA), microRNA (miRNA), proteins, and extracellular vesicles (EVs).


Functional heterogeneity in the default mode network edges.
The brain's default mode network (DMN) has attracted tremendous attention, but its topology still lacks a substantial and operative definition. At the same time, recent efforts based on coactivation analysis suggest significant involvement of concomitant activation as an origin of synchronous activity, which is the basis of the network detection. Therefore, to establish the biological significance of the intrinsic remote connectivity, understanding such co-occurrence networks may be crucial. This study shows the results of monitoring the network's signal variation during random transitions among two divergent tasks and rest epochs. The subset of the DMN nodes showed three distinct activity levels; it was simultaneously characterized by the lack of a transition response between blocks. Additional connectivity analysis revealed components covering the other DMN nodes showing overshooting in response to a transition that were still connected to the posterior cingulate cortices (PCC), but by different signal components. The overall finding of multiple connectivity modes in the DMN provides a relevant explanation about the two seemingly contradictory characteristics of the network, robustness and variation.


Hemimyelomeningocele: a rare and complex spinal dysraphism.
We report a case of hemimyelomeningocele. This is a rare spinal dysraphism, consisting of the association of a split cord malformation with myelomeningocele. MRI demonstrates division of the spinal cord into two hemicords which are separated by a bony spur. The left hemicord forms a myelomeningocele, thus resulting in a hemimyelomeningocele. Accurate and early diagnosis of spinal dysraphisms is essential for optimal, individualised neurosurgical treatment.


Effects of a transitional care programme on medication adherence in an older cardiac population: A randomized clinical trial.
Medication non-adherence post-discharge is common among patients, especially those suffering from chronic medical conditions, and contributes to hospital admissions and mortality. This study aimed to evaluate the effect of the Cardiac Care Bridge (CCB) intervention on medication adherence post-discharge. We performed a secondary analysis of the CCB randomized single-blind trial, a study in patients ≥70 years, at high risk of functional loss and admitted to cardiology departments in six hospitals. In this multi-component intervention study, community nurses performed medication reconciliation and observed medication-related problems (MRPs) during post-discharge home visits, and pharmacists provided recommendations to resolve MRPs. Adherence to high-risk medications was measured using the proportion of days covered (PDC), using pharmacy refill data. Furthermore, MRPs were assessed in the intervention group. For 198 (64.7%) of 306 CCB patients, data were available on adherence (mean age: 82 years; 58.9% of patients used a multidose drug dispensing [MDD] system). The mean PDC before admission was 92.3% in the intervention group (n = 99) and 88.5% in the control group (n = 99), decreasing to 85.2% and 84.1% post-discharge, respectively (unadjusted difference: -2.6% (95% CI -9.8 to 4.6, P = .473); adjusted difference -3.3 (95% CI -10.3 to 3.7, P = .353)). Post-hoc analysis indicated that a modest beneficial intervention effect may be restricted to MDD non-users (Pinteraction = .085). In total, 77.0% of the patients had at least one MRP post-discharge. Our findings indicate that a multi-component intervention, including several components targeting medication adherence in older cardiac patients discharged from hospital back home, did not benefit their medication adherence levels. A modest positive effect on adherence may potentially exist in those patients not using an MDD system. This finding needs replication.


Regional myocardial blood flow.
A method is described which measures the local effectiveness of the myocardial circulation, expressed as a clearance constant. Uniform clearance constants have been demonstrated in the normal canine and human myocardium. A distinct difference in clearance constants has been demonstrated between the normal canine myocardium and areas of naturally occurring disease. Heterogeneous clearance constants have been found in a majority of human subjects with coronary artery disease-the lowest rates being noted in areas of fibrous aneurysm.


Social Support From Family and Friends, Educational Attainment, and Cognitive Function.
This study assessed the extent to which associations between perceived and received social support from family and friends and changes in older adults' cognitive function were moderated by educational attainment. Sibling pairs in the Wisconsin Longitudinal Study (WLS) (N = 4,297) completed a survey about social support in 2011 and a cognitive battery in 2011 and 2020. Participants' mean age in 2020 was 80.2 years old. Multilevel linear regressions indicated that perceived, but not received, support from friends was associated with better cognitive function 9 years later. Perceived family support was cognitively advantageous for older adults at most levels of educational attainment. However, among postgraduates, perceived family support was unrelated to cognitive function. That the association between perceived support and cognitive function differs based on educational attainment gives interventionists additional information needed to identify groups of older adults most susceptible to cognitive impairment.


Heat shock and hydrogen peroxide responses of Escherichia coli are not changed by dinucleoside tetraphosphate hydrolase overproduction.
In Escherichia coli strains overproducing dinucleoside tetraphosphate hydrolase, the accumulation of dinucleoside tetraphosphates (AppppN, with N = A, C, G, or U) during heat shock or H2O2 treatment was reduced about 10-fold as compared with a control strain. This accumulation neither modified the pattern of the proteins induced by a temperature shift or H2O2 nor reduced the protection against oxidative damage induced by moderate H2O2 levels.


Unique molecular events during reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) at naïve state.
Derivation of human naïve cells in the ground state of pluripotency provides promising avenues for developmental biology studies and therapeutic manipulations. However, the molecular mechanisms involved in the establishment and maintenance of human naïve pluripotency remain poorly understood. Using the human inducible reprogramming system together with the 5iLAF naïve induction strategy, integrative analysis of transcriptional and epigenetic dynamics across the transition from human fibroblasts to naïve iPSCs revealed ordered waves of gene network activation sharing signatures with those found during embryonic development from late embryogenesis to pre-implantation stages. More importantly, Transcriptional analysis showed a significant transient reactivation of transcripts with 8-cell-stage-like characteristics in the late stage of reprogramming, suggesting transient activation of gene network with human zygotic genome activation (ZGA)-like signatures during the establishment of naïve pluripotency. Together, Dissecting the naïve reprogramming dynamics by integrative analysis improves the understanding of the molecular features involved in the generation of naïve pluripotency directly from somatic cells.


[Ion movement disorders in cystic fibrosis].
The most important of ion transport abnormalities is a reduced permeability to chlorine of certain epithelial cells, notably those of the sweat glands and bronchi. This abnormality is due to a defective regulation of the chlorine channels located in the apical membrane of these cells, and more precisely to the lack of activation of these channels by protein kinases A and C. Other epithelial ion transports are affected, but the mechanism of these disturbances is imperfectly known. In the airways, for instance, a decrease of chlorine secretion and an increase of sodium absorption concur to dehydrate the bronchial secretions and thus produce the respiratory manifestations of cystic fibrosis.


[Peptides of digestive system and brain. Model of the cholecystokinin].
The systemic administration of exogenous cholecystokinin (CCK), (a peptide released into the circulation when nutrients arrive in small intestine) provokes inhibition of food intake in numerous animal species and a sensation of satiation in humans. The mechanism involved requires participation of vagal afferent neurons to transmit information, possibly on gastric distension, to brain stem. Two crucial questions remain unanswered: does peripheral endogenous cholecystokinin transport information necessary for satiation at end of normal meals and if so, how and when is this message coded and deciphered; other studies have demonstrated that very small doses of exogenous cholecystokinin (too low to induce satiation if administrated peripherally) will induce satiety if injected into cerebral ventricles or directly into cerebral parenchyma. This suggest but does not prove that cerebral endogenous CCK also plays a role in satiety. It is not known how the satiating action of centrally-administered CCK is related to that of peripherally-administered CCK. Current studies aim at establishing a coherent schema of neuro-endocrine mechanisms implicated (from the gastrointestinal wall via the brain to a motivated behaviour) in the fact that food taken during a meal induces the end of the latter.


Cytosolic sulfotransferase 2B1b promotes hepatocyte proliferation gene expression in vivo and in vitro.
Cytosolic sulfotransferase 2B1b (SULT2B1b) catalyzes the sulfation of 3β-hydroxysteroids and functions as a selective cholesterol and oxysterol sulfotransferase. Activation of liver X receptors (LXRs) by oxysterols has been known to be an antiproliferative factor. Overexpression of SULT2B1b impairs LXR's response to oxysterols, by which it regulates lipid metabolism. The aim of this study was to investigate in vivo and in vitro effects of SULT2B1b on liver proliferation and the underlying mechanisms. Primary rat hepatocytes and C57BL/6 mice were infected with adenovirus encoding SULT2B1b. Liver proliferation was determined by measuring the proliferating cell nuclear antigen (PCNA) immunostaining labeling index. The correlation between SULT2B1b and PCNA expression in mouse liver tissues was determined by double immunofluorescence. Gene expressions were evaluated by quantitative real-time PCR and Western blot analysis. SULT2B1b overexpression in mouse liver tissues increased PCNA-positive cells in a dose- and time-dependent manner. The increased expression of PCNA in mouse liver tissues was only observed in the SULT2B1b transgenic cells. Small interference RNA SULT2B1b significantly inhibited cell cycle regulatory gene expressions in primary rat hepatocytes. LXR activation by T0901317 effectively suppressed SULT2B1b-induced gene expression in vivo and in vitro. SULT2B1b may promote hepatocyte proliferation by inactivating oxysterol/LXR signaling.


Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.
In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig) appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc), an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT). Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%). 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C) and in serum (37°C), even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe" and preserves Ig affinity for antigen, as shown by both in vitro and in vivo experiments. This method could easily be used with noncommercial IgG or other antibody isotypes.


Molting in C. elegans.
Molting is an essential developmental process for the majority of animal species on Earth. During the molting process, which is a specialized form of extracellular matrix (ECM) remodeling, the old apical ECM, or cuticle, is replaced with a new one. Many of the genes and pathways identified as important for molting in nematodes are highly conserved in vertebrates and include regulators and components of vesicular trafficking, steroid-hormone signaling, developmental timers, and hedgehog-like signaling. In this review, we discuss what is known about molting, with a focus on studies in Caenorhabditis elegans. We also describe the key structural elements of the cuticle that must be released, newly synthesized, or remodeled for proper molting to occur.


Repeated hyperstimulation affects the ultrastructure of mouse fallopian tube epithelium.
Controlled ovarian hyperstimulation (COH) is routinary used in assisted reproductive technologies (ARTs) to increase the yields of mature oocytes. The possibility that patients with a history of failures or poor-responders may develop side-effects following these treatments is still debated. Epidemiological studies reported controversial results about pregnancy outcome and the risk of developing gynecological cancers. By using a mouse model, here we compared the ultrastructural features of fallopian tubes (FTs) obtained from mice undergoing or not (control, CTR) four (4R) and eight (8R) rounds of gonadotropin stimulation. Although the morphological characteristics of oviductal layers seemed unaffected by repeated treatments, dose-response ultrastructural alterations in the ampulla appeared in the 4R group and even more in the 8R group. The targets were oviductal ciliated (CCs) and non-ciliated (NCCs) cells, which showed damaged mitochondria and glycogen accumulations in the cytoplasm. The drastic reduction of CCs, evident after 4R, was supported by the absence of cilia. After 8R, glycogen granules were significantly reduced and massive degeneration of mitochondria, which appeared swollen and/or vacuolated, occurred in NCCs. Moreover, disintegrated mitochondria were found at the periphery of mitophagic vacuoles with evident signs of cristolysis. The morphometric analysis evidenced a significant increase in the density and frequency of damaged mitochondria after 4R and 8R. The absence of cilia, necessary to sustain oviductal transport of oocytes, spermatozoa and embryos, may originate from either mitochondrial dysfunction or glycogen consumption. These results suggest that repeated COH treatments could induce alterations impairing fertilization and embryo transport toward the uterus.


Positioning of cysteine residues within the N-terminal portion of the BST-2/tetherin ectodomain is important for functional dimerization of BST-2.
BST-2/tetherin is a cellular host factor capable of restricting the release of a variety of enveloped viruses, including HIV-1. Structurally, BST-2 consists of an N-terminal cytoplasmic domain, a transmembrane domain, an ectodomain, and a C-terminal membrane anchor. The BST-2 ectodomain encodes three cysteine residues in its N-terminal half, each of which can contribute to the formation of cysteine-linked dimers. We previously reported that any one of the three cysteine residues is sufficient to produce functional BST-2 dimers. Here we investigated the importance of cysteine positioning on the ectodomain for functional dimerization of BST-2. Starting with a cysteine-free monomeric form of BST-2, individual cysteine residues were reintroduced at various locations throughout the ectodomain. The resulting BST-2 variants were tested for expression, dimerization, surface presentation, and inhibition of HIV-1 virus release. We found significant flexibility in the positioning of cysteine residues, although the propensity to form cysteine-linked dimers generally decreased with increasing distance from the N terminus. Interestingly, all BST-2 variants, including the one lacking all three ectodomain cysteines, retained the ability to form non-covalent dimers, and all of the BST-2 variants were efficiently expressed at the cell surface. Importantly, not all BST-2 variants capable of forming cysteine-linked dimers were functional, suggesting that cysteine-linked dimerization of BST-2 is necessary but not sufficient for inhibiting virus release. Our results expose new structural constraints governing the functional dimerization of BST-2, a property essential to its role as a restriction factor tethering viruses to the host cell.


Deformable spanners and applications.
For a set S of points in ℝ(d), an s-spanner is a subgraph of the complete graph with node set S such that any pair of points is connected via some path in the spanner whose total length is at most s times the Euclidean distance between the points. In this paper we propose a new sparse (1 + ε)-spanner with O(n/ε(d)) edges, where ε is a specified parameter. The key property of this spanner is that it can be efficiently maintained under dynamic insertion or deletion of points, as well as under continuous motion of the points in both the kinetic data structures setting and in the more realistic blackbox displacement model we introduce. Our deformable spanner succinctly encodes all proximity information in a deforming point cloud, giving us efficient kinetic algorithms for problems such as the closest pair, the near neighbors of all points, approximate nearest neighbor search (aka approximate Voronoi diagram), well-separated pair decompositions, and approximate k-centers.


Antley-Bixler syndrome from a prognostic perspective: report of a case and review of the literature.
The Antley-Bixler syndrome (ABS) is characterized by craniosynostosis, radiohumeral synostosis, and femoral bowing. Other findings include a trapezoid-shaped head, deformed ears, severe midface hypoplasia, choanal atresia or stenosis, and long bone fractures. Most ABS cases have died in the first months of life from respiratory complications. The poor prognosis in this condition makes counseling difficult and early termination of pregnancy a consideration. The medical and surgical management information presented here can be used as a guide for counseling parents in the future. We report on a new patient with ABS who now at age 3 yr, has been followed by the medical staff of Riley Children's Hospital since birth. She has had successful medical and surgical management. Although the multisynostoses seen in this disorder is undoubtedly related to the soft tissue malformations such as choanal stenosis and midface hypoplasia, the cause remains unknown. The literature is also reviewed in this condition.


Enzyme inactivation induced by thermal stabilization in highland barley and impact on lipid oxidation and aroma profiles.
Thermal stabilization is efficient for slowing lipid degradation and prolonging the shelf life of highland barley, but the impacts of different thermal stabilized treatments on highland barley and possible chemical reactions remain unclear. The effects of thermal stabilization treatments (bake, far-infrared, fry, microwave and steam) on the enzymes, lipids and aroma profiles of highland barley flour (HBF) were investigated in this study. Thermal stabilization significantly decreased the contents of ash and GABA. Baked HBF exhibited the lowest fatty acid value and peroxide value. Untreated HBF had higher lipase and lipoxygenase activities and fried mostly inactivated these enzymes. All thermal stabilization treatments increased the catalase activities and fried showed the higher level. Thus, fried might be an effective method to stabilize the HBF. The high temperatures during stabilizing triggered the complex reactions, leading to the loss of some volatile compounds, and in the meantime the formation of others such as furans and aldehydes. These productions contributed to the unique aroma profiles of different HBFs. Furthermore, a chemometric approach was used to analyze the changes of thermal stabilized treated HBFs and to identity six key volatile compounds, which provided important knowledge on possible chemical reactions caused by thermal stabilization. Overall, these results provide the theoretical basis for the wider application of thermal stabilization technologies in highland barley processing.


Differential roles of astrocyte and microglia in supporting oligodendrocyte development and myelination in vitro.
Oligodendrocyte (OL) development relies on many extracellular cues, most of which are secreted cytokines from neighboring neural cells. Although it is generally accepted that both astrocytes and microglia are beneficial for OL development, there is a lack of understanding regarding whether astrocytes and microglia play similar or distinct roles. The current study examined the effects of astrocytes and microglia on OL developmental phenotypes including cell survival, proliferation, differentiation, and myelination in vitro. Our data reveal that, although both astrocytes- and microglia-conditioned medium (ACDM and MCDM, respectively) protect OL progenitor cells (OPCs) against growth factor withdrawal-induced apoptosis, ACDM is significantly more effective than MCDM in supporting long-term OL survival. In contrast, MCDM preferentially promotes OL differentiation and myelination. These differential effects of ACDM and MCDM on OL development are highlighted by distinct pattern of cytokine/growth factors in the conditioned medium, which correlates with differentially activated intracellular signaling pathways in OPCs upon exposure to the conditioned medium.


The D2-like Dopamine Receptor Agonist Quinpirole Microinjected Into the Ventral Pallidum Dose-Dependently Inhibits the VTA and Induces Place Aversion.
The ventral pallidum (VP) is a dopaminoceptive forebrain structure regulating the ventral tegmental area (VTA) dopaminergic population activity. We have recently demonstrated that in the VP, the D2-like dopamine (DA) receptor agonist quinpirole dose dependently facilitates memory consolidation in inhibitory avoidance and spatial learning. According to our hypothesis, quinpirole microinjected into the VP can modulate the VTA DAergic activity and influence motivation and learning processes of rats. Quinpirole was microinjected at 3 different doses into the VP of male rats, and controls received vehicle. Single unit recordings were employed to assess VTA DAergic activity. To investigate the possible reinforcing or aversive effect of quinpirole in the VP, the conditioned place preference paradigm was used. Our results showed that intra-VP quinpirole microinjection regulates VTA DAergic neurons according to an inverted U-shaped dose-response curve. The largest dose of quinpirole decreased the population activity and strongly reduced burst activity of the DAergic neurons in the first hour after its application. In contrast, the 2 smaller doses increased DA population activity, but their effect started with a delay 1 hour after their microinjection. The CPP experiments revealed that the largest dose of quinpirole in the VP induced place aversion in the rats. Furthermore, the largest dose of quinpirole induced an acute locomotor activity reduction, while the medium dose led to a long-duration increase in locomotion. In summary, quinpirole dose dependently regulates VTA DAergic activity as well as the motivation and motor behavior of the rats at the level of the VP.


Metabolomic serum abnormalities in dogs with hepatopathies.
Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.