Switching the electrochemical impedance of low-density self-assembled monolayers.
Because the active remodeling of biointerfaces is a paramount feature of nature, it is very likely that future, advanced biomaterials will be required to mimic at least certain aspects of the dynamic properties of natural interfaces. This need has fueled a quest for model surfaces that can undergo reversible switching upon application of external stimuli. Herein, we report the synthesis and characterization of a model system for studying reversibly switching surfaces based on low-density monolayers of mercaptohexadecanoic acid and mercaptoundecanoic acid. These monolayers were assembled on both gold and silver electrodes. When conducting electrochemical impedance spectroscopy under physiological conditions, these monolayers exhibit significant changes in their electrochemical barrier properties upon application of electrical DC potentials below +400 mV with respect to a standard calomel electrode. We further found the impedance switching to be reversible under physiological conditions. Moreover, the impedance can be fine-tuned by changing the magnitude of the applied electrical potential. Before and during impedance switching at pH 7.4 in aqueous buffer solutions, the low-density monolayers showed good stability according to grazing angle infrared spectroscopy data. We anticipate low-density monolayers to be potentially useful model surfaces when designing active biointerfaces for cell-based studies or rechargeable biosensors.


Can active music making promote health and well-being in older citizens? Findings of the music for life project.
Although there is now an accepted need for initiatives that support older people's well-being, little attention has been paid to the potential for music making to effect a significant contribution to the quality of life of older people. The research summarised here explored the role of music in older people's lives and how participation in community music making can enhance their social, emotional and cognitive well-being. The research comprised three UK case study sites, each offering a variety of musical activities. At each site, a sample of people aged 50+ (total N = 398), some of whom had recently begun musical activities and others who were more experienced, were recruited to complete questionnaires that assessed quality of life. A control group (N = 102) completed the same measures. In-depth interviews were carried out with a representative sample, followed by observations of musical activities, focus groups and interviews with the facilitators of the activities. Higher scores on the quality of life measures were found consistently among the music participants, in comparison with the control group with ongoing benefits into the 4th age. Analysis of the qualitative data demonstrated: (1) cognitive benefits including challenge, the acquisition of new skills, a sense of achievement, and improvements in concentration and memory; (2) health benefits including increased vitality, improved mental health and mobility and feelings of rejuvenation; and (3) emotional benefits including protection against stress, protection against depression, support following bereavement, a sense of purpose, positive feelings, confidence and opportunities for creativity. Participants also identified a number of barriers to participation including lack of information about opportunities for making music. Ways that GP surgeries might support participation in music making are considered.


Differences in some haemostatic variables between fisheating and non-fish-eating populations.
The rare incidence of coronary artery disease in Eskimos has been ascribed to their diet of marine fish rich in n-3 fatty acids, which have an antithrombotic influence on haemostasis. In order to test this hypothesis, a crosssectional study was conducted on 1000 healthy individuals chosen randomly from coastal and inland villages in the state of Andhra Pradesh, India. A total of 500 fish-eating and 500 non-fish-eating age- and sex-matched subjects were selected based on fish-eating habits for parameters related to haemostasis. Mean cutaneous bleeding time and clotting time were decreased with advancing age in men and women of both populations.Women had more prolonged bleeding and clotting times than did men in both population groups. The platelet count was significantly lower in the fish-eating population. The mean bleeding time was observed to be prolonged significantly in men and women of the fish-eating population than that of the non-fish-eating population. However, the clotting time in the fish-eating population was significantly longer in certain age groups than in non-fish-eating population. The results indicate that fish consumption influences haemostatic function relative to a non-fish-eating population.


[Partial finger amputation after weever sting and second-degree burn].
The greater weever (Trachinus draco) is the only venomous fish in Denmark, and if stung by the weever the venom may cause symptoms such as pain, headache, nausea, dizziness and in severe cases systemic allergic reaction or tissue necrosis. The venom is heat-labile and should therefore be treated with warm water to the afflicted area. We report a case of a patient who was stung in the second finger and because of the treatment, he got a second-degree burn, that may have enhanced the effect of the venom, thus resulting in partial finger amputation.


Recipient cytotoxic T lymphocyte antigen-4 +49 G/G genotype is associated with reduced incidence of hepatitis B virus recurrence after liver transplantation among Chinese patients.
Single-nucleotide polymorphisms (SNP) of two-gene locus cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 and CD86 +1057 were previously reported to influence the outcome of liver transplantation (LT) with respect to allograft acceptance. SNP at CTLA-4 +49 was also suggested to be associated with the individual difference in the clearance of hepatitis B virus (HBV). However, their influence on the incidence of post-LT HBV reinfection was not clear. With the increasing knowledge of costimulatory mechanisms on LT and host immune response, we designed this study to investigate the relationship between different alleles as well as genotypes at these two locations and HBV reinfection after LT. Genomic DNA from 167 LT recipients with HBV-related diseases was genotyped for CTLA-4 +49 and CD86 +1057 genomic polymorphisms using a sequence-specific primer-polymerase chain reaction (PCR-SSP). HBV recurrence was diagnosed based on the serological and pathological finding of HBV DNA and HBsAg. The present study indicated that the recipients with CTLA-4 +49 GG genotype had a reduced risk (6.67%) of HBV recurrence compared with non-CTLA-4 +49 GG-carrying individuals (20.7%) (relative risk 3.098) (P=0.032). The allelic frequency of CTLA-4 +49 G was also significantly lower in patients with HBV recurrence, compared with that in patients without HBV recurrence (P=0.013, odds ratio 2.176, 95% confidence interval 1.170-4.046). However, no significant association was found between CD86 +1057 and HBV recurrence. Our result on CTLA-4 +49 A/G polymorphism indicated that the CTLA-4 +49 GG genotype was related to a reduced risk in the incidence of HBV recurrence.


CalDAG-GEFI deficiency protects mice from FcγRIIa-mediated thrombotic thrombocytopenia induced by CD40L and β2GPI immune complexes.
Platelet activation via the Fcγ receptor IIa (FcγRIIa) is implicated in the pathogenesis of immune complex (IC)-mediated thrombocytopenia and thrombosis (ITT). We previously showed that ICs composed of antigen and antibodies targeting CD40 ligand (CD40L) or β2 Glycoprotein I (β2GPI) induce ITT in mice transgenic for human FcγRIIa (hFcR) but not wild-type controls (which lack FcγRIIa). Here we evaluated the contribution of the guanine nucleotide exchange factor, CalDAG-GEFI, and P2Y12, key regulators of Rap1 signaling in platelets, to ITT induced by these clinically relevant ICs. Pre-formed anti-CD40L or anti-β2GPI ICs were injected into hFcR/Caldaggef1(+/+) or hFcR/Caldaggef1(-/-) mice, with or without clopidogrel pretreatment. Animals were observed for symptoms of shock for 30 min, during which time core body temperature was monitored. Platelet counts were obtained before and 30 min after IC injection. Lungs were assessed for thrombosis by histology or near-infrared imaging. Both CD40L and β2GPI ICs rapidly induced severe thrombocytopenia, shock and a reduction in body temperature in hFcR/Caldaggef1(+/+) mice. hFcR/Caldaggef1(-/-) mice were protected from CD40L and β2GPI IC-induced thrombocytopenia and shock, whereas P2Y12 inhibition had only a modest effect on IC-induced ITT. Consistent with these findings, IC-induced integrin activation in vitro and the accumulation of activated platelets in the lungs of IC-challenged mice was strongly dependent on CalDAG-GEFI. Our studies demonstrate that CalDAG-GEFI plays a critical role in platelet activation, thrombocytopenia and thrombosis induced by clinically relevant ICs in mice. Thus, CalDAG-GEFI may be a promising target for the intervention of IC-associated, FcγRIIa-mediated thrombotic conditions.


Phylogenetic and Structural Analysis of the Pluripotency Factor Sex-Determining Region Y box2 Gene of Camelus dromedarius (cSox2).
Although the sequencing information of Sox2 cDNA for many mammalian is available, the Sox2 cDNA of Camelus dromedaries has not yet been characterized. The objective of this study was to sequence and characterize Sox2 cDNA from the brain of C. dromedarius (also known as Arabian camel). A full coding sequence of the Sox2 gene from the brain of C. dromedarius was amplified by reverse transcription PCRjmc and then sequenced using the 3730XL series platform Sequencer (Applied Biosystem) for the first time. The cDNA sequence displayed an open reading frame of 822 nucleotides, encoding a protein of 273 amino acids. The molecular weight and the isoelectric point of the translated protein were calculated as 29.825 kDa and 10.11, respectively, using bioinformatics analysis. The predicted cSox2 protein sequence exhibited high identity: 99% for Homo sapiens, Mus musculus, Bos taurus, and Vicugna pacos; 98% for Sus scrofa and 93% for Camelus ferus. A 3D structure was built based on the available crystal structure of the HMG-box domain of human stem cell transcription factor Sox2 (PDB: 2 LE4) with 81 residues and predicting bioinformatics software for 273 amino acid residues. The comparison confirms the presence of the HMG-box domain in the cSox2 protein. The orthologous phylogenetic analysis showed that the Sox2 isoform from C. dromedarius was grouped with humans, alpacas, cattle, and pigs. We believe that this genetic and structural information will be a helpful source for the annotation. Furthermore, Sox2 is one of the transcription factors that contributes to the generation-induced pluripotent stem cells (iPSCs), which in turn will probably help generate camel induced pluripotent stem cells (CiPSCs).


Two mixed-valence vanadium(III,IV) phosphonoacetates with 16-ring channels: H2(DABCO)[V(IV)O(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O and H2(PIP)[V(IVO)(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O.
Two isostructural mixed-valence vanadium phosphonoacetates H2(DABCO)[V(IV)O(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O (1) and H2(PIP)[V(IV)O(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O (2) have been synthesized. They crystallize in the orthorhombic space group Pnna with a = 7.0479(10) A, b = 15.307(2) A, and c = 17.537(3) A for 1 and a = 7.0465(9) A, b = 15.646(2) A, and c = 17.396(2) A for 2. X-ray single-crystal diffraction reveals that 1 and 2 have a three-dimensional open framework featuring 16-ring ellipsoid channels that are filled with doubly protonated 1,4-diazabicyclo[2,2,2]octanium/piperazinium cations and water molecules. According to the classification in metal-organic frameworks, 1 and 2 contain infinite (-O-V-)(infinity) chains that are cross-linked by "metalloligand" [VO(H2O)(O3PCH2CO2)2](4-) into a 3-D net of the sra topology. The temperature dependence of the magnetic susceptibility of 1 shows that the chi(m)T value in the range of 60-320 K is constant of 1.105 cm3 K mol(-1)/V2 unit, and upon further cooling, the chi(m)T value rapidly increases to 1.81 cm3 K mol(-1) at 2 K. The corresponding effective magnetic moment (mu(eff))/V2 unit varies from 2.97 mu(B) at 320 K to 3.80 mu(B) at 2 K. The magnetic data in the range of 2-320 K follow the Curie-Weiss law with C = 1.074 cm3 K mol(-1) and Theta= -1.34 K.


Does the UK government's teenage pregnancy strategy deal with the correct risk factors? Findings from a secondary analysis of data from a randomised trial of sex education and their implications for policy.
Much of the UK government's 1999 report on teenage pregnancy was by necessity based on rather old or non-longitudinal research. To examine the associations between risk factors identified in the report and pregnancy at or before age 16 years among young women and partners of young men using the more recent data. Socioeconomic disadvantage, being born to a teenage mother, expectation of being a teenage parent, low educational expectations and various other behaviours are potential risk factors for teenage pregnancy, as suggested by unadjusted analyses. Those who cited school as providing information on sex had a reduced risk of pregnancy at or before age 16 years, as did girls reporting easy communication with parent or guardian at baseline. Various measures of low sexual health knowledge were not associated, in either adjusted or unadjusted analyses, with increased risk of pregnancy at or before age 16 years among boys or girls. A focus on many of the risk factors identified in the 1999 report is supported herein. It is suggested that knowledge may not be an important determinant, but that relationships with parents and school, as well as expectations for the future, may have important influences on teenage pregnancy. The analysis also provides new insights into risk factors for pregnancies among the partners of young men.


Sodium nitroprusside toxicity in Drosophila melanogaster: delayed pupation, reduced adult emergence, and induced oxidative/nitrosative stress in eclosed flies.
The toxicity of sodium nitroprusside (SNP) was tested on the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with SNP at concentrations of 0.01-1.5 mM. Food supplementation with SNP caused a developmental delay in flies and reduced adult eclosion. Biochemical analyses such as levels of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies emerged from control and SNP-fed larvae. Larval exposure to SNP resulted in lower activities of aconitase and catalase in adult flies relative to the control cohort. However, larval treatment with SNP led to higher carbonyl protein content and higher activities of superoxide dismutase, glucose-6-phosphate dehydrogenase, thioredoxin reductase, and glutathione-S-transferase in flies. Among the parameters tested, aconitase activity and developmental end points may be useful early indicators of toxicity caused by SNP. The study also suggests that the toxicity of SNP may arise not just from its direct effects, but also from its decomposition products such as nitric oxide and iron ions.


The Effect of Oral Health Promotion Program on Early Dental Decay in Students: a Cluster Randomized Controlled Trial.
Introduction: The use of different models play a significant role in health education and its promotion. Therefore, the present study aims to investigate the effect of the Theory of Planned Behavior (TPB) on early dental decay in elementary students. Methods: This study was a single-blinded, cluster randomized controlled trial, in which 470 elementary students in the fourth, fifth and sixth grades in Saveh, Iran were participated. A demographic questionnaire and a 5-item questionnaire consisting of questions on awareness, attitude, practice, tooth brushing, diet and referring to dentist, were used to data collection. The samples of the intervention (n=234) and control (n=236) groups filled out the questionnaires before intervention (pre-test), immediately after intervention and one month after intervention. The educational intervention based on the TPB was held in three 45-minute sessions. Finally, the data were analyzed, using the SPSS version 13. For analyzing, the Independent t-test, Chi-square, and repeated measures ANOVA were used. Results: This study showed that there is a significant difference in the mean scores obtained from knowledge, attitude, subjective norm, perceived behavioral control, behavioral intention and behavior among students in the experimental group (immediately after and one month after the intervention) and students in the control group. Conclusion: The results of this study showed that using of TPB, as a framework for providing behavior-led training, can be effective in promoting oral and dental health of students. Nurses as an important member of the treatment team can use the results of this study in school health programs.


Massless Leggett mode in three-band superconductors with time-reversal-symmetry breaking.
The Leggett mode associated with out-of-phase oscillations of the superconducting phase in multiband superconductors usually is heavy due to interband coupling, which makes its excitation and detection difficult. We report on the existence of a massless Leggett mode in three-band superconductors with time-reversal-symmetry breaking. The mass of this Leggett mode is small close to the time-reversal-symmetry-breaking transition and vanishes at the transition point, and thus locates within the smallest superconducting energy gap, which makes it stable and detectable, e.g., by means of the Raman spectroscopy. The thermodynamic consequences of this massless mode and possible realization in iron-based superconductors are also discussed.


Soft and hard tissue changes in Class III patients treated by bimaxillary surgery.
A cephalometric study of 17 non-growing dentate Class III subjects treated by bimaxillary surgery was undertaken to assess the results of treatment and to evaluate the correlation between soft and hard tissue change. It was concluded that: (i) the orthognathic profiles achieved were brought about by a combination of maxillary advancement and mandibular setback; (ii) a strong correlation in the horizontal direction occurred between all the selected landmarks of the lower lip and chin, but only between superior labial sulcus and point A in the upper lip; highest intra-group correlations were seen between corresponding soft and hard tissue points; the ratios of soft tissue to corresponding hard tissue movements in lower lip and chin approached 1:1; (iii) in the vertical direction, a strong correlation occurred in the lower lip and chin; highest intra-group correlations were not necessarily with corresponding landmarks; and (iv) vertical movement of landmarks on the nasal base and upper lip generally showed poor or weak correlation with corresponding soft tissue points. The most reliable hard tissue predictors of horizontal and vertical soft tissue change are tabulated for application in bimaxillary surgery for the Class III patient.


Development of a New and Fast Extraction Method Based on Solvent-Assisted Dispersive Solid-Phase Extraction for Preconcentration and Trace Detection of Atrazine in Real Matrices.
Because of trace amounts of atrazine in water samples and the complexity of the matrix, direct trace monitoring of atrazine is not feasible by the abovementioned techniques. Hence, an efficient sample pretreatment procedure is necessary for cleanup and preconcentration of atrazine from sample matrices. In the current paper, a new and efficient sample preparation method named solvent-assisted dispersive solid-phase extraction (SA-DSPE), followed by HPLC-UV, was introduced for the monitoring of atrazine at trace levels in environmental water samples. In the present method, benzophenone was used as a sorbent for extraction of target molecules. For dispersing solid sorbents in sample solution, very low milligram amounts of benzophenone and dispersive solvent were mixed and fast-injected into the extraction media. A cloudy solution formed, and after interaction of atrazine and the dispersed solid sorbent, the cloudy solution was centrifuged. The extracted atrazine in the solid phase was dissolved in ethanol and analyzed by HPLC-UV. The introduced method showed a low method detection limit (0.1 μg/L), good precision (relative SD: 3.9-6.9%), and appropriate relative recoveries (95-105%). Within this study, a sensitive and reliable method for the quantification of atrazine in wastewater samples was successfully developed. The obtained figures of merit for the presented sample preparation method were appropriate. The applicability of the method for analysis of atrazine in real matrices was excellent.


The role of neural tension in stretch-induced strength loss.
The purpose of this study was to determine if neural tension during passive stretching affected subsequent strength loss. Eleven healthy subjects (10 men, 1 woman; age 34 ± 12 years) performed maximal isometric hamstring contractions at 100°, 80°, 60°, and 40° knee flexion before and after five 1-minute hamstring stretches performed in either a spinal neutral position or a neural tension position. One leg was stretched in the neutral position and the other in the neural tension position. Hamstring electromyography (EMG) activity was recorded during all contractions and stretches. Passive resistance to stretch was reduced by 11% after stretching (p < 0.01; no difference between neutral or neural tension stretches p = 0.41). Stretch-induced strength loss was apparent after neural tension stretches (12%, p < 0.01) but not after neutral stretches (5%, p = 0.09). There was a rightward shift in the angle-torque curve after neutral stretches (strength loss on ascending limb, strength gain on descending limb, p < 0.01). This effect was not apparent after neural tension stretches (p = 0.43). Stretching did not affect EMG activity during isometric contractions (<2% decline p = 0.58; no difference between neutral and neural tension, p = 0.86). Hamstring stretching with the spine in a neutral position did not result in a significant strength loss but shifted the length-tension relationship such that strength was decreased at short muscle lengths and increased at long muscle lengths. Hamstring stretching with increased neural tension resulted in strength loss with no associated shift in the length-tension relationship.


Incorporating midmanagement skills in an oncology CNS program.
Today's health care system requires that CNSs be prepared to manage care within complex organizations as well as deliver expert care to individuals and their families. The integration of midmanagement preparation with clinical knowledge and skills is critical. In this paper, we (1) review the literature pertaining to the role of oncology CNS and management preparation, (2) describe the program at the University of Pennsylvania School of Nursing, and (3) identify the management content that was added to strengthen the theoretical and clinical components of the program and to prepare our graduates in assuming leadership positions.


[Clinical and morphological findings in 2 cases of angioimmunoblastic lymphadenopathy with dysproteinemia].
Two autopsy cases of angioimmunoblastic lymphadenopathy with dysproteinemia were examined. Clinical and morphological data did not differ greatly from those in other cases of the literature: patients died two and three months after the onset of the symptoms. The autopsy findings included moderately enlarged generalized lymph nodes, hepatosplenomegaly and lungs involvement. Microscopically the most prominent change was the vascular proliferation with pleiomorphic cellular infiltration.


Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD.
Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists' clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non-dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis.


Loss of flagellum-based motility by Listeria monocytogenes results in formation of hyperbiofilms.
Biofilm formation by the gram-positive, motile, food-borne pathogen Listeria monocytogenes was demonstrated to occur by an ordered series of stages. Biofilm development involves flagellum-based motility, which when blocked decreases initial bacterial surface attachment but subsequently leads to the formation of hyperbiofilms, surface-attached communities reaching high density.


A comparison of methods to assess changes in dietary patterns from pregnancy to 4 years post-partum obtained using principal components analysis.
Few studies have examined the longitudinal nature of dietary patterns obtained using principal components analysis (PCA); the methods used are inconsistent. This paper investigates the methodologies used to assess stability and changes in such patterns. Pregnant women recorded frequency of consumption of various food items as part of regular self-completed questionnaires in the Avon Longitudinal Study of Parents and Children. This was repeated when their children were 4 years of age; 8953 women provided data at both times. Dietary patterns were identified using PCA and component scores were calculated at each time point. Additional 'applied' scores were created at 4 years using the loadings obtained from the PCA on the pregnancy data. Correlations were similar for each component across the time points, though slightly larger using the applied method. The applied scores were considerably lower on average than those obtained from separate PCA at 4 years. Women's scores decreased on 'health conscious' and 'confectionery' components while 'processed' and 'vegetarian' scores both increased over the 4-year period. In contrast, applied scores were systematically lower for all components. When split into quintiles, weighted kappa was slightly higher between pregnancy and applied 4-year scores compared to the separate scores. In this cohort it was felt that the 'applied' method to obtain scores at the second time point was inappropriate, primarily due to the differences in FFQ between the two time points. We recommend that future studies using such 'applied' scores compare them with cross-sectional scores and consider the implications of any differences.


Ontogenic corticosteroidogenesis of the domestic fowl: response of isolated adrenocortical cells.
Ontogenic adrenocortical function of the domestic was investigated using adrenocortical cells isolated from embryonic chicks (18, 19, 20, and 21 days old) and male and female posthatch birds (1 day, 1 week, and 3 weeks old). Production of the predominant corticosteroids secreted by the chicken adrenal gland, corticosterone, cortisol, and aldosterone, was measured by radioimmunoassay after 2-hr incubation of cells with or without steroidogenic agents. Approaching hatch, basal and maximal ACTH-(1-24) (ACTH)-induced corticosteroid production increased steadily and peaked around 1 day posthatch (5-18 times and 3-9 times, respectively, the production values at 18 days embryonic life). Thereafter, corticosteroid production values decreased steadily to 3 weeks posthatch. Corticosterone predominated over the ages studied: Maximal ACTH-induced corticosterone production averaged 52 and 115 times the production values of aldosterone and cortisol, respectively. In addition, maximal ACTH-induced aldosterone production was roughly 2.2 times greater than cortisol production over the ages studied except for a short-lived, disproportionately greater aldosterone production at 1 day posthatch. In addition to perihatch and age-related differences in cellular corticosteroid production, there were also differences in cellular sensitivity to steroidogenic agents as indicated by the differences in half-maximal steroidogenic concentration values (ED50 values) of the steroidogenic agents. Sensitivity to ACTH increased 2.7 times from Day 18 of embryonic life to 1 day posthatch and then decreased steadily to 3 weeks posthatch. In addition, sensitivity to 8-bromo-cAMP (8-Br-cAMP) increased abruptly at 1 day posthatch (nearly 3 times) but then remained constant thereafter. However, a consistent change in cellular sensitivity to 25-hydroxycholesterol was not observed until 3 weeks posthatch (an increase in sensitivity of 3 times that at Day 18 of embryonic life). These data of cellular sensitivity suggest that there were distinct development and maturational alterations in the cellular loci at which ACTH, 8-Br-cAMP, and 25-hydroxycholesterol acted. Thus, during the transition from embryonic to postembryonic life of the domestic fowl, there are alterations in adrenocortical cell steroidogenic capacity and in the function of some cellular loci comprising the corticosteroidogenic pathway.


A reversed-phase compatible thin-layer chromatography autography for the detection of acetylcholinesterase inhibitors.
A dual readout autographic assay to detect acetylcholinesterase inhibitors present in complex matrices adsorbed on reversed-phase or normal-phase thin-layer chromatography plates is described. Enzyme gel entrapment with an amphiphilic copolymer was used for assay development. The effects of substrate and enzyme concentrations, pH, incubation time, and incubation temperature on the sensitivity and the detection limit of the assay were evaluated. Experimental design and response surface methodology were used to optimize conditions with a minimum number of experiments. The assay allowed the detection of 0.01% w/w of physostigmine in both a spiked Sonchus oleraceus L. extract chromatographed on normal phase and a spiked Pimenta racemosa (Mill.) J.W. Moore leaf essential oil chromatographed on reversed phase. Finally, the reversed-phase thin-layer chromatography assay was applied to reveal the presence of an inhibitor in the Cymbopogon citratus (DC.) Stapf essential oil. The developed assay is able to detect acetylcholinesterase inhibitors present in complex matrixes that were chromatographed in normal phase or reversed-phase thin-layer chromatography. The detection limit for physostigmine on both normal and reversed phase was of 1×10(-4) μg. The results can be read by a change in color and/or a change in fluorescence.


Comparison of 1-year cumulative live birth and perinatal outcomes following single blastocyst transfer with or without preimplantation genetic testing for aneuploidy: a propensity score-matched study.
We evaluated whether preimplantation genetic testing for aneuploidy (PGT-A) could increase the cumulative live birth rate (CLBR) in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). The clinical records of 7,668 patients who underwent oocyte retrieval (OR) with or without PGT-A were reviewed for 365 days and retrospectively analyzed. Using propensity score matching, 579 patients in the PGT-A group were matched one-to-one with 7,089 patients in the non-PGT-A (control) group. Their pregnancy and perinatal outcomes and CLBRs were statistically compared. The live birth rate per single vitrified-warmed blastocyst transfers (SVBTs) significantly improved in the PGT-A group in all age groups (P < 0.0002, all). Obstetric and perinatal outcomes were comparable between both groups regarding both RIF and RPL cases. Cox regression analysis demonstrated that in the RIF cases, the risk ratio per OR was significantly lower in the PGT-A group than in the control group (P = 0.0480), particularly in women aged < 40 years (P = 0.0364). However, the ratio was comparable between the groups in RPL cases. The risk ratio per treatment period was improved in the PGT-A group in both RIF and RPL cases only in women aged 40-42 years (P = 0.0234 and P = 0.0084, respectively). Increased CLBR per treatment period was detected only in women aged 40-42 years in both RIF and RPL cases, suggesting that PGT-A is inappropriate to improve CLBR per treatment period in all RIF and RPL cases.


Indications for resection and radiosurgery for brain metastases.
This review is focused on indications for resection, stereotactic radiosurgery, and fractionated radiotherapy for patients with single or multiple brain metastases. Our purpose is to summarize the indications and effect of these management approaches. Brain metastases are a frequent challenge in patients with extracranial solid cancers. More than 40% of patients with cancer will develop metastases to the brain. While some patients present with large lesions and symptoms related to mass effect, many are diagnosed when asymptomatic tumors are found on screening studies. The main options for patients with brain metastases are whole brain radiation therapy, surgical resection, and stereotactic radiosurgery. Much information regarding outcomes, survival, management morbidity, and quality of life is available. Randomized, class III clinical trials demonstrate that multimodal therapy is important for both life quality and extended survival. A better understanding of the current therapeutic options should result in improvements in patient care. This is a review of the literature from May 2004 to June 2005 with special attention on publications related to effect on quality of life with different procedures and therapies.


Are patients willing to remove, and capable of removing, their own nonabsorbable sutures?
Providing patients with instructions and equipment regarding self-removal of nonabsorbable sutures could represent a new efficiency in emergency department (ED) practice. The primary outcome was to compare the proportion of patients successfully removing their own sutures when provided with suture removal instructions and equipment versus the standard advice and follow-up care. Secondary outcomes included complication rates, number of physician visits, and patient comfort level. This prospective, controlled, single-blinded, pseudorandomized trial enrolled consecutive ED patients who met the eligibility criteria (age > 19 years, simple lacerations, nonabsorbable sutures, immunocompetent). The study group was provided with wound care instructions, a suture removal kit, and instructions regarding suture self-removal. The control group received wound care instructions alone. Outcomes were assessed by telephone contact at least 14 days after suturing using a standardized questionnaire. Overall, 183 patients were enrolled (93 in the intervention group; 90 in the control group). Significantly more patients performed suture self-removal in the intervention group (91.5%; 95% CI 85.4-97.5) compared to the control group (62.8%; 95% CI 52.1-73.6) (p < 0.001). Patients visited their physician less often in the intervention group (9.8%; 95% CI 3.3-16.2) compared to the control group (34.6%; 95% CI 24.1-45.2%) (p < 0.001). Complication rates were similar in both groups. Most patients are willing to remove, and capable of removing, their own sutures. Providing appropriate suture removal instructions and equipment to patients with simple lacerations in the ED appears to be both safe and acceptable.


Potential use of Colostrum Bovinum supplementation in athletes - A review.
Colostrum Bovinum is the first milk secreted from the mammary glands of mammals after parturition.  In calves, it is the only way to provide immunoglobulins, which are responsible for the proper maturation of the immune system. The benefits of calf colostrum have contributed to the investigation of the effects of colostrum in humans. Although the health properties of colostrum are not fully understood, its supplementation in athletes has been particularly interesting for over 20 years. The presence of growth factors, immunoglobulins, cytokines, lactoferrin and hormones suggests that colostrum may improve the functioning of the digestive, immune and neuroendocrine systems, and exercise performance. The administering of colostrum seems to be most effective during periods of high intensity training, probably due to its high concentration of IGF-I, the ability to increase muscle buffering capacity or its high SIgA concentration. Due to the lack of adjustment of specific doses and the period of colostrum supplementation, it is necessary to conduct further studies on the impact of colostrum supply on exercise performance. The aim of this review article is to analyze the available experimental studies and reviews on the use of colostrum in sport and to draw attention to the possibility of using colostrum to improve the health of athletes and the results they can achieve in their chosen sports.


Proteomics study of COI1-regulated proteins in Arabidopsis flower.
Jasmonates (JAs) are a new class of plant hormone that regulate expression of diverse genes to mediate various plant responses. The Arabidopsis F-box protein COI1 is required for plant defense and male fertility in JA signal pathway. To further investigate the regulatory role of COI1 in male fertility, we compared the proteomics profiles of Arabidopsis wild type (WT) flowers with coi1-1 mutant male-sterile flowers using two-dimensional difference gel electrophoresis coupled with matrix-assisted laser desoption/ionization-time-of-flight mass spectrometry. Sixteen proteins with potential function in specific biological processes such as metabolism processes and defense/stress responses were differentially expressed in WT and coi1-1 mutant flowers. Verification on a phi class glutathione transferase AtGSTF9, one out of these 16 identified proteins, revealed that the expression of AtGSTF9 was severely downregulated in flowers of coi1-1 mutant compared with that of WT. Further function analyses of these genes would provide new insights into the molecular basis of COI1-regulated male fertility.


[Evolutions of the "framework of benefits" system].
EVOLUTIONS OF THE "FRAMEWORK OF BENEFITS" SYSTEM. In the field of compliance, the last thirty years have been marked by an evolution of the regulatory framework in order to adapt an anti-corruption system to the whole ecosystem of health professionals and industrialists. Although the various developments now make the "framework of benefits" a solid legislative construction, the latest news shows the need to move towards a reinforcement of illegal practices as well as a framework of canvassing for promotion between industrialists and health professionals. However, the construction of this legal framework has given rise to concerns and questions, particularly from physicians' associations, concerning their training prospects and their search for funding.


Detecting growth hormone abuse in athletes.
There is widespread anecdotal evidence that growth hormone (GH) is used by athletes for its anabolic and lipolytic properties. Although GH is on the World Anti-doping Agency (WADA) list of banned substances, the detection of abuse with GH is challenging. Two approaches have been developed to detect GH abuse. The first is based on the measurement of pituitary GH isoforms and the second is based on the measurement of markers of GH action.Pituitary GH contains multiple isoforms whereas recombinant human GH comprises solely the 22-kDa isoform. Immunoassays that recognize the different isoforms have been developed and form the basis of the test introduced by WADA at the Athens Olympic Games. To date, no athlete has tested positive.The GH-2000 project proposed a test based on the measurement of insulin-like growth factor-I (IGF-I) and type III pro-collagen (P-III-P) as these markers increase in a dose-dependent manner in response to GH and their basal concentration varies much less than GH. When combined with discriminant function analysis, these markers were able to differentiate between those taking GH and placebo in double-blind placebo controlled trials. Subsequent studies have shown that the test is applicable across different ethnicities and is unaffected by injury.


[Angiomyolipoma of the kidney. Value of diagnosis in acute hemorrhage].
We report about a severe retroperitoneal bleeding of a ruptured angiomyolipoma of kidney. Despite of maximal diagnostic effort including CT and angiography it was not possible to find the exact diagnosis preoperative. The extensive bleeding did not allow to resect only the tumor, nephrectomy was necessary.


Enhanced needle visibility by microbubbles generated with negative pressure using an in-plane technique.
Our previous work found that needle visibility could be improved by introducing microbubbles into needles. The primary aim of this study was to test the hypothesis that the negative pressure method is superior to two other methods for enhancing needle visibility by introducing microbubbles into needles. The secondary aim was to evaluate the impacts of three factors on the visibility of microbubble-filled needles. In the first phase, three methods, including the negative pressure method, the mixing method and commercialized microbubbles, were applied to generate microbubbles inside needles for comparison of visibility in a porcine meat model. In the second phase, three factors were tested with a 2×5×5 factorial design to explore their influence on the visibility of microbubble-filled needles. The three factors included types of needles, insertion angles and types of contents inside needles. Needles filled with saline without microbubbles were used as the control in both phases. Insertion videos were recorded, and ultrasound images of needles were captured for the objective visibility analysis. Needle visibility was highest in the negative pressure method group (p<0.001). Needle visibility was mainly determined by insertion angles (p<0.001). Microbubble-filled needles were more visible than control needles at 40°, 50° and 60° (p<0.001, p<0.001 and p<0.001, respectively). Needle visibility can be significantly improved by microbubbles generated with the negative pressure method when insertion angles are 40°, 50° and 60° in porcine meat.


Hemokinin-1 is an important mediator of pain in mouse models of neuropathic and inflammatory mechanisms.
The Tac4 gene-derived hemokinin-1 (HK-1) is present in pain-related regions and activates the tachykinin NK1 receptor, but with binding site and signaling pathways different from Substance P (SP). NK1 receptor is involved in nociception, but our earlier data showed that it has no role in chronic neuropathic hyperalgesia, similarly to SP. Furthermore, NK1 antagonists failed in clinical trials as analgesics due to still unknown reasons. Therefore, we investigated the role of HK-1 in pain conditions of distinct mechanisms using genetically modified mice. Chronic neuropathic mechanical and cold hyperalgesia after partial sciatic nerve ligation (PSL) were determined by dynamic plantar aesthesiometry and withdrawal latency from icy water, motor coordination on the accelerating Rotarod. Peripheral nerve growth factor (NGF) production was measured by ELISA, neuronal and glia cell activation by immunohistochemistry in pain-related regions. Acute somatic and visceral chemonocifensive behaviors were assessed after intraplantar formalin or intraperitoneal acetic-acid injection, respectively. Resiniferatoxin-induced inflammatory mechanical and thermal hyperalgesia by aesthesiometry and increasing temperature hot plate. Chronic neuropathic mechanical and cold hypersensitivity were significantly decreased in HK-1 deficient mice. NGF level in the paw homogenates of intact mice were significantly lower in case of HK-1 deletion. However, it significantly increased under neuropathic condition in contrast to wildtype mice, where the higher basal concentration did not show any changes. Microglia, but not astrocyte activation was observed 14 days after PSL in the ipsilateral spinal dorsal horn of wildtype, but not HK-1-deficient mice. However, under neuropathic conditions, the number of GFAP-positive astrocytes was significantly smaller in case of HK-1 deletion. Acute visceral, but not somatic nocifensive behavior, as well as neurogenic inflammatory mechanical and thermal hypersensitivity were significantly reduced by HK-1 deficiency similarly to NK1, but not to SP deletion. We provide evidence for pro-nociceptive role of HK-1, via NK1 receptor activation in acute inflammation models, but differently from SP-mediated actions. Identification of its targets and signaling can open new directions in pain research.


[Change trends and related risk factors of disease burden on mesothelioma in Jiangsu Province from 1990 to 2019].
Objective: To analyze the change trends and risk factors of mesothelioma disease burden in Jiangsu Province from 1990 to 2019. Methods: In January 2022, using the 2019 Global Burden of Disease Study Data, the Joinpoint regression model was used to analyze the change trends of incidence, mortality, disable-adjusted life years (DALY) and premature mortality of mesothelioma residents in Jiangsu Province from 1990 to 2019, and the attribution level of mesothelioma risk factors was estimated by population attributing fraction. Results: The standardized incidence rates of mesothelioma in Jiangsu Province from 1990 to 2019 ranged from 0.07/10(5) to 0.09/10(5), with an average annual percentage change (AAPC) of -1.1% (t=-13.56, P<0.001). AAPCs in males and females were -0.3% (t=-2.18, P=0.029) and -1.6% (t=-11.39, P<0.001), respectively. The standardized mortality rates of mesothelioma ranged from 0.07/10(5) to 0.09/10(5), the AAPC was -1.1% (t=-12.23, P<0.001), AAPC was -1.6% (t=-14.09, P<0.001) for females, and there was no significant change in males (t=-1.83, P=0.068). The premature mortality was 0.004%-0.006%, the AAPC was -1.0% (t=-4.40, P<0.001), AAPC was -1.7% (t=-13.72, P<0.001) for females, and there was no significant change in males (t=-0.68, P=0.495). The standardized DALY rates ranged from 1.86/10(5) to 2.32/10(5), the AAPC was -0.9% (t=-11.08, P<0.001), AAPC was -1.6% (t=-11.05, P<0.001) for females, and there was no significant change in males (t=-0.95, P=0.343). Both the standardized years of life lost (YLL) rate and the standardized years lived with disability (YLD) rate showed a decreasing trend, and the AAPCs were -0.9% (t=-7.66, P<0.001) and -1.0% (t=-12.88, P<0.001), respectively. The proportion of YLL in DALY was more than 98.5%. Among the risk factors for mesothelioma burden attribution, the AAPC attributed to occupational asbestos exposure of DALY was 1.4% (t=3.43, P=0.001). The AAPC of DALY rate of standardized attribution was -1.7% (t=-12.11, P<0.001) . Conclusion: The overall burden of mesothelioma in Jiangsu Province is decreasing, occupational asbestos exposure is still the main risk factor of mesothelioma in Jiangsu Province, and early diagnosis and treatment should be strengthened.


Height SDS Changes (ΔhSDS) in Healthy Children from Birth to 18 Years, with Correction Factors for Measurement Intervals of Less than One Year.
Growth is volatile and non-linear. Assessing the instantaneous speed of growth (momentary height velocity) depends on the precision and the number of measurements and the duration of the observation period. Measurements at short intervals reflect both the non-linearity of growth and the technical error of measurements (TEM). We reanalyzed longitudinal measurements of body length at age 0, 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months, from 1879 healthy infants (956 girls, 923 boys) from France (180 girls, 173 boys), Vilnius, Lithuania (507 girls, 507 boys), Lublin, Poland (67 girls, 56 boys), Zürich, Switzerland (94 girls, 102 boys) and Spain (108 girls, 95 boys); and longitudinal measurements of annual body height from age 2 to 18 years from 1528 healthy children and adolescents (774 girls, 754 boys) from France (41 girls, 47 boys), Vilnius, Lithuania (23 girls, 27 boys), Lublin, Poland (70 girls, 58 boys), Zürich, Switzerland (111 girls, 120 boys), Spain (94 girls, 74 boys), the Czech Republic (65 girls, 69 boys), Hungary (316 girls, 320 boys), and Berkeley, USA (54 girls, 39 boys). We calculated age - and sex-specific mean values for height and SD for height separately for each country. In addition, we defined the instantaneous speed of growth by the difference of two measures of hSDS Formulas References A1 , or in the case of multiple measurements, by the slope of the linear regression (βhSDS(t)). Based on the longitudinal measurements of body length, we present reference values for annual growth velocity given in the form of SD of annual hSDS changes (ΔhSDS), from birth to maturity. Correction factors are added for validating measurements obtained at intervals of less than one year. The correction factors depend on number of measurements, and duration of the observation period.


Transfer of antioxidants at the interfaces of model food emulsions: distributions and thermodynamic parameters.
Knowledge on the driving force for the hydrophobic effect that partitions antioxidants (AOs) between the oil (O), aqueous (W) and interfacial (I) regions of food emulsions is crucial to predict their efficiency in inhibiting lipid oxidation and to preserve the organoleptic properties of lipid-based foods. Here, we have investigated the effects of temperature and surfactant volume fraction (ΦI) on the distribution of two representative AOs, the water insoluble α-tocopherol (TOC) and the oil insoluble caffeic acid (CA), in a model food emulsion composed of stripped corn oil, acidic water and the nonionic surfactant Tween 20. The distribution of the AOs is assessed in the intact emulsions by employing a well-established kinetic method based on the reaction between a hydrophobic arenediazonium ion and the AOs. The variations of the observed rate constant, kobs, with ΦI are interpreted on the grounds of the pseudophase kinetic model, which provides values for the interfacial rate constant kI and the partition constants between the aqueous-interfacial (P) and oil-interfacial (P) regions of the emulsions. From the variations of P, P and kI at a series of temperatures, we determined the Gibbs free energy, enthalpy and entropy values for the transfer of CA from the water to the interfacial (W → I) region and of TOC from the oil to the interfacial (O → I) regions of the emulsions, and the activation parameters for the reaction in the interfacial region. Activation energy values are in line with those expected for a bimolecular reaction. Results show that the W → I and O → I transfer processes are spontaneous and entropy driven.


Current management of skull base osteomyelitis.
Skull base osteomyelitis (SBO) is a life-threatening condition. Due to an aging and increasingly multimorbid population, clinicians are more often challenged with this disease. Yet, there is no consensus on the optimal diagnostic and follow-up management. This review should aid clinicians in decision-making for their patients. Treatment-resistant otalgia or headache is suspicious of SBO. Pseudomonas aeruginosa remains the most common pathogen but clinicians are challenged with increasing rates of sterile or fungal cultures due to previously applied antibiotics/steroids. No single imaging modality is able to detect the full extent of the disease. Whereas functional nuclear imaging with gallium-67 or methylene diphosphonate-technetium-99m was once advocated, its actual benefit is questionable. Newer modalities such as fluoro-D-glucose-positron emission tomography (PET)/computed tomography, PET/magnetic resonance imaging (MRI), or diffusion-weighted MRI seem to be promising in diagnosis and follow-up. Finding the causative pathogen is of utmost importance followed by long-term intravenous antibiotics until the disease has completely resolved. Surgery plays a minor role in treatment but can be helpful in selected cases. The numerous challenges in SBO render management difficult, but with a clear work-up including regular clinical, laboratory and imaging examinations, outcome can be improved.


N-Methyl Costaricine and Costaricine, Two Potent Butyrylcholinesterase Inhibitors from Alseodaphne pendulifolia Gamb.
Studies have been conducted over the last decade to identify secondary metabolites from plants, in particular those from the class of alkaloids, for the development of new anti-Alzheimer's disease (AD) drugs. The genus Alseodaphne, comprising a wide range of alkaloids, is a promising source for the discovery of new cholinesterase inhibitors, the first-line treatment for AD. With regard to this, a phytochemical investigation of the dichloromethane extract of the bark of A. pendulifolia Gamb. was conducted. Repeated column chromatography and preparative thin-layer chromatography led to the isolation of a new bisbenzylisoquinoline alkaloid, N-methyl costaricine (1), together with costaricine (2), hernagine (3), N-methyl hernagine (4), corydine (5), and oxohernagine (6). Their structures were elucidated by the 1D- and 2D-NMR techniques and LCMS-IT-TOF analysis. Compounds 1 and 2 were more-potent BChE inhibitors than galantamine with IC50 values of 3.51 ± 0.80 µM and 2.90 ± 0.56 µM, respectively. The Lineweaver-Burk plots of compounds 1 and 2 indicated they were mixed-mode inhibitors. Compounds 1 and 2 have the potential to be employed as lead compounds for the development of new drugs or medicinal supplements to treat AD.


Does pregnancy/paternity intention predict contraception use? A study among US soldiers who have completed initial entry training.
The US Army represents a community of young adults at risk for unintended pregnancy/paternity. Our study evaluated the effect of pregnancy/paternity intention on contraceptive choice amongst new, sexually active and non-pregnant recruits. A total of 592 males and 503 females completed self-administered surveys asking about pregnancy/paternity intention, contraceptive use at last intercourse, and potential confounding factors. A multidimensional measurement of pregnancy intention was developed. Contraceptive efficacy was categorised as a four-level ordinal variable. Multivariate ordinal regression measured the association between pregnancy/paternity intention and the most efficacious birth control method used at last intercourse. Only 7% of participants planned a pregnancy in the next 6 months, but almost 33% of them used no birth control at last intercourse. Each unit increase in pregnancy avoidance scale was associated with a 14% increase in efficacy of birth control method used (p<0.0001). Effectiveness of birth control method increased for age (p = 0.0873), post-secondary education (p = 0.0142) and male gender (p = 0.0019.). Binge drinking reduced the likelihood of being in a higher category of birth control use (p = 0.0258). Intention to avoid pregnancy and being male was associated with use of higher-level birth control methods.


Spatial distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in soils from typical oil-sewage irrigation area, Northeast China.
Spatial distribution and sources of 16 priority polycyclic aromatic hydrocarbons (16 EPA-PAHs) in soils were studied in Shenfu Irrigation Area (SIA) located at northeast of China. SIA (1.3 x 10(4) ha) was an important agricultural farmland irrigated with oil-sewage since the 1960s. Soil profiles at 91 sites controlling all SIA were sampled. The results demonstrated that four- and five-ring PAHs accounted for 71.2% and 73.0% of the total PAHs in surface (0-20 cm) and subsurface (20-30 cm) soil, respectively. Phenanthrene (Phe), Fluoranthene (Fla), Pyrene (Pyr), Benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP) were identified as five dominant individual PAHs. Generally, there was a decreasing trend in concentrations of 16 EPA-PAHs from upper to lower reaches (by distance away from source) within 0.6-12.36 mg kg(-1) and 0.04-4.99 mg kg(-1) in surface and subsurface soil, respectively. The concentrations of 16 EPA-PAHs in the surface soil were threefold higher than those in the subsurface soil. A combination of grass, wood or coal combustion and petroleum combustion in surface soil and a combination of grass, wood or coal combustion and petroleum sources in subsurface soil might be the most significant contributors of 16 EPA-PAHs in SIA, indicating different pollution periods.


Human ribosomal protein L13a is dispensable for canonical ribosome function but indispensable for efficient rRNA methylation.
Previously, we demonstrated that treatment of monocytic cells with IFN-gamma causes release of ribosomal protein L13a from the 60S ribosome and subsequent translational silencing of Ceruloplasmin (Cp) mRNA. Here, evidence using cultured cells demonstrates that Cp mRNA silencing is dependent on L13a and that L13a-deficient ribosomes are competent for global translational activity. Human monocytic U937 cells were stably transfected with two different shRNA sequences for L13a and clonally selected for more than 98% abrogation of total L13a expression. Metabolic labeling of these cells showed rescue of Cp translation from the IFN-gamma mediated translational silencing activity. Depletion of L13a caused significant reduction of methylation of ribosomal RNA and of cap-independent translation mediated by Internal Ribosome Entry Site (IRES) elements derived from p27, p53, and SNAT2 mRNAs. However, no significant differences in the ribosomal RNA processing, polysome formation, global translational activity, translational fidelity, and cell proliferation were observed between L13a-deficient and wild-type control cells. These results support the notion that ribosome can serve as a depot for releasable translation-regulatory factors unrelated to its basal polypeptide synthetic function. Unlike mammalian cells, the L13a homolog in yeast is indispensable for growth. Thus, L13a may have evolved from an essential ribosomal protein in lower eukaryotes to having a role as a dispensable extra-ribosomal function in higher eukaryotes.


Impact of Lactational Exposure to Polychlorinated Biphenyl Causes Epigenetic Modification and Impairs Sertoli Cells Functional Regulators in F1 Progeny.
Polychlorinated biphenyl (PCB) is an endocrine-disrupting chemical. Sertoli cells (SCs) provide physical and nutritional support for developing germ cells. Dysfunction in SCs has adverse effects on spermatogenesis. Previously, we found that the lactational exposure of PCBs (1, 2, and 5 mg/kg birth weight/day, orally from postnatal days 1 to 20) decreased the follicle-stimulating hormone receptor (FSHR) and androgen receptor (AR) expression in SCs of F1 progeny. Transcription factors initiate and regulate the transcription of genes. DNA methylation plays an important role in epigenetic gene regulation. Hence, this study was aimed to identify the level of transcription factors regulating FSHR, AR gene expression, and DNA methylation in the promoter of these genes in SCs of both F1 prepuberal and puberal offspring. DNA methylation in the promoter of FSHR and AR genes was examined by sodium bisulfite conversion technique. The protein levels of transcription factors (steroidogenic factor 1 [SF1], upstream stimulatory factors 1 and 2, c-fos, c-jun, and CREB-binding protein) and enzymes DNA methyltransferases (Dnmt1, Dnmt3ab, Dnmt3l, and histone deacetylase 1 [HDAC1]) were analyzed by Western blotting. The transcription factors that regulate the FSHR and AR gene in SCs were decreased in both the PCB-exposed F1 progeny. Methylation was observed in the promoter of FSHR, AR, and SF1. The protein levels of Dnmt1, Dnmt3ab, Dnmt3l, and HDAC1 were increased in the PCBs-treated groups. Subsequently, it leads to transcriptional repression of the genes in SCs. Our finding suggests that PCBs caused epigenetic change in SCs, thereby it impaired SCs function in F1 progeny.


Holding power of bioabsorbable ciprofloxacin-containing self-reinforced poly-L/DL-lactide 70/30 bioactive glass 13 miniscrews in human cadaver bone.
Antibiotics-plus bioactive glass-containing bioabsorbable self-reinforced (SR) polylactide screws have been developed for antibacterial osteoconductive bone fixation. The aim of the present study was to test the pullout properties of these recently developed miniscrews. Ciprofloxacin-plus bioactive glass-containing SR-polylactide miniscrews (BC) were compared with miniscrews made of neat SR-polylactide (A), SR-polylactide with bioactive glass (B), and ciprofloxacin-containing SR-polylactide (C). BC miniscrews and their controls (A, B, C) (all of length 6.0 mm, core diameter 1.45 mm, thread diameter 2.0 mm) were applied to one pair of cadaveric fibulae. Pullout force was measured using a materials testing machine. We carried out 49-50 pullout tests for each implant type. The Mann-Whitney test and Student's t-test were used for statistical evaluation. The pullout force for BC miniscrews was 114.9 +/- 34.0 (SD) N. Pullout forces for control miniscrews were 162.7 +/- 37.8 N (A), 99.1 +/- 16.2 N (B), and 142.9 +/- 26.9 N (C). Differences between the four groups were statistically significant (p < 0.001). Ciprofloxacin-plus bioactive glass-containing polylactide miniscrews have good holding power to human cadaver fibulae. However, adding bioactive glass and ciprofloxacin components to neat SR-polylactide results in lower pullout values.


Mental disorders, perceived health and quality of life of older prisoners in France.
People serving prison sentences have major needs in terms of their physical and mental health. However, little is known about the prevalence of mental disorders affecting older prisoners and about how they evaluate their state of health and their quality of life. The aim of our study is to identify whether there is a link between mental disorders and the level of perceived health and quality of life of older prisoners. For the group 1, we recruited 138 male prisoners aged 50 and over in 7 French prisons. The control group was composed of 138 community-dwelling men aged 50 and over. The research protocol comprised four scales (The mini international neuropsychiatric interview, The French version of the Nottingham health profile, The scale of the subjective state of mental health, The WHOQOL-BREF). The results reveal a very high prevalence of mental disorders among older prisoners, notably depression and anxiety. The evaluation of perceived health and quality of life is also significantly lower in the group of older prisoners. We discuss the link between having one or more mental disorders and a negative evaluation of perceived health and quality of life.


Preliminary studies of effectiveness and selectivity of Movento on Bemisia tabaci and its parasitoid Eretmocerus mundus.
The Bemisia tabaci Gennadius (Homoptera:Aleyrodidae) biotype complex is a key pest of several worldwide crops. The management and control of this pest has become difficult mainly due to its high reproductive rate and capacity to develop resistance to broad spectrum insecticides. In Argentina B. tabaci whitefly, causes economic losses in most areas of agricultural production. Eretmocerus mundus Mercet (Hymenoptera:Aphelinidae) is the most important parasitoid of B. tabaci and is commercialized as a biocontrol agent, mainly in Europe. Conservation of this biological control agent in Argentinean orchards requires the adoption of sustainable pest management practices due the negative impact of traditional pesticides on non-target organisms. Spirotetramat (Movento) belongs to a new class of pesticides that acts as a lipid biosynthesis inhibitor and claims to be selective towards natural enemies. The objectives of this work were 1) to evaluate the effectiveness of spirotetramat on eggs and nymphs of B. tabaci and 2) to determine the selectivity of spirotetramat towards E. mundus. Whitefly's eggs and nymphs (first nymphal settled instar) were exposed to the insecticide by foliar immersion whereas parasitoid adults (6 days old) were exposed to the insecticide by residual method for one hour, to simulate exposure of the parasitoid to the insecticide in the field. Lethal and sublethal effects of the insecticide were recorded daily. These preliminary studies have shown a high effectiveness of spirotetramat on the first nymphal instar of B. tabaci as well as a high selectivity for the pest in comparison to the parasitoid adults showing a low acute toxicity to them. These results suggest Movento could be included in Integrated Pest Management programs although more studies are required to complete its ecotoxicological profile.


Probabilistic model of resistance jumps in memristive devices.
Resistance switching memory cells such as electrochemical metallization cells and valence change mechanism cells have the potential to revolutionize information processing and storage. However, the creation of deterministic resistance switching devices is a challenging problem that is still open. At present, the modeling of resistance switching cells is dominantly based on deterministic models that fail to capture the cycle-to-cycle variability intrinsic to these devices. Herewith we introduce a state probability distribution function and associated integrodifferential equation to describe the switching process consisting of a set of stochastic jumps. Numerical and analytical solutions of the equation have been found in two model cases. This work expands the toolbox of models available for resistance switching cells and related devices and enables a rigorous description of intrinsic physical behavior not available in other models.


Nonpharmacologic Treatments for Chronic and Episodic Migraine: A Systematic Review and Meta-Analysis.
Minimally invasive techniques for treatment-resistant migraine have been developed on recent insights into the peripheral pathogenesis of migraines. Although there is a growing body of evidence supporting these techniques, no study has yet compared the effects of these treatments on headache frequency, severity, duration, and cost. PubMed, Embase, and Cochrane Library databases were searched to identify randomized placebo-controlled trials that compared radiofrequency ablation, botulinum toxin type A (BT-A), nerve block, neurostimulation, or migraine surgery to placebo for preventive treatment. Data on changes from baseline to follow-up in headache frequency, severity, duration, and quality of life were analyzed. A total of 30 randomized controlled trials and 2680 patients were included. Compared with placebo, there was a significant decrease in headache frequency in patients with nerve block ( P = 0.04) and surgery ( P < 0.001). Headache severity decreased in all treatments. Duration of headaches was significantly reduced in the BT-A ( P < 0.001) and surgery cohorts ( P = 0.01). Quality of life improved significantly in patients with BT-A, nerve stimulator, and migraine surgery. Migraine surgery had the longest lasting effects (11.5 months) compared with nerve ablation (6 months), BT-A (3.2 months), and nerve block (11.9 days). Migraine surgery is a cost-effective, long-term treatment to reduce headache frequency, severity, and duration without significant risk of complication. BT-A reduces headache severity and duration, but it is short-lasting and associated with greater adverse events and lifetime cost. Although efficacious, radiofrequency ablation and implanted nerve stimulators have high risks of adverse events and explantation, whereas benefits of nerve blocks are short in duration.


Increased fat mass negatively influences femoral neck bone mineral density in men but not women.
Obesity is known to be a protective factor against osteoporosis. However, recent studies have shown that excessive adiposity may be detrimental for bone health. To determine the association of lean mass (LM) and fat mass (FM) with bone mineral density (BMD) in Thais. Bone density studies of consecutive patients of Srinagarind Hospital, Khon Kaen, Thailand between 2010 and 2015 were reviewed. LM, FM, lumbar spine (LS) and femoral neck (FN) BMD were measured. Lean mass index (LMI) and fat mass index (FMI) were calculated [LMI=LM (kg)/height (m)2, FMI=FM (kg)/height (m)2] and analyzed to determine the association with LS and FN BMD using multiple regression analysis. This study was approved by the institutional ethical committee (HE42116). A total of 831 participants were included. The mean ± SD age was 50.0 ± 16.3 years. In men, LMI (per 1 kg/m2 increase) was positively correlated with FN BMD (g/cm2, β 0.033) and LS BMD (g/cm2, β 0.031), after adjusting for age, height and FMI. Whereas FMI (per 1 kg/m2 increase) was negatively correlated with FN BMD (g/cm2, β -0.015) but not with LS BMD (g/cm2, β 0.005) after adjusting for age, height and LMI. In women, both LMI and FMI were positively correlated with LS BMD (g/cm2, LMI: β 0.012; FMI: β 0.016) and FN BMD (g/cm2, LMI: β 0.034; FMI: β 0.007) with age, height, LMI and FMI included in the model. Our findings indicate that FM has a sex-specific influence on BMD in Thais.


Competitive Dominance within Biofilm Consortia Regulates the Relative Distribution of Pneumococcal Nasopharyngeal Density.
Streptococcus pneumoniae is a main cause of child mortality worldwide, but strains also asymptomatically colonize the upper airways of most children and form biofilms. Recent studies have demonstrated that ∼50% of colonized children carry at least two different serotypes (i.e., strains) in the nasopharynx; however, studies of how strains coexist are limited. In this work, we investigated the physiological, genetic, and ecological requirements for the relative distribution of densities, and spatial localization, of pneumococcal strains within biofilm consortia. Biofilm consortia were prepared with vaccine type strains (i.e., serotype 6B [S6B], S19F, or S23F) and strain TIGR4 (S4). Experiments first revealed that the relative densities of S6B and S23F were similar in biofilm consortia. The density of S19F strains, however, was reduced to ∼10% in biofilm consortia, including either S6B, S23F, or TIGR4, in comparison to S19F monostrain biofilms. Reduction of S19F density within biofilm consortia was also observed in a simulated nasopharyngeal environment. Reduction of relative density was not related to growth rates, since the Malthusian parameter demonstrated similar rates of change of density for most strains. To investigate whether quorum sensing (QS) regulates relative densities in biofilm consortia, two different mutants were prepared: a TIGR4ΔluxS mutant and a TIGR4ΔcomC mutant. The density of S19F strains, however, was similarly reduced when consortia included TIGR4, TIGR4ΔluxS, or TIGR4ΔcomC Moreover, production of a different competence-stimulating peptide (CSP), CSP1 or CSP2, was not a factor that affected dominance. Finally, a mathematical model, confocal experiments, and experiments using Transwell devices demonstrated physical contact-mediated control of pneumococcal density within biofilm consortia.IMPORTANCEStreptococcus pneumoniae kills nearly half a million children every year, but it also produces nasopharyngeal biofilm consortia in a proportion of asymptomatic children, and these biofilms often contain two strains (i.e., serotypes). In our study, we investigated how strains coexist within pneumococcal consortia produced by vaccine serotypes S4, S6B, S19F, and S23F. Whereas S6B and S23F shared the biofilm consortium, our studies demonstrated reduction of the relative density of S19F strains, to ∼10% of what it would otherwise be if alone, in consortial biofilms formed with S4, S6B, or S23F. This dominance was not related to increased fitness when competing for nutrients, nor was it regulated by quorum-sensing LuxS/AI-2 or Com systems. It was demonstrated, however, to be enhanced by physical contact rather than by a product(s) secreted into the supernatant, as would naturally occur in the semidry nasopharyngeal environment. Competitive interactions within pneumococcal biofilm consortia regulate nasopharyngeal density, a risk factor for pneumococcal disease.


The black cholera comes to the central valley of America in the 19th century - 1832, 1849, and later.
In mid-19th Century, cholera was epidemic throughout the world. Small towns of the American Midwest were not spared. The disease was blamed on miasmas arising from local causes, so flight from affected localities were logical and common. Flight, added to mortality, caused virtual depopulation of many small towns. Drinking water was drawn from rivers or shallow wells, often near seeping cesspools. Local merchants tried unsuccessfully to calm panic by suppressing information. Cholera was not good for business. Business was depressed. Organized religion thrived. National and state days of prayer were appointed to appease an angry God. During these frightening times, the people learned nothing about the infectiousness of cholera or about its prevention through sanitation. Their experiences tended to reinforce their belief in miasmas or divine retribution. The great epidemics of mankind describe human behavior in times of unavoidable and incurable crisis. Nineteenth Century cholera experiences illustrate a people's reaction to catastrophic disease, which they believed was incurable and unpreventable.


A study of hypothalamic-pituitary-adrenal suppression following curative surgery for Cushing's syndrome due to adrenal adenoma.
The hypothalamic-pituitary-adrenal axis was investigated in all six patients requiring glucocorticoid replacement 2.5-11 years after unilateral adrenalectomy for adrenal adenomas causing Cushing's syndrome. The hypothalamic-pituitary-adrenal axis was assessed by insulin induced hypoglycaemia and CRF testing in each patient. Two patients showed normal cortisol and ACTH responses to hypoglycaemia. Two patients showed subnormal cortisol responses to hypoglycaemia in the presence of high or normal basal ACTH concentrations. ACTH concentrations increased with both hypoglycaemia and CRF. Two patients showed subnormal cortisol responses to hypoglycaemia and CRF. One of these patients showed an ACTH rise following hypoglycaemia but not CRF. Defects at either hypothalamic-pituitary or adrenal levels were demonstrated and recovery of the axis appears to commence at the hypothalamic-pituitary level.


Evaluation of a simplified generic bi-substrate rate equation for computational systems biology.
The evaluation of a generic simplified bi-substrate enzyme kinetic equation, whose derivation is based on the assumption of equilibrium binding of substrates and products in random order, is described. This equation is much simpler than the mechanistic (ordered and ping-pong) models, in that it contains fewer parameters (that is, no K(i) values for the substrates and products). The generic equation fits data from both the ordered and the ping-pong models well over a wide range of substrate and product concentrations. In the cases where the fit is not perfect, an improved fit can be obtained by considering the rate equation for only a single set of product concentrations. Due to its relative simplicity in comparison to the mechanistic models, this equation will be useful for modelling bi-substrate reactions in computational systems biology.


Group B streptococcus (GBS) colonisation among expectant Irish mothers.
Group B streptococci (GBS) have been recognised for more than three decades as a serious cause of perinatal morbidity and neonatal mortality. The aim of this study was to accurately determine the prevalence of GBS carriage and the serotype distribution among pregnant Irish women. 504 women attending antenatal clinics had two swabs (one perianal and one low vaginal) taken in the last four weeks of their pregnancy. These were placed in Todd Hewitt broth and then subcultured onto solid media. Serotyping of the isolates was performed by the Central Public Health Laboratory, London. GBS colonised women were treated with prophylactic antibiotics in labour and their infants received prophylaxis for 48 hours. 129 women (25.6%) were found to be asymptomatically colonised with GBS. Dual site screening (low-vaginal and perianal) identified 5% more GBS carriers than one site would have done. Serotypes identified included types I (30%), II (17%), III (30%), IV (1%) and V (9%). GBS colonisation is very common in Irish pregnant women and therefore a strategy for management in pregnancy ought to be developed in order to reduce the recognised occurrence of neonatal morbidity and mortality caused by this organism.


Bioavailability of synthetic and biosynthetic deuterated lycopene in humans.
Current knowledge of the bioavailability of lycopene in humans is limited due to the inability to distinguish newly administered lycopene from the body reserves of lycopene. A quantitative method to assess the absorption and relative bioavailability of newly absorbed synthetic or natural lycopene was developed using two deuterated lycopene sources, in conjunction with an advanced LC/APCI-MS (liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry) to analyze newly absorbed lycopene in blood samples of study subjects. Two subjects (1 male and 1 female) consumed hydroponically grown tomatoes containing deuterium-enriched lycopene (80-84 g wet weight tomato containing 16.3 and 17.4 micromol lycopene, respectively) and two subjects (1 male, and 1 female) consumed 11 micromol synthetic (2)H(10) lycopene in 6 g of corn oil. Tomatoes were steamed and pureed. The doses were given together with a liquid formulated drink with 25% energy from fat. Our results showed that up to 34 days after taking an oral (2)H(10) lycopene dose (synthetic or from tomato) with a liquid formula drink, the area under the curve of the average serum percent enrichment response of synthetic lycopene reached 33.9 (+/-1.7) nmol-day/micromol lycopene in the dose, whereas that of lycopene from the tomato dose was 11.8 (+/-0.3) nmol-day/mumol lycopene in the dose. Our study provides evidence that the absorption of physiological levels of lycopene in intrinsically labeled tomatoes can be studied in humans. From these preliminary investigations, we find that the bioavailability of synthetic lycopene in oil appears to be about three times higher than that of lycopene from steamed and pureed tomatoes.


Evidence of fibrinogen degradation in rat anaphylaxis.
In active anaphylactic shock of rats pretreated with Bordetella pertussis vaccine, both plasma thrombin clotting time and the amount of antigenically active fibrinogen degradation products in the serum were increased. The formation of clottable fibrinogen fragments was shown by SDS polyacrylamide gel electrophoresis of thrombin-induced clots. When plasma of rats pretreated with 125I rat fibrinogen and then subjected to anaphylaxis was submitted to SDS polyacrylamide gel electrophoresis, fibrinogen-split products were also detected. Fibrinogen degradation results from the proteolytic effect of an activated fibrinolytic enzyme.


High ambient temperatures associations with children and young adult injury emergency department visits in NYC.
Injury is a significant health burden for children and young adult and may be an increasing concern in a warming climate. Research reveals many impacts to children's health associated with hot weather and heatwave events, including a growing literature on the association between high ambient temperature and injury, which may vary by intent such as injury resulting from violence. However, little is known about how this association varies across different types of injury and subgroups of young people. We examined relationships between warm season ambient temperature and intentional and unintentional injury among children and young adults in New York City (NYC). Within a case-crossover design, our study observed injury-related emergency department (ED) visits from the New York Statewide Planning and Research Cooperative System administrative dataset. Injuries were categorized as unintentional or intentional injuries during the warm season (May through September) in NYC from 2005 to 2011 among patients (0, 1-4, 5-9, 10-14, 15-19, 20-25 years old (y.o.)). Conditional logistic regression models with distributed lag non-linear functions were used to model the cumulative odds ratio (OR) injury-related ED visit over 0-5 lag days. Analyses were stratified by age group and sex to understand how associations vary across young people of different age and sex. There were a total of 572 535 injury-related ED visits. The largest effect of elevated temperature (daily minimum 77°F vs 48°F) was for unintentional injury among 5-9 y.o. (OR 1.32, 95% CI 1.23, 1.42) and for intentional injury among 20-25 y.o. (OR 1.54, 95% CI 1.28, 1.85). Further stratified analyses revealed that the highest risk of unintentional injury was among 5-9 y.o. males and 20-25 y.o. males for intentional injury. Our results suggest that high ambient temperatures are associated with higher odds of unintentional and intentional injuries among children. This work adds to a growing body of literature demonstrating the adverse impacts of heat on children, and suggests the need for messaging to parents and children about adopting adaptive strategies to prevent injuries when it is hot outside.


Inclusive design in electrical stimulation technologies and neurorehabilitation for clinician and patient end users.
Dr. Tamsyn Street is an interdisciplinary researcher working for the National Health Service (NHS) in the UK with a background in motor neurorehabilitation. In the last couple of decades there has been a rapid advancement in assistive technology solutions using electrical stimulation for neurorehabilitation. This editorial examines whether these advancements have translated into good inclusive design performance for clinician and patient end users. Suggestions for overcoming some of the existing challenges are proposed.


Charge regulation in biomolecular solution.
Proteins and other biomolecules contain acidic and basic titratable groups that give rise to intricate charge distributions and control electrostatic interactions. 'Charge regulation' concerns how the proton equilibria of these sites are perturbed when approached by alien molecular matter such as other proteins, surfaces and membranes, DNA, polyelectrolytes etc. Importantly, this perturbation generates a charge response that leads to attractive intermolecular interactions that can be conveniently described by a single molecular property – the charge capacitance. The capacitance quantifies molecular charge fluctuations, i.e. it is the variance of the mean charge and is an intrinsic property on par with the net charge and the dipole moment. It directly enters the free energy expression for intermolecular interactions and can be obtained experimentally from the derivative of the titration curve or theoretically from simulations. In this review, we focus on the capacitance concept as a predictive parameter for charge regulation and demonstrate how it can be used to estimate the interaction of a protein with other proteins, polyelectrolytes, membranes as well as with ligands.


Direct observation of the critical relaxation of polarization clusters in BaTiO3 using a pulsed x-ray laser technique.
We have developed a new method to investigate the relaxation time of the dipole moment in polarization clusters in BaTiO3. Time correlation of speckle intensities was measured by the use of a double pulsed soft x-ray laser. The evolution of the relaxation time of the dipole moment near the Curie temperature (T(C)) was investigated. The maximum relaxation time (approximately 90 ps) is shown to appear at a temperature of 4.5 K above the T(C), being coincident with the one where the maximum polarization takes place. This method is widely applicable to any other critical decay processes at phase transitions.


Differentiation of Lymphoma Presenting as Retroperitoneal Mass and Retroperitoneal Fibrosis: Evaluation with Multidetector-row Computed Tomography.
Retroperitoneal fibrosis (RPF) and lymphoma presenting as retroperitoneal mass may closely resemble each other and misdiagnosis may occur. This study investigated the differential imaging features of RPF and lymphoma which presented as a retroperitoneal soft tissue using multidetector-row computed tomography (MDCT). The 42 consecutive patients were included in this retrospective review, including 19 RPF patients (45.2%; including 13 males and 6 females; mean age: 56.7 ± 6.2 years) and 23 patients with lymphoma (54.8%; including 14 males and 9 females; mean age: 57.4 ± 12.3 years). An array of qualitative computed tomography (CT) features of lesions in 42 consecutive patients with newly diagnosed untreated RPF and lymphoma were retrospectively analyzed. The quantitative size of the lesion at the para-aortic region and attenuation in the precontrast, arterial, and portal phases were calculated in regions of interest and compared between the patients with newly diagnosed untreated RPF and with lymphoma. Receiver operating characteristic curve analysis was used to assess the potential diagnostic value of each quantitative parameter. Inter-reader concordance was also calculated. Mean ages between patients with RPF and lymphoma were not significantly different (56.7 ± 6.2 years vs. 57.4 ± 12.3 years P = 0.595). Compared to those in patients with lymphoma, homogeneous enhancement (65.2% vs. 94.7%, P = 0.027) and pelvic extension (52.2% vs. 89.5%, P = 0.017) were significantly more common while the involvement of additional nodes (78.3% vs. 5.3%, P < 0.001), suprarenal extension (60.9% vs. 15.8%, P = 0.004), and aortic displacement (43.5% vs. 5.3%, P = 0.006) were significantly less common in patients with RPF. Lesion size at the para-aorta was significantly greater in patients with lymphoma, compared with RPF patients (3.9 ± 1.2 cm vs. 1.8 ± 0.6 cm; P < 0.001). The attenuation values in three phases were not significantly different between patients with RPF and lymphoma. Inter-reader concordance for subjective features ranged from very good to excellent (range: 85.7-100.0%). This study showed that MDCT can help differentiate between untreated RPF and lymphoma on the basis of qualitative CT features and lesion sizes. Differentiating RPF from lymphoma on the basis of attenuation values in the precontrast, arterial, and portal phases was difficult to accomplish.


Marker-specific sorting of rare cells using dielectrophoresis.
Current techniques in high-speed cell sorting are limited by the inherent coupling among three competing parameters of performance: throughput, purity, and rare cell recovery. Microfluidics provides an alternate strategy to decouple these parameters through the use of arrayed devices that operate in parallel. To efficiently isolate rare cells from complex mixtures, an electrokinetic sorting methodology was developed that exploits dielectrophoresis (DEP) in microfluidic channels. In this approach, the dielectrophoretic amplitude response of rare target cells is modulated by labeling cells with particles that differ in polarization response. Cell mixtures were interrogated in the DEP-activated cell sorter in a continuous-flow manner, wherein the electric fields were engineered to achieve efficient separation between the dielectrophoretically labeled and unlabeled cells. To demonstrate the efficiency of marker-specific cell separation, DEP-activated cell sorting (DACS) was applied for affinity-based enrichment of rare bacteria expressing a specific surface marker from an excess of nontarget bacteria that do not express this marker. Rare target cells were enriched by >200-fold in a single round of sorting at a single-channel throughput of 10,000 cells per second. DACS offers the potential for automated, surface marker-specific cell sorting in a disposable format that is capable of simultaneously achieving high throughput, purity, and rare cell recovery.


Protein-acrylamide copolymer hydrogels for array-based detection of tyrosine kinase activity from cell lysates.
We describe the development of an array-based assay for the molecular level detection of tyrosine kinase activity directly from cellular extracts. Glutathione S-transferase-Crkl (GST-Crkl) fusion proteins are covalently immobilized into polyacrylamide gel pads via copolymerization of acrylic monomer and acrylic-functionalized GST-Crkl protein constructs on a polyacrylamide surface. The resulting hydrogels resist nonspecific protein adsorption, permitting quantitative and reproducible determination of Abl tyrosine kinase activity and inhibition, even in the presence of a complex cell lysate mixture. Half-maximal inhibition (IC50) values for imatinib mesylate inhibition of GST-Crkl (SH3) phosphorylation by v-Abl in a purified system and Bcr-Abl within a K562 cell lysate were determined to be 1.5 and 20 microM, respectively. Additionally, the protein-acrylamide copolymer arrays detected CML cell levels as low as 15% in a background of Bcr-Abl- leukemic cells and provided the framework for the parallel evaluation of six tyrosine kinase inhibitors. Such a system may have direct application to the detection and treatment of cancers resulting from upregulated tyrosine kinase activity, such as chronic myeloid leukemia (CML). These findings also establish a basis for screening tyrosine kinase inhibitors and provide a framework on which protein-protein interactions in other complex systems can be studied.


Prospective Cohort Study of Remote Patient Monitoring with and without Care Coordination for Hypertension in Primary Care.
Out-of-office blood pressure (BP) measurements contribute valuable information for guiding clinical management of hypertension. Measurements from home devices can be directly transmitted to patients' electronic health record for use in remote monitoring programs. This study aimed to compare in primary care practice care coordinator-assisted implementation of remote patient monitoring (RPM) for hypertension to RPM implementation alone and to usual care. This was a pragmatic observational cohort study. Patients aged 65 to 85 years with Medicare insurance from two populations were included: those with uncontrolled hypertension and a general hypertension group seeing primary care physicians (PCPs) within one health system. Exposures were clinic-level availability of RPM plus care coordination, RPM alone, or usual care. At two clinics (13 PCPs), nurse care coordinators with PCP approval offered RPM to patients with uncontrolled office BP and assisted with initiation. At two clinics (39 PCPs), RPM was at PCPs' discretion. Twenty clinics continued usual care. Main measures were controlling high BP (<140/90 mm Hg), last office systolic blood pressure (SBP), and proportion with antihypertensive medication intensification. Among the Medicare cohorts with uncontrolled hypertension, 16.7% (39/234) of patients from the care coordination clinics were prescribed RPM versus <1% (4/600) at noncare coordination sites. RPM-enrolled care coordination group patients had higher baseline SBP than the noncare coordination group (148.8 vs. 140.0 mm Hg). After 6 months, in the uncontrolled hypertension cohorts the prevalences of controlling high BP were 32.5% (RPM with care coordination), 30.7 % (RPM alone), and 27.1% (usual care); multivariable adjusted odds ratios (95% confidence interval) were 1.63 (1.12-2.39; p = 0.011) and 1.29 (0.98-1.69; p = 0.068) compared with usual care, respectively. Care coordination facilitated RPM enrollment among poorly controlled hypertension patients and may improve hypertension control in primary care among Medicare patients.


Evaluation of Tp-E interval and Tp-E/Qtc ratios in patients with overt hypothyroidism and subclinical hypothyroidism.
Tp-e interval and Tp-e/QTc are among the new-generation indicators used for predicting cardiac arrhythmia and ventricular repolarization. In this study, we aimed to evaluate Tp-e and Tp-e/QTc ratios in patients with overt hypothyroidism and subclinical hypothyroid patients. In this study, a total of 105 patients were included with 35 overt hypothyroidism, 35 subclinical hypothyroidism, and 35 healthy euthyroid patients. The anthropometric measurements, laboratory results, and electrocardiographic data of the patients were measured. The groups were compared in terms of Tp-e interval, Tp-e/QT and Tp-e QT/c ratios. When the Tp-e interval and Tp-e/QTc values of the patients were compared, a significant difference was found (p<0.001). A positive correlation was found between thyroid stimulating hormone (TSH) with Tp-e interval and Tp-e/QT ratio. Tp-e interval and Tp-e/QTc duration increased in overt hypothyroidism and subclinical hypothyroidism patients compared to euthyroid patients. We believe that regular use of levothyroxine therapy in overt hypothyroidism patients will decrease cardiac mortality. Cardiac risk factors should be considered to decide on levothyroxine therapy for subclinical hypothyroidism patients.


Metabolomics of Multimorbidity: Could It Be the Quo Vadis?
Multimorbidity, the simultaneous presence of two or more chronic diseases, affects the health care to a great extent. Its association with health care cost, more disability, and poor quality of life makes it a major public health risk. The matter of worry is that management of a multimorbid condition is complicated by the fact that multiple types of treatment may be required to treat different diseases at a time, and the interaction between some of the therapies can be detrimental. Understanding the causal factors of simultaneously occurring disease conditions and investigating the connected pathways involved in the whole process may resolve the complication. When different disease conditions present in an individual share common responsible factors, treatment strategies targeting at those common causes will certainly reduce the chance of development of multimorbidity occurring because of those factors. Metabolomics that can dig out the underlying metabolites/molecules of a medical condition is believed to be an effective technique for identification of biomarkers and intervention of effective treatment strategies for multiple diseases. We hypothesize that understanding the metabolic profile may shed light on targeting the common culprit for different/similar chronic diseases ultimately making the treatment strategy more effective with a combinatorial effect.


Midterm clinical results of osteochondral autograft transplantation for advanced stage Freiberg disease.
We aimed to evaluate the midterm clinical results of osteochondral autograft transplantation (OAT) for advanced stage Freiberg disease. This study included consecutive patients who underwent OAT for advanced stage Freiberg disease and were followed postoperatively for more than five years. In all cases, the autograft was harvested from the ipsilateral knee joint. Clinical evaluation was performed based on the American Orthopaedic Foot and Ankle Society Lesser Metatarsophalangeal-Interphalangeal Scale (AOFAS) score and visual analogue scale (VAS) score, which were done pre-operatively and at the most recent follow-up. Radiological evaluation was performed at two years after the operation. Furthermore, the most recent six patients underwent magnetic resonance imaging (MRI) five years after the operation to assess the configuration of the articular surface. A total of 13 patients (all female; mean age 16.7 years; range 10-38 years) were included and followed up for a mean duration of 67.2 months (range 60-100 months). The mean AOFAS significantly improved from a score of 66.9 ± 5.3 (range 59-77) to 93.0 ± 7.6 (range 82-100) (p < 0.0001). Likewise, the mean VAS significantly improved from a score of 72.7 ± 10.3 (range 60-90) to 7.8 ± 7.2 (range 0-20) (p < 0.0001). Radiographs at two years after the operation revealed no osteoarthritic change in all cases. MRI at five years after the operation showed consolidation of the transplanted autograft and smooth configuration of the articular surface in the six cases. OAT may be effective for advanced stage Freiberg disease. Further studies are necessary before this technique can become the standard operative treatment.


Crystallization of the Ets1-Runx1-CBFβ-DNA complex formed on the TCRα gene enhancer.
Gene transcription is regulated in part through the assembly of multiple transcription factors (TFs) on gene enhancers. To enable examination of the mechanism underlying the formation of these complexes and their response to a phosphorylation signal, two kinds of higher-order TF-DNA assemblies were crystallized composed of an unmodified or phosphorylated Ets1 fragment, a Runx1(L94K) fragment and a CBFβ fragment on the T-cell receptor (TCR) α gene enhancer. Within these complexes, the Ets1 and Runx1 fragments contain intrinsically disordered regulatory regions as well as their DNA-binding domains. Crystals of the complex containing unmodified Ets1 belonged to space group P212121, with unit-cell parameters a = 78.7, b = 102.1, c = 195.0 Å, and diffracted X-rays to a resolution of 2.35 Å, and those containing phosphorylated Ets1 belonged to the same space group, with unit-cell parameters a = 78.6, b = 101.7, c = 194.7 Å, and diffracted X-rays to a similar resolution. To facilitate crystallization, a Runx1 residue involved in a hydrophobic patch that was predicted to be engaged in crystal packing based on the previously reported structures of Runx1-containing crystals was mutated.