Effect of modified graded recession and anteriorization on unilateral superior oblique palsy: a retrospective study.
Several inferior oblique (IO) weakening methods exist for correction of superior oblique palsy (SOP). A previously reported method involved recession and anteriorization according to IO overaction (IOOA) grade, which might be subjective and cause upgaze limitation and opposite vertical strabismus. Therefore, this study attempted to examine the efficacy of modified graded recession and anteriorization of the IO muscle in correction of unilateral SOP without resulting in upgaze limitation or opposite vertical strabismus. A total of 26 patients (male, 16; female, 10; age: 3-40 years) with SOP and head tilt or diplopia underwent modified graded recession and anteriorization. Patients were grouped by the position at which the IO muscle was attached inferior/temporal to the lateral border of the inferior rectus (IR) as follows: (1) 7.0/2.0 mm (4 patients), (2) 6.0/2.0 mm (3 patients), (3) 5.0/2.0 mm (3 patients), (4) 4.0/2.0 mm (11 patients), (5) 3.0/0.0 mm (2 patients), and (6) 2.0/0.0 mm (3 patients). Recession and anteriorization were matched to vertical deviation in the primary position at far distance. Remaining diplopia, head tilt, vertical deviation (≤3 prism diopter (PD), excellent; 4-7 PD, good; and ≥ 8 PD, poor), upgaze limitation, and opposite vertical strabismus were evaluated. The average pre and postoperative 1-year vertical deviation angles in the primary position at far distance were 15.0 ± 5.6 PD and 1.2 ± 2.0 PD, respectively. At 1 year post-surgery, the vertical deviation angles were reduced by 6.8-21.0 PD from those at baseline. Few patients exhibited remaining head tilt, diplopia, upgaze limitation, or opposite vertical strabismus. Correction of hypertropia was excellent in 22 and good in 4 patients. Modified graded recession and anteriorization of the IO muscle is an effective surgical method for treating unilateral SOP. It exhibits good results and reduces the incidence of opposite vertical strabismus.


Development, standardization and validation of molecular techniques for malaria vector species identification, trophic preferences, and detection of Plasmodium falciparum.
Knowledge on prevalence of malaria vector species of a certain area provides important information for implementation of appropriate control strategies. The present study describes a rapid method for screening of major Anopheline vector species and at the same time detection of Plasmodium falciparum sporozoite infection and blood meal preferences/trophic preferences. The study was carried from February 2012 to March 2013 in three seasons, i.e. rainy, winter and summer in Jhumpura PHC of Keonjhar district, Odisha, India. Processing of mosquitoes was carried out in two different methods, viz. mosquito pool (P1) and mosquito DNA pool (P2). Pool size for both the methods was standardized for DNA isolation and multiplex PCR assay. This PCR based assay was employed to screen the major vector com- position in three different seasons of four different ecotypes of Keonjhar district. Pearson's correlation coefficient was determined for a comparative analysis of the morphological identification with the pool prevalence assay for each ecotype. A pool size of 10 was standardized for DNA isolation as well as PCR. PCR assay revealed that the average pool prevalence for all ecotypes was highest for An. annularis in winter and summer whereas for An. culicifacies it was rainy season. Foothill and plain ecotypes contributed to highest and lowest vectorial abundance respectively. The results of the prevalence of vector species in pool from PCR based assay were found to be highly correlated with that of the results of morphological identification. Screening by pool based PCR assay is relatively rapid as compared to conventional identification and can be employed as an important tool in malaria control programmes.


Sonohysterographic imaging of the endometrial cavity.
Vaginal ultrasound is the most effective method of imaging the contents of the true pelvis in the female. Saline influsion sonohysterography (SIS) is a simple refinement of the standard vaginal sonographic exam. Here, we briefly describe and demonstrate our use of this latter technique.


A Highly Sensitive CRISPR-Empowered Surface Plasmon Resonance Sensor for Diagnosis of Inherited Diseases with Femtomolar-Level Real-Time Quantification.
The clustered regularly interspaced short palindromic repeats (CRISPR) molecular system has emerged as a promising technology for the detection of nucleic acids. Herein, the development of a surface plasmon resonance (SPR) sensor that is functionalized with a layer of locally grown graphdiyne film, achieving excellent sensing performance when coupled with catalytically deactivated CRISPR-associated protein 9 (dCas9), is reported. dCas9 protein is immobilized on the sensor surface and complexed with a specific single-guide RNA, enabling the amplification-free detection of target sequences within genomic DNA. The sensor, termed CRISPR-SPR-Chip, is used to successfully analyze recombinant plasmids with only three-base mutations with a limit of detection as low as 1.3 fM. Real-time monitoring CRISPR-SPR-Chip is used to analyze clinical samples of patients with Duchenne muscular dystrophy with two exon deletions, which are detected without any pre-amplification step, yielding significantly positive results within 5 min. The ability of this novel CRISPR-empowered SPR (CRISPR-eSPR) sensing platform to rapidly, precisely, sensitively, and specifically detect a target gene sequence provides a new on-chip optic approach for clinical gene analysis.


Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study.
SSc causes intractable ischaemic ulcers. To avoid major amputation, we examined the safety and efficacy of therapeutic vascular angiogenesis for digital ulcers due to SSc. A single-centre, open-label pilot study was conducted in patients with an ischaemic digital ulcer [n = 40, mean age 65 years (s.d. 8), Rutherford class III-5 or III-6) due to lcSSc (n = 11) or arteriosclerosis obliterans (ASO; n = 29). Bone marrow mononuclear cells (0.4-5.1 × 10(10) cells in total) were administered into the ischaemic limbs. We evaluated short-term safety and efficacy by means of a pain scale, (99m)Tc-tetrofosmin scintigraphy and transcutaneous oxygen tension (TcPO2) before and 4 weeks after treatment. Also, the 2-year outcome was compared. There was a case of amputation in each group within 4 weeks after therapy. The pain scale significantly decreased in both groups [lcSSc 93 mm (s.d. 9) to 11 (s.d. 16), P < 0.01; ASO 77 mm (s.d. 22) to 16 (s.d. 13), P < 0.01] and TcPO2 significantly improved [lcSSc 9.0 mmHg (s.d. 9) to 35 (s.d. 14), P < 0.01; ASO 18 mmHg (s.d. 10) to 29 (s.d. 21), P < 0.05). At the 2-year follow-up, the limb amputation rate was 9.1% in lcSSc and 20.7% in ASO (P = 0.36), while the recurrence rate was 18.2% in lcSSc and 17.2% in ASO (P = 0.95). All-cause mortality was 27.3% in lcSSc and 17.2% in ASO (P = 0.65). In patients with lcSSc, bone marrow mononuclear cell implantation provides clinical benefit and is safe, without major adverse reactions, and may become an effective strategy. UMIN-CTR, http://www.umin.ac.jp/ctr/index-j.htm, no. UMIN000004112.


The use of an intra-oral injection of ketorolac in the treatment of irreversible pulpitis.
To examine whether an intra-oral injection of a nonsteroidal anti-inflammatory drug (ketorolac), in association with conventional local anaesthetic techniques, would improve the pulp extirpation rate in teeth with irreversible pulpitis. A two group double-blind clinical trial was undertaken in the Dental Casualty Department of the University of Manchester School of Dentistry. Patients were randomly allocated to either the test or control group. The test group received an intra-oral injection of ketorolac (30 mg in 1 mL) in the buccal sulcus adjacent to the tooth being treated. After an interval of 15 min, they then received 2.2 mL of 2% lidocaine with 1 : 80 000 epinephrine by buccal infiltration in the maxilla or by inferior dental block in the mandible. The control group received an intra-oral injection of normal saline (1 mL) in the buccal sulcus adjacent to the tooth being treated, followed by the same local anaesthetic regime as the test group after the 15 min interval. Fifteen minutes after the local anaesthetic injections, pulp extirpation was attempted. All patients completed the short-form McGill pain questionnaire prior to treatment and completed identical questionnaires at 6 and 24 h after treatment. The study protocol set the number of patients to be treated at twenty. However, as the study progressed it became apparent that the intra-oral injection of ketorolac caused significant pain to four of the five patients who received it; therefore the study was terminated after ten patients had been treated. The results from the patients treated showed no significant difference in the pulp extirpation rate between the test and control groups. However, patients with higher pain scores at baseline were less likely to have the pulp completely extirpated, irrespective of whether they were in the test or control group. Pain scores for all patients decreased significantly from baseline to 24 h. An intra-oral injection of ketorolac did not improve the pulp extirpation rate in a small group of patients with irreversible pulpitis compared with a placebo. In addition, it was associated with such significant pain on injection that it cannot be recommended as a treatment in this situation.


Modulated structures of flexoelectric origin in nematic liquid crystals.
A structural instability of flexoelectric origin is predicted in a homeotropic cell, of insulating nematic liquid crystal, by the action of an electric field applied in the direction of the initially nonperturbed nematic director. The instability gives rise to a two-dimensional periodic structure. The critical field to observe the predicted modulated structure as well as the wavelength at the threshold are evaluated. Both vary as the inverse square root of the cell thickness. The role of the dielectric anisotropy on the phenomenon is investigated. Our analysis is performed in the limit of weak anchoring energy strength, where the extrapolation length is large with respect to the thickness of the nematic sample.


The effect of nitrendipine on renal haemodynamics and tubular reabsorption and its neural control in anaesthetised rats with chronic renal failure.
This study examined the influence of a calcium channel antagonist, nitrendipine, on blood pressure and kidney function in a rat model of chronic renal failure. Additionally, the effects of low frequency renal nerve stimulation were studied in the presence and absence of nitrendipine. Male Wistar rats were fed a diet high in adenine for 4 weeks and then acutely anaesthetised and prepared for renal functional measurements. Blood pressure was elevated but renal blood flow and glomerular filtration rate were reduced, between 30 to 50%, urine flow and absolute sodium excretion were lower and fractional sodium excretion was two to three times higher than in normal rats. Nitrendipine (0.25 microg/kg/min i.v.) decreased blood pressure at 114+/-7 mm Hg, by 11% (P<0.05), increased left renal blood flow, at 1.3+/-0.2 ml/min(-1) g(-1), by 16% (P<0.01), and urine flow, absolute and fractional sodium excretions, by between 50-83% (all P<0.05). Renal nerves stimulation (0.7-1.3 Hz, 15V, 0.2 ms) decreased (P<0.02) left renal blood flow by 10% but had no effect on excretory variables, irrespective of nitrendipine administration. These results show that in renal failure rats the vascular and tubular responses to nitrendipine are preserved. However, the neural regulation of tubular reabsorption is abolished in this experimental model, irrespective of nitrendipine administration.


Near infrared spectroscopy as a tool for the determination of eumelanin in human hair.
Eumelanins are brown-black pigments present in the hair and in the epidermis which are acknowledged as protection factors against cell damage caused by ultraviolet radiation. The quantity of eumelanin present in hair has recently been put forward as a means of identifying subjects with a higher risk of skin tumours. For epidemiological studies, chromatographic methods of determining pyrrole-2,3,5-tricarboxylic acid (PTCA; the principal marker of eumelanin) are long, laborious and unsuitable for screening large populations. We suggest near infrared (NIR) spectroscopy as an alternative method of analysing eumelanin in hair samples. PCTA was determined on 93 samples of hair by means of oxidizing with hydrogen peroxide in a basic environment followed by chromatographic separation. The same 93 samples were then subjected to NIR spectrophotometric analysis. The spectra were obtained in reflectance mode on hair samples which had not undergone any preliminary treatment, but had simply been pressed and placed on the measuring window of the spectrophotometer. The PTCA values obtained by means of HPLC were correlated with the near infrared spectrum of the respective samples. A correlation between the PTCA values obtained by means of HPLC and the PTCA values obtained from an analysis of the spectra was obtained using the principal component regression (PCR) algorithm. The correlation obtained has a coefficient of regression (R(2)) of 0.89 and a standard error of prediction (SEP) of 13.8 for a mean value of 108.6 ng PTCA/mg hair. Some considerations about the accuracy of the obtained correlation and the main sources of error are made and some validation results are shown.


Basal levels of (p)ppGpp differentially affect the pathogenesis of infective endocarditis in Enterococcus faecalis.
The alarmone (p)ppGpp mediates the stringent response and has a recognized role in bacterial virulence. We previously reported a stringent response-like state in Enterococcus faecalis isolated from a rabbit foreign body abscess model and showed that E. faecalis mutants with varying levels of cellular (p)ppGpp [Δrel, ΔrelQ and the (p)ppGpp0 ΔrelΔrelQ] had differential abilities to persist within abscesses. In this study, we investigated whether (p)ppGpp contributes to the pathogenesis of E. faecalis infective endocarditis (IE), a biofilm infection of the heart valves. While the stringent response was not activated in heart valve-associated E. faecalis, deletion of the gene encoding the bifunctional (p)ppGpp synthetase/hydrolase Rel significantly impaired valve colonization. These results indicate that the presence of (p)ppGpp is dispensable for E. faecalis to cause IE, whereas the ability to regulate (p)ppGpp levels is critical for valve colonization. Next, we characterized how basal (p)ppGpp levels affect processes associated with IE pathogenesis. Despite being defective in binding to BSA-coated polystyrene surfaces, the Δrel strain bound to collagen- and fibronectin-coated surfaces and ex vivo porcine heart valves as well as the parent and ΔrelΔrelQ strains, ruling out the possibility that the impaired IE phenotype was due to an attachment defect. Moreover, differences in cellular (p)ppGpp levels did not affect extracellular gelatinase activity but significantly impaired enterococcal invasion of human coronary artery endothelial cells. Taken together, this study uncovers for the first time the fact that differences in basal (p)ppGpp levels, rather than the stringent response, differentially affect processes that contribute to the pathogenesis of IE.


Effects of metabolic rate on protein evolution.
Since the modern evolutionary synthesis was first proposed early in the twentieth century, attention has focused on assessing the relative contribution of mutation versus natural selection on protein evolution. Here we test a model that yields general quantitative predictions on rates of protein evolution by combining principles of individual energetics with Kimura's neutral theory. The model successfully predicts much of the heterogeneity in rates of protein evolution for diverse eukaryotes (i.e. fishes, amphibians, reptiles, birds, mammals) from different thermal environments. Data also show that the ratio of non-synonymous to synonymous nucleotide substitution is independent of body size, and thus presumably of effective population size. These findings indicate that rates of protein evolution are largely controlled by mutation rates, which in turn are strongly influenced by individual metabolic rate.


Manipulation of single-stranded DNA by using an artificial site-selective DNA cutter composed of cerium(IV)/EDTA and phosphonate-oligonucleotide conjugates.
An artificial site-selective DNA cutter to hydrolyze single-stranded DNA at a desired site was prepared from Ce(IV)/ethylenediamintetraacetic acid (EDTA) and two ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid)-oligonucleotide conjugates. By using this cutter, the sense strand of a blue fluorescent protein (BFP) gene was selectively cut at a predetermined site in the chromophore-coding region. The upstream fragment obtained by the site-selective scission was ligated with the downstream fragment of the closely related green fluorescent protein (GFP) gene so that the 5'- and 3'-end portions of the chromophore came from the BFP fragment and the GFP fragment, respectively. The recombinant gene was successfully expressed in E. coli and the chimeric chromophore emitted green fluorescence as expected.


The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency.
Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Sixty-seven cocaine-dependent patients were stabilized on methadone for 2 weeks and then randomized into disulfiram (250 mg/day, N = 32) and placebo groups (N = 35) for 10 weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10 weeks of the study (N = 56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. The CT or TT MTHFR genotype group (N = 32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p = 0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N = 24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81-69% (p = 0.007). This study indicates that a patient's MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence. Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630.


Dexamethasone increases hepatic insulin-like growth factor binding protein-1 (IGFBP-1) mRNA and serum IGFBP-1 concentrations in the rat.
Glucocorticoid excess is associated with growth retardation in both man and experimental animals. We have previously reported that dexamethasone (DXM) inhibits growth hormone induction of insulin-like growth factor-I (IGF-I) mRNA in the hypophysectomized rat and reduces steady-state IGF-I mRNA levels in the intact rat. However, in these experiments, DXM had surprisingly little effect on serum IGF-I concentrations. Here, we have examined the effect of DXM on hepatic insulin-like growth factor binding protein-1 (IGFBP-1) mRNA levels and on serum IGFBP-1 concentrations. After a single ip injection of DXM, 6 micrograms/100 g body wt, IGFBP-1 mRNA increased 2.24 +/- 0.25-fold, P less than 0.05 at 1 h and declined to normal levels in 6-12 h. A dose-dependent increase in increased hepatic IGFBP-1 mRNA abundance was seen in rats killed 1 h after an ip injection of DXM, 0.1 to 60 micrograms/100g body wt. As little as 1 microgram/100g body wt, significantly enhanced hepatic IGFBP-1 mRNA levels; 2.02- +/- 0.38-fold, P less than 0.05. This effect appeared to be post-transcriptional, since IGFBP-1 transcription in hepatic nuclei from rats treated with DXM was not significantly different from untreated rats. When DXM, 1 microgram/rat, was administered daily for 6 days a significant increase in IGFBP-1 mRNA was detected; 2.02 +/- 0.39-fold, P less than 0.05. A more marked increase was seen with 6 and 60 micrograms/rat of DXM; 4.47 +/- 1.08- and 10.61 +/- 0.31-fold, respectively. Serum was analyzed by sodium dodecyl sulfate-plyacrylamide gel electrophoresis and immunoblotting using antisera raised against a synthetic peptide derived from the predicted sequence of rat IGFBP-1. The antisera recognized a doublet of approximately 30 kDa. A dose-dependent increase in the abundance of these BPs were seen in the serum from rats treated chronically with DXM. The observations reported here clearly demonstrate that DXM increases hepatic IGFBP-1 mRNA and serum IGFBP-1 concentrations. If IGFBP-1 functions to decrease the bioavailability of IGF-1 in vivo the enhanced expression of IGFBP-1 may be an additional mechanism whereby glucocorticoid excess results in growth retardation.


White matter tractography by diffusion tensor imaging plays an important role in prognosis estimation of acute lacunar infarctions.
The aim of this study was to evaluate the anatomical and clinical relationship between lacunar infarction and the corticospinal tract (CST) in patients with acute lacunar infarction and predict clinical outcome. We examined 28 pyramidal tract stroke patients in the acute phase or early subacute phase (<3 days) with a marked motor deficit. The anatomical location and the extent of CST involvement within the infarcts were visualized on three-dimensional colour-coded diffusion tensor tractography (DTT). With regard to the CST, all patients were divided into three clinical subgroups: Group 1 (intact type), Group 2 (partial involvement type) and Group 3 (whole involvement type). Subsequently, the severity of the motor deficit of each patient was determined according to the National Institutes of Health Stroke Scale (NIHSS) scores at the acute/early subacute phase (<3 days after onset of symptoms), early chronic phase (8-14 days) and outcome (30-60 days). NIHSS scores of Group 1 (12/28) were significantly lower than those of Group 2 (9/28) at the acute phase or early subacute phase (U = -2.816, p<0.01), and those of Group 2 were significantly lower than those of Group 3 (7/28) (U = -3.136, p<0.01). At outcome,NIHSS scores of Group 1 were significantly lower than those of Group 2 (U = -2.846, p<0.01), and scores of Group 2 were significantly lower than those of Group 3 (U = -3.130, p<0.01). At the same time, the NIHSS scores of each group gradually decreased from acute phase to outcome, Neurological improvement was statistically different among the three topographical types of infarction (H = 26.15, p<0.01; H = 11.03, p<0.01; H = 10.05, p<0.01). In conclusion, the three-dimensional colour-coded DTT allows in vivo differentiation of distinct CST stroke subtypes and may help in better establishing the prognosis for patients after CST stroke.


Global positioning system watches for estimating energy expenditure.
Global positioning system (GPS) watches have been introduced commercially, converting frequent measurements of time, location, speed (pace), and elevation into energy expenditure (EE) estimates. The purpose of this study was to compare EE estimates of 4 different GPS watches (Forerunner, Suunto, Polar, Adeo), at various walking speeds, with EE estimate from a triaxial accelerometer (RT3), which was used as a reference measure in this study. Sixteen healthy young adults completed the study. Participants wore 4 different GPS watches and an RT3 accelerometer and walked at 6-minute intervals on an outdoor track at 3 speeds (3, 5, and 7 km/hr). The statistical significance of differences in EE between the 3 watches was assessed using linear contrasts of the coefficients from the overall model. Reliability across trials for a given device was assessed using intraclass correlation coefficients as estimated in the mixed model. The GPS watches demonstrated lower reliability (intraclass correlation coefficient) across trials when compared with the RT3, particularly at the higher speed, 7 km/hr. Three GPS watches (Forerunner, Polar, and Suunto) significantly and consistently underestimated EE compared with the reference EE given by the RT3 accelerometer (average mean difference: Garmin, -50.5%; Polar, -41.7%; and Suunto, -41.7%; all p < 0.001). Results suggested that caution should be exercised when using commercial GPS watches to estimate EE in athletes during field-based testing and training.


The relationship of structure and function in human Hageman factor. The association of enzymatic and binding activities with separate regions of the molecule.
Three regions of the human Hageman factor molecule termed the c, d, and e regions have been defined. Division of the molecule into these three regions is based on the analysis of fragments obtained by enzymatic cleavage during fluid-phase activation. The three regions have the following properties: (a) the c region has a mol wt of 40,000, has the capacity to bind to negatively charged surfaces, and does not have detectable enzymatic activity; (b) the e region possess a mol wt of 28,000 has enzymatic activity, and does not bind to negatively charged surfaces; (c) the d region has a mol wt of 12,000, is located between the c and e fragments but has not been detected as a freely existing polypeptide, and can bind firmly to negatively charged surfaces. The preparation of antibodies specific for the c and e regions is described as well as their use in defining the electrophoretic characteristics of the cde, cd, de, c, and e polypeptide fragments of Hageman factor. Evidence is given showing that the e region, but not the c or d, is released from a negatively charged surface when bound Hageman factor is exposed to proteolytic enzymes or whole plasma and that when this occurs in the presence of normal plasma, the e fragment becomes bound to C1 esterase inhibitor.


Influence of Triplet Diffusion on Lead Halide Perovskite-Sensitized Solid-State Upconversion.
The emerging field of lead halide perovskite-sensitized triplet-triplet annihilation (TTA) in rubrene shows great promise in upconversion applications. By rapidly transferring single charge carriers instead of bound triplet states, perovskites enable a high triplet population in rubrene, yielding low Ith values. In this contribution, we investigate the role of the triplet population on the upconverted emission. Interestingly, two independent rates of TTA can be observed, as well as a sharp drop in the visible emission intensity over several seconds. This effect can be attributed to the triplet-density-based diffusion length: (i) at low triplet populations slow diffusion-mediated TTA yields singlets far from the interface and (ii) higher triplet populations lead to rapid TTA close to the perovskite/rubrene interface. Because of the proximity of the strongly absorbing perovskite, the singlet states created closer to the interface undergo stronger back-transfer to the perovskite film and therefore appear to exhibit a lower photoluminescence quantum yield.


Development of a MAb-based immunoassay for the simultaneous determination of O,O-diethyl and O,O-dimethyl organophosphorus pesticides in vegetable and fruit samples pretreated with QuEChERS.
To develop a broad-specificity immunoassay for organophosphorus pesticides (OPs), a broad-specificity monoclonal antibody (MAb) for OPs against a generic hapten, O,O-diethyl O-(3-carboxyphenyl) phosphorothioate with the carboxy group in the meta position of the benzene ring, was produced. Eight haptens were prepared and covalently attached to ovalbumin (OVA) for use as coating antigens, and the optimum coating antigen was selected. Then, a sensitive and broadly class selective competitive indirect enzyme-linked immunosorbent assay (ciELISA) based on the MAb and the optimum coating antigen (hapten H-OVA, possessing an O,O-dimethyl generic structure and linked through a linear spacer arm) was developed and optimized. The MAb developed in this study showed quite different cross-reactivity and selectivity compared to previously produced anti-OPs broad-specificity MAbs. Specifically, the MAb showed high and uniform sensitivity to seven O,O-diethyl OPs and six O,O-dimethyl OPs. With the optimum ciELISA, the IC50 values of the 13 OPs were determined as 23.1∼151.2 ng mL(-1). The average IC50 and coefficient of variation (CV) for the IC50 values of the 13 OPs were 74.6 ng mL(-1) and 33.9%, respectively. For the recovery study, a QuEChERS approach based on dispersive solid-phase extraction (d-SPE) was implemented to decrease the matrix effects of vegetable and fruit samples. The recoveries of six representative OPs from the spiked samples ranged from 89.4 to 135.5%; the CV ranged from 3.5 to 15.7%. The ciELISA was also applied to real samples, followed by confirmation with gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. The results demonstrated that the ciELISA is suitable for monitoring OP contamination in vegetable and fruit samples.


[Effects of citrus reticulata blanco extract on fibroblasts from human hypertrophic scar in vitro].
To investigate the effects of citrus reticulata blanco extract on the proliferation and collagen metabolism of fibroblasts from human hypertrophic scar. Human hypertrophic scar fibroblasts from two burn patients obtained from plastic surgery were cultured in vitro and divided into experimental group (n = 12, with basic culture medium and 2.5, 5.0, 10.0,25.0 mg/L citrus reticulata blanco extract, respectively, 3 bottles for each concentration of citrus reticulata blanco extract ), control group 1 (n = 3, with basic culture medium) , and control group 2 ( n = 3, with basic culture medium and 5% ethyl alcohol). The cell proliferation in each group was observed with MTT method, then the inhibition rate was calculated. Apoptosis and its index ( AI) in each group were determined after TUNEL staining . The changes in the content of ICTP and PINP in each group were observed by radioimmunity. The inhibition rate in the experimental group with the citrus reticulata blanco extract in concentration of 2. 5, 5.0, 10.0, 25. 0 microg/ ml were (7. 100+/-0.038)% , (8. 100+/- 0. 048)% , (10. 900+/-0. 055)%, (15.900+/-0. 097) %, respectively, which were significantly higher than those in other two groups ( P <0.05 ). The Al (69. 7% , 71.7%, 86.4% , 95.2% ), ICTP [(17.2+/-0.6), (18.3+/-0.6), (19.8+/-0.5), (23.2+/-0.6) microg/L] and PINP [ (101.7+/-1.4) , (107. 8+/-1. 1) , (111.6+/-1.2) , (124. 6+/-1.3) microg/L] in experimental group with the citrus reticulata blanco extract in concentration of 2.5, 5.0, 10.0 , 25.0 mg/L were also obviously higher than other two control groups( P <0.05) ,but these indices in control 1 group were similar to those in control 2 group( P >0. 05). The citrus reticulata blanco extract might be beneficial for the management of hypertrophic scar through inhibition of the proliferation of fibroblasts in hypertrophic scar, by promoting apoptosis and collagen degradation.


General framework for multiple scattering of polarized waves including anisotropies and Berry phase.
We develop a framework for the multiple scattering of a polarized wave. We consider particles with spin propagating in a medium filled with scatterers. We write the amplitudes of each spin eigenstate in a local mobile frame. One of the axes is in the direction of propagation of the particle. We use this representation to define a directional Green's operator of the homogeneous medium and also to write the spin-dependent scattering amplitudes. We show that this representation reveals a Berry phase. We establish a generalized Green-Dyson equation for the multiple-scattering problem in this framework. We show that the generalized Green-Dyson equation can be solved by linear algebra if one uses a representation of the rotations based on Wigner D matrices. The properties of light scattering are retrieved if we use spin 1 particles. Our theory allows to take into account several kinds of anisotropies such as circular or linear dichroism and birefringence, Faraday effects, and Mie scattering within the same formalism. Several anisotropies can be present at the same time.


Spatio-temporal dynamics of rabies and habitat suitability of the common marmoset Callithrix jacchus in Brazil.
Rabies transmitted by wildlife is now the main source of human rabies in the Americas. The common marmoset, Callithrix jacchus, is considered a reservoir of rabies causing sporadic and unpredictable human deaths in Brazil, but the extent of the spillover risk to humans remains unknown. In this study, we described the spatiotemporal dynamics of rabies affecting C. jacchus reported to Brazil's Ministry of Health passive surveillance system between 2008 and 2020, and combined ecological niche modelling with C. jacchus occurrence data to predict its suitable habitat. Our results show that 67 outbreaks (91 cases) of rabies affecting C. jacchus were reported by 41 municipalities between January 2008 and October 2020, with a mean of 5 outbreaks/year [range: 1-14]. The maximum number of outbreaks and municipalities reporting cases occurred in 2018, coinciding with higher surveillance of primate deaths due to Yellow Fever. A mean of 3 [1-9] new municipalities reported outbreaks yearly, suggesting potential spatial expansions of the C. jacchus variant in northeastern Brazil and emerging rabies spillover from vampire bat Desmodus rotundus to C. jacchus in the north and south. Outbreaks were concentrated in the states of Ceará (72%) and Pernambuco (16%) up to 2012, but are now reported in Piauí since 2013, in Bahia since 2017 (D. rotundus' antigenic variant, AgV3) and in Rio de Janeiro since 2019 (AgV3). Besides confirming suitable habitat for this primate in the northeast and the east coast of Brazil, our Maximum Entropy model also predicted suitable habitat on the north and the west states of the country but predicted low habitat suitability among inland municipalities of the Caatinga biome reporting rabies. Our findings revealed new areas reporting rabies infecting C. jacchus, highlighting the need to implement strategies limiting spillover to humans and to better understand the drivers of C. jacchus rabies dynamics.


Regulation of heartbeat by G protein-coupled ion channels.
The coupling of ion channels to receptors by G proteins is the subject of this American Physiological Society Walter B. Cannon Memorial "Physiology in Perspective" Lecture. This subject is particularly appropriate because it includes a molecular explanation of a homeostatic mechanism involving the autonomic nervous system and the latter subject preoccupied Dr. Cannon during most of his career. With the use of reconstitution methods, we and others have shown that heterotrimeric guanine nucleotide-binding (G) proteins couple receptors to ion channels by both membrane-delimited, direct pathways and cytoplasmic second messenger pathways. Furthermore, one set of receptors may be coupled to as many as three different sets of ion channels to form networks. Dual G protein pathways lead to the prediction of biphasic ion current responses in cell signaling, and this prediction was confirmed. In sinoatrial pacemaker cells, the pacemaking hyperpolarization-activated inward current (If) is directly regulated by the G proteins Gs and Go, and the two can act simultaneously. This could explain the classical observation that vagal inhibition of heart rate is greater during sympathetic stimulation. Because deactivation of the muscarinic response occurs much faster than the G protein alpha-subunit hydrolyzes guanosine 5'-triphosphate, we looked for accessory cellular factors. A surprising result was that the small monomeric ras G protein blocked the muscarinic pathway. The significance of this observation is unknown, but it appears that small and large G proteins may interact in ion channel signaling pathways.


Inhibitory effect of C-reactive protein on alternative C pathway activation by liposomes and Streptococcus pneumoniae.
C-reactive protein (CRP) is an acute phase serum protein found associated with damaged tissue at sites of inflammation. CRP bound to multivalent phosphocholine-containing or polycationic ligands activates C by the classical pathway. We have previously described liposomes of a particular lipid composition that are able both to activate the alternative pathway of C and to bind CRP. In addition many strains of Streptococcus pneumoniae activate the alternative pathway. We have shown CRP binding to these bacteria as well. Because antibody to an activating surface in many cases enhances alternative pathway activation, we tested CRP for a similar function in these systems. Our results indicate that, in contrast to antibody, CRP inhibits alternative pathway activation. This inhibition by CRP is apparently restricted to surfaces that bind CRP. Thus, CRP binding to membrane or bacterial surfaces can convert them from alternative pathway activation to classical pathway activation.


Efficacy of Portable Air Cleaners and Masking for Reducing Indoor Exposure to Simulated Exhaled SARS-CoV-2 Aerosols - United States, 2021.
SARS-CoV-2, the virus that causes COVID-19, can be spread by exposure to droplets and aerosols of respiratory fluids that are released by infected persons when they cough, sing, talk, or exhale. To reduce indoor transmission of SARS-CoV-2 between persons, CDC recommends measures including physical distancing, universal masking (the use of face masks in public places by everyone who is not fully vaccinated), and increased room ventilation (1). Ventilation systems can be supplemented with portable high efficiency particulate air (HEPA) cleaners* to reduce the number of infectious particles in the air and provide enhanced protection from transmission between persons (2); two recent reports found that HEPA air cleaners in classrooms could reduce overall aerosol particle concentrations by ≥80% within 30 minutes (3,4). To investigate the effectiveness of portable HEPA air cleaners and universal masking at reducing exposure to exhaled aerosol particles, the investigation team used respiratory simulators to mimic a person with COVID-19 and other, uninfected persons in a conference room. The addition of two HEPA air cleaners that met the Environmental Protection Agency (EPA)-recommended clean air delivery rate (CADR) (5) reduced overall exposure to simulated exhaled aerosol particles by up to 65% without universal masking. Without the HEPA air cleaners, universal masking reduced the combined mean aerosol concentration by 72%. The combination of the two HEPA air cleaners and universal masking reduced overall exposure by up to 90%. The HEPA air cleaners were most effective when they were close to the aerosol source. These findings suggest that portable HEPA air cleaners can reduce exposure to SARS-CoV-2 aerosols in indoor environments, with greater reductions in exposure occurring when used in combination with universal masking.


Noninfectious doughnut-shaped human immunodeficiency virus type 1 can induce syncytia mediated by fusion of the particles with CD4-positive cells.
A defective doughnut-shaped human immunodeficiency virus type 1 (HIV-1)-producing cell clone (designated as L-2) was isolated from persistently HIV-1-infected MT-4 cells. The syncytium-forming capacity of the cell and virus particle fractions was examined in human CD4-positive T cells. Several cell lines producing infectious HIV-1 particles, such as persistently HIV-1-infected MOLT-4 (MOLT-4/HIV-1) cells, were used as controls. Syncytia were formed within 20 h by the cell fraction of both L-2 and MOLT-4/HIV-1 and the virus particle fraction of L-2, but not MOLT-4/HIV-1. These formations were not affected by 3'-azido-3'-deoxythymidine (ZDV). In contrast, similar syncytium formation was first observed 2 days after the incubation of the virus particle fraction of MOLT-4/LAV-1 and this syncytium formation mediated by the cell fractions of MOLT-4/HIV-1 and L-2 or the virus particle fraction of L-2 differently.


Personal protective behaviors in response to COVID-19: a longitudinal application of protection motivation theory.
Disease outbreaks are expected to occur more frequently and spread more rapidly in the age of globalization. Personal protective behaviors strongly affect infection and death rates worldwide. It is therefore of prime importance to better understand which factors predict personal protective behaviors during a pandemic. Protection motivation theory (PMT) proposes that people's motivation to protect themselves is based on two appraisal processes: threat appraisal and coping appraisal. Building on PMT, this longitudinal study aimed to predict personal protective behaviors in response to COVID-19, including hand hygiene, physical distancing, and mask wearing. In the first wave of the study (November, 2020), the two appraisal processes as specified in PMT as well as intentions to perform protective behaviors were assessed in a representative sample of German adults (N = 328). In the second wave of this study, which was conducted one month later, the frequency of protective behaviors was measured. Structural equation modeling was used to test whether threat and coping appraisal predicted intentions and protective behaviors. Response rate for the second wave was high (87%). For all three behaviors, self-efficacy predicted intentions and also indirectly behavior (i.e., mediated via intentions). Furthermore, exploratory tests of alternative theoretical models suggested that both self-efficacy and costs have direct effects (i.e., independent from their relationship with intentions) on performed behavior. To support individuals to engage in protective behaviors during a pandemic, it is important to reduce barriers to action and to foster individuals' self-efficacy.


Scanning electron microscopy of upper urinary tract tumors.
Scanning electron microscopy (SEM) was performed on specimens from 16 patients with low-grade tumors, and 4 patients with benign lesions of the upper urinary tract. Pleomorphic microvilli could be seen at a low frequency on the majority of the tumor specimens as well as on surface cells of specimens from patients with inverted papilloma, fibroepithelial polyp, and hydronephrosis. The SEM appearance of the lining cells was similar whether the specimen was obtained from a patient with a tumor, or an inflammatory or proliferative lesion. Furthermore, pleomorphic microvilli were observed in five histologically normal bladders in which the covering cells had been rubbed off with a cold loop of a resectoscope. Pleomorphic microvilli are thus not morphologic markers of preneoplastic hyperplasia or tumor. It is likely that their presence merely reflects an increased rate of detachment of superficial epithelial cells which are replaced by cells from the deeper part of the epithelium. The demonstration of pleomorphic microvilli is therefore of questionable value in the preoperative diagnosis of tumors of the upper urinary tract and, consequently, their significance must be re-evaluated.


The interplay between DNA topology and accessory factors in site-specific recombination in bacteria and their bacteriophages.
Site-specific recombination is employed widely in bacteria and bacteriophage as a basis for genetic switching events that control phenotypic variation. It plays a vital role in the life cycles of phages and in the replication cycles of chromosomes and plasmids in bacteria. Site-specific recombinases drive these processes using very short segments of identical (or nearly identical) DNA sequences. In some cases, the efficiencies of the recombination reactions are modulated by the topological state of the participating DNA sequences and by the availability of accessory proteins that shape the DNA. These dependencies link the molecular machines that conduct the recombination reactions to the physiological state of the cell. This is because the topological state of bacterial DNA varies constantly during the growth cycle and so does the availability of the accessory factors. In addition, some accessory factors are under allosteric control by metabolic products or second messengers that report the physiological status of the cell. The interplay between DNA topology, accessory factors and site-specific recombination provides a powerful illustration of the connectedness and integration of molecular events in bacterial cells and in viruses that parasitise bacterial cells.


Sunitinib produces neuroprotective effect via inhibiting nitric oxide overproduction.
Sunitinib is an inhibitor of the multiple receptor tyrosine kinases (RTKs) for cancer therapy. Some sunitinib analogues could prevent neuronal death induced by various neurotoxins. However, the neuroprotective effects of sunitinib have not been reported. Cerebellar granule neurons (CGNs) and SH-SY5Y cells were exposed to low-potassium and MPP(+) challenges, respectively. MTT assay, FDA/PI staining, Hoechst staining, DAF-FM, colorimetric nitric oxide synthase (NOS) activity assay, and Western blotting were applied to detect cell viability, NO production, NOS activity, and neuronal NOS (nNOS) expression. Short hairpin RNA was used to decrease nNOS expression. In vitro NOS enzyme activity assay was used to determine the direct inhibition of nNOS by sunitinib. Sunitinib prevented low-potassium-induced neuronal apoptosis in CGNs and MPP(+) -induced neuronal death in SH-SY5Y cells. However, PTK787, another RTK inhibitor, failed to decrease neurotoxicity in the same models. Sunitinib reversed the increase in NO levels, NOS activity, and nNOS expression induced by low potassium or MPP(+) . Knockdown of nNOS expression partially abolished the neuroprotective effects of sunitinib. Moreover, sunitinib directly inhibited nNOS enzyme activity. Sunitinib exerts its neuroprotective effects by inhibiting NO overproduction, possibly via the inhibition of nNOS activity and the decrease in nNOS expression.


Studies of the macroscopic and microscopic morphology (hippocampus) of brain in Vencobb broiler.
The aim of this study was to study the anatomy of different parts of brain and histology of hippocampus of Vencobb broiler chicken. A 12 adult experimental birds were sacrificed by cervical dislocation. After separation of the brain, gross anatomy features were studied. Brain tissue was fixed in 10% buffered neutral formalin for 2-3 days, and then routine dehydration process in ascending grades of ethyl alcohol was done. After xylene cleaning, paraffin impregnation was prepared. Paraffin blocks were cut, and slides were stained by Harris hematoxylin and eosin. Photography was carried out both under lower (×10) and higher (×40) magnifications. The brain structure (dorsal view) of Vencobb bird resembled the outline of a playing card symbol of a "spade." The brain subdivisions are cerebrum, cerebellum, and medulla oblongata. Cerebrum was devoid of usual convolutions (elevations), gyri, depressions (grooves), and sulci. The cerebral hemispheres were tightly apposed along a median sulcus called interhemispheric fissure and cerebrum and cerebellum were separated by a small transverse fissure. The olfactory bulb was small structures, and the pineal body was clearly visible. The optic lobes were partially hidden under cerebral hemispheres, but laterally, it was large, prominent rounded or spherical bodies of the midbrain. The hippocampal area appeared as dorso-medial protrusion. Different types of neurons were distinguished in the hippocampus were pyramidal neurons, pyramidal-like neurons, and multipolar neurons, etc. There was rich vascularization in the form of blood capillaries throughout the hippocampus. Cerebrum was pear shaped and largest part of the brain. Cerebrum hemisphere was smooth devoid of convolutions, gyri, and depressions, but in the surface of cerebellum, there was the presence of a number of transverse depression (grooves) and sulci subdividing into many folds. Olfactory bulb was poorly developed, whereas optic lobes were rounded and large. The exact boundary line of the hippocampus was not discernable. In hippocampus histology, two categories of neuron local circuit neurons and projection neurons, high vascularization and epididymal lining of lateral ventricle were observed. Hippocampal neurons were comparatively larger without any distinct layers. The afferent neurons projected to the medium septum.


Lysophospholipase I identified as a ghrelin deacylation enzyme in rat stomach.
Ghrelin, discovered in rat stomach as an endogenous growth hormone secretagogue, is octanoylated at the Ser3 residue. Since this octanoylation is essential for the functions of ghrelin, the enzymes that catalyze acylation for ghrelin biosynthesis and deacylation (deactivation step) must be considered as important regulators. We found that rat stomach homogenate contained ghrelin deacylation activity, and we isolated the active fractions by column chromatography. After sequencing and expressing candidate proteins, the ghrelin deacylation enzyme in the stomach was identified as lysophospholipase I (LysoPLA I). The enzyme properties were examined using recombinant rat LysoPLA I expressed in Escherichia coli. K(m) and V(max) values were determined as 6.5 microM and 2.3 micromol/min/mg for ghrelin and 2.2 x 10(2) microM and 0.5 micromol/min/mg for lysophosphatidylcholine (LysoPC), respectively. The deacylation of both substrates was inhibited by methyl arachidonyl fluorophosphonate (MAFP), which is known as an irreversible inhibitor of LysoPLA I. These results reveal that LysoPLA I catalyzes the removal of n-octanoic acid from ghrelin to form des-acyl ghrelin. Identification of the ghrelin deacylation enzyme in the stomach and a deacylation inhibitor will be helpful in investigating ghrelin biosynthesis.


Patient preferences regarding cancer group psychotherapy interventions: a view from the inside.
Group interventions for cancer patients have commanded notable interest among investigators, but utilization rates are low and little is known about the features that patients themselves deem most important. The authors examined the views of potential participants, among 425 patients with diverse malignancies. A large number (64.6%) expressed interest, although few had attended a group. Preferences were strongest for interventions convened during diagnostic or active treatment periods rather than later, and those focusing on medical education or health-promotion, rather than emotional support or coping. Most were amenable to drop-in formats and to heterogeneous membership. In subgroup analyses, preferences were associated with disease site and not strongly related to psychosocial or demographic predictors. Understanding patient preferences may be critical for successful program development and utilization.


Stimuli-responsive controlled growth of mono- and bidimensional particles from basic zirconium sulfate hydrosols.
A thermostimulated sol-gel transition in a system prepared by mixing a ZrOCl(2) acidified solution to a hot H(2)SO(4) aqueous solution was studied by dynamic rheological measurements and quasi-elastic light scattering. The effect of temperature and of molar ratio R(S) = [Zr]/[SO(4)] on the gelation kinetics was analyzed using the mass fractal aggregate growth model. This study shows that the linear growth of aggregates occurs at the early period of transformation, while bidimensional growth occurs at the advanced stage. The bidimensional growth can be shifted toward monodimensional growth by decreasing the aggregation rate by controlling the temperature and/or molar ratio R(S). EXAFS and Raman results gave evidence that the linear chain growth is supported by covalent sulfate bonding between primary building blocks. At the advanced stage of aggregation, the assembly of linear chains through hydrogen bonding gave rise to the growth of bidimensional particles.


Pathological satiety caused by brainstem hemangioblastoma.
Because of the multiplicity and saltatory growth pattern associated with central nervous system hemangioblastomas in von Hippel-Lindau (VHL) disease, resection of individual tumors is usually reserved until symptoms occur, to avoid unnecessary surgery over the lifetime of a patient. Brainstem hemangioblastomas in VHL typically cause lower cranial nerve dysfunction, long-tract signs, sensory impairment, and gait abnormalities. The authors report on a 16-year-old girl with VHL who presented with abnormal early satiety resulting in growth and developmental arrest associated with a growing obex hemangioblastoma. Tumor resection resulted in restoration of appetite, with rapid weight gain, growth in stature, and onset of menses. These findings indicate that caudal brainstem-mediated mechanisms have a profound effect on satiety. Moreover, brainstem hemangioblastomas may present with abnormalities in satiety and feeding that can be effectively reversed with resection.


[Peripheral refraction: cause or effect of refraction development?]
to study peripheral refraction and the shape of the eyeball in children with different clinical refraction. Using an original method, peripheral refraction was measured at 10-12 degrees temporally and nasally from the fovea in 56 right eyes with different clinical, or axial, refraction of 20 boys and 36 girls aged 7 to 16 years (11.9±1.17 years on average). The shape of the eyeball was judged of by the ratio of its anterior-posterior axial length (AL) to horizontal diameter (HD). The incidence and value of peripheral myopic defocus in children appeared to decrease with clinical refraction increasing from high hyperopia to high myopia. This was the first time, mixed peripheral refraction was found in children, occurring more frequently in higher myopia. This mixed peripheral defocus, shown to be a transitional stage between relative peripheral myopia and relative hyperopia, indicates non-uniform stretching of posterior pole tissues in the course of refraction development and myopia progression. As ocular refraction increases from high hyperopia to high myopia, the growth of AL outpaces that of HD. Obviously, natural peripheral defocus results from changes in size and shape of the eyeball in the course of refraction development.


The exposure of honey bees (Apis mellifera; Hymenoptera: Apidae) to pesticides: Room for improvement in research.
Losses of honey bees have been repeatedly reported from many places worldwide. The widespread use of synthetic pesticides has led to concerns regarding their environmental fate and their effects on pollinators. Based on a standardised review, we report the use of a wide variety of honey bee matrices and sampling methods in the scientific papers studying pesticide exposure. Matrices such as beeswax and beebread were very little analysed despite their capacities for long-term pesticide storage. Moreover, bioavailability and transfer between in-hive matrices were poorly understood and explored. Many pesticides were studied but interactions between molecules or with other stressors were lacking. Sampling methods, targeted matrices and units of measure should have been, to some extent, standardised between publications to ease comparison and cross checking. Data on honey bee exposure to pesticides would have also benefit from the use of commercial formulations in experiments instead of active ingredients, with a special assessment of co-formulants (quantitative exposure and effects). Finally, the air matrix within the colony must be explored in order to complete current knowledge on honey bee pesticide exposure.


The Pediatric Stroke Outcome Measure: A predictor of outcome following arterial ischemic stroke.
To evaluate the relationship between neurologic outcome at 1 month following diagnosis of pediatric arterial ischemic stroke (AIS) and motor and adaptive behavior outcomes at 12 months. This prospective longitudinal observational cohort study recruited children from a single tertiary children's hospital diagnosed with first AIS between December 2007 and November 2013. Neurologic impairment was evaluated at 4 time points using the Pediatric Stroke Outcome Measure (PSOM) or Recovery and Recurrence Questionnaire following diagnosis of AIS (acute, 1, 6, and 12 months). Motor function and adaptive behavior were assessed at 12 months using standardized measures. Children were grouped for analysis, according to age at diagnosis (neonates vs preschool vs school-aged). The relationship between neurologic impairment and 12-month functional outcomes were examined. Sixty-four children were recruited (27 neonates, 19 preschool-aged, and 18 school-aged). Presence of impairment on the PSOM at 1 month was associated with lower 12-month fine motor z scores (p = 0.004), gross motor z scores (p = 0.001), and adaptive behavior standard scores (p = 0.004). One-month PSOM impairment score was more predictive than age group or lesion size of 12-month motor and adaptive behavior outcome. The PSOM has value as a predictive tool when used at 1 month after first AIS diagnosed acutely in relation to motor and adaptive behavior, with variation according to age group.


Sequence of the 3' half of the Murray Valley encephalitis virus genome and mapping of the nonstructural proteins NS1, NS3, and NS5.
We have determined the nucleotide sequence of the 3'-terminal half of the RNA genome of Murray Valley encephalitis virus (MVE) using seven overlapping cDNA clones; an estimated 80-90 nucleotides at the extreme 3'-end remain to be sequenced. In conjunction with previous sequence data for the 5' half (16), we can conclude that the MVE genome contains a long open reading frame of 10,302 nucleotides that encodes a polyprotein of 3434 residues. Comparison of the MVE deduced amino acid sequence with that of other flaviviruses shows that MVE is most closely related to Japanese encephalitis virus, consistent with serological studies. Using N-terminal amino acid sequence analysis, three nonstructural proteins (NS1, NS3, and NS5) have been identified and mapped on the MVE genome. MVE NS3 contains sequence motifs suggesting that its amino terminus may function as a serine protease. The central region of NS3 (in the linear amino acid sequence) has motifs that are found in NTP-binding proteins and helicases. MVE NS5 contains a conserved Gly-Asp-Asp sequence that is thought to be essential for RNA-dependent RNA polymerases.


Image-Guided Radar Reflector Localization for Small Soft-Tissue Lesions in the Musculoskeletal System.
Preoperative localization of nonpalpable breast lesions using a radar reflector surgical guidance system has become commonplace, but the clinical utility of this emerging technology in the musculoskeletal system has not yet been well established. The system components include a console, a handpiece, an implanted radiofrequency reflector that works as a lesion marker, and an infrared light-emitting probe to guide the surgeon. The reflector can be deployed to localize small nonpalpable nodules within the subcutaneous fat as well as lesions within the deeper soft tissues. It can also be used for lymph nodes and foreign bodies. Localization can be performed both before and after treatment. The objective of this article is to describe the potential applications and our technique and initial experience for radar reflector localization within the musculoskeletal system.


Mg-protoporphyrin IX and heme control HEMA, the gene encoding the first specific step of tetrapyrrole biosynthesis, in Chlamydomonas reinhardtii.
HEMA encodes glutamyl-tRNA reductase (GluTR), which catalyzes the first step specific for tetrapyrrole biosynthesis in plants, archaea, and most eubacteria. In higher plants, GluTR is feedback inhibited by heme and intermediates of chlorophyll biosynthesis. It plays a key role in controlling flux through the tetrapyrrole biosynthetic pathway. This enzyme, which in Chlamydomonas reinhardtii is encoded by a single gene (HEMA), exhibits homology to GluTRs of higher plants and cyanobacteria. HEMA mRNA accumulation was inducible not only by light but also by treatment of dark-adapted cells with Mg-protoporphyrin IX (MgProto) or hemin. The specificity of these tetrapyrroles as inducers was demonstrated by the absence of induction observed upon the feeding of protoporphyrin IX, the precursor of both heme and MgProto, or chlorophyllide. The HEMA mRNA accumulation following treatment of cells with light and hemin was accompanied by increased amounts of GluTR. However, the feeding of MgProto did not suggest a role for Mg-tetrapyrroles in posttranscriptional regulation. The induction by light but not that by the tetrapyrroles was prevented by inhibition of cytoplasmic protein synthesis. Since MgProto is synthesized exclusively in plastids and heme is synthesized in plastids and mitochondria, the data suggest a role of these compounds as organellar signals that control expression of the nuclear HEMA gene.


LO-Phonon Emission Rate of Hot Electrons from an On-Demand Single-Electron Source in a GaAs/AlGaAs Heterostructure.
Using a recent time-of-flight measurement technique with 1 ps time resolution and electron-energy spectroscopy, we develop a method to measure the longitudinal-optical-phonon emission rate of hot electrons traveling along a depleted edge of a quantum Hall bar. Comparison to a single-particle model implies the scattering mechanism involves a two-step process via an intra-Landau-level transition. We show that this can be suppressed by control of the edge potential profile, and a scattering length >1 mm can be achieved, allowing the use of this system for scalable single-electron device applications.


Crusted scabies in acquired selective IgA deficiency.
Crusted scabies, an unusual clinical variant of human scabies mite infestation, is usually reported in cases of gross debility, mental deficiency, or immunosuppression. We report here the occurrence of crusted scabies in a 40-year-old man with acquired selective IgA deficiency suspected to be caused by long-term medication with phenytoin for epilepsy.


Oral Anticoagulant Use in Patients with Morbid Obesity: A Systematic Review and Meta-Analysis.
Obesity is associated with increased risks of atrial fibrillation (AF) and venous thromboembolism (VTE) for which anticoagulation is commonly used. However, data on the efficacy and safety of oral anticoagulants in patients with morbid obesity are limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) for AF or VTE in patients with morbid obesity. We included three randomized controlled trials (5 studies) and 18 observational studies in adult patients with a body weight ≥120 kg, body mass index ≥40 kg/m2, or classified as morbid obesity who received DOACs or VKAs for AF or VTE (N = 77,687). The primary efficacy outcome was stroke/systemic embolism or recurrent VTE, and the primary safety outcome was major bleeding. DOACs were associated with a pooled incidence rate of stroke/systemic embolism of 1.16 per 100 person-years, compared to 1.18 with VKAs. The incidence of recurrent VTE on DOACs was 3.83 per 100 person-years, compared to 6.81 on VKAs. In both VTE and AF populations, DOACs were associated with lower risks of major bleeding compared to VKAs. However, all observational studies had moderate to serious risks of bias. Patients with morbid obesity on DOACs had similar risks of stroke/systemic embolism, lower rates of recurrent VTE, and major bleeding events compared to those on VKAs. However, the certainty of evidence was low given that studies were mostly observational with high risk of confounding.


Improved Synthesis of Larger Resorcinarenes.
The synthesis of the larger resorcin[5 and 6]arene macrocycles [5](OMe) and [6](OMe) has been realized by a Lewis acid-catalyzed condensation of 1,3-dimethoxy-2-methylbenzene with paraformaldehyde in o-dichlorobenzene as the solvent. The methoxy-resorcin[5 and 6]arenes were quantitatively demethylated by treatment with BBr3 to obtain the corresponding macrocycles with free OH groups. X-ray studies showed that in the solid state both the conformation and the packing of [6](OMe) and [5](OMe) are driven by C-H···O, C-H···π, and π···π interactions.


Handheld Ultrasound (HHUS): Potential for Home Palliative Care.
Due to the severity of their disease, palliative care patients often present complex clinical symptoms and complaints like pain, shortness of breath, nausea, loss of appetite, and fatigue. Solely relying on the information available from the history and physical examination often causes uncertainty among palliative care physicians regarding treatment decisions during home visits, potentially leading to unnecessary hospitalizations or transfer to cross-sectional imaging in radiological practices. A rational approach is essential to avoid diagnostic aggressiveness while still providing the imaging information required for optimal palliative care. Bedside use of handheld ultrasound (HHUS) has the potential to expand the diagnostic and therapeutic spectrum in the case of symptom exacerbation but is still underutilized. In this review, we evaluate the potential uses of HHUS in home care settings to provide a more accurate diagnosis of the most common symptoms in palliative patients and to guide bedside interventions such as bladder catheterization, thoracentesis, paracentesis, venous access, and regional anesthesia. Specific training programs for ultrasound in palliative care are currently not available. Adequate documentation is warranted but fraught with technological and privacy issues. Expert supervision and quality assurance are necessary. Despite its limitation and challenges, we suggest that HHUS leads to improved clinical decision-making, expedited symptom relief, and reduced complications without burdening of the patient and costly transfer to hospital or specialty consultations.


Metastatic patterns in patients with carcinomas of the lower esophagus and upper rectum.
The frequency of metastatic involvement of eight target organs was examined in people dying as a consequence of squamous cell carcinomas of the lower third of the esophagus or adenocarcinomas of the upper third of the rectum. In both groups, there was a stronger association of metastatic incidence in the target organs with organ blood flow per gram in patients with liver metastases than without. The results suggest that this association, which is consistent with the 'mechanical' hypothesis of metastatic pattern, is only seen in people with advanced disease and that in the others temporal limitations imposed by death or cure prevent full development of the pattern. The data suggest that in accord with the 'cascade' theory, cancer cells must first form metastases in the liver, that cells from these metastases not the primary cancer, then form metastases in the lungs; cancer cells from the lung metastases then subsequently disseminate with a trend towards an arterial pattern. Data from animal experiments suggest that owing to the inefficiency of the metastatic process in terms of cancer cells, this sequential process is slow relative to tumor development and that this time base affects expression of metastatic pattern. This proposed scheme for metastatic pattern development provides evidence in favor of Ewing's 'mechanical' hypothesis for two histologic types of cancer, each growing in one designated primary site. It does not exclude a role for 'seed and soil' effects in these and other cancers.


The effects of meteorological factors on airborne fungal spore concentration in two areas differing in urbanisation level.
Although fungal spores are an ever-present component of the atmosphere throughout the year, their concentration oscillates widely. This work aims to establish correlations between fungal spore concentrations in Porto and Amares and meteorological data. The seasonal distribution of fungal spores was studied continuously (2005-2007) using volumetric spore traps. To determine the effect of meteorological factors (temperature, relative humidity and rainfall) on spore concentration, the Spearman rank correlation test was used. In both locations, the most abundant fungal spores were Cladosporium, Agaricus, Agrocybe, Alternaria and Aspergillus/Penicillium, the highest concentrations being found during summer and autumn. In the present study, with the exception of Coprinus and Pleospora, spore concentrations were higher in the rural area than in the urban location. Among the selected spore types, spring-autumn spores (Coprinus, Didymella, Leptosphaeria and Pleospora) exhibited negative correlations with temperature and positive correlations both with relative humidity and rainfall level. On the contrary, late spring-early summer (Smuts) and summer spores (Alternaria, Cladosporium, Epicoccum, Ganoderma, Stemphylium and Ustilago) exhibited positive correlations with temperature and negative correlations both with relative humidity and rainfall level. Rust, a frequent spore type during summer, had a positive correlation with temperature. Aspergillus/Penicillium, showed no correlation with the meteorological factors analysed. This knowledge can be useful for agriculture, allowing more efficient and reliable application of pesticides, and for human health, by improving the diagnosis and treatment of respiratory allergic disease.


Multiplex PCR as a tool for the diagnosis of Leishmania spp. kDNA and the gapdh housekeeping gene of mammal hosts.
The PCR assays usually employed for Leishmania diagnosis does not simultaneously detect a constitutive gene that would certify the viability of the DNA sample. We present a multiplex PCR approach for the simultaneous diagnosis of the Leishmania sp. kDNA fragment and a catalytic domain segment of a conserved region of the mammalian gapdh gene. The proposed multiplex protocol was designed through in silico PCR. The annealing temperature, concentration of primer pairs, number of cycles, distinct polymerase enzymes and premix kit were defined to achieve an optimal reaction. The DNA detection sensitivity was tested with different concentrations of known L. tropica DNA, and the reproducibility of the assay was confirmed using samples from 106 wild mammals that were previously subject to Leishmania sp. kDNA analysis through singleplex reactions. The following optimal conditions were established: 95°C for 1 min followed by 30 cycles of 95°C for 30 s, 61°C for 30 s, and 72°C for 30 s and a final extension at 72°C for 1 min. The multiplex PCR system was capable of detecting 0.1 ng of L. tropica diluted in 100 ng of mammalian DNA. Of 51 kDNA samples that were previously found to be positive, 45 (88.2%) were positive for both targets, two were positive only for kDNA and four were negative for both. Of 55 kDNA samples that were previously identified as negative, 38 (69.1%) were positive for gapdh whereas the other 17 were negative for both targets. The proposed multiplex PCR system allows the simultaneous detection of the gapdh gene and Leishmania sp. kDNA in tissue samples derived from distinct wild mammal species. The amplification of the gapdh mammalian gene in the same reaction ensures the quality and viability of the DNA in the sample, eliminating the possibility of false-negative results that would impair an accurate description of the infection rates in a given population.


Investigations of the effect of the non-manganese metal in heterometallic-oxido cluster models of the oxygen evolving complex of photosystem II: lanthanides as substitutes for calcium.
We report the syntheses and electrochemical properties of nine new clusters ([LLnMn(IV)3O4(OAc)3(DMF)n](+) (Ln = La(3+), Ce(3+), Nd(3+), Eu(3+), Gd(3+), Tb(3+), Dy(3+), Yb(3+), and Lu(3+), n = 2 or 3)) supported by a ligand (L(3-)) based on a 1,3,5-triarylbenzene motif appended with alkoxide and pyridine donors. All complexes were obtained by metal substitution of Ca(2+) with lanthanides upon treatment of previously reported LMn3CaO4(OAc)3(THF) with Ln(OTf)3. Structural characterization confirmed that the clusters contain the [LnMn3O4] cubane motif. The effect of the redox-inactive centers on the electronic properties of the Mn3O4 cores was investigated by cyclic voltammetry. A linear correlation between the redox potential of the cluster and the ionic radii or pKa of the lanthanide metal ion was observed. Chemical reduction of the LMn(IV)3GdO4(OAc)3(DMF)2 cluster with decamethylferrocene, resulted in the formation of LGdMn(IV)2Mn(III)O4(OAc)3(DMF)2, a rare example of mixed-valence [MMn3O4] cubane. The lanthanide-coordinated ligands can be substituted with other donors, including water, the biological substrate.


Infrared spectroscopic study of polytypic effects on the crystal-growth mechanism of n-hexatriacontane (n-C36H74).
The solution-crystallization mechanism was investigated for two polytypes in the M011 modification of n-hexatriacontane (n-C36H74), single-layered structure Mon, and double-layered one Orth II. The crystal growth under controlled supersaturation was followed with a micro- Fourier-transform-infrared spectrometer equipped with an optical system for oblique transmission measurements. Supersaturation dependence of growth behavior was significantly different between Mon and Orth II. Although the Mon crystal continued growing at a supersaturation of 0.27, the overgrowth of Orth II on the (001) face of the Mon crystal was confirmed at supersaturations below 0.21. Such a polytypic transformation was not observed for the Orth II crystal at any supersaturation below 0.30. The growth rate of Mon showed a quadratic dependence on supersaturation, while that of Orth II was approximately linear, suggesting spiral growth and two-dimensional-nucleation mechanisms for Mon and Orth II, respectively.


Social Anxiety and Subjective Quality of Life Among Chinese Left-Behind Children: The Mediating Role of Social Support.
The issue of left-behind children has become a key focus in China. In this study, we investigate the mediating role of social support between social anxiety and the subjective quality of life among left-behind children in China (N = 379, M age = 13.65). A total of 710 junior high school students were recruited using clustering random sampling from five middle schools in China and investigated using the Social Anxiety Scale for Children, Social Support Rating Scale for Adolescents, and Inventory of Subjective Life Quality. The results show that social anxiety is negatively associated with social support and subjective quality of life, and social support is positively correlated with subjective quality of life. In addition, social support partially mediates the relationship between social anxiety and subjective quality of life. In conclusion, these findings provide new insights to improve the subjective quality of life of left-behind children. The focus should be on alleviating social anxiety and increasing social support in order to help left-behind children improve their subjective quality of life.


A Strange Manifestation of Malaria in a Native Nigerian Boy.
The protective role of Sickle Cell Trait (SCT) in malaria endemic areas has been proved, and prevalence of HbS gene in malaria endemic areas is high. Splenic infarction is a well-known complication of SCT, while the association with malaria is considered rare. A Nigerian boy was admitted to our ward after returning from his country of origin, for P. falciparum malaria. He underwent abdominal ultrasound for upper right abdominal pain, showing cholecystitis and multiple splenic lesions suggestive of abscesses. Empiric antibiotic therapy was undertaken. Bartonella, Echinococcus, Entamoeba serologies, blood cultures, Quantiferon test, copro-parasitologic exam were negative; endocarditis was excluded. He underwent further blood exams and abdomen MRI, confirming the presence of signal alterations areas, with radiographic appearance of recent post-infarction outcomes. Hemoglobin electrophoresis showed a percentage of HbS of 40.6% and a diagnosis of SCT was then made. Splenic infarction should be taken into account in patients with malaria and localized abdominal pain. Moreover, diagnosis of SCT should be considered.


The assessment of a relationship disposition, "fantasy withdrawal," from Rorschach face sheet data.
This study investigated the predictive relationship of Rorschach face sheet variables, selected on the basis of psychoanalytic considerations of the patient-examiner relationship, to a dimension of clinical-theoretical relevance in the evaluation of treatment outcome, "fantasy withdrawal." The first step in the present study involved rank ordering and grouping of 19 nosological subgroups along the dimension of fantasy withdrawal. This ranking and grouping served as the criterion against which several quantified aspects of fantasy production on the Rorschach were assessed. The score categories were selected on an a priori basis as most likely to predict the ordering of the patient groups along the dimension of fantasy withdrawal. A formula for such prediction was developed, applied to the original groups, and then reapplied to a patient group in the present hospital setting.


Treatment of cytomegalovirus pneumonia after marrow transplant with combined vidarabine and human leukocyte interferon.
Seven marrow transplant recipients were treated with human leukocyte interferon and vidarabine for cytomegalovirus pneumonia. Although the mean virus titer in biopsy and autopsy lung specimens from five patients decreased from 5 x 10(4) to 1 x 10(2) 50% tissue culture infective doses, there was little clinical evidence of efficacy and only one patient survived. Treatment was stopped in four patients because of declining neutrophil counts, and two of these four patients also showed severe neurotoxicity. The combination of these agents was neither safe nor effective for the treatment of cytomegalovirus pneumonia after marrow transplantation.


Depth extraction of three-dimensional objects in space by the computational integral imaging reconstruction technique.
A novel approach to extract the depth data of 3D objects in space by using the computational integral imaging reconstruction (CIIR) technique is proposed. With elemental images of 3D objects captured by the CCD camera through a pinhole array, depth-dependent object images can be reconstructed on the output plane by the CIIR technique. Only the images reconstructed on the output planes where 3D objects were located are clearly focused; so the depth data of 3D objects in space can be extracted by discriminating these focused output images from the others by using an image separation technique. A feasibility test of the proposed CIIR-based depth extraction method is carried out, and its results are discussed as well.


Cell death-inducing activity of opiates in human oral tumor cell lines.
In screening cytotoxic agents in morphine alkaloids [TE1-10], codeinone [TE8] was cytotoxic against two human oral tumor cells lines (HSC-2 and HSG). The cytotoxic activity of codeinone (CC50=1.0-1.2 microg/mL) against HSC-2 or HSG cells was higher than that of doxorubicin (CC50=1.9-2.0 microg/mL). Human oral gingival fibroblasts (HGF) were relatively resistant to codeinone, as judged by higher SI ratio (3.7) suggesting the tumor-selective cytotoxicity of codeinone. The cytotoxic activity of morphine (CC50=221 microg/mL) against HSC-2 was slightly lower than that of codeine (CC50=186 microg/mL), thebaine (CC50=125 microg/mL), etorphine (CC50=94 microg/mL) or dihydroetorphine (CC50=60 microg/mL). A study of structurally-related compounds suggested that the alpha,beta-unsaturated ketone group of codeinone was responsible for its antitumor cytotoxicity. The cytotoxic activity of codeinone was significantly reduced by N-acetylcysteine, but not affected by FeCl3, CuCl2, CoCl2, sodium ascorbate or catalase. Neither codeinone nor morphine inhibited P-glycoprotein-mediated rhodamine-123 efflux in multidrug resistant mouse T lymphoma L5178 transfected with human MDR 1 gene. These data suggest that codeinone induces cytotoxicity in oral tumor cell lines, possibly by a Michael-like addition of a protein SH or of an amino group to the bouble bond of codeinone.


Bim expression indicates the pathway to retinal cell death in development and degeneration.
Programmed cell death (PCD) during development of the mouse retina involves activation of the mitochondrial pathway. Previous work has shown that the multidomain Bcl-2 family proteins Bax and Bak are fundamentally involved in this process. To induce mitochondrial membrane permeabilization, Bax and Bak require that prosurvival members of the family be inactivated by binding of "BH3-only" members. We showed previously that the BH3-only protein BimEL is highly expressed during postnatal retinal development but decreases dramatically thereafter. The purpose of this study was to investigate a possible role for Bim, in retinal development and degeneration, upstream of Bax and Bak. Bim-/- mice analyzed for defective retinal development exhibit an increase in retinal thickness and a delay in PCD, thereby confirming a role for Bim. We also demonstrate that in response to certain death stimuli, bim+/+ retinal explants upregulate BimEL leading to caspase activation and cell death, whereas bim-/- explants are resistant to apoptosis. Finally, we analyzed Bim expression in the retinal degeneration (rd) mouse, an in vivo model of retinal degeneration. Bim isoforms, which decrease during development, are not reexpressed during retinal degeneration and ultimately photoreceptor cells die by a caspase-independent mechanism. Thus, we conclude that in cases in which BimEL is reexpressed during pathological cell death, developmental cell death pathways are reactivated. However, the absence of BimEL expression correlates with caspase-independent death in the rd model.


Alice in Wonderland Syndrome: somesthetic vs visual perceptual disturbance.
In 1955, English psychiatrist John Todd (1914-1987) described Alice in Wonderland syndrome (AIWS) as self-experienced paroxysmal body image illusions involving distortions of the size, mass, or shape of the patient's own body or its position in space, often occurring with depersonalization and derealization.(1) Todd named AIWS for the perceptual disorder of altered body image experienced by the protagonist in the novel Alice's Adventures in Wonderland (1865), written by Lewis Carroll(2) (the pseudonym of Reverend Charles Lutwidge Dodgson [1832-1898]), possibly based in part on Dodgson's own migrainous experiences.(3) In the story, Alice followed a talking white rabbit down a rabbit hole and then experienced several dramatic changes in her own body size and shape (e.g., shrinking to 10 inches high, growing unnaturally large, and growing unnaturally tall but not any wider).(2) Although Todd's report was the most influential, Lippman(4) provided an earlier description in 1952. In Lippman's article, one of the patients reported feeling short and wide as she walked, and referenced Alice's Adventures in Wonderland in regard to her body image illusions, referring to them as a "Tweedledum" or "Tweedledee" feeling.


Practice characteristics of male and female physician assistants.
In a national survey of 3,294 non-military responding physician assistants, sociodemographic and practice characteristics of male and female physician assistants were compared. Differences by specialty, practice setting, size of community, and hours of work were generally similar in nature, but smaller in magnitude, than those reported for physicians, and may not be of practical significance.


Onivyde for the therapy of multiple solid tumors.
Drug delivery system based on nanobiotechnology can improve the pharmacokinetics and therapeutic index of chemotherapeutic agents, which has revolutionized tumor therapy. Onivyde, also known as MM-398 or PEP02, is a nanoliposomal formulation of irinotecan which has demonstrated encouraging anticancer activity across a broad range of malignancies, including pancreatic cancer, esophago-gastric cancer, and colorectal cancer. This up-to-date review not only focuses on the structure, pharmacokinetics, and pharmacogenetics of Onivyde but also summarizes clinical trials and recommends Onivyde for patients with advanced solid tumors.


Thoracolumbar disc disease in 71 paraplegic dogs: influence of rate of onset and duration of clinical signs on treatment results.
Seventy-one paraplegic dogs with confirmed intervertebral thoracolumbar disc disease and intact deep pain sensation were treated by hemilaminectomy and fenestration of at least two adjacent discs. The success rate of treatment in the overall population was 86 per cent (61/71 cases), with a mean length of time to regaining the ability to walk of 10.8 days and a mean follow-up time of 29 months. The rate of onset of clinical signs significantly influenced the clinical outcome (P=0.01) but not the length of recovery time (P=0.45). Conversely, the duration of clinical signs did not seem to significantly affect the outcome (P=0.27), but did affect the length of recovery time (P=0.001). Animals which had shown clinical signs for more than six days took significantly longer to regain the ability to walk (ie, an additional 6.9 days, P=0.04 and 4.5 days, P=0.01), when compared with those which had shown clinical signs for less than two days, or more than two but less than six days, respectively.


Protein Nanocage as a pH-Switchable Pickering Emulsifier.
Encapsulation of active compounds in Pickering emulsions using bioderived protein-based stabilizers holds potential for the development of novel formulations in the fields of foods and cosmetics. We employ a dodecahedron hollow protein nanocage as a pH-switchable Pickering emulsifier. E2 protein nanocages are derived from pyruvate dehydrogenase multienzyme complex from Geobacillus stearothermophilus which adsorb at the oil/water interface at neutral and basic pH's and stabilize the Pickering emulsions, while in the acidic range, at pH ∼4, the emulsion separates into emulsion and serum phases due to flocculation. The observed process is reversible for at least five cycles. Optimal formulation of a Pickering emulsion composed of rosemary oil, an essential oil, and water has been achieved by ultrasonication and results in droplets of approximately 300 nm in diameter with an oil/water ratio of 0.11 (v/v) and 0.30-0.35% (wt %). Ionic stabilization is observed for concentrations up to 250 mM NaCl and pH values from 7 to 11. The emulsions are stable for at least 10 days when stored at different temperatures up to 50 °C. The resulting Pickering emulsions of different compositions also form a gel-like structure and show shear thinning behavior under shear stress at a higher oil/water ratio.


Transposable elements and early evolution of sex chromosomes in fish.
In many organisms, the sex chromosome pair can be recognized due to heteromorphy; the Y and W chromosomes have often lost many genes due to the absence of recombination during meiosis and are frequently heterochromatic. Repetitive sequences are found at a high proportion on such heterochromatic sex chromosomes and the evolution and emergence of sex chromosomes has been connected to the dynamics of repeats and transposable elements. With an amazing plasticity of sex determination mechanisms and numerous instances of independent emergence of novel sex chromosomes, fish represent an excellent lineage to investigate the early stages of sex chromosome differentiation, where sex chromosomes often are homomorphic and not heterochromatic. We have analyzed the composition, distribution, and relative age of TEs from available sex chromosome sequences of seven teleost fish. We observed recent bursts of TEs and simple repeat accumulations around young sex determination loci. More strikingly, we detected transposable element (TE) amplifications not only on the sex determination regions of the Y and W sex chromosomes, but also on the corresponding regions of the X and Z chromosomes. In one species, we also clearly demonstrated that the observed TE-rich sex determination locus originated from a TE-poor genomic region, strengthening the link between TE accumulation and emergence of the sex determination locus. Altogether, our results highlight the role of TEs in the initial steps of differentiation and evolution of sex chromosomes.


Meta-analysis of early adolescent self-regulation interventions: Moderation by intervention and outcome type.
Self-regulation has been identified as a highly promising target for interventions promoting broad wellbeing across development; however, there appear to be notable limitations in efficacy for early adolescents in particular. One possible reason is that the emotion regulation needs of youth have not been intentionally targeted in many interventions for this age group. The aim of this study is to advance understanding of how different intervention approaches defined from a clear theoretical model may impact different types of outcomes and with regard to different types of measures. We conducted a systematic literature review of four databases using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 33 studies of early adolescents (aged 10-15) using five different intervention approaches that were methodologically rigorous (e.g., randomized controlled trial design with low risk of bias). Studies were conducted predominantly in North America (58%), and Western Europe (30%). A two-level mixed-effects meta-analysis indicated a small but significant overall intervention effect (Hedges g = 0.12). When examined by intervention type, effects were significant only for approaches focusing predominantly on emotion regulation (g = 0.20), which significantly improved behavioral outcomes as well as emotional outcomes. Approaches examining cognitive regulation, parent training, physical activity, and working memory did not differ significantly from zero. Across intervention types, outcomes demonstrated the largest effects for youth report of emotional distress. Overall, results suggest that emotion regulation may be a critically important self-regulation mechanism during early adolescence and demonstrates value in the use of applied theoretical frameworks to operationalize intervention approaches and outcomes.


A validated LC-MS/MS method for simultaneous determination of linagliptin and metformin in spiked human plasma coupled with solid phase extraction: Application to a pharmacokinetic study in healthy volunteers.
Combination therapy has a pivotal role in type II diabetes mellitus management in patients unable to maintain normal glycemic level using metformin alone. Addition of linagliptin, dipeptidyl peptidase-IV inhibitor, to metformin improves glycemic control. This study is concerned with the development of an HPLC-MS/MS method for simultaneous quantification of linagliptin and metformin in spiked human plasma. The method was applied to evaluate the potential pharmacokinetic interactions between the cited drugs in healthy volunteers. Solid phase extraction was applied using Strata™ X cartridge. Separation was carried out on Symmetry® C18 column using methanol: 10 mM ammonium formate buffer (containing 0.2% formic acid) in a ratio of (95: 5, v/v) as mobile phase at flow rate 0.25 mL min-1. Quantification was performed with multiple reaction monitoring in positive ionization mode. The monitored transitions were set at m/z 473.24 → 419.94, 130.14 → 60.18 and 340.27 → 116.07 for linagliptin, metformin and alogliptin (internal standard), respectively. The method was validated according to FDA guidelines. The method showed excellent linearity over concentration ranges 0.25-10 and 25-2000 ng mL-1 for linagliptin and metformin, respectively. The validated HPLC-MS/MS method was successfully applied to pharmacokinetic study of linagliptin and metformin in healthy volunteers after oral administration of Jentadueto® tablets.


Efficient high-rate satellite clock estimation for PPP ambiguity resolution using carrier-ranges.
In order to catch up the short-term clock variation of GNSS satellites, clock corrections must be estimated and updated at a high-rate for Precise Point Positioning (PPP). This estimation is already very time-consuming for the GPS constellation only as a great number of ambiguities need to be simultaneously estimated. However, on the one hand better estimates are expected by including more stations, and on the other hand satellites from different GNSS systems must be processed integratively for a reliable multi-GNSS positioning service. To alleviate the heavy computational burden, epoch-differenced observations are always employed where ambiguities are eliminated. As the epoch-differenced method can only derive temporal clock changes which have to be aligned to the absolute clocks but always in a rather complicated way, in this paper, an efficient method for high-rate clock estimation is proposed using the concept of "carrier-range" realized by means of PPP with integer ambiguity resolution. Processing procedures for both post- and real-time processing are developed, respectively. The experimental validation shows that the computation time could be reduced to about one sixth of that of the existing methods for post-processing and less than 1 s for processing a single epoch of a network with about 200 stations in real-time mode after all ambiguities are fixed. This confirms that the proposed processing strategy will enable the high-rate clock estimation for future multi-GNSS networks in post-processing and possibly also in real-time mode.


Hypermethylated DNA, a circulating biomarker for colorectal cancer detection.
Colorectal cancer (CRC) is one of the most common cancers in the western world. Screening is an efficient method of reducing cancer-related mortality. Molecular biomarkers for cancer in general and CRC in particular have been proposed, and hypermethylated DNA from stool or blood samples are already implemented as biomarkers for CRC screening. We aimed to evaluate the performance of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC detection. We conducted a cross-sectional case-control study of 193 CRC patients and 102 colonoscopy-verified healthy controls. Using methylation specific polymerase chain reaction, we evaluated 30 DNA promoter regions previously found to be CRC specific. We used multivariable logistic regression with stepwise backwards selection, and subsequent leave-pair-out cross validation, to calculate the optimism corrected area under the receiver operating characteristics curve (AUC) for all stage as well as early stage CRC. None of the individual DNA promoter regions provided an overall sensitivity above 30% at a reasonable specificity. However, seven hypermethylated promoter regions (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5% specificity using a cut point value of 0.5. Individual hypermethylated DNA promoter regions have limited value as CRC screening markers. However, a panel of seven hypermethylated promoter regions show great promise as a model for CRC detection.


Why families deny consent to organ donation.
Advances in medical practice and technology and the success of organ transplantation over the past 2 decades have resulted in an increased demand for organ donors. However, the health care community and organ procurement organisations (OPO) are faced with a worldwide shortage of donor organs. The non-consent of families is the most common reason that organs of medically suitable potential donors are not recovered. A review of published research post 1990 was conducted to primarily determine the major factors that influence a family's decision to deny consent to donation. Other objectives included providing suggestions for health care personnel to facilitate the donation request experience and to suggest strategies that would increase donation consent rates to benefit the organ procurement process. Databases predominately used in the review included CINAHL and Medline. The world wide web (www) was also accessed. The literature review indicates that the significant factors associated with denial of consent include: the misunderstanding of brain death; cultural beliefs; the specific timing of the request; the setting in which the request is made; the approach of the individual making the request; and characteristics of the deceased. Organ donation and transplantation rates could be increased by the joint involvement of medical, nursing and OPO personnel to enhance the quality of hospital care and to ensure that requests for donation are handled in a way that meets the family's informational and emotional needs. Increased consent rates have the potential to save lives and improve the quality of life for organ recipients.


Pleiotropic effects of polysaccharide capsule loss on selected biological properties of Streptococcus suis.
In this study, an unencapsulated Streptococcus suis mutant was used to investigate the pleiotropic effects resulting from capsule loss. The capsule deficient mutant of S. suis acquired a biofilm-positive phenotype, which was associated with significantly increased cell surface hydrophobicity. Cell-associated fibrinogen-binding and chymotrypsin-like activities were decreased in the unencapsulated mutant. The mutant did not differ significantly from the encapsulated parent strain for minimal inhibitory concentrations to penicillin G, ampicillin, and tetracycline. However, while the encapsulated strain was highly resistant to the bactericidal action of penicillin G and ampicillin, the unencapsulated mutant was approximately 60-fold more sensitive. Compared with the parent strain, the unencapsulated mutant induced a much higher inflammatory response in monocyte-derived macrophages resulting in an increased secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8. The capsule appears to hinder important adhesins or hydrophobic molecules that mediate biofilm formation, as well as cell wall components capable of stimulating immune cells.