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DNA microarrays are used to profile changes in gene expression between samples in a high-throughput manner, but measurements of genes with low expression levels can be problematic with standard microarray substrates. In this work, we expand the detection capabilities of a standard microarray experiment using a photonic crystal (PC) surface that enhances fluorescence observed from microarray spots. This PC is inexpensively and uniformly fabricated using a nanoreplica molding technique, with very little variation in its optical properties within- and between-devices. By using standard protocols to process glass microarray substrates in parallel with PCs, we evaluated the impact of this substrate on a one-color microarray experiment comparing gene expression in two developmental stages of Glycine max. The PCs enhanced the signal-to-noise ratio observed from microarray spots by 1 order of magnitude, significantly increasing the number of genes detected above substrate fluorescence noise. PC substrates more than double the number of genes classified as differentially expressed, detecting changes in expression even for low expression genes. This approach increases the dynamic range of a surface-bound fluorescence-based assay to reliably quantify small quantities of DNA that would be impossible with standard substrates.

In the vibrissal system, touch information is conveyed by a receptorless whisker hair to follicle mechanoreceptors, which then provide input to the brain. We examined whether any processing, that is, meaningful transformation, occurs in the whisker itself. Using high-speed videography and tracking the movements of whiskers in anesthetized and behaving rats, we found that whisker-related morphological phase planes, based on angular and curvature variables, can represent the coordinates of object position after contact in a reliable manner, consistent with theoretical predictions. By tracking exposed follicles, we found that the follicle-whisker junction is rigid, which enables direct readout of whisker morphological coding by mechanoreceptors. Finally, we found that our behaving rats pushed their whiskers against objects during localization in a way that induced meaningful morphological coding and, in parallel, improved their localization performance, which suggests a role for pre-neuronal morphological computation in active vibrissal touch.

The concept of biological markets aims to explain how organisms interact with each other. Market theory predicts that organisms choose the most rewarding partner in mutualisms. However, partner choice may also be influenced by advertisement which may not be reliable. In seed dispersal mutualism, we analysed whether seed dispersers prioritise taste cues over visual advertisement to select the most rewarding fruits and whether they select against partners with unreliable advertisement. We conducted experiments on black elder (Sambucus nigra), a species of which the colours of the peduncles match the sugar content of their fruits. We created infructescences the colours of which matched or mismatched the sugar content of their fruits. There was no selection against cheaters in the field or by captive blackcaps (Sylvia atricapilla) as seed dispersers. Blackcaps were constrained to select against unreliable advertisement because they swallowed fruits entirely and thus did not obtain an immediate feedback by taste. Instead, blackcaps selected fruits according to the colour variation of red peduncles. Overall, we suggest that the concept of constraints should be incorporated into biological markets. We further contend that biological markets can be more complex than currently acknowledged because a moderate degree of reliability occurred in black elder even in the absence of selection against cheaters.

In this paper, imidazolium-based ionic liquids [C(4)mim][PF(6)], [C(6)mim][PF(6)], [C(8)mim][PF(6)], [C(6)mim][BF(4)] and [C(8)mim][BF(4)] were tested as extracting solvents for removal of 3-indole butyric acid (IBA) from aqueous media with subsequent determination using HPLC. Percent extraction of IBA was strongly affected by pH of aqueous phases and the chemical structures of ionic liquids (ILs). Extraction of IBA was quantitative in the pH values lower than pK(a) of IBA. Considering both extraction and stripping efficiencies of IBA, [C(4)mim][PF(6)] was found to act more efficient than other studied ILs. Capacity of [C(4)mim][PF(6)] was 17.6x10(-4)mmol IBA per 1.0 mL of IL. Ionic strength of aqueous phase and temperature had shown no serious effects on extraction efficiency of IBA. A preconcentration factor of 100 and a relative standard deviation of 1.16% were obtained. It was found that ionic liquid phase was reusable almost five times for extraction/stripping purposes. 3-Indole acetic acid showed interferential effect in the extraction step. In order to assess the applicability of the method, extraction and stripping of IBA from pea plants and some other samples were studied.

Effective clinical faculty are essential for disseminating substance abuse screening, brief intervention, and referral to treatment (SBIRT). The authors developed an 8-hour SBIRT training for internal medicine faculty preceptors. Trainers conducted SBIRT lectures and small-group communication practice sessions. The authors assessed participants' (n = 27) knowledge, skills, and attitudes using an enhanced Alcohol and Alcohol Problems Perceptions Questionnaire (AAPPQ). Participants self-assessed their changes in SBIRT competence and comfort. Faculty trainees did not feel competent in SBIRT, particularly in intervention and referral to treatment. AAPPQ subscale scores were highest in Role Legitimacy and Motivation and lowest in Role Adequacy and Satisfaction. After training, faculty members reported greater likelihood of performing and teaching SBIRT. In some topic areas, faculty attending an SBIRT training reported limited knowledge and competence for treating drinkers; however, their interest and motivation for doing so was high. Ongoing faculty and organizational development efforts may help close these gaps.

We compared central venous oxygen saturation and central venous pressure (CVP) as indices of the effective blood volume during 50 degrees head-up tilt (anti-Trendelenburg's position) induced hypovolaemic shock in eight healthy subjects. Head-up tilt increased thoracic electrical impedance from 31 (28-36) (median and range) to 34 (30-40) Ohm, mean arterial pressure (MAP) from 79 (70-88) to 86 (80-99) mmHg, heart rate (HR) from 67 (56-71) to 99 (78-119) beats min-1 (p < 0.01) and total peripheral resistance (TPR) from 20 (16-32) to 36 (15-52) mmHg min l-1 (p < 0.03). Cardiac output decreased from 4.3 (3.0-4.8) to 2.7 (1.8-4.8) l min-1 (p < 0.03). After 29 (9-56) min presyncopal symptoms appeared, together with a decrease in MAP to 63 (43-79) mmHg, HR to 68 (30-112) beats min-1 and TPR to 22 (13-33) mmHg min l-1 (p < 0.02). During tilting CVP decreased from 3 (1-6) to 1 (-3-5) mmHg (p < 0.05) but thereafter remained stable. In contrast, central venous oxygen saturation showed a linear decrease with time from 0.75 (0.69-0.78) at rest to 0.60 (0.49-0.67) (p < 0.01) when presyncopal symptoms appeared. Central venous catheterization is a tool for measurement of central venous oxygen saturation in addition to recording of CVP. The results suggest that a reduced central blood volume is reflected more clearly in central venous oxygen saturation than in CVP.

Bland-Altman analysis used to determine the extent of bias, agreement, and precision between self-report and the "gold standard" of actual weight and height measurement revealed significant discrepancies between methods. Use of self-report data by health care providers and researchers should be made based on the clinical situation, patient safety, and research goals.

The two related protein-tyrosine kinases Syk and Zap are rapidly phosphorylated on tyrosine residues and enzymatically activated upon crosslinking of the T cell antigen receptor. We have previously reported that the activation of Syk is less dependent on the Src family kinase Lck than the activation of Zap. Here we report that overexpression of Syk in the Lck-negative JCaM1 cells enabled the T cell antigen receptor/CD3 complex to induce a normal activation of the mitogen-activated protein kinase (MAPK) pathway and expression of a nuclear factor of activated T cells reporter construct. In contrast, Zap and other protein-tyrosine kinases were unable to reconstitute these signaling pathways when expressed at the same levels. In parallel, Syk was phosphorylated on tyrosine, while Zap was not. The Syk-mediated T cell antigen receptor-induced MAPK activation was detectable within 1 min of receptor stimulation and peaked at 3-5 min. The capacity of Syk to reconstitute the MAPK response required the catalytic activity of Syk, an intact autophosphorylation site (Y518 and Y519), both Src homology 2 domains and it was blocked by the inhibitory N17-mutated dominant-negative Ras construct. A Y341-->F mutant of Syk, which is deficient in its interaction with phospholipase Cy1 and Vav, was less efficient than wild-type Syk. Our results suggest that Syk, in contrast to Zap, can transduce signals from the T cell antigen receptor independently of Lck.

Ultrasound microbubbles are contrast agents used for diagnostic ultrasound imaging and as carriers for noninvasive payload delivery. Understanding the acoustic properties of individual microbubble formulations is important for optimizing the ultrasound imaging parameters for improved image contrast and efficient payload delivery. We report here a practical and simple optical tool for direct real-time characterization of ultrasound contrast microbubble dynamics based on light scattering. Fourier transforms of raw linear and nonlinear acoustic oscillations, and microbubble cavitations are directly recorded. Further, the power of this tool is demonstrated by comparing clinically relevant microbubble cycle-to-cycle dynamics and their corresponding Fourier transforms.

A new unsaturated glutamic acid analog, 4-amino-3-chloro-2-pentenedioic acid ( ACPA ) was isolated from a fermentation broth produced by a strain of Streptomyces. ACPA has a very narrow antibacterial spectrum, which is virtually limited to Micrococcus luteus.

BACKGROUND: Ä(9)-Tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), and cannabinol (CBN) were measured in breath following controlled cannabis smoking to characterize the time course and windows of detection of breath cannabinoids.METHODS: Exhaled breath was collected from chronic (?4 times per week) and occasional (<twice per week) smokers before and after smoking a 6.8% THC cigarette. Sample analysis included methanol extraction from breath pads, solid-phase extraction, and liquid chromatography-tandem mass spectrometry quantification.RESULTS: THC was the major cannabinoid in breath; no sample contained THCCOOH and only 1 contained CBN. Among chronic smokers (n = 13), all breath samples were positive for THC at 0.89 h, 76.9% at 1.38 h, and 53.8% at 2.38 h, and only 1 sample was positive at 4.2 h after smoking. Among occasional smokers (n = 11), 90.9% of breath samples were THC-positive at 0.95 h and 63.6% at 1.49 h. One occasional smoker had no detectable THC. Analyte recovery from breath pads by methanolic extraction was 84.2%-97.4%. Limits of quantification were 50 pg/pad for THC and CBN and 100 pg/pad for THCCOOH. Solid-phase extraction efficiency was 46.6%-52.1% (THC) and 76.3%-83.8% (THCCOOH, CBN). Matrix effects were -34.6% to 12.3%. Cannabinoids fortified onto breath pads were stable (?18.2% concentration change) for 8 h at room temperature and -20°C storage for 6 months.CONCLUSIONS: Breath may offer an alternative matrix for identifying recent driving under the influence of cannabis, but currently sensitivity is limited to a short detection window (0.5-2 h).

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.

A 5 month old boy was found by his mother to have a bony mass behind the left ear which extended intracranially on MRI scan. At surgery it was entirely extradural in location. Microscopically, a biphasic appearance consisting of large pigmented cells arranged into tubules and small nonpigmented basophilic cells arranged into nests gave rise to a diagnosis of melanotic neuroectodermal tumour of infancy [MNETI]. One year after a wide local excision the patient is tumor-free and developing normally. The prognosis for MNETI in general is excellent with no requirement for additional radiotherapy or chemotherapy.

Complex small supernumerary marker chromosomes (sSMC) constitute one of the smallest subgroups of sSMC in general. Complex sSMC consist of chromosomal material derived from more than one chromosome. We report a complex sSMC derived from chromosomes 9 and 8, characterized as der(8;9)(p10;p10) resulting from unbalanced transition of maternal balanced translocation. Besides dysmorphic face and mental-motor retardation, the patient had Dandy-Walker malformation (DWM) in cranial MR also. As far as we are concerned, this is the first complex sSMC case comprising short arms of 8th and 9th chromosomes.

Non-insulin-dependent diabetes mellitus (NIDDM) with onset below 35 years of age was studies in 43 Indian and 9 Black patients. NIDDM was diagnosed in 10.0% and 1.6% of diabetes in the respective racial groups. The mean age of the patients was 35.4 years and the mean duration of diabetes 7.5 years. Nearly 50% of patients were significantly obese, and more than 50% had a positive family history of diabetes. In all patients the diabetes was symptomatic at presentation, although frequently insidious in onset. In all cases the symptoms could be controlled without insulin therapy. Despite persistence significant hyperglycaemia in several patients, ketosis did not occur at any stage. Complications were detected in 40% of the Indian and 22% of the Black patients, but were unrelated to the duration of diabetes or severity of hyperglycaemia. Basal insulin levels and postglucose insulinaemic responses were lower in the Black than the Indian diabetes.

Postoperative delirium is one of the most common adverse outcomes in elderly patients undergoing surgery and is associated with increased morbidity, length of stay, and patient care costs. The purpose of this quality improvement project was to evaluate the effectiveness of a multicomponent strategy to identify and treat general surgical patients 65 years of age or older at risk for and who develop postoperative delirium at Cape Cod Hospital, a community hospital in southern New England. We evaluated 96 patients using the Mini-Cog assessment tool preoperatively and the Confusion Assessment Method (CAM) delirium screening tool or CAM-Intensive Care Unit (CAM-ICU) assessment tool postoperatively. Patients who tested positive during preoperative assessment underwent a postoperative delirium management protocol. We summarized data using descriptive statistics. The results showed an association between compliance and outcomes. High compliance with implementation of CAM and CAM-ICU assessment tools resulted in increased identification of postoperative delirium in the older surgical population. The use of screening tools helped facilitate early identification of postoperative delirium in elderly surgical patients.

INTRODUCTION: Student radiographers have expressed difficulty in performing image appraisal tasks. The purpose of this study was to investigate the value of a workshop delivered to level 4 undergraduate students. All students completed an image appraisal activity, inputting their appraisal into software that displayed their response alongside an expert opinion. They were asked to identify and discuss any discrepancy.METHODS: All Level 4 students participated in an image appraisal workshop and were subsequently invited to take part in a focus group immediately after the activity. Twenty-three students took part in three focus groups (n = 7; n = 8; n = 8). A thematic analysis of transcripts was performed alongside validation from observations during the image appraisal activity.RESULTS: Findings demonstrate that despite teaching and resources being available, students had focused on learning a generic checklist for image appraisal, had not appreciated the application of projection specific criteria and felt underprepared. The use of specific criteria and repetition within the task was considered useful. They identified learning needs and misconceptions through peer discussion and via the expert opinion, highlighting the value of feedback. Students enjoyed the workshop and made suggestions for implementation into the curriculum.CONCLUSION: Educators must not assume that the provision of resources will result in students developing deep knowledge. Teaching and learning strategies that are task specific are recommended to avoid a surface approach to learning. Time, repetition and appropriate feedback are essential to enable learners to develop competence and confidence for complex visual tasks, such as image appraisal.

It could be advantageous for the parathyroids to be able to sense not only the absolute concentration of extracellular Ca2+, but also the rate and direction of change of Ca2+, thereby allowing the parathyroids to respond earlier to threats to Ca2+ homeostasis. By using high and low Ca2+ dialysis in a single session, we examined the parathyroid response to direction of change of Ca2+ during acute Ca2+ perturbation in nine hemodialysis patients. Separate PTH/ionized calcium (PTH/iCa) response curves were generated for rising Ca2+ and falling Ca2+. Significant directional hysteresis (higher PTH level during falling than during rising Ca2+) was found. During hypercalcemia, PTH levels were between 2.2 and 1.6 times higher at iCa concentrations of between 0 and +0.1 mM above the baseline iCa, when Ca2+ was falling than when it was rising. During the phase of induced hypocalcemia, parathyroid fatigue was seen in six of the nine patients. Fatigue patients tended to have higher basal PTH (1-84) levels than those not showing fatigue. The existence of fatigue provides an explanation for directional hysteresis during hypocalcemia, and therefore parathyroid sensing of the direction of change of Ca2+ could not be assessed during hypocalcemia. These studies demonstrate a capacity of the parathyroids to sense the direction of movement of Ca2+ during hypercalcemia.

The duration of a woman's reproductive period is determined by the size and persistence of a dormant oocyte pool. Specific oocyte genes are essential for follicle maintenance and female fertility. The mechanisms that regulate the expression of these genes are poorly understood. We found that a cullin-ring finger ligase-4 (CRL4) complex was crucial in this process. Oocyte-specific deletion of the CRL4 linker protein DDB1 or its substrate adaptor VPRBP (also known as DCAF1) caused rapid oocyte loss, premature ovarian insufficiency, and silencing of fertility maintaining genes. CRL4(VPRBP) activates the TET methylcytosine dioxygenases, which are involved in female germ cell development and zygote genome reprogramming. Hence, CRL4(VPRBP) ubiquitin ligase is a guardian of female reproductive life in germ cells and a maternal reprogramming factor after fertilization.

OBJECTIVE: Adenosine triphosphate (ATP) can promote the repair of spinal cord injury (SCI). To investigate the effect of ATP combined with bone marrow mesenchymal stem cells (BMSCs) transplantation on SCI, and to evaluate the synergistic action of ATP and BMSCs in the repair of SCI and the feasibility of the combined transplantation in the treatment of SCI.METHODS: BMSCs were isolated from the marrow of the tibia and the femur of a male SD rat (weighing 120 g), the 3rd generation BMSCs were labeled with BrdU, then BMSCs suspension of 5.0 x 10(7) cell/mL were prepared. Forty-eight adult female SD rats (weighing 240-260 g) were made SCI models at T2 levels according to the improved Allen's method, and were randomly divided into 4 groups (groups A, B, C, and D, n = 12). In group A, ATP (40 mg/kg) and BMSCs (6 microL) were injected to the central point and the other 2 points which were 1 mm from the each side of head and tail of the injured spinal cord; after blending the BMSCs suspension, the cells amount was about 3.0 x 10(5). In groups B, C, and D, the BMSCs suspension (6 microL), ATP (40 mg/kg), and PBS (40 mg/kg) were injected to the points by the same method as group A, respectively. The general conditions of the rats were observed after operation. The nerve function of low extremities was evaluated using the improved Tarlov scale and the Rivlin inclined plane test at 1, 3, 7, 14, 21, and 28 days after operation. At 28 days after operation, the reparative effect of SCI was observed using histological and immunohistochemical staining.RESULTS: One rat of group A, 2 of group B, 2 of group C, and 3 of group D died of infection and anorexic, the others survived to the end of the experiment. Paralysis symptom in low extremities occurred in all rats after operation and was improved at 2-3 weeks postoperatively, the improvement of group A was the best, groups B and C were better, group D was the worst. There was no significant difference in the Tarlov scale and the Rivlin inclined plane test among 4 groups at 1 and 3 days after operation and between groups B and C at 7, 14, 21, and 28 days after operation (P > 0.05), but there were significant differences among other groups at 7, 14, 21, and 28 days after operation (P < 0.05). At 28 days after operation, HE staining demonstrated that the injured region in group A was finely restored, without obvious scar tissue and cavity, and there existed clear stem cell differentiation characters; there was small amount of scar tissue and cavity in the injury site of groups B and C; and there was great deal of scar tissue in the injury site of group D, in which there were numerous inflammatory cells and fibroblasts infiltration and bigger cavity. Immunohistochemical staining showed that BrdU-positive BMSCs were seen in groups A and B, and positive cells of group A was significantly more than that of group B (P < 0.05). The expressions of neurofilament protein 200 and glial fibrillary acidic protein in group A were significantly higher than those in groups B, C, and D, and groups B and C were significantly higher than group D (P < 0.05).CONCLUSION: ATP has protective effects on injured spinal cord, a combination of ATP and BMSCs can synergistically promote the reparation of SCI.

Originally from tropical Asia, the Red Palm Weevil (RPW Rhynchophorus ferrugineus (Olivier)) is the most dangerous and deadly pest of many palm trees, and there have been reports of its recent detection in France, Greece and Italy. At present, emphasis is on the development of integrated pest management based on biological control rather than on chemical insecticides, however the success of both systems is often insufficient. In this regard, RPW appears to be one pest that is very difficult to control. Thus investigations into the natural defences of this curculionid are advisable. RPW hemocytes, the main immunocompetent cells in the insect, are described for the first time. We identified five hemocyte cell types from the hemolymph of R. ferrugineus: plasmatocytes (~50%), granulocytes (~35%), prohemocytes (~8%), oenocytes (~4%) and spherulocytes (~3%). SEM observations were also carried out. Some aspects of RPW interaction with non-self organisms, such as Saccharomyces cerevisiae and the entomopathogen bacterium, Bacillus thuringiensis (Bt), are discussed. Plasmatocytes and granulocytes were involved in nodules and capsule formation as well as in the phagocytosis of yeast. The hemocyte response of RPW larvae to sub-lethal doses of commercial products containing Bt was examined. In vivo assays were carried out and Bt in vegetative form was found in the hemolymph. After a diet containing Bt, the number of total hemocytes, mainly plasmatocytes, in the RPW larva hemolymph declined sharply (~12%) and then remained at a low level, while the number of other circulating cells was almost unchanged.

Separation and on-line concentration of bisphenol A and three alkylphenols were investigated by micellar electrokinetic chromatography with the anionic surfactant, sodium dodecyl sulfate. The separation conditions were optimized by the simultaneous addition of the organic solvent and cyclodextrin to the running solution. The separation of hydrophobic analytes and 4-nonylphenol isomers was improved by the addition of 10% methanol and 5 mM beta-cyclodextrin to the running solution. When the sweeping with the running solution was used as the on-line concentration procedure, 69-, 48-, 55- and 41-fold increases in detection sensitivity were obtained for bisphenol A, 4-tert.-butylphenol and 4-(1,1,3,3-tetramethylbutyl)phenol, and the second peak of 4-nonylphenol isomers, respectively. The detection limits were 0.0071, 0.0065, 0.021 and 0.055 mg/l, respectively. These results were better than those with the cationic surfactant, tetradecyltrimethylammonium bromide.

Incubation of prostaglandin D2 (PGD2) with human plasma yielded a product that has been identified as 9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydro-PGD2 (9-deoxy-delta 9, delta 12-13,14-dihydro-PGD2). The identification was based on mass spectrometry, UV spectrometry, mobilities and retention time on TLC and HPLC, and NMR. The conversion of PGD2 to this product was dependent on the incubation time and the amount of plasma added to a reaction mixture and was abolished by prior boiling. The conversion rate of PGD2 to this metabolite was 0.03 nmol/min per mg of protein of whole plasma at pH 8.0 at 37 degrees C. Similar conversion was also found by incubating PGD2 with human serum albumin added at the concentration found in plasma. These results suggest that the conversion of PGD2 to this product is catalyzed by the enzymatic action of a plasma protein, probably serum albumin. The biological activities of this compound were examined in several systems. It showed negligible activity in inhibition of human platelet aggregation and relaxation of rabbit stomach strip. On the other hand, it exhibited a three times stronger inhibitory activity (IC50, 1.8 microM) than PGD2 (IC50, 5 microM) on the growth of L-1210 cultured cells.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) often results in functional impairment and premature osteoarthritis despite surgical treatment. Treatment decisions are commonly based on the clinical history and radiographic appearance. This study assesses the pre-treatment features of SCFE and correlates them to the clinical history to: (1) define the underlying pathological mechanisms; (2) correlate the morphological hip abnormalities with the clinical classifications; (3) identify specific magnetic resonance imaging (MRI) features that could carry prognostic implications for treatment approach and outcome.METHODS: Clinical history and pre- and posttreatment radiographs and pre-treatment MRIs of 14 patients with 15 affected hips were reviewed. Alignment, impingement, fulcrum formation, remodelling, osteopenia, synovitis, joint effusion, bone marrow and soft tissue oedema and status of the physis and the periosteal sleeve were assessed and related to the clinical history, in particular history of trauma, duration of clinical symptoms and ability to bear weight.RESULTS: Bone marrow oedema around the growth plate and joint effusion occurred in all patients. Synovitis occurred in 13/15 patients. 6 patients had a fall before presenting with SCFE. 5/6 had periarticular soft tissue oedema, complete disruption of the physis and partial periosteal sleeve disruption. 9 patients had no fall prior to presentation, physis and periost were intact in 7/9; periarticular oedema was not seen. 14/15 showed evidence of chronic remodelling. Despite an acute clinical history remodelling was present. A fulcrum-like alignment, impingement of the epiphysis on the metaphysis with a small area of physical contact, was seen in 8 patients, 6/8 had a prior fall. There was no case of avascular necrosis. Spontaneous reduction of SCFE occurred in 1 case, the only case without chronic remodelling. With MRI as gold standard radiographs underestimate the severity of SCFE.CONCLUSION: Synovitis, periphyseal oedema and joint effusion are regular features of SCFE. The clinical history and findings are unreliable for the classification of SCFE. Radiographs underestimate the severity of SCFE. SCFE is often a Salter Harris I injury due to a fall with considerable periarticular soft tissue trauma and a potentially unstable alignment of epi- and metaphysis. This can lead to spontaneous reduction prior to surgery, MRI can potentially identify unstable, reducible slips. If the mode of surgical treatment depends on the particular nature of the SCFE then MRI contributes to surgical decision-making.LEVEL OF EVIDENCE: Level 4, case series.

BACKGROUND AND PURPOSE: This study compared the ability of 2 stroke impairment scales, Orpington Prognostic Scale and National Institutes of Health (NIH) Stroke Scale, to predict disability as measured by the Barthel activities of daily living (ADL) Index and higher level of self-reported physical functioning as measured by the SF-36 physical functioning index (PFI) at 1, 3, and 6 months after stroke.METHODS: The participants in this ongoing study are 184 individuals who sustained an eligible stroke and were recruited for the Kansas City Stroke Study. All patients were prospectively evaluated using standardized assessments at enrollment (within 14 days of stroke onset) and followed at 1, 3, and 6 months after stroke. Coefficient of determination (R2) was used to assess the ability of the 2 stroke scales to prognosticate outcomes.RESULTS: Means and SDs of the Orpington Prognostic Scale and NIH Stroke Scale measured at baseline were 3.6+/-1.31 and 5.5+/-4.58, respectively. The Spearman's rank correlation between the 2 baseline measures was 0.83 (P=0.0001). The Orpington Prognostic Scale and the NIH Stroke Scale explained well the variance in Barthel ADL Index (P<0.001). However, the Orpington Prognostic Scale explained more variance than did the NIH Stroke Scale. Similarly, the Orpington Prognostic Score explained more variance in higher level of physical function than did the NIH Stroke Scale. The amount of variance in Barthel ADL Index and SF-36 PFI, which were explained by both stroke severity measures, decreased over time.CONCLUSIONS: Our results demonstrate that in a sample of mostly mild and moderate strokes, the Orpington Prognostic Scale compared with the NIH Stroke Scale is simpler to use and is a slightly better predictor of ADL and higher levels of physical function.

This article reviews the current literature characterizing potential factors associated with the etiologies of gender identity. The PubMed database was searched for all literature that assessed key elements affecting development of gender identity. Current models attribute gender identity etiology to endogenous biology along with prenatal androgen exposure. However, no genetic loci or specific neuroanatomic regions have been consistently identified as the single explanation for transgender identity. Although environment may play a role in gender expression, there are no data to suggest an exogenous explanation for the development of gender identity.

The uncontrolled release of nutrients from waste sludge results in nitrogen and phosphorus overloading in wastewater treatment plants when supernatant is returned to the inlet. A controlled release, recovery and removal of nutrient from the waste sludge of a Biological Nutrient Removal system (BNR) are investigated. Results showed that the supernatant was of high mineral salt, high electrical conductivity and poor biodegradability, in addition to high nitrogen and phosphorus concentrations after the waste sludge was hydrolysed through sodium dodecyl sulphate addition. Subsequently, over 91.8% of phosphorus and 10.5% of nitrogen in the supernatants were extracted by the crystallization method under the conditions of 9.5 pH and 400 rpm. The precipitate was mainly struvite according to X-ray diffraction and morphological examination. A multistage anoxic-oxic Moving Bed Biofilm Reactor (MBBR) was then adopted to remove the residual carbon, nitrogen and phosphorus in the supernatant. The MBBR exhibited good performance in simultaneously removing carbon, nitrogen and phosphorus under a short aeration time, which accounted for 31.25% of a cycle. Fluorescence in situ hybridization analysis demonstrated that nitrifiers presented mainly in floc, although higher extracellular polymeric substance content, especially DNA, appeared in the biofilm. Thus, a combination of hydrolysis and precipitation, followed by the MBBR, can complete the nutrient release from the waste sludge of a BNR system, recovers nutrients from the hydrolysed liquor and removes nutrients from leftovers effectively.

The dynamic assembly/disassembly of non-muscle myosin II filaments is critical for the regulation of enzymatic activities and localization. Phosphorylation of three threonines, 1823, 1833 and 2029, in the tail of Dictyostelium discoideum myosin II has been implicated in control of myosin filament assembly. By systematically replacing the three threonines to aspartates, mimicking a phosphorylated residue, we found that position 1823 is the most critical one for the regulation of myosin filament formation and in vivo function. Surprisingly, a single charge change is able to perturb filament formation and in vivo function of myosin II.

Nuclear medicine continues to represent one of the important modalities for cancer management. While diagnostic nuclear medicine for cancer management is fairly well established, therapeutic strategies using radionuclides are yet to be utilized to their full potential. Even if 1% of the patients undergoing diagnostic nuclear medicine procedures can benefit from subsequent nuclear therapeutic intervention, the radionuclide requirement for nuclear therapeutics would be expected to be in the multi-million Curie levels. Meeting the demand for such high levels of therapeutic radionuclides at an affordable price is an important task for the success of radionuclide therapy. Although different types of particle emitters (beta, alpha, Auger electron etc.) have been evaluated for treating a wide variety of diseases, the use of â⁻ emitting radionuclides is most feasible owing to their ease of production and availability. Several â⁻ emitting radionuclides have been successfully used to treat different kind of diseases. However, many of these radionuclides are not suitable to meet the projected demand owing to the non-availability with sufficiently high specific activity and adequate quantity because of high production costs, relatively short half-lives etc. This article describes the advantages and disadvantages for broader uses of some of the well known therapeutic radionuclides. In addition, radioisotopes which are expected to have the potential to meet the growing demand of therapeutic radionuclides are also discussed.

BACKGROUND: The 'hygiene hypothesis' suggests that a reduction in the microbial exposure due to improved health measures has contributed to an immunological imbalance in the intestine and increased the incidence of autoimmune diseases such as inflammatory bowel diseases (IBD). Accordingly, we investigated associations between oral hygiene practices and IBD.METHODS: We developed and administered a multiple choice questionnaire to evaluate oral hygiene and dental care practices of 137 subjects (83 with IBD and 54 healthy controls).RESULTS: Of the 83 IBD cases, 31% had ulcerative colitis and 69% had Crohn's disease. For subjects with IBD, the frequency of brushing at disease onset was significantly higher than in controls (P=0.005). Also, the frequency of use of dental floss and breath freshener at disease onset was significantly higher in IBD patients (P=0.005 and<0.001, respectively). Also, patients with IBD more frequently visited their dentist at disease onset (P<0.001) and continued to visit their dentist more often (P<0.001). IBD cases had a higher frequency of dental complications such as tooth caries (P=0.007), oral ulcers (P=0.04) and dry mouth (P=0.001).CONCLUSIONS: These findings suggest that oral hygiene practices may cause alterations in the flora of the oral mucosa, which causes imbalance in the gut microbiome (dysbiosis), and thereby contributes to the pathogenesis of IBD. Conversely, the increased frequency of dental problems in IBD patients might be due, at least in part, to alterations in oral flora or to their disease.

Hematopoietic progenitor kinase 1 (HPK1) is a hematopoietic cell-restricted member of the Ste20 kinases that acts as a negative regulator of T cell functions through the AP-1, NFAT, and NFkappaB pathways. Using HPK1-deficient (HPK1(-/-)) mice, we report in this study a novel role for HPK1 in dendritic cells (DCs). Specifically, we observed that matured HPK1(-/-) bone marrow-derived DCs (BMDCs) are superior to their wild-type (WT) counterpart in stimulating T cell proliferation in vivo and in vitro. Several characteristics of HPK1(-/-) BMDCs may account for this enhanced activity: Matured HPK1(-/-) BMDCs express higher levels of costimulatory molecules CD80, CD86, and I-A(b) as well as produce more proinflammatory cytokines IL-12, IL-1beta, TNF-alpha, and IL-6 than their WT littermates. The role of HPK1 as a proapoptotic molecule was assessed post activation with LPS, and results indicated that HPK1(-/-) BMDCs are significantly resistant to LPS-induced apoptosis. Our results led us to investigate the role of HPK1(-/-) BMDCs in tumor immunotherapy. Using a s.c. murine model of Lewis Lung Carcinoma, we found that HPK1(-/-) BMDCs eliminate established s.c. Lewis Lung Carcinoma more efficiently than their WT counterpart. Our data reveal a novel role for HPK1 as a negative regulator of DC functions, identifying its potential as a molecular target for DC-based immunotherapy against cancers.

Previous studies have demonstrated that repeated restraint stress in rodents increased depression-like behavior and altered the expression of corticotrophin-releasing factor in the hypothalamus. The current study focused on verifying the impact of fucoidan (FCN) administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST). Additionally, we examined the effect of FCN on the central noradrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brains. Male rats received 10, 20, or 50 mg/kg FCN (i.p.) 30 min before daily exposures to repeated restraint stress (2 h/day) for 14 days. Repeated restraint stress increased immobility in the FST. Daily administration of FCN during the repeated restraint stress period significantly inhibited the stress-induced behavioral deficits in this behavioral test. Administration of FCN also significantly blocked the increase in TH expression in the locus coeruleus and the basolateral nucleus of the amygdala, and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of FCN prior to restraint stress significantly improved helpless behavior in rats, possibly through modulating the central noradrenergic system. Therefore, FCN may be a useful agent for treating complex symptoms of depression disorder.

Suicidal behavior is a multifactorial phenomenon, with a significant genetic predisposition. To assess the contribution of genes in the 4p region to suicide risk, we genotyped 36 single nucleotide polymorphisms from a 49Mb region on the chromosome arm 4p11-16 in a total of 288 male suicide victims and 327 healthy male volunteers. The nonsynonymous variants rs1383180 in EVC gene, rs6811863 in TBC1D1 gene, rs362272 in HTT gene, and rs734312 in WFS1 gene were associated to the male completed suicide. However, only EVC polymorphism remained significant after correcting for multiple comparisons (P < .05 after 10 K permutations). The function of these genes is not clear yet. WFS1 and HTT are related to the unfolded protein response and endoplasmic reticulum stress, and TBC1D1 is a GTPase activator. EVC is a protein with transmembrane and leucine zipper domains, its function has not been elucidated yet. Further studies are required in order to reveal the role of these four polymorphisms in the pathoetiology of suicide.

A patient is described with multiple, benign, chondromatous intrapulmonary and endobronchial mesenchymomas of the lung, which recurred after resection on two occasions over a period of 30 years. In such a patient presenting at a young age or with a history of previous recurrence, a wedge excision may be necessary to prevent further recurrence.

The Notch signaling pathway is an ubiquitous cell-cell interaction mechanism, which is essential in controlling processes like cell proliferation, cell fate decision, differentiation or stem cell maintenance. Recent data have shown that Notch signaling is RBP-Jê-dependent in melanocytes, being required for survival of these pigment cells that are responsible for coloration of the skin and hairs in mammals. In addition, Notch is believed to function as an oncogene in melanoma, whereas it is a tumor suppressor in mouse epidermis. In this study, we addressed the implication of the Notch signaling in the development of another population of pigment cells forming the retinal pigment epithelium (RPE) in mammalian eyes. The constitutive activity of Notch in Tyrp1::NotchIC/° transgenic mice enhanced RPE cell proliferation, and the resulting RPE-derived pigmented tumor severely affected the overall eye structure. This RPE cell proliferation is dependent on the presence of the transcription factor RBP-Jê, as it is rescued in mice lacking RBP-Jê in the RPE. In conclusion, Notch signaling in the RPE uses the canonical pathway, which is dependent on the transcription factor RBP-Jê. In addition, it is of importance for RPE development, and constitutive Notch activity leads to hyperproliferation and benign tumors of these pigment cells.

During the development of synthetic calcitonins for therapeutic use in bone disease, a "diabetogenic" (hyperglycemic) effect was observed, particularly with salmon calcitonin. The effect was attributed by some to inhibition of insulin secretion. We have recently reported high-affinity (28 pmol/L) amylin-binding sites in certain areas of rat brain, and found that these sites also bind salmon but not rat calcitonin with comparable high affinity. Rat amylin and salmon calcitonin have been determined to have significant structural homology. In vitro and in vivo studies indicate that rat amylin can exert calcitonin-like effects on osteoclasts and on plasma calcium. Here we report that salmon calcitonin mimics the actions of rat amylin on skeletal muscle glycogen metabolism in vitro; it stimulates glycogenolysis and inhibits incorporation of radiolabeled glucose into glycogen (50% effective concentration [EC50], 0.4 +/- 0.11 nmol/L log and 8.4 +/- 0.05 nmol/L log, respectively). In anesthetized rats, salmon calcitonin, like rat amylin, rapidly increases plasma lactate concentration, followed by a slower increase in glucose concentration. Like amylin, salmon calcitonin also inhibits the insulin response to 2 mmol infused glucose (insulin increments suppressed by 52% and 57% at 10 minutes for salmon calcitonin and amylin). Other shared actions, such as suppression of appetite, stimulation of renin secretion, inhibition of gastric acid secretion, and inhibition of gastric emptying, further affirm our proposal that the exogenous peptide, salmon calcitonin, is a mimic of endogenous amylin in the rat.

The serine-threonine protein kinase encoded by the tumor progression locus 2 (Tpl2) proto-oncogene transduces Toll-like receptor and death receptor signals in a variety of cell types. Here we show that Tpl2 undergoes phosphorylation at Thr(290) both in cells overexpressing Tpl2 and in cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-alpha and that phosphorylation on this site parallels Tpl2 activation. Reconstitution of Tpl2(-/-) macrophages with wild type Tpl2 or Tpl2 T290D restored ERK activation by LPS, whereas reconstitution of the same cells with Tpl2 T290A did not, suggesting that phosphorylation at Thr(290) is required for the physiological activation of Tpl2 by external signals. Both the wild type Tpl2 and the kinase-inactive mutant Tpl2 K167M undergo Thr(290) phosphorylation, suggesting that Thr(290) may be a site of trans-phosphorylation rather than auto-phosphorylation. Pretreatment of 293 cells and primary macrophages with the Ikappa-B kinase-beta (IKKbeta) inhibitor PS-1145 blocked Tpl2 phosphorylation at Thr(290), suggesting that phosphorylation depends on IKKbeta, an obligatory positive regulator of Tpl2. We conclude that Tpl2 phosphorylation at Thr(290) is induced by LPS, depends on IKKbeta, and is required for the physiological activation of Tpl2 by external signals.

UNLABELLED: Primary aldosteronism has been associated with myocardial fibrosis, and is the most common cause of secondary hypertension. We previously showed that aldosterone can induce the secretion of galectin-3. The aim of this study was to investigate the association between myocardial fibrosis and plasma galectin-3 level in patients with primary aldosteronism. We prospectively analyzed 11 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008, and 17 patients with essential hypertension as controls. Levels of plasma galectin-3 were determined in both groups, and both groups underwent echocardiography with cyclic variations of integrated backscatter (CVIBS) to characterize tissue initially and 1 year after surgery in the APA group. Diastolic blood pressure, concentration of plasma aldosterone and aldosterone-renin ratio were significantly higher, and serum potassium level and plasma renin activity significantly lower in the APA group compared to the controls. In addition, left ventricular mass index was significantly higher and CVIBS significantly lower in the APA group (7.3±2.0 vs 9.2±1.7 dB, p=0.015). Furthermore, the concentration of plasma galectin-3 was significantly higher in the APA group (2.1±0.9 vs 1.1±0.6 ng/mL, p=0.005) compared to the controls. CVIBS was correlated to plasma galectin-3 level. In the APA group, CVIBS increased significantly (7.3±2.0 to 9.2±2.4 dB, p=0.032) and plasma galectin-3 decreased (2.1±0.9 to 1.2±0.6, p=0.049) 1 year postadrenalectomy. The patients with APA had increased myocardial fibrosis, and this was associated with a higher plasma galectin-3 level. Both increased myocardial fibrosis and plasma galectin-3 level recovered at least partially after adrenalectomy.TRIAL REGISTRATION NUMBER: 200611031R; Results.

BACKGROUND: Over recent years there has been a paradigm shift towards a patient-centred biopsychosocial care model in physical therapy. This new paradigm features a growing interest in understanding the contextual factors that influence the patient's experience of disease, pain and recovery. This includes generalized consensus regarding the importance of establishing a therapeutic relationship that is centred on the patient.OBJECTIVE: To explore physical therapists' perceptions and experiences regarding barriers and facilitators of therapeutic patient-centred relationships in outpatient rehabilitation settings.METHODS: This is a qualitative study with four focus groups including twenty-one physical therapists. Two researchers conducted the focus groups, using a topic guide with predetermined questions. The focus group discussions were audiotaped and videotaped, transcribed verbatim and analysed thematically using a modified grounded theory approach.RESULTS: Physical therapists perceived that the therapeutic patient-centred relationship not only depends on the personal qualities of the professional, but also on the patient's attitudes and the characteristics of the context, including the organization and team coordination.CONCLUSIONS: Although being more linked towards the patients' contextual factors and needs than towards the practice of the profession, a therapeutic relationship is worth considering by physical therapists. Furthermore this study highlights the need for physical therapists and administrators to rethink the situation and propose strategies for improvement.

BACKGROUND: A composite tissue consists of tissues derived from ectoderm and mesoderm typically containing skin, fat, muscle, nerves, lymph nodes, bone, bone marrow or any combination of these. Solid organ transplants possessing larger allograft mass were reported to survive better. As for the vascularized composite tissues however, thus far no study has comparatively studied the survival of grafts possessing different tissue burdens. The purpose of this study was to explore the effect of transplanted tissue burden and tissue type on survival of skin element of composite tissues.MATERIALS AND METHODS: Forty-five transplantations were performed using four different vascularized composite tissue allotransplantation models. The survival periods and rejection severity of the skin parts of the transplants were compared by histological, immunological, and macroscopic evaluation: (a) under no immunosuppressive treatment (control group) (n = 21); (b) after 1 week of Cyclosporine (CsA) treatment (16 mg/kg) (experimental group) (n = 24). Total rejection was defined as necrosis of >90% of the skin flaps. Histopathologic evaluation and flow cytometric analysis to detect chimerism rates in the blood was performed in the CsA treated animals on day 18.RESULTS: The differences of mean survival times between and within the experimental and control groups were statistically significant (P < 0.05). Histopathological outcomes showed lower rejection grades in skin allografts transplanted with a higher tissue burden. Total CD4+ and CD8+ T-cell chimerism rates were less than 1% in isolated skin transplant groups and ranged from 6.1 to 33.5% in skin flaps transplanted with the entire hindlimb or a part of it.CONCLUSION: The transplanted tissue burden as well as the tissue type can be an important factor for the skin transplant outcome.

Memory performance was examined in patients with schizophrenia to determine whether subgroups conforming to cortical and subcortical dementias could be identified and, if so, whether subgroups differed on clinical, neuroanatomical, and neurophysiological measures. A cluster analysis of California Verbal Learning Test performance classified patients into 3 subgroups. Two groups exhibited memory deficits consistent with the cortical-subcortical distinction, whereas 1 group was unimpaired. Cortical patients tended to be male, and they had earlier illness onset, reduced temporal lobe gray matter, and hypometabolism. Subcortical patients had ventricular enlargement and more negative symptoms. Unimpaired patients had fewer negative symptoms and dorsal medial prefrontal hypermetabolism. The authors conclude that categorizing patients on the basis of memory deficits may yield neurobiologically meaningful disease subtypes.

The aim of this study was to investigate Parkinson's disease (PD) using a murine model of PD. Specifically, we aimed to explore the mechanism by which puerarin prevents inflammation and apoptosis in neurocytes. Eighty healthy male C57/BL6 mice were randomly selected and divided into four groups (N = 20 each): control group; PD group; PD+puerarin group; and puerarin group. At the end of the treatment period, the animals' brains were removed after perfusion and decollation. The protein expression levels of tyrosine hydroxylase (TH) in the murine brains were assessed by immunohistochemistry and the protein expression levels of TH, glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS), cleaved Caspase-3, and Bax in the substantia nigra and corpus striatum of the animals were assessed by western blotting. The spontaneous activity of the PD mice was found to be significantly higher after puerarin treatment and the distance traveled by mice in an open field assessment was 1700 cm further in puerarin-treated PD mice than in PD mice. Immunohistochemistry and western blotting analyses indicated that the expression of TH was significantly higher (2.63-fold) in puerarin-treated PD mice than in untreated PD mice and that the expression of GFAP in PD mice was significantly reduced (~45%) by puerarin treatment. These findings lead us to conclude that puerarin significantly alleviates 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-induced injury in dopaminergic neurons. Puerarin mediates anti-apoptotic and anti-inflammatory activities and plays a neuroprotective role.

OBJECTIVES: To compare retention of tocilizumab (TCZ) as monotherapy vs combination therapy with MTX in RA patients achieving clinical improvements during the first year.METHODS: We performed a multicentre cohort study using a real-life registry containing RA patients who had begun TCZ with or without MTX between April 2008 and November 2016. Among patients with ?50% improvement of clinical disease activity index (CDAI) during the first year (CDAI50 responders), we evaluated whether MTX use may have affected TCZ discontinuation during the second and subsequent years (maintenance therapy).RESULTS: Among 510 patients with high or moderate CDAI, 328 (64.3%) were CDAI50 responders. The rate of MTX use was 53.0% among responders and 54.4% among non-responders. During maintenance therapy (mean follow-up 30.7 months), 43.9% of CDAI50 responders discontinued TCZ. The most common cause was efficacy loss followed by adverse events. Kaplan-Meier estimates for TCZ retention were 48.3 months (95% CI 42.0, 54.5) for monotherapy and 50.0 months (95% CI 45.9, 54.0) for combination therapy. According to Gray's test, there was no significant impact of MTX use on cumulative incidence of efficacy loss or adverse events. In the Fine-Gray competing risk regression model, CDAI >10 at the start of maintenance therapy and age were predictive factors for TCZ discontinuation due to efficacy loss (hazard ratio 2.58, 95% CI 1.41, 4.72) and adverse events (hazard ratio 1.04, 95% CI 1.01, 1.08), respectively.CONCLUSION: There was no significant difference in TCZ retention between monotherapy and combination therapy with MTX.

Consideration regarding human aging and sympathetic nervous system activity suggests that old age represents a hyperadrenergic state. With advancing age the sympathetically mediated stress on the body, specifically the cardiovascular system, may outweigh the benefits an intact sympathetic nervous system conveys for short-term survival. Beta blockers temper the effects of the sympathetic nervous system by slowing heart rate and decreasing blood pressure. Recently, beta blockers have been shown to improve outcome and survival following surgery and myocardial infarction, have beneficial effects in patients with heart failure, and may have an antiatherosclerotic effect. We propose that instituting beta receptor blockade pharmacotherapy at an early age will increase longevity by countering the adverse effects of sympathetically mediated stress.

Monocyte chemotactic protein-1 (MCP-1), also known as "chemokine ligand 2" (CCL2), is a monocyte-attracting chemokine produced in lung epithelial cells. We previously reported an association of increased levels of plasma MCP-1 with primary graft dysfunction (PGD) after lung transplantation in a nested case-control study of extreme phenotypes using a multiplex platform. In this study, we sought to evaluate the role of plasma MCP-1 level as a biomarker across the full spectrum of PGD. We performed a prospective cohort study of 108 lung transplant recipients within the Lung Transplant Outcomes Group cohort. Plasma MCP-1 levels were measured pretransplantation and 6 and 24 hours after transplantation. The primary outcome was development of grade 3 PGD within 72 hours of transplant, with secondary analyses at the 72-hour time point. Multivariable logistic regression was used to evaluate confounding. Thirty subjects (28%) developed PGD. Median MCP-1 measured at 24 hours post-transplant was elevated in subjects with PGD (167.95 vs 103.5 pg/mL, P = .04). MCP-1 levels at 24 hours were associated with increased odds of grade 3 PGD after lung transplantation (odds ratio for each 100 pg/mL, 1.24; 95% confidence interval, 1.00-1.53) and with grade 3 PGD present at the 72-hour time point (odds ratio for each 100 pg/mL, 1.57; 95% confidence interval, 1.18-2.08), independent of confounding variables in multivariable analyses. MCP-1 levels measured preoperatively and 6 hours after transplant were not significantly associated with PGD. Persistent elevations in MCP-1 levels at 24 hours are a biomarker of grade 3 PGD post-transplantation. Monocyte chemotaxis may play a role in the pathogenesis of PGD.

The data obtained from studies of 84 patients with polyps of the stomach and colonic were used to consider the capacities of transabdominal and transrectal ultrasound studies and their diagnostic efficiency in the diagnosis of polyps of the stomach and colon. The ultrasound semiotics of polyps of the gastric and colon was described. A place of transabdominal ultrasound sonography (US) in the algorithm of radiation and endoscopic studies was established. This investigation led to the conclusion that transabdominal US, along with indirect diagnosis, permits solution of number of fundamental problems facing prior to polypectomy--these are primarily to define the nature of a detected polyp (epithelial and non-epithelial), based on an analysis of the laminar structure of the wall of an organ at the polyp base, a possible polyp malignancy and the degree of invasion into the depths of the gastric wall, as well as to detect a feeding vessel (in the CDC mode) and to predict the likelihood of possible complications. It is advisable to use transabdominal US in a complex of diagnostic techniques for polyps of the stomach and colon.

The effect of Na+, H+ and Mg2+ ions on net calcium exchange induced in digitonin-treated myocytes has been investigated. Raising the [Na] from 1.4 to 31.4 mM revealed a sodium-sensitive fraction of net calcium exchange with a K1/2 for Na+ ions of 12 mM, alongside the respiration-dependent accumulation of calcium. An acidosis, but not an alkalosis, was found to depress both of these processes. Mg2+ ions exerted an effect solely on the respiration-dependent calcium sequestration. A simple semi-empirical model based on the experimental data was formulated to assess the effects that altering sarcoplasmic [Na+] and [H+] would have on the calcium-handling properties of cardiac mitochondria. It is concluded that part of the inotropic effects of these ions could be mediated via this organelle.

OBJECTIVE: End-stage renal disease (ESRD), characterized by multi-organ dysfunction, has been shown to co-occur with abnormal brain function. Previous resting-state fMRI studies suggested that regional brain spontaneous activity and functional connectivity within the default mode network are abnormal in ESRD patients. The current study aimed to depict intrinsic dysconnectivity pattern of whole-brain functional networks in voxel level in neurologically asymptomatic patients with ESRD.METHODS: fMRI datasets were acquired from 22 ESRD patients (without clinical neurological disease) and 29 healthy control (HC) subjects. We investigated the degree centrality for a given element in a network to reveal the changes of functional connectivity throughout the huge human functional network. In the brain regions showing a difference between the HC and ESRD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the accuracy, sensitivity and specificity of our results.RESULTS: ESRD patients showed decreased functional connectivity in the left inferior parietal and left precuneus within the brain network; both regions are important components of the default-mode network (DMN). In contrast, patients showed increased connectivity in depression-related regions including bilateral inferior frontal gyrus and right superior temporal gyrus. These regions showed an acceptable accuracy (0.68-0.75), sensitivity (0.64-0.70) and high specificity (0.82-0.96) in distinguishing between the two groups.CONCLUSIONS: Our findings reveal abnormal intrinsic dysconnectivity pattern of whole-brain functional networks in ESRD patients.SIGNIFICANCE: Our results could lead to a better understanding of the intrinsic dysconnectivity patterns of default-mode network-related regions in ESRD patients from the whole brain network perspective.

In Malysia, the proportion of children fully immunized againest diphtheria is generally low (20%). On the other hand, the Schick conversion rate rises with age and reaches 90% by 11 years of age. It is noted that asymptomatic carriers are an important epidemiological factor in diphtheria and that carrier rates for school children are high (prevalence of 7.5% while the rate of coloization with C. diphtheriae over a period of one year was 30%). Although immunization protects against clinical diphtheria, it does not prevent the carrier state. Thus, for the control of diphtheria, one should aim for 100% compliance. Some suggestions as to how higher levels of immunity may be achieved are described.

BACKGROUND AND AIMS: This study reviewed the outcome of endoscopic transanal resection (ETAR) for the treatment of patients with villous rectal adenomas (VRA).PATIENTS AND METHODS: This study included 28 consecutive patients who underwent ETAR for VRA between October 1992 and December 2000. All tumors were believed to be benign (clinical examination, endorectal ultrasonography, multiples biopsies) A retrospective evaluation of the outcome of ETAR was performed.RESULTS: Thirteen patients (46.4%) had a large VRA with a tumor length of more than 5 cm. The tumor involved the anterior rectal wall in ten cases. Ten patients (35.7%) required more than one procedure. Median operating time was 35 min (range 20-50). Morbidity was 5% ( n=2); no patient died. Median postoperative stay was 3 days (range 1-5). Three patients (9.3%) were confirmed on histology as having adenocarcinoma of the rectum and underwent a conventional surgical procedure. At a median follow-up of 5 years (2.5-10.5), two recurrences were noted.CONCLUSION: Our data suggest that the technique of transanal resection has a limited but valuable place in rectal surgery. ETAR is a simple, minimally invasive, and economical method for treatment of patient with VRA. ETAR should be performed in collaboration with an experienced urological endoscopist. ETAR is a useful addition to the surgeon's armamentarium together with laser destruction and transanal endoscopic microsurgery.

BACKGROUND: Previous studies demonstrate that graft survival from older living kidney donors (LD; age>60 years) is worse than younger LD but similar to deceased standard criteria donors (SCD). Limited sample size has precluded more detailed analyses of transplants from older LD.METHODS: Using the United Network for Organ Sharing database from 1994 to 2012, recipients were categorized by donor status: SCD, expanded criteria donor (ECD), or LD (by donor age: <60, 60-64, 65-69, ?70 years). Adjusted models, controlling for donor and recipient risk factors, evaluated graft and recipient survivals.RESULTS: Of 250,827 kidney transplants during the study period, 92,646 were LD kidneys, with 4.5% of these recipients (n=4,186) transplanted with older LD kidneys. The use of LD donors 60 years or older increased significantly from 3.6% in 1994 to 7.4% in 2011. Transplant recipients with older LD kidneys had significantly lower graft and overall survival compared to younger LD recipients. Compared to SCD recipients, graft survival was decreased in recipients with LD 70 years or older, but overall survival was similar. Older LD kidney recipients had better graft and overall survival than ECD recipients.CONCLUSIONS: As use of older kidney donors increases, overall survival among kidney transplant recipients from older living donors was similar to or better than SCD recipients, better than ECD recipients, but worse than younger LD recipients. With increasing kidney donation from older adults to alleviate profound organ shortages, the use of older kidney donors appears to be an equivalent or beneficial alternative to awaiting deceased donor kidneys.

PURPOSE: The efficacy of aerosolization of ciprofloxacin (CPFX) incorporated into PEGylated liposomes (PEGylated CPFX-liposomes) for the treatment of respiratory infections was evaluated.METHOD: PEGylated CPFX-liposomes with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] (particle size: 100 nm) were prepared, and the drug distribution characteristics in lung epithelial lining fluid (ELF) following aerosolization of PEGylated CPFX-liposomes were examined in rats. Furthermore, the antibacterial effects of PEGylated CPFX-liposomes in ELF were evaluated by pharmacokinetic/pharmacodynamic analysis.RESULTS: The elimination rate of CPFX from ELF following aerosolization of PEGylated CPFX-liposomes was significantly slower than that of CPFX incorporated into unmodified liposomes (unmodified CPFX-liposomes; particle size: 100 nm). According to pharmacokinetic/pharmacodynamic analysis, the PEGylated CPFX-liposomes exhibited potent antibacterial effects against pathogenic microorganisms in ELF.CONCLUSION: This study shows that PEGylated CPFX-liposomes are a useful aerosol-based pulmonary drug delivery system for the treatment of respiratory infections.

PURPOSE: The aim of this study was to assess the progression of radiological cartilage changes and to document the functional, long-term results during a follow-up of 10 years after osteoautograft transplantation (OAT) knee surgery.METHODS: The study was a retrospective analysis of all patients who underwent OAT at Turku University Hospital from 1999 to 2007. Pre- and postoperative cartilage changes were estimated based on standardised radiographs. The extent of osteoarthritis (OA) was graded according to the Kellgren-Lawrence scale. Clinical outcomes were evaluated with the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire.RESULTS: A total of 60 patients (64 knees) with a median age of 30 years (range 14-62) were included. The median follow-up was 140 months (range 47-205). Of the 64 knees examined, 14 (22%) had a traumatic chondral lesion and 50 (78%) had osteochondritis dissecans (OCD). Preoperatively, 71% of the patients had Kellgren-Lawrence grades of 0-1; during the follow-up period, 50% of the patients showed radiographical progression of OA. OA progressed most significantly in patients with normal preoperative Kellgren-Lawrence grades (p = 0.0003). Patients with no progression in joint space narrowing had statistically significantly better overall KOOS (p = 0.02) than patients whose Kellgren-Lawrence grades worsened. Patients with defect sizes > 3.0 cm2 scored statistically significantly better in all subscales than patients with smaller defect sizes (p = 0.02). Patients with OCD had statistically significantly better KOOS than patients with chondral defects (p = 0.008).CONCLUSIONS: OAT surgery for treating patients with cartilage defects of the knee had good clinical results after a mean follow-up of 11 years. Radiological analyses revealed a progression of cartilage degeneration in 50% of the operated knees. Patients with no progression of the degenerative changes scored statistically significantly better on the KOOS self-assessment test. These results indicate that OAT surgery appears to be a reasonable therapeutic option to restore knee function in patients with cartilage lesions.LEVEL OF EVIDENCE: IV.

Rats were decapitated and the complete head stored at 4 degrees C. At various time intervals, up to a maximum of 14 days, the brains and pituitary glands were removed and fixed in formalin-picric acid. Neurosecretory material (NSM), as revealed with crotonaldehyde fuchsin, and neurophysin as demonstrated by means of immunoperoxidase histochemistry were localized in the hypothalamic magnocellular nuclei, median eminence and posterior pituitary gland. NSM and neurophysin were present in the paraventricular (PVN) and supra-optic (SON) nuceli up to periods of 14 days although the cellular morphology was disrupted after about 4 days. After 4 days there was an abundance of positive staining "droplets" in both the SON, PVN and along the nerve fibers of the supraoptico-neurohypophysial tract. Pituitary gland NSM and neurophysin were still present 14 days post mortem. The slab gradient polyacrylamide gel electrophoresis pattern of soluble proteins extracted from the posterior pituitary gland from the experimental and normal animals showed almost complete identity confirming the minimal action of proteolytic enzymes at 4 degrees C up to a period of 6 days. It is concluded that as long as the tissue is cooled, rapid fixation of hypothalamic tissue is not essential for the localization of NSM and neurophysin.

We report two unique cases of 50- and 28-year-old Turkish men with coincidence of conchachoanal polyp and mulberry hypertrophy of the inferior concha. We operated on both cases with endoscopic stripping of the polypoid tissue while preserving the periosteum and healthy mucosa of the inferior nasal concha. The polypoid tile of the left inferior nasal concha was resected in the case with mulberry hypertrophy at only the tail of the concha. Both cases reported significant relief of symptoms after the operations.

In order to evaluate the specific effects of blood volume pulse (BVP) biofeedback in the treatment of migraine headaches, 21 female migraine patients were randomly assigned to one of three experimental conditions: temporal artery constriction feedback, temporal artery dilation feedback, or waiting list. Biofeedback training consisted of 15 sessions over an 8-week period. All patients completed 5 weeks of daily self-monitoring of headache activity and medication before and after treatment. Results showed that constriction and dilation biofeedback were equally effective in controlling migraines and produced greater benefits than the waiting-list condition. No significant relationships were found between therapeutic gains and BVP self-regulation skills. However, further analyses revealed that changes in headache activity and medication were associated with changes in vasomotor variability. The current rationale for the use of BVP biofeedback in the treatment of migraine is questioned and a new one is proposed.

Proteins of the transferrin family play a key role in iron homeostasis through their extremely strong binding of iron, as Fe3+. They are nevertheless able to bind a surprisingly wide variety of other metal ions. To investigate how metal ions of different size, charge and coordination characteristics are accommodated, we have determined the crystal structure of human lactoferrin (Lf) complexed with Ce4+. The structure, refined at 2.2 A resolution (R=20.2%, Rfree=25.7%) shows that the two Ce4+ ions occupy essentially the same positions as do Fe3+, and that the overall protein structure is unchanged; the same closed structure is formed for Ce2Lf as for Fe2Lf. The larger metal ion is accommodated by small shifts in the protein ligands, made possible by the presence of water molecules adjacent to each binding site. The two Ce4+ sites are equally occupied, indicating that the known difference in the pH-dependent release of Ce4+ arises from a specific protonation event, possibly of the His ligand in one of the binding sites. Comparing the effects of binding Ce4+ with those for the binding of other metal ions, we conclude that the ability of transferrins to accommodate metal ions other than Fe3+ depends on an interplay of charge, size, coordination and geometrical preferences of the bound metal ion. However, it is the ability to accept the six-coordinate, approximately octahedral, site provided by the protein that is of greatest importance.

The objective of this study was to describe the messages about treatment decision-making on popular cancer web sites, with particular reference to gender differences. The two most popular UK based web sites for breast and prostate cancer were chosen. Qualitative and quantitative comparative content analysis of the two case study web sites were performed. Web site portrayals of treatment decision-making by men with prostate cancer emphasize the obligation to be decisive, using information derived from medical sources, with minimal consultation with families and friends. Portrayals of treatment decision-making by women with breast cancer emphasize their family obligations, their need to make decisions about matters other than treatment, their right to opt out of decision-making, to take time, sometimes change their minds, consult with families and friends, and thereby take non-medical factors into account. This study will help health care practitioners understand the different factors that men and women feel obliged to consider when making decisions about their cancer treatments, and the role of the Internet in reinforcing gender differences.

A simple pretreatment method with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated to simultaneously determine dichlorvos and phoxim in tobacco and soil matrices. Satisfactory linearity (R2  ? 0.9991) of the method was obtained for both analytes. The limits of detection and limits of quantification for dichlorvos and phoxim in three matrices were 0.0015-0.006 and 0.005-0.02 mg/kg, respectively. Average recoveries were 78.24-92.21% for dichlorvos and 76.62-100.51% for phoxim in soil, green tobacco leaves and cured tobacco leaves. The intra- and inter-day relative standard deviations were <6%. The established method was successfully applied for the residual analysis of dichlorvos and phoxim in real soil and tobacco samples. The results indicated that the established method could be used to detect trace amounts of dichlorvos and phoxim in tobacco. The data could also help the Chinese government establish maximum residue limits of dichlorvos and phoxim on tobacco and establish proper and safe use of dichlorvos and phoxim on tobacco plants in China.

Polymyositis/dermatomyositis (PM/DM) is an autoimmune disorder of unknown aetiology. In order to study whether immunoregulatory abnormalities might be involved in this autoimmune state, we investigated the autologous mixed lymphocyte reaction (AMLR) and concanavalin A-induced suppressor cell function (Con A-induced suppression) in adult patients with primary PM/DM. We found the AMLR to be significantly depressed in patients; responsiveness could not be enhanced by increasing the numbers of non-T stimulator cells in culture, nor by varying the day on which cultures were harvested. Con A-induced suppression of T cell proliferative responses to mitogenic stimuli was normal. These findings implicate abnormal immunoregulation in the pathophysiology of PM/DM. Further, the dissociation of AMLR reactivity from Con A-inducible suppression suggests that events important for immunoregulatory competence may occur in the AMLR culture, despite the absence of an observed proliferative response.

Cardiopulmonary bypass surgery induces an inflammatory reaction among others by activation of granulocytes. Leukocyte filtration has been shown to reduce the postoperative morbidity mediated by activated granulocytes. However, little is known about the mechanism of filter-leukocyte interaction. This study examines whether a leukocyte filter removes activated granulocytes or a general leukocyte population. Eleven patients undergoing cardiopulmonary bypass surgery were included in this study. Leukocyte filtration was achieved before the reperfusion phase with a Pall non-woven polyester filter located at the venous side of the heart-lung machine. After filtration, the trapped granulocytes inside the filter were examined morphologically with light and scanning electron microscopy and immunologically by CD45RO antigen binding to the filter material. Furthermore, leukocyte release markers were measured to determine whether cells were activated during filtration. Microscopic evaluation revealed 84% granulocytes and 14% lymphocytes trapped in the filter, compared with 78% granulocytes and 22% lymphocytes in the blood before filtration. Granulocytes were trapped significantly more in the first blood contact layer of the filter material than in the middle layer and last layer, whereas lymphocytes trapped slightly more in the middle layer. The near maximum level of CD45RO expression was measured on granulocytes trapped inside the filter material, whereas CD2 and CD19 measured on lymphocytes were bound to a minor extent. Beta-glucuronidase concentration did not increase after filtration, suggesting the absence of activation of granulocytes by filtration. A leukocyte filter made of non-woven polyester material removes the activated granulocytes rather than leukocytes at random. This implies that this particular type of leukocyte removal filter is suitable for use in cardiopulmonary bypass patients whose granulocytes in the circulation are activated. Furthermore, measurement of activated granulocytes instead of total leukocyte count is likely preferable for functional assessment of leukocyte removal devices.

Subject reports of efficacy of treatment of haemophilia-related joint bleeding are by definition subjective, yet are often the primary outcome in studies comparing therapies. Verbal descriptors such as effective, partially effective, poorly effective, not effective are treated as dichotomous or categorical variables in analyses, lowering the statistical power relative to that which might be achieved with a continuous variable. The aims of this study were to examine reports of pain recorded on a 100-mm visual analogue scale (VAS) during the course of joint bleeding; determine whether pain varied by treatment period among pairs reporting discordant outcomes on a verbal scale (one product effective, the other not effective); test whether the two products under study were equivalent with respect to VAS scores; and evaluate their relationship to verbal reports of efficacy. Data from the international, prospective, randomized, crossover FEIBA NovoSeven Comparative study of two bypassing agents used for treatment of 96 bleeding episodes in 48 participants were examined. VAS scores were associated with verbal descriptors of efficacy at every time point, and were equivalent between treatment periods. There were differences in mean scores at time points at which participants rated one treatment effective, the other not effective. As a continuous variable, the VAS score may have more power than a dichotomous variable and when used with verbal descriptions of efficacy can improve the overall accuracy of assessment. This report highlights an important consideration in the selection of outcome measurement that can be generalized to other haemophilia treatment research.

Narrow window width photography of magnetic resonance (MR) images of knee menisci is promoted as a useful tool in the detection of meniscal tears. To assess the diagnostic efficacy of this method, conventional and narrow window width MR images of 48 patients (96 menisci, 37 tears) were interpreted by two experienced observers. Images were graded on a five-point scale to enable receiver operating characteristic (ROC) curve analysis. The ROC curves constructed from the conventional window width interpretations were similar to those of the narrow window width interpretations for both observers. It was not possible to prove that the areas under the two curves were significantly different. This suggests that there is no globally significant improvement in the detection of meniscal tears when narrow window width images are used for interpretation.

BACKGROUND: Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. However, the role of ATF2 in renal cell carcinoma (RCC) remains unclear.METHODS: ATF2 knockdown and overexpression studies were performed in RCC cells to evaluate changes in cell viability, cell cycle, apoptosis, migration and invasion. Xenograft models were used to examine the tumorigenic and metastatic capability of RCC cells upon ATF2 suppression. The expression of ATF2 in human RCC samples was determined using immunohistochemistry on a tissue microarray.RESULTS: ATF2 knockdown in RCC cells reduced their proliferative and metastatic potentials, whereas ATF2 overexpression enhanced these properties. Mechanistic studies revealed that the transcription of CyclinB1, CyclinD1, Snail and Vimentin was directly regulated by ATF2 in RCC cells. Moreover, ATF2 was shown to be highly expressed in RCC tissues, especially in tumors with metastases. High expression of ATF2 correlated with aggressive clinico-pathological characteristics and predicted poor prognosis of RCC patients.CONCLUSIONS: ATF2 exerts an oncogenic role in RCC and could serve as an important prognostic biomarker.

HI-6 (1-2-hydroxyiminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino -2- oxapropane dichloride) has been evaluated as an oxime alternative to pralidoxime, and toxogonin in the treatment of organophosphorus (OP) poisoning. The dose response effects of atropine (ATR) and HI-6 were investigated to more fully explore the interaction of these compounds in the treatment of OP poisoning. ATR, HI-6 and various combinations of the two drugs were evaluated against lethal poisoning by soman (GD) and tabun (GA) in guinea pigs. The effect of adjunctive diazepam treatment on the efficacy of atropine and HI-6 against soman was also investigated. Animals of either sex were challenged s.c. with OP and treated i.m. 1 min later with ATR and/or HI-6. When used, diazepam was injected immediately after ATR+HI6. LD50s of each treatment were calculated from probit models based on 24-hour survival against 5 levels of nerve agent and 6 animals per challenge level. A protective index (PI) was calculated by dividing the nerve agent LD50 in the presence of treatment by the LD50 in the absence of treatment. Treatment with HI6 alone had little effect on the toxicity of either OP. Treatment with ATR alone was more effective than HI-6 alone and was significantly more effective against soman than against tabun. When used in combination atropine and HI-6 had a strong synergistic effect against both agents. The dose of atropine used with HI-6 was critical in determining the efficacy of HI-6 against either agent. The slopes of the dose-lethality curves were minimally affected by the dose of ATR or HI-6. Adjunctive treatment with diazepam enhanced the efficacy of HI-6 and atropine against soman. It is concluded that 1) ATR has a large effect on the efficacy of HI-6 against OP poisoning, 2) the dose of ATR must be carefully selected in studies investigating the efficacy of HI-6 against OP poisoning, 3) the effective dose of ATR in the guinea pig is approximately 16 mg/kg, and 4) diazepam is a useful adjunct to atropine and HI-6.

OBJECTIVE: To analyze the effect of drain placement on postoperative hematoma formation and other associated outcomes post-thyroid surgery in a large national cohort.METHODS: This was a retrospective study that analyzed data from the 2016-2017 National Surgical Quality Improvement Program (NSQIP) public use files. Baseline characteristics and perioperative outcomes were compared between drain and no drain cohorts.RESULTS: A total of 11,626 patients were included; 3281 had a drain placed intraoperatively and 8345 did not. Otolaryngologists were 6.98 times more likely to place a drain after thyroidectomy than general surgeons (P < .001), and patients undergoing subtotal or total thyroidectomy were 2.17 times more likely to have a drain placed than if undergoing partial thyroidectomy (P < .001). Drain placement did not reduce hematoma formation on both univariate and multivariate analyses (adjusted OR = 0.93, P = .696). A slightly larger proportion of patients underwent unplanned intubation postoperatively among those who had a drain placed (0.76% vs. 0.29%, P < .001). Patients who received a drain were on average 4.63 times as likely to remain in the hospital for 2 or more days compared to those who did not receive a drain.CONCLUSION: Drain placement did not significantly affect postoperative hematoma formation following thyroidectomy. Drain placement should not be routinely employed in these patients. However, surgeon judgement and intraoperative considerations should be taken into account, as to when to place a drain.LEVEL OF EVIDENCE: N/A Laryngoscope, 130:1349-1356, 2020.

CuI/L-proline-catalyzed coupling of 2-halotrifluoroacetanilides with pyrrole-2-carboxylate esters in DMSO at 80-90 degrees C followed by in situ hydrolysis at 60 degrees C afforded pyrrolo[1,2-a]quinoxalines. Indole-2-carboxylate esters underwent the same process smoothly to provide the corresponding tetracyclic products.

The effect of regulatory system on the engineered biosynthetic pathway in chassis cells remains incompletely understood in microorganisms. Acyl-CoAs function as key precursors for the biosynthesis of various natural products and the dominant donors for protein acylation. The polyphenol pinosylvin, with high antimicrobial and antifungal activities, is biosynthesized with malonyl-CoA as its direct precursors. But correlation between lysine malonylation and pinosylvin biosynthesis remains unknown. Herein, we found that the malonyl-CoA-driven lysine malonylation plays an important role in interaction between the engineered pathway of pinosylvin synthesis and E. coli chassis cell. Oversupply of malonyl-CoA leads to an increase in malonylation level of global proteome as well as the enzymes in the artificial pathway, thereby decreasing yield of pinosylvin. The results revealed that the intricate balance of cellular acyl-CoA concentrations is critical for the yields of acyl-CoA-derived natural products. We next modified the enzymes in the biosynthetic pathway to adjust their acylation level and successfully improved the yield of pinosylvin. Our study uncovers the effect of protein acylation on the biosynthetic pathway, helps optimization of synthetic constructs, and provides new strategies in metabolic engineering and synthetic biology at the protein post-translational level.

The influence of individual lifestyle factors is widely described in studies on semen quality. However, their synergistic effect is often neglected. The aim of the study was to examine the association between semen quality and dietary approaches to stop hypertension (DASH) diet, physical activity (PA), and the two separately and in combination. A cross-sectional study was carried out among 207 men aged 20-55. Dietary data were collected by a food frequency questionnaire (FFQ) and analysed according to the DASH scoring index. Physical activity was evaluated by the International Physical Activity Questionnaire. Semen parameters were assessed via the computer-aided semen analysis (CASA). Adherence to the DASH diet was associated with higher sperm count (ÄT3-T1 = 82.1 mln/ej) and concentration (ÄT3-T1 = 24.6 mln/mL). Higher PA was related to higher sperm count (ÄT3-T1 = 69.4 mln/ej), total (ÄT3-T1 = 11.9%), and progressive motility (ÄT3-T1 = 8.5%) and morphology (ÄT3-T1 = 2.8%) in the crude model and remained significant after adjustment. The combination of the DASH diet and PA, was significantly positively associated with sperm count (ÄT3-T1 = 98.1 mln/ej), sperm concentration (ÄT3-T1 = 17.5 mln/mL), total (ÄT3-T1 = 11.8%), and progressive motility (ÄT3-T1 = 10.0%) and morphology (ÄT3-T1 = 3.3%) in both models. Adherence to the DASH diet was related to higher sperm count and concentration, whereas after its combination with physical activity it was also positively correlated with sperm motility and morphology.

Endothelial dysfunction (ED) has been suggested as a possible causal link between postprandial hyperglycemia and cardiovascular events in patients with type 2 diabetes. Recent trials demonstrated a reduction of cardiovascular events by treatment with alpha-glucosidase inhibitor acarbose - a drug which mainly reduces postprandial glucose excursions. We were interested to know whether patients with newly diagnosed type 2 diabetes showed postprandial ED and if so whether acarbose was able to improve this condition. Forearm blood flow (FBF) measurements for assessment of ED were performed in the fasting and postprandial state in 20 newly diagnosed type 2 diabetic patients and 10 healthy control subjects. After baseline examination, patients were randomly assigned to a 20-week treatment of acarbose 100 mg t.i.d or matching placebo, thereafter FBF measurements were repeated. FBF of patients in the fasting state was significantly impaired compared to healthy control subjects (max. FBF 5.3+/-0.7 vs. 8.0+/-0.9 ml/100 ml, p<0.02) and did not change in the postprandial state (max. FBF 5.6+/-0.7 ml/100 ml). In contrast, healthy controls showed a significant improvement of FBF in the postprandial state (11.5+/-1.2 ml/100 ml), which is compatible with postprandial ED in the group of patients. Twenty weeks of acarbose treatment did not affect either fasting or postprandial FBF in patients. Early type 2 diabetes is a state of both fasting and postprandial ED, which is not sensitive to acarbose treatment. Protective cardiovascular effects of acarbose might involve other mechanisms.

This paper deals with the results of the first-field use in the Balkans, i.e. Serbia and Republic of Srpska (Bosnia and Hercegovina), of a passive polycarbonate Mark II type and poliallyldiglycol carbonate (Cr-39) alpha track detectors sensitive to thoron as well as to radon. Both types of solid state nuclear track detectors were designed and supplied by National Institute of Radiological Sciences (NIRS), Chiba, Japan. The commercial names for these detectors which all have been field tested in Balkan rural communities are known as: UFO and RADUET passive discriminative radon/thoron detectors. No database of thoron and thoron progeny concentrations in dwellings in Serbia or Balkans region exist, and as a result, the level of exposure of the Serbian population to thoron and its progeny is unknown so far.

Although microRNA (miRNA) enclosed in exosomes can mediate intercellular communication, the roles of exosomal miRNA and angiogenesis in lung cancer remain unclear. We investigated functions of STAT3-regulated exosomal miR-21 derived from cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells in the angiogenesis of CSE-induced carcinogenesis. miR-21 levels in serum were higher in smokers than those in non-smokers. The medium from transformed HBE cells promoted miR-21 levels in normal HBE cells and angiogenesis of human umbilical vein endothelial cells (HUVEC). Transformed cells transferred miR-21 into normal HBE cells via exosomes. Knockdown of STAT3 reduced miR-21 levels in exosomes derived from transformed HBE cells, which blocked the angiogenesis. Exosomes derived from transformed HBE cells elevated levels of vascular endothelial growth factor (VEGF) in HBE cells and thereby promoted angiogenesis in HUVEC cells. Inhibition of exosomal miR-21, however, decreased VEGF levels in recipient cells, which blocked exosome-induced angiogenesis. Thus, miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of HBE cells. These results, demonstrating the function of exosomal miR-21 from transformed HBE cells, provide a new perspective for intervention strategies to prevent carcinogenesis of lung cancer.

Prokaryote-expressed polyomavirus structural protein VP1 with an N-terminal glutathione-S-transferase tag (GST-VP1) self-assembles into pentamer structures that further organize into soluble aggregates of variable size (3.4 x 10(2)-1.8 x 10(4)kDa) [D.I. Lipin, L.H.L. Lua, A.P.J. Middelberg, J. Chromatogr. A 1190 (2008) 204]. The adsorption mechanism for the full range of GST-VP1 soluble aggregates was described assuming a dual-component model [T.Y. Gu, G.J. Tsai, G.T. Tsao, AICHE J. 37 (1991) 1333], with components differentiated by size, and hence pore accessibility, rather than by protein identity. GST-VP1 protein was separated into two component groups: aggregates small enough to access resin pores (LMW: 3.4 x 10(2)-1.4 x 10(3)kDa) and aggregates excluded from the resin pores (HMW: 9.0 x 10(2)-1.8 x 10(4)kDa). LMW aggregates bound to resin at a higher saturation concentration (29.7 g L(-1)) than HMW aggregates (13.3 g L(-1)), while the rate of adsorption of HMW aggregates was an order of magnitude higher than for LMW aggregates. The model was used to predict both batch and packed bed adsorption of GST-VP1 protein in solutions with known concentrations of HMW and LMW aggregates to Glutathione Sepharose HP resin. Asymmetrical flow field flow fractionation with UV absorbance was utilized in conjunction with adsorption experimentation to show that binding of HMW aggregates to the resin was strong enough to withstand model-predicted displacement by LMW aggregates. High pore concentrations of LMW aggregates were also found to significantly inhibit the diffusion rate of further protein in the resin pores. Additional downstream processing experimentation showed that enzymatic cleavage of LMW aggregates to remove GST tags yields more un-aggregated VP1 pentamers than enzymatic cleavage of HMW aggregates. This model can be used to enhance the chromatographic capture of GST-VP1, and suggests an approach for modeling chromatographic purification of proteins that have a range of quaternary structures, including soluble aggregates.

Little is known about healing or recurrence of aspirin-induced gastric ulcers if aspirin intake is continued. A double-blind controlled study compared cimetidine plus antacids as needed (prn) with placebo plus prn antacids in healing aspirin-associated gastric ulcers during continued salicylate ingestion in 18 rheumatic disease patients over a 2-month period. Healing occurred in 44% of the placebo and 56% of the cimetidine-treated patients (P greater than 0.05). Subjects in both groups ingested potentially therapeutic doses of antacid. Ulcer size had an effect on healing rate, irrespective of treatment. Ninety percent of gastric ulcers less than 0.5 cm in diameter healed in 2 months but only 25% of ulcers greater than 0.5 cm. Six of seven patients with unhealed ulcers at 2 months eventually healed medically at intervals of 6--26 months. Of 11 patients managed medically and followed endoscopically for a mean of 15 months after healing, only one had a recurrent ulcer. In conclusion, placebo and antacid therapy were as effective as cimetidine and antacids in healing ulcers over a 2-month period. In spite of continued aspirin intake, most benign gastric ulcers less than 0.5 cm in diameter heal medically in two months. Aspirin-induced ulcers greater than or equal to 1 cm in diameter are relatively resistant to therapy but can be healed with prolonged cimetidine and antacid treatment; once healed, recurrence rate is low with prophylactic therapy even with continued aspirin intake.

INrf2 tethering of the transcription factor Nrf2 in the cytosol prevents Nrf2 activation of antioxidant response element (ARE) mediated gene expression. This investigation was undertaken to determine if tethering affected Nrf2 degradation. Data is presented showing that Nrf2 is degraded by the ubiquitin-proteasome pathway. Nrf2 co-immunoprecipitated with a HA tagged ubiquitin polymer and accumulated in cells expressing inactive ubiquitin activating enzyme El. Inhibition of proteasome activity resulted in accumulation of Nrf2. The rate of Nrf2 degradation, measured under conditions where the majority of Nrf2 was not tethered, exhibited a T(1/2) of approximately 3 h. Over-expression of human INrf2, KIAA0132, blocked Nrf2 conjugation to the ubiquitin polymer and blocked Nrf2 degradation. These results suggest that association of Nrf2 with INrf2 inhibits ubiquitin-proteasome degradation of Nrf2. Maintaining the majority of Nrf2 in a tethered form, resistant to ubiquitin-proteasome dependent degradation, allows a pool of Nrf2 to be available for rapid Nrf2/ARE-dependent gene transcription following stress mediated release from INrf2. Further, the observation that free Nrf2 is degraded by the ubiquitin proteasome pathway provides a potential mechanism by which ARE-dependent gene transcription is attenuated after induction.

Complement component C3 was investigated in sera of a group of schistosomal patients free from obvious nephritis. C3 was studied in relation to S. mansoni egg count, presence of HBsAg, and liver functions. C3 level was low in schistosomal patients than normal individuals. Levels were low in both HBsAg --ve and HBsAG +ve schistosomal patients. No significant difference was found between HBsAg --ve and HBsAg +ve in one hand, and between patients with egg counts more than 400 and those with egg counts less than 400 eggs/1 gr as regards level of C3 on the other hand. Presence of ascites did not affect C3 concentration. Positive correlation was found with Serum albumin, but not with prothrombin concentration serum alkaline phosphatase or serum transaminases.

INTRODUCTION: The purpose of this study was to investigate the method of canal negotiation in the presence of differently C-shaped orifices using the micro-computed tomography technique.METHODS: Forty-four extracted mandibular second molars with C-shaped roots were collected from a Chinese population. Size 10 or 15 K files were used to explore the canal orifices when viewed under the surgical operating microscope. Choices in the number and position of the files inserted into the canal system were based on the different orifice shape. After the teeth with files were scanned and reconstructed, the number and position of the files were analyzed.RESULTS: Among 44 teeth, a total of 132 initial files were inserted into 83 orifices, in which 42 orifices had only one initial file, 33 with two, and 8 orifices had three files inserted. Eight main canals were not located because of canal bifurcations in the root, calcification, and dentin fusion.CONCLUSION: This new method for negotiation combined with careful exploration may provide an effective way for indentifying the nature of the canal system and enhancing debridement in these complex canal anatomies.

Among HLA-DP specificities, HLA-DP4 specificity involves at least two molecules, HLA-DPA1*0103/DPB1*0401 (DP401) and HLA-DPA1*0103/DPB1*0402 (DP402), which differ from each other by only three residues. Together, they are present worldwide at an allelic frequency of 20-60% and are the most abundant human HLA II alleles. Strikingly, the peptide-binding specificities of these molecules have never been investigated. Hence, in this study, we report the peptide-binding motifs of both molecules. We first set up a binding assay specific for the immunopurified HLA-DP4 molecules. Using multiple sets of synthetic peptides, we successfully defined the amino acid preferences of the anchor residues. With these assays, we were also able to identify new peptide ligands from allergens and viral and tumor Ags. DP401 and DP402 exhibit very similar patterns of recognition in agreement with molecular modeling of the complexes. Pockets P1 and P6 accommodate the main anchor residues and interestingly contain only two polymorphic residues, beta86 and beta11, respectively. Both positions are almost dimorphic and thus produce a limited number of pocket combinations. Taken together, our results support the existence of three main binding supertypes among HLA-DP molecules and should significantly contribute to the identification of universal epitopes to be used in peptide-based vaccines for cancer, as well as for allergic or infectious diseases.

CD4+ T lymphocyte responses are thought to play a major role in control of the hepatitis C virus (HCV). Few, however, have been mapped down to the level of peptide and HLA restriction. Furthermore, the ability of such T cells to respond to viruses which differ in genotype has not been addressed in detail. In most cases of persistent infection with HCV, CD4 proliferative responses are weak or absent. From a large cohort of persistently infected patients, we identified an individual with unusually robust and persistent responses in the face of chronic infection. We firstly mapped two peptide epitopes to regions of the nonstructural protein NS4 (aa1686-1705 and aa 1746-1765). However, in contrast to the genotype 1a derived antigens used for mapping, the infecting virus was identified as genotype 3a. Strikingly, the patient's CD4 response to these epitopes were specific only for the genotype 1a sequence, and did not recognize genotype 3a synthetic peptides. Serologic assays indicated that prior exposure to HCV of genotype 1 had occurred. This patient therefore maintains strong CD4 proliferative responses which are genotype specific and not cross-reactive. The apparent 'misdirection' of these nonprotective responses has important implications for the role of natural and vaccine induced CD4 responses in the face of variable viruses.

Gastrointestinal bleeding is a common cause of hospitalisation. In most patients, the origin and location of bleeding can be established in routine endoscopic and radiological examinations. The undiagnosed cases of so-called gastrointestinal bleeding of unknown origin require more sophisticated diagnostic methods. We present a case of 35-year old man with recurrent gastrointestinal bleeding due to a gastrointestinal stromal tumor of the jejunum that was revealed in the visceral angiography.

The regulation of the 2-oxoglutarate dehydrogenase complex is central to intramitochondrial energy metabolism. In the present study, the active full-length E1 subunit of the human complex has been expressed and shown to be regulated by Ca2+, adenine nucleotides and NADH, with NADH exerting a major influence on the K0.5 value for Ca2+. We investigated two potential Ca2+-binding sites on E1, which we term site 1 (D114ADLD) and site 2 (E139SDLD). Comparison of sequences from vertebrates with those from Ca2+-insensitive non-vertebrate complexes suggest that site 1 may be the more important. Consistent with this view, a mutated form of E1, D114A, shows a 6-fold decrease in sensitivity for Ca2+, whereas variant ?site1 (in which the sequence of site 1 is replaced by A114AALA) exhibits an almost complete loss of Ca2+ activation. Variant ?site2 (in which the sequence is replaced with A139SALA) shows no measurable change in Ca2+ sensitivity. We conclude that site 1, but not site 2, forms part of a regulatory Ca2+-binding site, which is distinct from other previously described Ca2+-binding sites.

BACKGROUND: Questions remain regarding the sustainment of evidence-based practices following implementation. The present study examined the sustainment of community clinicians' implementation (i.e., penetration) of cognitive-behavioral therapy, attitudes toward evidence-based practices, and knowledge of cognitive-behavioral therapy for youth anxiety two years following training and consultation in cognitive-behavioral therapy for youth anxiety.METHODS: Of the original 115 participants, 50 individuals (43%) participated in the two-year follow-up. A t- test examined sustainment in penetration over time. Hierarchical linear modeling examined sustainment in knowledge and attitudes over time. Time spent in consultation sessions was examined as a potential moderator of the change in knowledge and attitudes.RESULTS: Findings indicated sustained self-reported penetration of cognitive-behavioral therapy for anxious youth, with low fidelity to some key CBT components (i.e., exposure tasks). Follow-up knowledge was higher than at baseline but lower than it had been immediately following the consultation phase of the study. Belief in the utility of evidence-based practices was sustained. Willingness to implement an evidence-based practice if required to do so, appeal of evidence-based practices, and openness toward evidence-based practices were not sustained. Participation in consultation positively moderated changes in knowledge and some attitudes.CONCLUSIONS: Sustainment varied depending on the outcome examined. Generally, greater participation in consultation predicted greater sustainment. Implications for future training include higher dosages of consultation.

Racemic 5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT), a potent and selective dopamine (DA) D2-receptor agonist, was resolved into the enantiomers by a new method. The enantiomers of 5-OH DPAT were determined by chiral ion-pair chromatography using N-benzyloxycarbonylglycyl-L-proline as the counter ion. The enantiomeric purity of (R)-5-OH DPAT was found to be greater than 99.7%. The ability of the enantiomers to change the rat brain DOPA levels was evaluated in vivo. The results indicate that (R)-5-OH DPAT is a weakly potent DA D2-receptor antagonist.

The preeminence of science in the United States is endangered for multiple reasons, including mediocre achievement in science education by secondary school students. A group of scientists at Oregon Health and Science University has established a class to teach the process of scientific inquiry to local high school students. Prominent aspects of the class include pairing of the student with a mentor; use of a journal club format; preparation of a referenced, hypothesis driven research proposal; and a "hands-on" laboratory experience. A survey of our graduates found that 73% were planning careers in health or science. In comparison to conventional science classes, including chemistry, biology, and algebra, our students were 7 times more likely to rank the scientific inquiry class as influencing career or life choices. Medical schools should make research opportunities widely available to teenagers because this experience dramatically affects one's attitude toward science and the likelihood that a student will pursue a career in science or medicine. A federal initiative could facilitate student opportunities to pursue research.

Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF-beta's ability to bind to the cell, and not by any effect of suramin on the TGF-beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it.

This paper analyses the behavior of different density functionals in the description of the most stable structures of Cu(2+)-(H(2)O)(n) complexes (n = 1-6). From n = 3 to n = 6, different coordination numbers of the metal cation were considered. The structures and energies of the complexes were theoretically determined by means of density functional methods that include different amounts of exact exchange: the BLYP functional (0% of exact exchange), the B3LYP functional (20% of exact exchange), the MPWB1K functional (44% of exact exchange), and BHLYP functional (50% of exact exchange). In addition, CCSD(T) calculations with a large basis set were carried out. It has been found that the functionals with lesser amount of exact exchange, especially BLYP, fail to describe the relative energies between the different structures of each cluster because these functionals tend to overestimate the stability of low-coordinated structures. The inclusion of the exact exchange into the functional improves the results, those obtained with MPWB1K and BHLYP being in very good agreement with the CCSD(T) ones. This behavior is related to the poor description of the second ionization energy of Cu by pure functionals, which leads to a too delocalized spin density in the complex with GGA functionals.

Water, sand, and sediment from a Lake Superior harbor site continuously receiving wastewater effluent was sampled monthly for June to October 2010 and from May to September 2011. Understanding the dynamics of genetic markers of fecal bacteria in these matrices is essential to accurately characterizing health risks. Genetic markers for enterococci, total Bacteroides, and human-associated Bacteroides were measured in site-water, sand, and sediment and in final effluent by quantitative PCR. The similarity between the quantity of molecular markers in the water column and effluent indicated that the abundance of genetic markers in the water column was likely controlled by effluent inputs. Effluent turbidity was positively correlated (p ? 0.05) with AllBac and HF183 in final effluent and AllBac in the water column. In sand and sediment, Entero1 and AllBac were most abundant in the upper 1-3 cm depths, whereas HF183 was most abundant in the upper 1 cm of sand and at 7 cm in sediment. The AllBac and Entero1 markers were 1- and 2-orders of magnitude more abundant in sand and sediment relative to the water column per unit mass. These results indicate that sand and sediment may act as reservoirs for genetic markers of fecal pollution at some freshwater sites.

The objective of this analysis was to identify variables that predict the initiation of smoking among adolescents, and the development of susceptibility to smoking, over a 2-year period. We assessed variables that might predict later smoking among nonsmoking students in grades 7 and 9 and assessed their smoking status 2 years later, when they were in grades 9 and 11, thus receiving data from 4,130 students at two time points. Initiation of weekly smoking over the 2 years was associated with having a parent, sibling, or close friend who smokes; low school grades; higher levels of deviant behavior; susceptibility to smoking; use of smokeless tobacco; and for 7th graders, perception of higher levels of normative smoking. Susceptibility, defined as not being able to rule out the idea of smoking a year after the survey, was identified as a strong predictor of smoking and a valuable intermediary measure. We also assessed factors associated with the prediction of susceptibility 2 years post-test. Susceptibility to smoking was associated with deviant behavior, low grades, lower parental monitoring, relaxed parental attitude toward youth smoking, ease of access to tobacco, and lower exposure to anti-tobacco messages. This study provides support for the idea that susceptibility to smoking could be a useful outcome variable for tobacco research, as an intermediary to the initiation of smoking. In addition, evidence indicates that theoretically manipulable variables, including access to tobacco and exposure to anti-tobacco information, have the potential to influence susceptibility to smoking over a time.

Psychometric functions for the S omicron N omicron and S pi N omicron conditions and masking level differences were obtained for a subgroup of 10 words having the largest masking-level differences of 36 CID W-1 spondaic words. The mean masking-level difference obtained from 36 young normal adults was 9.4 dB with a standard deviation of 1.2 dB. The smallest masking-level difference of 7.4 dB was suggested as the low cut-off for normalcy. A shorter version of the masking-level difference procedure was suggested for clinical implementation. The subgroup of 10 words may permit a wider separation between normal and abnormal performance, and thus may enhance the clinical utility of the masking-level difference task for speech recognition. Because the magnitude of the masking-level difference will vary with the materials and procedures used, each clinic must establish its own norms.

Hybrid QM/MM molecular dynamics simulations have been carried out for the Watson-Crick base pair of 9-ethyl-8-phenyladenine and 1-cyclohexyluracil in deuterochloroform solution at room temperature. Trajectories are analyzed paying special attention to the geometric correlations within the N-HN and N-HO hydrogen bonds in the base pair. Even though the two hydrogen bonds are only approximately linear and the heterocycles are tilted with respect to each other, hydrogen bond and N-H lengths follow a simple empirical correlation based on Pauling's valence bond order model. In order to describe the IR line shape of the two NH-stretching vibrations, the correlation between their fundamental transition frequencies and the hydrogen bond lengths is exploited. This facilitates efficient evaluation of the fluctuating transition frequencies along the QM/MM trajectory which allows the determination of the line shape function.

Apoptosis-associated speck-like protein (ASC) is an adaptor molecule of caspase-1 activation that stimulates the secretion of multiple pro-inflammatory cytokines. We investigated the regulatory effects of ASC in the P388D1 macrophage-like cell line. Data showed that ASC overexpression induced by pEGFP-ASC-C2 transfection significantly increased caspase-1 expression and interleukin (IL)-1â and IL-6 secretion, but did not affect tumor necrosis factor (TNF)-á secretion. However, siRNA against ASC significantly decreased the caspase-1 expression and IL-1â and IL-6 secretion, but did not affect TNF-á secretion in the P388D1 cells. We suggest that ASC acts as an inflammatory response-associated gene by regulating caspase-1 activation and IL-1â and IL-6 secretion, which may correlate with its biological effects.

Mixed-effects models are increasingly used in many areas of applied science. Despite their popularity, there is virtually no systematic approach for examining the homogeneity of the random-effects covariance structure commonly assumed for such models. We propose two tests for evaluating the homogeneity of the covariance structure assumption across subjects: one is based on the covariance matrices computed from the fitted model and the other is based on the empirical variation computed from the estimated random effects. We used simulation studies to compare performances of the two tests for detecting violations of the homogeneity assumption in the mixed-effects models and showed that they were able to identify abnormal clusters of subjects with dissimilar random-effects covariance structures; in particular, their removal from the fitted model might change the signs and the magnitudes of important predictors in the analysis. In a case study, we applied our proposed tests to a longitudinal cohort study of rheumatoid arthritis patients and compared their abilities to ascertain whether the assumption of covariance homogeneity for subject-specific random effects holds.

Background: The characterization of hepatic metastases as having neuroendocrine origins is essential and the main markers currently used are chromogranin A (CgA) and synaptophysin (Syn). However, these markers may exhibit certain limitations, and the use of CD56 and CD57 can also be considered, although, due to low specificity, their use is discouraged.Aim: This study sought to compare the immunohistochemical expression of these markers in hepatic metastases of neuroendocrine neoplasms (NEN).Materials and Methods: Eighteen samples, were used for immunohistochemical staining with CgA, Syn, CD56, and CD57 antibodies. The immunostaining reactions were compared according to its intensity (I), the percentage of labeled cells (P), and a final score (I ? P). Statistical agreement between the markers was also evaluated.Results: CD57 was expressed in the highest number of cases and also showed the most intense expression. CgA showed the highest number of cases with more than 80% positively stained area (72.2%), followed by CD57 (61.1%). The highest average score (I ? P) was obtained for CD57 (9.1 ± 4.1). The best indices of agreement were between CgA and CD57 with respect to positivity (P = 0.021) and score (P = 0.014). According to the primary site, stomach/duodenum, lungs, and undetermined subgroups showed the highest average scores for CD57, followed by CgA. For the small bowel subgroup, the highest average score was obtained for CgA, followed by CD57.Conclusion: Our results highlight the importance of CD57 in the evaluation of hepatic metastases of NEN and indicate that this marker should be included with CgA and Syn in routine diagnostic panels.

Live performance, bone health and metabolic responses to the interaction among stocking density and dietary concentrations of total calcium (TCa) and non-phytate phosphorus (NPP) were determined on 2,232 Ross 308 female broilers over a 3-wk experimental period. From 22 d of age, birds were randomly divided into 48 groups and provided with different corn-soybean meal-based diets varying in TCa (0.70% or 0.90%) and NPP (0.28% or 0.36%) content at 1 of 2 stocking densities [28.6 (LSD, 13 broilers/m2) and 39.6 (HSD, 18 broilers/m2) kg of predicted final BW/m2 floor space], according to a 2 ? 2 ? 2 factorial design with 6 replications in each treatment. Regardless of NPP supplementation, a high-TCa (0.90%) diet aggravated the impact of HSD on growth (BW gain and feed efficiency, P < 0.001) and motility (gait score, P < 0.001). This might be explained by deteriorating tibia quality (relative weight, mineral composition and biomechanical property; P < 0.01), due to the involvement of decreasing duodenal absorption (type IIb sodium-phosphate co-transporter mRNA, P < 0.001) in reduced phosphorus retention (P < 0.001). On the contrary, increasing dietary NPP (0.36%), particularly if high in TCa (0.90%), boosted TCa retention (P < 0.05) by improving absorption (calcium-binding protein D28k transcription, P < 0.05) for LSD chickens, hence enhancing bone development (relative tibia weight and tibia breaking strength, P < 0.05) and leg health (walking ability, P < 0.05). Together, HSD and LSD birds show an impaired TCa tolerance and a higher TCa+NPP threshold, respectively, to allow the optimization of bone quality via altered intestinal absorption.

BACKGROUND AND OBJECTIVE: To show that sclerostomy, a glaucoma filtering surgery, can be performed using an Er:YAG laser. Scarring at the filtering site, a recurrent problem, may be reduced through proper positioning of the sclerostomy by using an intraocular endoscope.MATERIALS AND METHODS: Ab interno full-thickness sclerostomies were performed on eye bank eyes with an Er:YAG laser through a custom made optical delivery system. The intraocular laser probe consisted of a low OH silica fiber inserted in a metallic tapered sheathing. A rigid intraocular endoscope based on gradient-index lenses allowed visualization of the filtration site.RESULTS: A clear view of the anterior chamber angle was obtained through the endoscope, allowing for precise location of the sclerostomy. Full-thickness sclerostomies could then be performed at the desired location. Histologic sections showed thermal necrosis less than 50 microm thick in tissue adjacent to the sclerostomy.CONCLUSIONS: A sclerostomy performed with a combined procedure using an Er:YAG laser and intraocular endoscopy increases the speed of the procedure. The use of a high-resolution intraocular endoscope may increase the success rate of ab interno laser glaucoma surgeries.

An immunosensor using a long-period grating (LPG) was used for sensitive detection of antibody-antigen reactions. Goat anti-human IgG (antibody) was immobilized on the surface of the LPG, and detection of specific antibody-antigen binding was investigated. This sensor operates using total internal reflection where an evanescent field interacts with bound antibody immobilized over the grating region. The reaction between antibody and antigen altered the LPG transmission spectrum and was monitored in real time as a change in refractive index, thereby eliminating the need for labeling antigen molecules. Human IgG binding was observed to be concentration dependent over a range of 2-100 microg mL-1, and equilibrium bound antigen levels could be attained in approximately 5 min using an initial rate determination. Binding specificity was confirmed using human interleukin-2 and bovine serum albumin as controls, and nonspecific adsorption of proteins did not significantly interfere with detection of binding. Antigen detection in a heterogeneous protein mixture and in crude cell lysate from Escherichia coli was also confirmed. Moreover, regeneration of the LPG surface via diethylamine treatment resulted in approximately 80% removal of bound antigen. Subsequently, fibers reexposed to antigen retained greater than 85% of the initial signal after five consecutive regeneration cycles.

There is a significant difference in the collaborative process between whether a public health nursing research project is requested (of the researchers) by the agency or if it is conceived by an outside investigator. This article discusses the underlying concepts of negotiation, mutuality, and respect that support the process of an externally initiated study in an agency. In a progressive listing format, the important components within the planning, development, implementation, and completion phases are then described so that they can be useful to beginning researchers as a guide and to experienced researchers as a reminder.

There are three known criteria that underlie drug reimbursement decisions: therapeutic value, cost effectiveness and burden of disease. However, evidence from recent reimbursement decisions in several jurisdictions points to residual unexplained variables, one of which may be budget impact. An economic rationale for carrying out budget impact analyses is opportunity cost, measured by the economic benefits foregone by using resources in one way rather than another. Under certain assumptions, cost-effectiveness analysis accounts for opportunity cost while conveying to the decision maker the price of maximising health gains, subject to a budget constraint. However, the underlying assumptions are implausible, particularly in the context of pharmaceutical care. Although drugs that are cost effective may lead to unambiguous health gains among patient groups for whom the drugs are indicated, the opportunity costs could conceivably lead to a reduction in aggregate health gains, or failure to meet different kinds of equity considerations. The pertinent policy question is where to find the resources to fund new innovations, such as cost-effective pharmaceuticals, or drugs targeting severe diseases. It may be a matter of redeployment of resources across healthcare sectors, cancelling the funding of (older) pharmaceuticals that are less cost effective, or delisting drugs that are cost effective but target less burdensome conditions.

OBJECTIVE: To prepare a novel apatite-wollastonite bioactive glass-ceramic-calcium sulphate hemihydrate(AW-BGC-CSH) composite, to study its biocompatibility, and to provide experimental support for its further clinical application.METHODS: Samples of AW-BGC-CSH composite were prepared with different AW-BGC granules-CSH ratios (50%, 40%, 30%, 20%). Surface morphology, microstructure and mechanical features of the composite were measured. Osteoblasts were cultivated in vitro on the composite. Cell morphology, proliferation, and the alkaline phosphatase (ALP) activity of osteoblasts were examined to determine the biocompatibility of the composite.RESULTS: The composite showed a three-dimensional pored structure with communicated micropores under scanning electron microscopy (SEM). The plasticity of the composite could be maintained within 3 - 5 min. Its top solidification temperature was 36.4°C and the maximum compressive strength was 9.3 MPa. The osteoblasts adhered to the composite and grew well. At 1, 3, 5, 7 d after cultivated, the microprotein contents of the composite were (251 ± 12), (296 ± 31), (580 ± 13) and (571 ± 15) mg/L, and the ALP activity of the composite were (4.50 ± 0.68), (6.90 ± 0.27), (12.05 ± 0.28) and (11.86 ± 0.63) U/mg. The results of the ALP activity and microprotein contents in the experiment group were significantly higher than those in the control group (P < 0.05).CONCLUSIONS: The prepared AW-BGC-CSH composite has a three-dimensional pored structure, favourable plasticity, mechanical property and good biocompatibility.

OBJECTIVES: To describe the distribution of pure-tone hearing thresholds of a Caucasian population living in the south of France aged 70 years and older. To establish age- and sex-adjusted normative hearing thresholds based on results of subjects free of noise and ototoxic drug exposure and to compare them with hearing thresholds of exposed (E) subjects.DESIGN: Cross-sectional analysis of a longitudinal epidemiologic cohort study.SETTING: Montpellier suburb, south of France.PARTICIPANTS: A total of 778 subjects 70 years old and older were examined. Noise exposure, ototoxic medication use, and medical history were collected. Hearing thresholds were obtained via pure-tone audiometry. After excluding patients with ear-related disease, 659 subjects were further analyzed (270 men and 389 women). Noise or ototoxic medication exposure was found in 364 subjects (E subjects), whereas 295 had no exposure (nonexposed [NE] subjects).METHODS: Median pure-tone thresholds, lower deviation, and upper deviation were calculated for the NE subjects with a statistical method similar to the ISO 7029 norm and were compared with thresholds of E subjects.RESULTS: Hearing thresholds, especially in high frequencies, increased with age more for women than for men. Median thresholds of E subjects were significantly higher than those for the NE sample in men.CONCLUSION: Age- and sex-adjusted hearing thresholds could well be useful in the study of the impact of environmental and genetic factors on hearing loss in the elderly. The next step would be to quantify the impact of noise, ototoxic drug exposure, and genetics using these age- and sex-adjusted thresholds.