MMG-EMG cross spectrum and muscle fiber type.
The purpose of this study was to investigate fiber type-related differences in the patterns of responses for mechanomyographic-electromyographic (MMG-EMG) cross spectrum mean power frequency (MPF) in resistance-trained and aerobically-trained subjects during a fatiguing muscle action. Five resistance-trained and five aerobically-trained men performed a 45-s isometric muscle action of the dominant leg extensors at 50% MVC while MMG and EMG signals were recorded simultaneously from the vastus lateralis muscle. In addition, a biopsy was taken to determine the myosin heavy chain (MHC) isoform content of the vastus lateralis. The resistance-trained and aerobically-trained subjects demonstrated similar patterns of responses for MMG-EMG cross spectrum MPF during the sustained muscle action. The vastus lateralis of the resistance-trained subjects demonstrated primarily Type II MHC isoform expression, indicative of fast-twitch muscle fibers, while that of the aerobically-trained subjects was composed mostly of Type I MHC isoform expression, indicative of slow-twitch fibers. Thus, the differences in fiber type characteristics were not manifested in the patterns of responses for MMG-EMG cross spectrum MPF.


Absorption and electrochromic modulation of near-infrared light: realized by tungsten suboxide.
In the present study, needle-like tungsten suboxide W18O49 nanocrystals were fabricated as the optical active substance to realize the aim of optical control of near-infrared light. The W18O49 nanocrystals were selected in this regard due to their unique optical performance. As revealed by the powder absorption result, the needle-like W18O49 nanocrystals show strong and wide photoabsorption in the entire near infrared region of 780-2500 nm, from which thin films with the W18O49 nanocrystal coating thus benefits and can strongly shield off almost all near infrared irradiation, whereas transmitting the majority of visible light. To make it more tunable, the W18O49 nanocrystals were finally assembled onto an ITO glass via the layer-by-layer strategy for later electrochromic investigation. The nanostructured architectures of the W18O49 nanocrystal electrochromic films exhibit high contrast, faster switching response, higher coloration efficiencies (150 cm(2) C(-1) at 650 nm and 255 cm(2) C(-1) at 1300 nm), better long-term redox switching stability (reversibility of 98% after 500 cycles) and wide electrochromic spectrum coverage of both the visible and infrared regions.


Crossover design and its application in late-phase diabetes studies.
Crossover design has been widely used in late-phase clinical studies, as well as in pharmacokinetic and pharmacodynamic, bioequivalence, and medical device studies; however, its interpretability and applicability continue to be debated. Herein we provide discussions around a crossover design's scientific benefit, applicability, and how it can be implemented in late-phase diabetes studies by properly handling key issues: carryover effect, washout period, and baseline selection. Specifically, detailed considerations are provided about the validity and situations of having appropriate length of study duration to deal with carryover effects so that a washout period may not be needed. A simulation study and data mining results on 12 crossover late-phase insulin clinical trials are presented to examine the discussion points and proposals.


Radical 4-exo cyclizations via template catalysis.
The mechanism of catalytic 4-exo cyclizations without gem-dialkyl substitution was investigated by a comparison of cyclic voltammetry, EPR, and computational studies with previously published synthetic results. The most active catalyst is a super-unsaturated 13-electron titanocene(III) complex that is formed by supramolecular activation through hydrogen bonding. The template catalyst binds radicals via a two-point binding that is mandatory for the success of the 4-exo cyclization. The computational investigations revealed that formation of the observed trans-cyclobutane product is not possible from the most stable substrate radical. Instead, the most stable product is formed with the lowest energy of activation from a disfavored substrate in a Curtin-Hammett related scenario.


The Parkin'Play study: protocol of a phase II randomized controlled trial to assess the effects of a health game on cognition in Parkinson's disease.
In Parkinson's disease (PD), cognitive impairment is an important non-motor symptom heralding the development of dementia. Effective treatments to slow down the rate of cognitive decline in PD patients with mild cognitive impairment are lacking. Here, we describe the design of the Parkin'Play study, which assesses the effects of a cognitive health game intervention on cognition in PD. This study is a multicentre, phase-II, open-randomized clinical trial that aims to recruit 222 PD patients with mild cognitive impairment. Eligible patients have PD, Hoehn & Yahr stages I-III, are aged between 40 and 75 years, and have cognitive impairment but no dementia. The intervention group (n = 111) will be trained using a web-based health game targeting multiple cognitive domains. The control group (n = 111) will be placed on a waiting list. In order to increase compliance the health game adapts to the subjects' performance, is enjoyable, and can be played at home. From each group, 20 patients will undergo fMRI to test for potential functional brain changes underlying treatment. The primary outcome after 12 weeks of training is cognitive function, as assessed by a standard neuropsychological assessment battery and an online cognitive assessment. The neuropsychological assessment battery covers the following domains: executive function, memory, visual perception, visuoconstruction and language. A compound score for overall cognitive function will be calculated as the mean score of all test Z-scores based on the distribution of scores for both groups taken together. Secondary outcomes at follow-up visits up to 24 weeks include various motor and non-motor symptoms, compliance, and biological endpoints (fMRI). This study aims at evaluating whether a cognitive intervention among PD patients leads to an increased cognitive performance on targeted domains. Strengths of this study are a unique web-based health game intervention, the large sample size, a control group without intervention and innovations designed to increase compliance. NTR5637 on 7-jan-2016.


Strong, flexible, and highly conductive cellulose nanofibril/PEDOT:PSS/MXene nanocomposite films for efficient electromagnetic interference shielding.
Flexible and light weight electromagnetic interference (EMI) shielding materials with high electromagnetic shielding efficiency (SE) and excellent mechanical strength are highly demanded for wearable and portable electronics. In this work, for the first time, a freestanding and flexible cellulose nanofibril (CNF)/PEDOT:PSS/MXene (Ti3C2Tx) nanocomposite film with a ternary heterostructure was manufactured using a vacuum-assisted filtration process. The results show that compared with pure MXene films, the tensile strength of the optimized nanocomposite film increases from 8.88 MPa to 59.99 MPa, and the corresponding fracture strain increases from 0.87% to 4.60%. Intriguingly, the optimized nanocomposite film exhibited an impressive conductivity of 1903.2 S cm-1, which is among the highest values reported for MXene and cellulose-based nanocomposites. Owing to the superior conductivity and unique heterostructure, the nanocomposite film exhibits a high EMI SE value of 76.99 dB at a thickness of only 58.0 μm. Taking into account the robust mechanical properties and remarkable EMI shielding performance, the CNF/PEDOT:PSS/MXene nanocomposite film could be a prospective EMI shielding material for a variety of high-end applications.


The role of cardiac output response in blood flow distribution during exercise in patients with chronic heart failure.
The relationship between blood flow in the working leg and cardiac output (Q) response was determined for patients with chronic heart failure. The ratio of leg blood flow (LBF) to Q (LBF/Q) at the same workload during submaximal exercise was significantly different in three groups of patients classified by peak cardiac index: it was 0.22 +/- 0.08 in the 'satisfactory' Q group vs 0.33 +/- 0.09 in the moderate Q group, and 0.38 +/- 0.08 in the poor Q group (P < 0.01) in the first stage of exercise. delta LBF/delta Q, the slope of change in leg blood flow to Q from rest to peak exercise, was significantly larger in the poor Q group than in the satisfactory Q group (P < 0.01). The intergroup arteriovenous oxygen difference (AVO2D) in organs other than the leg was large, while that in the working leg was small. Leg vascular resistance at submaximal workload was similar in the three groups, but vascular resistance in other organs was significantly higher in the poor Q group than in the satisfactory Q group (P < 0.001). These findings suggested that metabolic vasodilating stimuli in the working leg attenuated excessive vasoconstriction and caused a shift in blood flow from other organs to the working leg under conditions of severely reduced Q response.


FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness.
A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence. Obese young Danish men (n = 753, BMI > or = 31.0 kg/m(2)) and a randomly selected group (n = 879) from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively). The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype), for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10(-6), OR = 1.20, p = 1.7*10(-7), OR = 1.17, p = 3.4*10(-3), respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10(-7) and OR = 1.21, p = 1.0*10(-3)). Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10(-6) and OR = 1.19, p = 5.9*10(-3)), sagittal abdominal diameter (OR = 1.17, p = 1.3*10(-4) and OR = 1.18, p = 0.011) and intra-abdominal adipose tissue (OR = 1.21, p = 0.005). Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10(-5) and OR = 1.18, p = 0.004) and lower body fat mass (OR = 1.26, p = 0.002) was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02) and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037), but not with any other of the metabolic traits. However, all significant results for both body fat distribution and metabolic traits were explained by a mediating effect of total fat mass. The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol. The SNP was not significantly associated with other metabolic traits suggesting that they are not derived from the general accumulation of body fat.


Effective Adsorption of Congo Red from Aqueous Solution Using Fe/Al Di-Metal Nanostructured Composite Synthesised from Fe(III) and Al(III) Recovered from Real Acid Mine Drainage.
This study presents the first known exploration of Congo red dye (CR) adsorption by a polycationic Fe/Al Di-metal nanostructured composite (PDFe/Al) synthesised using Fe(III) and Al(III) recovered from authentic acid mine drainage (AMD). The PDFe/Al successfully removed CR from the aqueous solution. The mineralogical, microstructural, and chemical properties of the synthesised PDFe/Al adsorbent (before and after adsorption) were studied using state-of-the-art analytical instruments. The optimum conditions were observed to be 100 mg·L-1 CR, 1 g of the PDFe/Al in 500 mL adsorbate solution, 20 min of shaking, pH = 3-8, and a temperature of 35 °C. At optimised conditions, the PDFe/Al showed ≥99% removal efficacy for CR dye and an exceptionally high Langmuir adsorption capacity of 411 mg·g-1. Furthermore, a diffusion-limited adsorption mechanism was observed, with two distinct surfaces involved in the adsorption of CR from an aqueous solution. It was determined that the adsorption of CR induced internal strain and deformation within the matrices and interlayers of the PDFe/Al which resulted in a marked increase in the adsorbent pore surface area and pore volume. The remarkably high adsorption capacity could be attributed to the high surface area. A regeneration study showed that the adsorbent could be reused more than four times for the adsorption of CR. The findings from this study demonstrated the feasibility of recovering valuable minerals from toxic and hazardous AMD and demonstrated their potential for the treatment of industrial wastewaters.


Membranoproliferative glomerulonephritis due to Hepatitis C in renal allograft.
Membranoproliferative glomerulonephritis type 1 is an etiologically divergent disorder. Hepatitis C with or without cryoglobulinemia is considered one of the principal causes of de novo and post transplant membranoproliferative glomerulonephritis type 1. A 49-year-old male who underwent renal allograft for end stage renal disease developed proteinuria and positive hepatitis C serology during the post-transplant period. This was associated with moderate hepatic dysfunction, which necessitated both liver and renal biopsies. Features of both chronic active hepatitis and membranoproliferative glomerulonephritis type 1 were seen as a result of histological examination of both liver and renal biopsies. Ultra structural studies showing mesangial and membranous deposits which are characteristic of membranoproliferative glomerulonephritis have been observed. The case is reported with a review of pertinent medical literature.


Effect of insulin resistance on whole blood mRNA and microRNA expression affecting bone turnover.
To evaluate the effect of insulin resistance in obesity on the expression in whole blood of mRNA and miRNA affecting bone homeostasis as well as to estimate the influence of oral glucose load (OGTT) on serum osteocalcin concentration in obese individuals with and without insulin resistance. Cross-sectional study. Carboxylated (cOC), undercarboxylated (ucOC) and total osteocalcin were measured by ELISA in the serum of obese subjects with insulin resistance (n = 41) and obese subjects without insulin resistance (n = 41) (control group) during OGTT. Analysis of gene expression (microarray) and miRNAs (real-time PCR) was performed in venous blood (representating samples) collected before OGTT from obese with insulin resistance and controls. Obese subjects with insulin resistance (higher HOMA-IR and lower oral glucose insulin sensitivity index) presented significantly increased expression of WNT signalling inhibitors (DKK1, DKK2, SOST, SFRP1) and downregulation of the key factor in WNT signalling - β catenin participating in osteoblasts differentiation. Expression of miRNA involved in osteoblastogenesis was also inhibited (miR-29b, miR-181a, miR-210, miR-324-3p). During OGTT, contrary to the control group, subjects with insulin resistance presented suppression of cOC and total OC decrease after 1 and 2 h of oral glucose load. Obese subjects with insulin resistance may have defects in osteoblastogenesis that was demonstrated via key signalling molecules mRNA downregulation, and increased expression of WNT antagonists as well as inhibition of expression of miRNA participating in the regulation of osteoblast differentiation. Disturbed osteoblastogenesis in insulin-resistant subjects results in the suppression of blood carboxylated and total osteocalcin decrease during OGTT.


Analytical performance of a monoclonal digoxin assay by dry chemistry on the Vitros 950.
Digoxin assay in plasma/serum samples is used for therapeutic measurements as a guide to clinical management of cardiac patients. A thin dry film multilayer monoclonal immunoassay for digoxin, Vitros, was evaluated for analytical performance. The effect of digoxin-like immunoreactive substances (DLIS) was studied assaying plasma samples taken from 100 renal disease patients, 62 hepatic disease patients and 40 pregnant women not receiving digoxin. The Vitros digoxin assay was compared with the AxSym digoxin II assay using plasma samples from 180 patients treated with digoxin. The results revealed satisfactory precision and accuracy for therapeutic drug monitoring purposes: the coefficient of variation (CV%) was lower than 5%; results for dilutions were linear in the range 0.4-3.9 microlg/L and mean analytical recovery was 105%. Measurable DLIS concentrations were observed in 29% of hepatic disease patients and in 7% of renal disease patients with apparent digoxin concentration ranging from 0.4 to 0.75 microg/L. The incidence of DLIS was comparable to that observed with AxSym digoxin II. Comparative results from patient samples gave a regression line equation: Yvitros 950=0.96XAxym +0.14, r=0.89. The data revealed a mean difference of 0.09+/-0.26 microg/L significantly greater than zero (p=0.02). We concluded that Vitros digoxin assay for precision, accuracy and extent of DLIS interference may be a good method for therapeutic drug monitoring; care needs to be taken since assay results generated by Vitros and AxSym analysers are not necessarily interchangeable.


Heterogeneous distribution of glycosyltransferases in the endoplasmic reticulum of castor bean endosperm.
Endoplasmic reticulum membranes stripped of attached ribosomes were isolated from homogenates of germinating castor bean (Ricinus communis L.) endosperm by sucrose density gradient centrifugation. The isolated endoplasmic reticulum fraction was further separated into two major membrane subfractions by centrifugation on a flotation gradient. Both subfractions appeared to be derived from the endoplasmic reticulum inasmuch as they share several enzymic markers including cholinephosphotransferase, NADH-cytochrome c reductase, and glycoprotein fucosyl-transferase and phase separation of membrane polypeptides using Triton X-114 revealed a striking similarity in both their hydrophilic and hydrophobic protein components. The endoplasmic reticulum membrane subfractions contain glycoproteins which were readily labeled by incubating intact endosperm tissue with radioactive sugars prior to fractionation.Castor bean endosperm endoplasmic reticulum apparently exhibits a degree of enzymic heterogeneity, however, since the enzymes responsible for the synthesis of dolicholpyrophosphate N-acetylglucosamine and dolicholmonophosphate mannose together with their incorporation into the oligosaccharide-lipid precursor of protein N-glycosylation were largely recovered in a single endoplasmic reticulum subfraction.


Synthesis of five- and six-membered dihalogenated heterocyclic compounds by electrophile-triggered cyclization.
Highly substituted dihalogenated dihydrofurans, dihydropyrroles, and dihydro-2H-pyrans bearing alkyl, vinyl, aryl, and heteroaryl moieties can be prepared in good to excellent yields (up to 99%) by allowing 1,4-butyne-diol, 4-aminobut-2-yn-1-ol, and pent-2-yne-1,5-diol derivatives to react with different electrophiles (I(2), IBr, and ICl) at room temperature. Both halogen atoms generated from electrophiles were used effectively. The resulting halides can be further exploited by using palladium-catalyzed coupling reactions. The presence of trace amount of water is essential for this electrophilic cyclization.


Isolation and in vitro translation of polysomes from mature rye leaves.
Cytoplasmic polysomes have been prepared from mature leaves of winter rye (Secale cereale L. cv Puma). This is the first time a method has been developed for isolation of highly polymerized polysomes from mature leaves. The degree of intactness of isolated plant polysomes has been determined by two independent but complementary methods: size class distribution by sucrose gradient centrifugation and in vitro translation. The polymerization of isolated polysomes was estimated by the ratio of the proportion of large polysomes to the proportion of small polysomes obtained from the profiles. Our results show that the composition of the optimal polysome isolation buffer for mature rye leaves is different from that reported for young tobacco and pea leaves. Polysomes were translated in vitro with the S-105 wheat germ fraction. The degree of polysome polymerization has a significant effect on their in vitro translation since both the incorporation of amino acid and the presence of high molecular weight polypeptides are proportional to the large polysomes/small polysomes ratio. This study emphasizes the need to evaluate isolation conditions carefully before proceeding with polysome studies in any particular tissue or in tissues under different physiological status.


[Interdisciplinary Simulation of Emergency Caesarean Section to Improve Subjective Competence].
The emergency caesaran section is a gynecological emergency situation which is potentially life-threatening for mother and child. In the management of these time-critical situations human factors as well as the competence of the crisis resource management team have been shown to be important factors for success. The concept "simulation" has not been validated as a training tool for professional competence of multidisciplinary teams in the delivery suite. The aim of this study was, to assess the competence gain by subjective evaluation of the team members after taking part in an emergency caesarian section training which is integrable into the daily clinic setting. Method 36 members of a multidisciplinary team of a delivery suite took part in a 4-hourly "high-fidelity" simulation training "emergency caesarian section". Scenarios were created around the case setting of eclampsia with bradycardia of the child, uterus rupture, placenta abruption and cord prolapse. Each participant was involved in 2 scenarios as either a spectator or a team member. Using a questionnaire, the course performance and debriefing were evaluated and the subjective professional competence in Crisis Resource Management were recorded. Results In the collective of the trainee (over/equal 5 years), 25% had no experience in any cases of emergency caesarean in practice. On a scale of 1 to 6 (1=very good, 6=fail) the course was given an overall mark of 1.4 and a mark of 1.8 for its relevance to daily work. 6 months after the training, participants rated their competencies in prioritising necessary actions, following treatment plans, communicating among the team members as well as integrating new information as significantly improved. Conclusion The 4-hour simulation training can be easily integrated into everyday clinical practice. The participants marked the course scenarios as realistic and relevant for their clinical practice. The number of years of prior work experience is not significanty related with the experience in rare emergency situations. The interdisciplinary team training is a way to improve individual performance as well as to establish and practise interdisciplinary emergency concepts.


Wave-current interaction as a spatial dynamical system: analogies with rainbow and black hole physics.
We study the hydrodynamic phenomenon of waves blocking by a countercurrent with the tools of dynamical systems theory. We show that, for a uniform background velocity and within the small wavelength approximation, the stopping of gravity waves is described by a stationary saddle-node bifurcation due to the spatial resonance of an incident wave with the converted "blueshifted" wave. We explain why the classical regularization effect of interferences avoids the height singularity in complete analogy with the intensity of light close to the principal arc of a rainbow. The application to the behavior of light near a gravitational horizon is discussed.


Functional Characterization of Neutrophils Allows Source Control Evaluation in a Murine Sepsis Model.
Current surgical guidelines for the treatment of intra-abdominal sepsis recommend interventional source control as the key element of therapy, alongside resuscitation and antibiotic administration. Past trials attempted to predict the success of interventional source control to assess whether further interventional therapy is needed. However, no predictive score could be developed. We utilized an established murine abdominal sepsis model, the cecal ligation and puncture (CLP), and performed a successful surgical source control intervention after full development of sepsis, the CLP-excision (CLP/E). We then sought to evaluate the success of the source control by characterizing circulating neutrophil phenotype and functionality 24 h postintervention. We showed a significant relative increase of neutrophils and a significant absolute and relative increase of activated neutrophils in septic mice. Source control with CLP/E restored these numbers back to baseline. Moreover, main neutrophil functions, the acidification of cell compartments, such as lysosomes, and the production of Tumor Necrosis Factor-alpha (TNF-α), were impaired in septic mice but restored after CLP/E intervention. Neutrophil characterization by phenotyping and evaluating their functionality indicates successful source control in septic mice and can serve as a prognostic tool. These findings provide a rationale for the phenotypic and functional characterization of neutrophils in human patients with infection. Further studies will be needed to determine whether a predictive score for the assessment of successful surgical source control can be established.


The MLC response of lymphocytes from mice neonatally primed and tolerating skin allografts.
Newborn B10.A mice were primed intravenously with semiallogeneic spleen cells differing in the whole H-2 complex or in individual regions of H-2. Neonatally treated mice were grafted with respective skin allografts and cells from tolerant animals were tested in mixed lymphocyte culture. These cells were found to be a reactive or hyporeactive to MLC-stimulating determinants. Using a panel of restimulating cells, MLC tolerance was found to be immunologically specific. Lymphocytes from tolerant mice did not react only to the alloantigens used for neonatal priming, whereas they showed similar reactions to third party antigens as did lymphocytes from normal untreated mice. The results indicate that neonatal priming leads to the tolerance which is manifested already in the recognitive phase of the allotransplantation reaction and that this MCL tolerance is specific, at least in B10.A mice.


Cardiac emergencies in neonates and young infants.
Cardiac emergencies in children are not infrequent. Early recognition and management are essential to save life and prevent any comorbidity. The presentation of cardiac emergencies and etiologies is variable depending on the age of child at the time of presentation and type of cardiac lesion. Cyanotic and noncyanotic congenital heart diseases are the main causes in neonates and infants. Acquired heart diseases and dysrhythmia are more common causes for cardiac emergencies in toddler and childhood. In this review, we discuss the most common causes for cardiac emergencies in neonates and young infants highlighting important points in the presentation and management that are essential for early recognition and timely management of infants presenting with these conditions.


Expanding the family of collagen proteins: recombinant bacterial collagens of varying composition form triple-helices of similar stability.
The presence of the (Gly-Xaa-Yaa)(n) open reading frames in different bacteria predicts the existence of an expanded family of collagen-like proteins. To further explore the triple-helix motif and stabilization mechanisms in the absence of hydroxyproline (Hyp), predicted novel collagen-like proteins from Gram-positive and -negative bacteria were expressed in Escherichia coli and characterized. Soluble proteins capable of successful folding and in vitro refolding were observed for collagen proteins from Methylobacterium sp 4-46, Rhodopseudomonas palustris and Solibacter usitatus . In contrast, all protein constructs from Clostridium perfringens were found predominantly in inclusion bodies. However, attachment of a heterologous N-terminal or C-terminal noncollagenous folding domain induced the Clostridium perfringens collagen domain to fold and become soluble. The soluble constructs from different bacteria had typical collagen triple-helical features and showed surprisingly similar thermal stabilities despite diverse amino acid compositions. These collagen-like proteins provide a resource for the development of biomaterials with new properties.


The beginnings of word segmentation in english-learning infants.
A series of 15 experiments was conducted to explore English-learning infants' capacities to segment bisyllabic words from fluent speech. The studies in Part I focused on 7.5 month olds' abilities to segment words with strong/weak stress patterns from fluent speech. The infants demonstrated an ability to detect strong/weak target words in sentential contexts. Moreover, the findings indicated that the infants were responding to the whole words and not to just their strong syllables. In Part II, a parallel series of studies was conducted examining 7.5 month olds' abilities to segment words with weak/strong stress patterns. In contrast with the results for strong/weak words, 7.5 month olds appeared to missegment weak/strong words. They demonstrated a tendency to treat strong syllables as markers of word onsets. In addition, when weak/strong words co-occurred with a particular following weak syllable (e.g., "guitar is"), 7.5 month olds appeared to misperceive these as strong/weak words (e.g., "taris"). The studies in Part III examined the abilities of 10.5 month olds to segment weak/strong words from fluent speech. These older infants were able to segment weak/strong words correctly from the various contexts in which they appeared. Overall, the findings suggest that English learners may rely heavily on stress cues when they begin to segment words from fluent speech. However, within a few months time, infants learn to integrate multiple sources of information about the likely boundaries of words in fluent speech.


Urolithiasis: how accurate are plain radiographs?
To determine the value of the kidneys, ureters, and bladder radiograph (KUB) in the diagnosis of urolithiasis using unenhanced helical computerized tomography (UHCT) as the gold standard. A retrospective study was performed on 100 consecutive patients being investigated for suspected urolithiasis. All patients presented with acute renal colic and had a KUB and UHCT within a 3-hour period. UHCT and KUB pairs were assessed separately by 2 radiologists in consensus who were blinded to the clinical details of the patients and the results of the other tests and examinations. The presence, location, number, and size of stones were recorded. Each UHCT and KUB pair was then compared for concordance on a stone-by-stone basis. KUB was concordant with the gold standard UHCT in only 50% of patients (11 positive, 39 negative), giving a sensitivity of 18.6%, a specificity of 95.1%, a positive predictive value of 84.6%, and a negative predictive value of 44.8%. KUB has a very low sensitivity for the detection of urolithiasis, although specificity is acceptable.


LSOSS: Detection of Cancer Outlier Differential Gene Expression.
Detection of differential gene expression using microarray technology has received considerable interest in cancer research studies. Recently, many researchers discovered that oncogenes may be activated in some but not all samples in a given disease group. The existing statistical tools for detecting differentially expressed genes in a subset of the disease group mainly include cancer outlier profile analysis (COPA), outlier sum (OS), outlier robust t-statistic (ORT) and maximum ordered subset t-statistics (MOST). In this study, another approach named Least Sum of Ordered Subset Square t-statistic (LSOSS) is proposed. The results of our simulation studies indicated that LSOSS often has more power than previous statistical methods. When applied to real human breast and prostate cancer data sets, LSOSS was competitive in terms of the biological relevance of top ranked genes. Furthermore, a modified hierarchical clustering method was developed to classify the heterogeneous gene activation patterns of human breast cancer samples based on the significant genes detected by LSOSS. Three classes of gene activation patterns, which correspond to estrogen receptor (ER)+, ER- and a mixture of ER+ and ER-, were detected and each class was assigned a different gene signature.


Cloning of S4D-SRCRB, a new soluble member of the group B scavenger receptor cysteine-rich family (SRCR-SF) mapping to human chromosome 7q11.23.
The scavenger receptor cysteine-rich superfamily (SRCR-SF) is a highly conserved group of membrane and/or secreted proteins related to the innate and adaptive immune system. Here, we report the cloning of the gene encoding human S4D-SRCRB, a novel soluble member of the SRCR-SF, which is composed of four group B SRCR domains separated by Pro-, Ser- and Thr-rich polypeptides. The longest cDNA sequence found is 2,806 bp in length and encodes a mature protein of 528 aa, with a predicted molecular mass of M(r) 55,600. The S4D-SRCRB gene is located at Chromosome 7q11.23, telomeric to the Williams-Beuren syndrome deletion. It extends over 20 kb and consists of 11 exons, with each SRCR domain being encoded by a single exon. Northern blot analysis indicated that S4D-SRCRB has a broad tissue distribution and is expressed as two major mRNA species: one of 2.8 kb, with a restricted tissue expression pattern (mainly kidney and placenta), and another of 1.5 kb, with a broader distribution. A similar mRNA expression pattern was observed during the analysis of several tumor cell lines. The highest degree of similarity found between S4D-SRCRB and other group B SRCR-SF members was with human DMBT1 (a mosaic protein composed of fourteen SRCR domains, which is involved in innate defense and epithelia polarization) and chicken 18-B (a turpentine-induced soluble acute-phase protein composed of four SRCR domains). Our data indicate that S4D-SRCRB constitutes a novel SRCR-SF member, which could be involved in basic homeostatic functions such as innate host defense.


Mechanisms of ex vivo aortic hypocontractility in endotoxemic rat.
To clarify the mechanism of the vascular hypocontractility in endotoxemia, the effect of endotoxin injection on phosphatidylinositol turnover and the contractile responses to NH4Cl and okadaic acid were investigated in aorta dissected from rats. The basal level of phosphatidylinositol hydrolysis and the phenylephrine- and 5-hydroxytryptamine-stimulated increase in hydrolysis were all markedly reduced in endotoxemic aortas as compared to in control aortas. Stimulation with KCl did not increase phosphatidylinositol hydrolysis in control or endotoxemic aortas. The NH4Cl-induced contractile response was significantly diminished in endotoxemic aorta, whereas the okadaic acid-induced contractile response was not altered. These results suggest that both transmembrane and intracellular signal transduction mechanisms are impaired in the endotoxemic artery whereas the contractile machinery remains intact.


Atherosclerotic lesions in humans--plaque stabilization and regression.
Although lowering of total- and LDL-cholesterol with different methods, like dietary restrictions mostly combined with lipid-lowering drugs (monotherapy or combined drug therapy) or changes in lifestyle (e.g., cessation from smoking) have demonstrated significant clinical benefits in a number of clinical trials, the magnitude of angiographically proven regression of atherosclerotic lesions is relatively small despite aggressive lipid-lowering regimens. A potentially important therapeutic target especially for limited indications includes the use of LDL-apheresis, where functional and later morphological regression occurs.


Chloride molecular doping technique on 2D materials: WS2 and MoS2.
Low-resistivity metal-semiconductor (M-S) contact is one of the urgent challenges in the research of 2D transition metal dichalcogenides (TMDs). Here, we report a chloride molecular doping technique which greatly reduces the contact resistance (Rc) in the few-layer WS2 and MoS2. After doping, the Rc of WS2 and MoS2 have been decreased to 0.7 kΩ·μm and 0.5 kΩ·μm, respectively. The significant reduction of the Rc is attributed to the achieved high electron-doping density, thus a significant reduction of Schottky barrier width. As a proof-of-concept, high-performance few-layer WS2 field-effect transistors (FETs) are demonstrated, exhibiting a high drain current of 380 μA/μm, an on/off ratio of 4 × 10(6), and a peak field-effect mobility of 60 cm(2)/(V·s). This doping technique provides a highly viable route to diminish the Rc in TMDs, paving the way for high-performance 2D nanoelectronic devices.


Properties of Acanthamoeba myosin I heavy chain kinase bound to phospholipid vesicles.
The actin-activated Mg(2+)-ATPase and in vitro motility activities of the three Acanthamoeba myosin I isozymes depend upon phosphorylation of their single heavy chains by myosin I heavy chain kinase. Previously, the kinase had been shown to be activated by autophosphorylation, which is enhanced by acidic phospholipids, or simply by binding to purified plasma membranes in the absence of significant autophosphorylation. In this paper, we show that the rate of phosphorylation of myosin I by unphosphorylated kinase is approximately 20-fold faster when both the myosin I and the kinase are bound to acidic phospholipid vesicles than when both are soluble. This activation is not due to an increase in the local concentrations of vesicle-bound kinase and myosin I. Thus, acidic phospholipids, like membranes, can activate myosin I heavy chain kinase in the absence of significant autophosphorylation, i.e. membrane proteins are not required. Kinetic studies show that both binding of kinase to phospholipid vesicles and autophosphorylation of kinase in the absence of phospholipid increase the Vmax relative to soluble, unphosphorylated kinase with either an increase in the apparent Km (when myosin I is the substrate) or no significant change in Km (when a synthetic peptide is the substrate). Kinetic data showed that autophosphorylation of phospholipid-bound kinase is both intermolecular and intervesicular, and that phosphorylation of phospholipid-bound myosin I by phospholipid-bound kinase is also intervesicular even when the kinase and myosin are bound to the same vesicles. The relevance of these results to the activation of myosin I heavy chain kinase and phosphorylation of myosin I isozymes in situ are discussed.


Gynecological radiation oncology in sub-Saharan Africa: status, problems and considerations for the future.
Gynecological malignancies in Africa form a significant part of the burden of disease. The high prevalence of HIV in some countries creates a heightened risk for development of human papilloma virus related cancers such as cervical, vulval and vaginal cancers. Radiotherapy is an important modality of treatment for cancer and in Africa compensates for the lack of adequate surgical services for a large proportion of cancers as well as being a cornerstone of treatment for locally advanced cancers and palliation. In this review we look at the status of radiotherapy services in sub-Saharan Africa and critical factors that influence its delivery with a focus on gynecological malignancies. This unveils that radiotherapy for gynecological cancers in sub-Saharan Africa is a significant example of the need for a holistic development approach across different sectors of the economy and different disciplines of medicine. The complexity of its management continues to expose the underdevelopment of health and financial systems and the lack of universal health coverage and social systems as we continue to see unnecessary morbidity and mortality due to the lack of organization. More systematic and scientifically robust investigations tailored to the various sub-Saharan Africa countries need to be conducted to elicit disruptive local solutions to the status quo.


A survey of the opinions of obesity experts on the causes and treatment of obesity.
A survey of opinions on the causes and effectiveness of treatment of obesity was carried out on 50 physicians and scientists involved in obesity research. Responses were grouped by region (Europe, North America, and United Kingdom), sex, age (30-50 and greater than 50 y) and degree (MD or PhD). Genetic factors were considered the most important causes of obesity overall. Females viewed lack of physical activity, carbohydrate craving, and weight cycling as significantly more important causes than did their male colleagues and viewed exercise as a more effective treatment. There were regional variations in the assessment of the importance of metabolic defects and weight cycling as causes of obesity and in the usefulness of diet in the treatment of obesity. The older group of respondents rated low-fat diet more highly as a treatment than did their younger colleagues. All groups viewed serotonergic and thermogenic drugs as effective treatments whose usefulness would increase during the next 10 years.


[A case of recurrent mantle cell lymphoma with gastrointestinal bleeding].
A 64-year-old man had a sudden onset of gastrointestinal bleeding. He had been diagnosed as systemic mantle cell lymphoma (MCL) 27 months ago, and the first-line chemotherapy was undergone. After maintaining CR state during 12 months, he showed PD. Upper gastrointestinal endoscopy revealed multiple lymphomatous polyps, and active bleeding was noticed from the ulceration of the top of these polyps. After hemostasis was gained, biopsies were done twice and a local recurrence of MCL was diagnosed finally by immunohistological examination. In consequence of the second-line chemotherapy including bendamustine, he was introduced into CR again. We present this rare case of long-term follow up of MCL with a series of upper gastrointestinal endoscopy.


[Heart failure and respiratory sleep disorders].
Chronic cardiac failure is often associated with sleep respiratory disorders. These abnormalities are often unrecognised and represent a marker of the severity of cardiac failure and carry a poor prognosis. The mechanism of apnoea is either central, resulting in periodic nocturnal Cheyne-Stokes respiration, or peripheral by obstruction of the upper respiratory tract. Both mechanisms may be observed in the same patient. Oxygen desaturation, fragmentation of sleep and inspiratory depression lead to sympathetic activation and an increase in let ventricular afterload which can aggravate the cardiac failure. Treatment by continuous positive pressure with a nasal mask can help some patients. It is therefore important to diagnoses these nocturnal disorders using simplified polysomnographic recordings.


Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors.
The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI) increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Thirty-four companion animals (27 dogs and 7 cats) were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats) whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6%) the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17%) experienced short lived partial responses (1-3 months duration) while all the others died of progressive disease within two months. high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of the quality of life in pets with down staged cancer and in the majority of the treated animals PPI were well tolerated. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans.


Alkylguanidines as inhibitors of k transport in isolated barley roots.
It has been shown that plants can accumulate K(+) through an energy-dependent process. The effect of alkylguanidines, in particular octylguanidine on the uptake of (86)Rb(+) by excised barley roots (Hordeum vulgare var. Apizaco LV-72), has been studied. (86)Rb(+) was used as tracer of K(+). The uptake of (86)Rb(+) which is linear with time and shows saturation kinetics is inhibited by octylguanidine. Half-maximal inhibition of (86)Rb(+) uptake is attained at 50 muM octylguanidine. Octylguanidine induces a decrease in the V(max) of the process and increases the Km of the system for Rb(+). When the effects of various alkylguanidines were studied, the following order of effectiveness was encountered; octylguanidine = hexilguanidine > butylguanidine > ethylguanidine > guanidine. This suggests that guanidines inhibit Rb(+) uptake by interacting through its positively charged guanidinium group with a Rb(+) carrier while the alkyl chain interacts with the hydrophobic milieu of the membrane.


Anaerobic degradation of phthalate isomers by methanogenic consortia.
Three methanogenic enrichment cultures, grown on ortho-phthalate, iso-phthalate, or terephthalate were obtained from digested sewage sludge or methanogenic granular sludge. Cultures grown on one of the phthalate isomers were not capable of degrading the other phthalate isomers. All three cultures had the ability to degrade benzoate. Maximum specific growth rates (microseconds max) and biomass yields (YXtotS) of the mixed cultures were determined by using both the phthalate isomers and benzoate as substrates. Comparable values for these parameters were found for all three cultures. Values for microseconds max and YXtotS were higher for growth on benzoate compared to the phthalate isomers. Based on measured and estimated values for the microbial yield of the methanogens in the mixed culture, specific yields for the phthalate and benzoate fermenting organisms were calculated. A kinetic model, involving three microbial species, was developed to predict intermediate acetate and hydrogen accumulation and the final production of methane. Values for the ratio of the concentrations of methanogenic organisms, versus the phthalate isomer and benzoate fermenting organisms, and apparent half-saturation constants (KS) for the methanogens were calculated. By using this combination of measured and estimated parameter values, a reasonable description of intermediate accumulation and methane formation was obtained, with the initial concentration of phthalate fermenting organisms being the only variable. The energetic efficiency for growth of the fermenting organisms on the phthalate isomers was calculated to be significantly smaller than for growth on benzoate.


Quality in obstetric care: measuring what matters.
Quality measures allow providers, payers, and patients to assess and compare the performance of medical teams. The ideal quality measure is easy to define and observe, important to patients and physicians, and identifies areas ripe for improvement. There are several challenges unique to obstetrics that complicate quality measurement. Nationally available data are flawed and limited. Adverse outcomes are rare and difficult to compare between groups. An appropriate emphasis on teamwork makes assigning outcomes to individuals improper and impractical. We suggest some strategies that address these challenges and may improve obstetric measures: applying measures to teams rather than individuals, using sentinel events for internal root cause analysis rather than comparisons between groups, devising measures that account for alternatives, and developing data-collection fields that address important quality metrics directly. We highlight four measures that meet these criteria: 1) elective delivery before 39 weeks of gestation, 2) prophylactic antibiotic use for cesarean delivery, 3) the Adverse Outcome Index, and 4) the nulliparous term singleton vertex cesarean delivery rate. We suggest that each institution evaluate local priorities, select a measure, then continue to refine measures based on feedback from frontline clinicians.


[Application of PET in radiation oncology].
Positron emission tomography (PET), especially F-18 fluorodeoxyglucose (FDG)-PET, has been recently used to verify the target volume in radiation treatment planning (RTP) for malignancies. The utility of FDG-PET/CT in defining gross tumor volume (GTV) has been shown in many studies, and the target delineation by a fixed threshold of the maximum standardized uptake value (40-50%) is suggested to be useful in RTP for lung cancer, head and neck cancer, etc. But, the spatial resolution, sensitivity, and specificity of PET are not always enough to define the difference between the GTV and the clinical target volume(CTV). Furthermore, FDG-PET is frequently used in the clinical staging before the treatment, and is also applied to the response evaluation after the treatment. This review focuses on the developing applications of PET in radiation oncology.


Towards a genus-wide reference linkage map for Eucalyptus based exclusively on highly informative microsatellite markers.
A novel set of 50 highly polymorphic microsatellite markers were developed and mapped on existing RAPD framework maps of Eucalyptus grandis and E. urophylla. Together with the twenty previously developed microsatellite markers, these were used to align the existing maps for the two most commercially important Eucalyptus species in the tropics. Sixty-three microsatellite markers were placed on the E. grandis map in 11 linkage groups, and 53 on the E. urophylla map distributed in 10 linkage groups. Approximately 66% of the microsatellite markers segregated in a fully informative fashion, allowing the establishment of colinear syntenic linkage groups between the two maps. The 50 new microsatellite markers were highly informative, with an average of 14 alleles per locus, and average expected heterozygosity between 0.82 and 0.87. Furthermore, within the subgenus Symphyomyrtus, to which the vast majority of commercially important Eucalyptus species belong, these markers display on average 90% transportability. This set of 70 mapped microsatellite markers represents a significant step toward the development of a genus-wide reference linkage map for Eucalyptus. These highly multiallelic and transportable markers constitute a powerful tool for QTL discovery and validation, and can be used in directed searches for QTL allele variation across Eucalyptus pedigrees.


Acridino-Diaza-20-Crown-6 Ethers: New Macrocyclic Hosts for Optochemical Metal Ion Sensing.
Acridino-diaza-20-crown-6 ether derivatives as new turn-on type fluorescent chemosensors with an excellent functionality and photophysical properties have been designed and synthesized for metal ion-selective optochemical sensing applications. Spectroscopic studies revealed that in an acetonitrile-based semi-aqueous medium, the sensor molecules exhibited a remarkable fluorescence enhancement with high sensitivity only toward Zn2+, Al3+ and Bi3+, among 23 different metal ions. Studies on complexation showed a great coordinating ability of logK > 4.7 with a 1:1 complex stoichiometry in each case. The detection limits were found to be from 59 nM to micromoles. The new ionophores enabled an optical response without being affected either by the pH in the range of 5.5-7.5, or the presence of various anions or competing metal ions. Varying the N-substituents of the new host-backbone provides diverse opportunities in both immobilization and practical applications without influencing the molecular recognition abilities.


Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetes-related renal injury.
Type 2 diabetes mellitus (T2DM) is associated with a high risk of chronic kidney disease (CKD). About 20% of patients with T2DM have CKD of stage ≥ 3; up to 40% have some degree of CKD. Beyond targeting all renal risk factors together, renin-angiotensin-aldosterone system blockers are to date the only effective mainstay for the treatment of diabetic kidney disease (DKD). Indeed, several potentially nephroprotective agents have been in use, which have been unsuccessful. Some glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i), have shown promising results. Here, we discuss the evidence that glucose lowering with DPP-4i may be an option for protecting against diabetes-related renal injury. A comprehensive search was performed of the literature using the terms "alogliptin," "linagliptin," "saxagliptin," "sitagliptin," and "vildagliptin" for original articles and reviews addressing this topic. DPP-4i are an effective, well-tolerated treatment option for T2DM with any degree of renal impairment. Preclinical observations and clinical studies suggest that DPP-4i might also be a promising strategy for the treatment of DKD. The available data are in favor of saxagliptin and linagliptin, but the consistency of results points to the possible nephroprotective effect of DPP-4i. This property appears to be independent of glucose lowering and can potentially complement other therapies that preserve renal function. Larger prospective clinical trials are ongoing, which might strengthen these hypothesis-generating findings. The improvement in albuminuria associated with DPP-4i suggests that these agents may provide renal benefits beyond their glucose-lowering effects, thus offering direct protection from DKD. These promising results must be interpreted with caution and need to be confirmed in forthcoming studies.


Cloning and characterization of retinol dehydrogenase transcripts expressed in human epidermal keratinocytes.
The normal growth and differentiation of the epidermis require an adequate supply of vitamin A. The active form of vitamin A for normal epidermal homeostasis is retinoic acid (RA). Retinoic acid controls the expression of retinoid-responsive genes via interactions of the retinoic acid/nuclear receptor complexes at specific DNA sequences in their control regions. The message conveyed by RA is likely modulated by the concentration of the ligand available for binding to the receptors. Following the uptake of plasma retinol, epidermal keratinocytes synthesize retinoic acid via two sequential reactions with retinaldehyde as an intermediate. Several retinol dehydrogenase (RDH) enzymes, members of the short-chain dehydrogenase/reductase (SDR) gene superfamily, catalyze the first and rate-limiting step that generates retinaldehyde from retinol bound to cellular retinol-binding protein (holo-CRBP). However, little is known about these enzymes and their genes in the epidermal cells. Our work describes the first member of the RDH family found in epidermis. We show that this gene is expressed predominantly in the differentiating spinous layers and that it is under positive, feed-forward regulation by retinoic acid. It encodes a protein that, using NAD+ as a preferred cofactor, utilizes free and CRBP-bound all-trans-retinol and steroids as substrates.


Histamine-2 Receptor Antagonists and Semen Quality.
Histamine-2 receptor antagonists are a class of drugs used to treat the acid-related gastrointestinal diseases such as ulcer and gastro-oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine-2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine-2 receptor-independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine-2 receptor antagonists.


Exosomal miRNA-223-3p as potential biomarkers in patients with cerebral small vessel disease cognitive impairment.
Cerebrovascular disease is a common clinical illness. Many patients with cerebrovascular disease can be accompanied by cognitive impairment. The exosomal microRNA (miRNA)-223-3p is related to vascular endothelial injury, synaptic function, inflammatory response, and other mechanisms. In this study, we investigated the levels of plasma exosomal miRNA-223-3p in patients with cerebral small vessel disease (CSVD), in order to determine whether it could be used as a more accessible potential biomarker for the early diagnosis and treatment of CSVD. This study aimed to explore whether the development of cognitive impairment can be explained by differentially expressed miRNA-223-3p by detecting the level of miRNA-223-3p, which is abundant in peripheral blood exosomes related to cognitive impairment in CSVD. The three groups of participants included 40 patients with CSVD cognitive impairment (CSVDCI), 38 patients with CSVD, and 35 normal controls (NC). The real-time polymerase chain reaction (RT-PCR) was used to detect the expression level of blood exosomal miRNA-223-3p. In addition, we also studied the relationship between exosomal miRNA-223-3p and blood Hcy and C-reactive protein (CRP). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of plasma exosomal miRNA-223-3p. The expression of exosomal miRNA-223-3p in CSVD increased, and the expression of miRNA-223-3p increased significantly with the occurrence of cognitive impairment. Exosomal miRNA-223-3p was positively correlated with the expression levels of Hcy and CRP in the blood. The expression of plasma exosomal miRNA-223-3p is associated with the development of cognitive impairment in patients with CSVD. It may be involved in the pathogenesis of CSVD and cognitive impairment, and can be used as a sensitive predictive biomarker.


Resting energy expenditure before and after surgical resection of gut lesions in pediatric Crohn's disease.
In pediatric Crohn's disease (CD), resection of gut lesions is necessary to remove stenoses and when frequent relapses occur despite nutritional support and medical treatment. After surgery, improved nutritional status and accelerated growth usually follow increased nutritional intake and lower doses of steroids. The aim of this study was to compare energy balance before and after surgery while nutritional intake and steroid therapy were unchanged. Eleven patients, aged 14.5 +/- 2.5 years and with mildly active CD, were explored 1 week before and 1 month after gut resection for stenosis (n = 7) and medical treatment failure (n = 4). Eleven matched children participated in the study as controls. Disease activity was assessed by the Pediatric Crohn's Disease Activity Index and serum orosomucoid concentration. Resting energy expenditure (REE) was measured by indirect calorimetry, and fat-free body mass (FFM) was measured by anthropometry. The patients' mean REE decreased from 46.6 +/- 10.5 kcal/kg FFM/day before surgery to 42.6 +/- 10.3 kcal/kg FFM/day after surgery, while the controls' mean REE was 39 +/- 7 kcal/kg FFM/day (analysis of variance, p = 0.02). After surgery, body weights were not significantly different, but the mean protein oxidation rate was reduced and arm muscle area was increased. Changes in REE per kilogram of FFM per day were not correlated with changes in orosomucoid serum concentrations (r2 = 0.35; p = 0.4). In conclusion, in children with mildly active CD, while nutritional intake and steroid therapy were maintained at preoperative levels, a significant decrease in REE and improved nitrogen utilisation were observed 1 month after resection of the CD gut lesion. This finding suggests better use of energy substrates when CD lesions are removed.


Epidemiology of Injuries in National Collegiate Athletic Association Men's Baseball: 2014-2015 Through 2018-2019.
The National Collegiate Athletic Association has supported men's baseball championships since 1947. Since its inception, the number of participating teams and athletes has considerably expanded. Frequently conducting injury surveillance of collegiate baseball athletes is essential for identifying developing temporal patterns. Exposure and injury data collected in the National Collegiate Athletic Association Injury Surveillance Program during 2014-2015 through 2018-2019 were analyzed. Injury counts, rates, and proportions were used to describe injury characteristics; injury rate ratios were used to examine differential injury rates. The overall injury rate was 3.16 per 1000 athlete-exposures. The preseason injury rate was significantly higher than the regular season injury rate. The most commonly injured body parts were shoulder (16.1%), arm or elbow (16%), and hand or wrist (13.9%). The most reported specific injury was hamstring tear (7.9%). The findings of this study aligned with previous studies-most injuries were due to noncontact and overuse mechanisms, less than one-half of injuries were related to upper extremity body parts, and one-third of all injuries were reported among pitchers.


Pharmacologic management of behavioral instability in medically ill pediatric patients.
Behavioral instability in children and adolescents is a vexing problem faced by many clinicians. This dilemma is magnified when it presents in a child with an acute medical condition. Effective treatment in these cases with medications may help to reduce morbidity and facilitate appropriate medical care for the underlying condition. There are many reviews, but few studies examine the treatment of behavioral instability in the pediatric population. There are even fewer that address behavioral instability in the presence of a comorbid medical condition. Many effective agents may worsen a given condition or interfere with the treatment of that condition. There are no prospective studies addressing this issue. Many psychotropic medications must be considered when treating behavioral instability in medically ill children. Antihistamines, benzodiazepines, and antipsychotics may be of particular benefit. Definitive research is lacking and necessary to develop appropriate clinical guidelines. This article considers the most current literature and provides an overall summary of the topic.


Indirect techniques in nuclear astrophysics: a review.
In this review, we discuss the present status of three indirect techniques that are used to determine reaction rates for stellar burning processes, asymptotic normalization coefficients, the Trojan Horse method and Coulomb dissociation. A comprehensive review of the theory behind each of these techniques is presented. This is followed by an overview of the experiments that have been carried out using these indirect approaches.


Subfoveal Choroidal Thickness and Axial Length in Preschool Children with Hyperopic Anisometropic Amblyopia.
To investigate the relationship between subfoveal choroidal thickness and axial length in Japanese preschool children with hyperopic anisometropic amblyopia. Twenty-four children between the age of 3 and 6 years exhibiting hyperopic anisometropic amblyopia were examined. Differences in spherical equivalent between the two eyes were over 1.5 D in all children. Twenty-four eyes in 12 children without anisometropia and amblyopia were examined as age-matched normal controls. Subfoveal choroidal thickness was measured by using enhanced depth imaging optical coherence tomography. Axial length was measured with noncontact optical biometer. The spherical equivalent ranged from +3.50 to +7.25 D in amblyopic eyes and from +0.75 to +3.50 D in fellow eyes. The subfoveal choroidal thickness was significantly greater in the amblyopic eyes than that in the fellow eyes (407.3 ± 54.2 μm versus 357.7 ± 54.3 μm, Paired t-test, p < 0.05). The axial length in the amblyopic eyes was significantly shorter than that in the fellow eyes (21.16 ± 0.64 mm versus 22.08 ± 0.72 mm, Paired t-test, p < 0.05). The mean choroidal thickness of the fellow eyes in hyperopic anisometropic amblyopia was greater than that in age matched normal children, although this difference did not reach statistical significance (326.0 ± 62.1 μm, p = 0.07). The subfoveal choroidal thickness in amblyopic children was negatively correlated with their axial length (r = -0.50, p < 0.01). The subfoveal choroidal thickness of amblyopic children abnormally increased and the thicker subfoveal choroid is mildly correlated with their shorter axial length. The anomalous subfoveal choroidal thicknesses in our amblyopic children may reflect a delay in emmetropization.


[The progress in the application of optical coherence tomography angiography in multiple sclerosis].
Multiple sclerosis (MS) is an inflammatory reactive autoimmune disease characterized by diffuse axonal degeneration of the central nervous system. The exact etiology and pathogenesis remain unclear. Optical coherence tomography angiography is a new technology of angiography, which can obtain the images of each layer of blood vessels in the scanning area. It is non-invasive, fast and quantifiable. Observation of retinal vasculopathy may assist in the evaluation of brain diseases. This article reviews the previous research results at home and abroad of ocular blood flow changes observed by optical coherence tomography angiography in MS in recent years, in order to provide reference for the study of the underlying pathogenesis of MS and clinical evaluation.


Multivalent alteration of quorum sensing in Staphylococcus aureus.
Virulence in Staphylococcus aureus is strongly and positively correlated with local cell density. Here we present an effective approach to modulate this group behaviour using multivalent peptide-polymer conjugates. Our results show that by attaching multiple AIP-4' units to macromolecular scaffolds, the agr QS response in S. aureus was affected strongly, while displaying a clear multivalency effect.


Genes and social justice: a Rawlsian reply to Moore.
In this article I critically examine Adam Moore's claim that the threshold for overriding intangible property rights and privacy rights is higher, in relation to genetic enhancement techniques and sensitive personal information, than is commonly suggested. I argue that Moore fails to see how important advances in genetic research are to social justice. Once this point is emphasized one sees that the issue of how formidable overriding these rights are is open to much debate. There are strong reasons, on grounds of social justice, for thinking the importance of such rights is likely to be diminished in the interests of ensuring a more just distribution of genes essential to pursuing what John Rawls calls a person's 'rational plan of life'.


A combinatorial chemistry method for fast screening of perovskite-based NO oxidation catalyst.
A fast parallel screening method based on combinatorial chemistry (combichem) has been developed and applied in the screening tests of perovskite-based oxide (PBO) catalysts for NO oxidation to hit a promising PBO formulation for the oxidation of NO to NO2. This new method involves three consecutive steps: oxidation of NO to NO2 over a PBO catalyst, adsorption of NOx onto the PBO and K2O/Al2O3, and colorimetric assay of the NOx adsorbed thereon. The combichem experimental data have been used for determining the oxidation activity of NO over PBO catalysts as well as three critical parameters, such as the adsorption efficiency of K2O/Al2O3 for NO2 (α) and NO (β), and the time-average fraction of NO included in the NOx feed stream (ξ). The results demonstrated that the amounts of NO2 produced over PBO catalysts by the combichem method under transient conditions correlate well with those from a conventional packed-bed reactor under steady-state conditions. Among the PBO formulations examined, La0.5Ag0.5MnO3 has been identified as the best chemical formulation for oxidation of NO to NO2 by the present combichem method and also confirmed by the conventional packed-bed reactor tests. The superior efficiency of the combichem method for high-throughput catalyst screening test validated in this study is particularly suitable for saving the time and resources required in developing a new formulation of PBO catalyst whose chemical composition may have an enormous number of possible variations.


The Involvement of the csy1 Gene in the Antimicrobial Resistance of Acinetobacter baumannii.
Acinetobacter baumannii is an important, opportunistic nosocomial pathogen that causes a variety of nosocomial infections, and whose drug resistance rate has increased in recent years. The CRISPR-Cas system exists in several bacteria, providing adaptive immunity to foreign nucleic acid invasion. This study explores whether CRISPR-Cas is related to drug resistance. Antibiotics were used to treat strains ATCC19606 and AB43, and the expression of CRISPR-related genes was found to be changed. The Csy proteins (Csy1-4) were previously detected to promote target recognition; however, the potential function of csy1 gene is still unknown. Thus, the RecAb homologous recombination system was utilized to knock out the csy1 gene from A. baumannii AB43, which carries the Type I-Fb CRISPR-Cas system, and to observe the drug resistance changes in wild-type and csy1-deleted strains. The AB43Δcsy1 mutant strain was found to become resistant to antibiotics, while the wild-type strain was sensitive to antibiotics. Moreover, transcriptome analysis revealed that the csy1 gene regulates genes encoding CRISPR-Cas-related proteins, drug-resistant efflux pumps, membrane proteins, and oxidative phosphorylation-related proteins, inhibiting antimicrobial resistance in A. baumannii. The in vitro resistance development assay revealed that the complete CRISPR-Cas system could inhibit the development of bacterial resistance. Our findings expand our understanding of the role of CRISPR-Cas csy1 gene in A. baumannii and link the CRISPR-Cas system to the biogenesis of bacterial drug-resistant structures.


Necrotizing Urethritis due to Aerococcus urinae.
A 49-year-old male presented to the emergency with hematuria and pain in the shaft of the penis for one day. The patient was found to be in a state of shock. The shaft of the penis and the scrotum were swollen and tender. No skin necrosis was observed and no crepitus was palpable. Serum white count (WBC) was 29.5 × 10(3)/μL. A CT scan showed gas in the corpus spongiosum. Antibiotics were started with IV metronidazole, vancomycin, and piperacillin/tazobactam. Metronidazole was then replaced by clindamycin. Exploration was performed but no necrotic tissue was identified. Cystourethroscopy revealed dusky looking urethra. A suprapubic tube and a urethral catheter were placed in the bladder. WBC trended down to 13.9 × 10(3)/μL on the fourth postoperative day. Urine culture grew Aerococcus urinae and blood cultures grew Alpha Hemolytic Streptococcus. On the sixth day, the patient was feeling worse and WBC increased. MRI revealed absent blood flow to the corpus spongiosum. Urethroscopy revealed necrosis of the urethra. Urethrectomy was performed via perineal approach. The patient immediately improved. The patient was discharged on the sixth postoperative day to continue ampicillin/sulbactam IV every 6 hours for a total of 4 weeks from the day of urethrectomy.


Linear IgA/IgG bullous dermatosis: successful treatment with dapsone and mycophenolate mofetil.
A 21-year-old female presenting linear IgA and IgG disease initially responded well to dapsone therapy. However, the treatment with dapsone was withdrawn due to severe anemia induced by malaria, which led to worsening of the clinical picture. Although prednisone and methylprednisolone were tried, the patient responded only to the association of dapsone and mycophenolate mofetil.


Relationships among perceived enactment of autonomy, self-care, and holistic health in community-dwelling older adults.
The purpose of this article is to report findings from two studies of community-dwelling older adults. The focus of both studies was on delineating relationships among perceived enactment of autonomy (PEA) and selected self-care and health variables from the perspective of Modeling and Role-Modeling nursing theory. Results indicated that PEA, representing the potential for self-care action, was positively correlated to perceived control and morale in Study 1 and to life satisfaction in Study 2. Significant differences in PEA scores were found based on the health indicators of participation in social activities and reliance on others for shopping in Study 2. In addition, Study 1 found that morale, gender, age, perceived control, and education accounted for 39% of the variance in PEA. Implications are discussed for designing theory-based holistic nursing interventions to support PEA in older adults and to direct future research.


Human genes encoding U3 snRNA associate with coiled bodies in interphase cells and are clustered on chromosome 17p11.2 in a complex inverted repeat structure.
Coiled bodies (CBs) are nuclear organelles whose morphological structure and molecular composition have been conserved from plants to animals. Furthermore, CBs are often found to co-localize with specific DNA loci in both mammalian somatic nuclei and amphibian oocytes. Much as rDNA sequences are called nucleolus organizers, we term these coiled body-associated sequences 'coiled body organizers' (CBORs). The only sequences that have been shown to be CBORs in human cells are the U1, U2 and histone gene loci. We wanted to determine whether other snRNA genes might also act as CBORs. In this paper we show that human U3 genes (the RNU3 locus) preferentially associate with CBs in interphase cells. In addition, we have analyzed the genomic organization of the RNU3 locus by constructing a BAC and P1 clone contig. We found that, unlike the RNU1 and RNU2 loci, U3 genes are not tandemly repeated. Rather, U3 genes are clustered on human chromosome 17p11.2, with evidence for large inverted duplications within the cluster. Thus all of the CBORs identified to date are composed of either tandemly repeated or tightly clustered genes. The evolutionary and cell biological consequences of this type of organization are discussed.


Estimating the size of treatment effects: moving beyond p values.
To increase understanding of effect size calculations among clinicians who over-rely on interpretations of P values in their assessment of the medical literature. We review five methods of calculating effect sizes: Cohen's d (also known as the standardized mean difference)-used in studies that report efficacy in terms of a continuous measurement and calculated from two mean values and their standard deviations; relative risk-the ratio of patients responding to treatment divided by the ratio of patients responding to a different treatment (or placebo), which is particularly useful in prospective clinical trials to assess differences between treatments; odds ratio- used to interpret results of retrospective case-control studies and provide estimates of the risk of side effects by comparing the probability (odds) of an outcome occurring in the presence or absence of a specified condition; number needed to treat-the number of subjects one would expect to treat with agent A to have one more success (or one less failure) than if the same number were treated with agent B; and area under the curve (also known as the drug-placebo response curve)-a six-step process that can be used to assess the effects of medication on both worsening and improvement and the probability that a medication-treated subject will have a better outcome than a placebo-treated subject. Effect size statistics provide a better estimate of treatment effects than P values alone.


Spatial distribution and initial changes of SSEA-1 and other cell adhesion-related molecules on mouse embryonic stem cells before and during differentiation.
We examined the distribution of cell adhesion-related molecules (CAMs) among mouse embryonic stem (ES) cells and the spatial distribution on cell surfaces before and during differentiation. The cell-cell heterogeneity of SSEA-1, PECAM-1, and ICAM-1 among the undifferentiated cells in the ES cell colonies was evident by immunohistochemistry and immuno-SEM, supporting the flow cytometry findings. In contrast, most undifferentiated ES cells strongly expressed CD9. SSEA-1 was located preferentially on the edge of low protuberances and microvilli and formed clusters or linear arrays of 3-20 particles. PECAM-1 and ICAM-1 were randomly localized on the free cell surfaces, whereas CD9 was preferentially localized on the microvilli or protuberances, especially in the cell periphery. Both the SSEA-1(+) fraction and the SSEA-1(-) fraction of magnetic cell sorting (MACS) formed undifferentiated colonies after plating. Flow cytometry showed that these populations reverted separately again to a culture with a mixed phenotype. Differentiation induced by retinoic acid downregulated the expression of all CAMs. Immuno-SEM showed decreases of SSEA-1 in the differentiated ES cells, although some clustering still remained. Our findings help to elucidate the significance of these molecules in ES cell maintenance and differentiation and suggest that cell surface antigens may be useful for defining the phenotype of undifferentiated and differentiated ES cells.


Occurrence of Cryptosporidium spp. in Antillean manatees (Trichechus manatus) and Amazonian manatees (Trichechus inunguis) from Brazil.
Infections by Cryptosporidium spp. in aquatic mammals is a major concern due to the possibility of the waterborne transmission of oocysts. The aim of the present study was to report the occurrence of Cryptosporidium spp. in Antillean manatees (Trichechus manatus) and Amazonian manatees (Trichechus inunguis) from Brazil. Fecal samples were collected and processed using Kinyoun's method. Positive samples were also submitted to the direct immunofluorescence test. The results revealed the presence of Cryptosporidium spp. oocysts in 12.5% (17/136) of the material obtained from the Antillean manatees and in 4.3% (05/115) of the samples from the Amazonian manatees. Cryptosporidium spp. infection was more prevalent in captive animals than in free-ranging specimens.


[Principles of PET/CT and clinical application].
Medicine today imposes high demands on diagnosing disease. Techniques should be preferably noninvasive, identify the disease at an early stage, and be quick and accurate. Frequently, these demands can only be met by employing various diagnostic modalities. Consequently, the integration of two imaging modalities, such as the combination of PET and CT, increases the quality of coregistration and facilitates a timely diagnosis. However, complex imaging procedures require a judicious choice of the areas of application. If, for example, both PET and CT are indicated then a combined PET/CT exam results in improved diagnosis, whereby the actual benefit will depend upon the clinical problem. Typically we expect an advantage of 10% with PET/CT compared to separate examinations with CT and PET. In addition, PET/CT allows for new indications and applications, which cannot be performed satisfactorily with independent examinations and retrospective image alignment. One example is the application of PET/CT in radiation therapy planning.


Oxidative Stress Responses and Nutrient Starvation in MCHM Treated Saccharomyces cerevisiae.
In 2014, the coal cleaning chemical 4-methylcyclohexane methanol (MCHM) spilled into the water supply for 300,000 West Virginians. Initial toxicology tests showed relatively mild results, but the underlying effects on cellular biology were underexplored. Treated wildtype yeast cells grew poorly, but there was only a small decrease in cell viability. Cell cycle analysis revealed an absence of cells in S phase within thirty minutes of treatment. Cells accumulated in G1 over a six-hour time course, indicating arrest instead of death. A genetic screen of the haploid knockout collection revealed 329 high confidence genes required for optimal growth in MCHM. These genes encode three major cell processes: mitochondrial gene expression/translation, the vacuolar ATPase, and aromatic amino acid biosynthesis. The transcriptome showed an upregulation of pleiotropic drug response genes and amino acid biosynthetic genes and downregulation in ribosome biosynthesis. Analysis of these datasets pointed to environmental stress response activation upon treatment. Overlap in datasets included the aromatic amino acid genes ARO1, ARO3, and four of the five TRP genes. This implicated nutrient deprivation as the signal for stress response. Excess supplementation of nutrients and amino acids did not improve growth on MCHM, so the source of nutrient deprivation signal is still unclear. Reactive oxygen species and DNA damage were directly detected with MCHM treatment, but timepoints showed these accumulated slower than cells arrested. We propose that wildtype cells arrest from nutrient deprivation and survive, accumulating oxidative damage through the implementation of robust environmental stress responses.


Effects of Orthophosphate and Adenosine 5'-Phosphate on Threonine Synthase and Cystathionine gamma-Synthate of Lemna paucicostata Hegelm. 6746.
Inorganic phosphate (Pi) inhibits threonine synthase of Lemna, and cystathionine gamma-synthase less strongly. AMP is an extremely potent and structurally specific inhibitor of threonine synthase. Each inhibition progressively decreases with increasing concentrations of O-phosphohomoserine (OPH). To study the in vivo effects of these inhibitions, Lemna was grown with a range of Pi concentrations. A 25,000-fold increase in Pi concentration in the culture medium caused an increase of only 6-fold in total phosphorus of the plants. This is explained by the fact that a high affinity Pi uptake system is selectively down-regulated during growth with high concentrations of Pi. Pi and AMP in plants grown with various Pi concentrations were determined, and concentrations estimated for chloroplasts, the organelle containing threonine synthase and cystathionine gamma-synthase. Calculations indicated that for growth at standard external Pi (0.4 millimolar) or above, if total OPH were uniformly distributed within the plants, activities of the two enzymes in question would be severely inhibited, and each would fall two orders of magnitude below the amount required to provide threonine (plus isoleucine) or methionine adequate for growth. If OPH were restricted to chloroplasts, these inhibitions would be much less severe, resulting in enzyme activities approaching the required physiological amounts. Evidence is presented that even up to 50 millimolar external Pi, this ion does not limit production of threonine or methionine sufficiently to retard growth, consistent with the postulated localization of OPH within chloroplasts.


Defining conditions for covalent immobilization of angiogenic growth factors onto scaffolds for tissue engineering.
Rapid vascularization of engineered tissues in vitro and in vivo remains one of the key limitations in tissue engineering. We propose that angiogenic growth factors covalently immobilized on scaffolds for tissue engineering can be used to accomplish this goal. The main objectives of this work were: (a) to derive desirable experimental conditions for the covalent immobilization of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) on porous collagen scaffolds; and (b) to determine whether primary endothelial cells respond to these scaffolds with covalently immobilized angiogenic factors. VEGF and Ang1 were covalently immobilized onto porous collagen scaffolds, using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry. To improve covalent immobilization conditions: (a) different reaction buffers [phosphate-buffered saline (PBS), distilled water, or 2-(N-morpholino)ethanesulphonic acid (MES)] were used; and (b) step immobilization was compared to bulk immobilization. In step immobilization, growth factors are applied after EDC activation of the scaffold, while in bulk immobilization, reagents are simultaneously applied to the scaffold. PBS as the reaction buffer resulted in higher amounts of VEGF and Ang1 immobilized (ELISA), higher cell proliferation rates (XTT) and increased lactate metabolism compared to water and MES as the reaction buffers. Step immobilization in PBS buffer was also more effective than bulk immobilization. Immobilized growth factors resulted in higher cell proliferation and lactate metabolism compared to soluble growth factors used at comparable concentrations. Tube formation by CD31-positive cells was also observed in collagen scaffolds with immobilized VEGF or Ang1 using H5V and primary rat aortic endothelial cells but not on control scaffolds.


Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces.
We describe a method based on a phagemid vector with helper phage rescue for the construction and rapid analysis of combinatorial antibody Fab libraries. This approach should allow the generation and selection of many monoclonal antibodies. Antibody genes are expressed in concert with phage morphogenesis, thereby allowing incorporation of functional Fab molecules along the surface of filamentous phage. The power of the method depends upon the linkage of recognition and replication functions and is not limited to antibody molecules.


The neuropsychological profile of early and continuously treated phenylketonuria: orienting, vigilance, and maintenance versus manipulation-functions of working memory.
In this paper, we review neuropsychological test results of early and continuously treated Phenylketonuria (PKU) patients. To increase insight into the neuropsychological profile of this population, we have attempted to place the results within an attentional network model [Images of the mind, 1994], which proposes interacting but dissociable attentional networks for orienting, vigilance, and executive control of attention. Executive control of attention is discussed against the background of the process-specific theory of working memory (WM) [Handbook of neuropsychology, 1994], which postulates a distinction between the 'maintenance'-function of WM and the 'manipulation and monitoring'-function. Neuropsychological results are presented for 67 early and continuously treated PKU patients and 73 controls aged 7-14 years. Four neuropsychological tasks were employed to measure orienting, mnemonic processing, interference suppression, and top-down control in visual search. No differences were found in orienting and the maintenance-function of WM. In addition to previously reported impairments in sustained attention/vigilance and inhibition of prepotent responding, PKU patients exhibited deficits when top-down control was required in a visual search task, but showed no impairment when interference suppression was required. It is discussed how the specific neuropsychological impairments in PKU may be a consequence of mid-dorsolateral prefrontal cortex (DLPFC) dysfunctioning due to deficiencies in catecholamine modulation.


The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex.
As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.


Professional nurse information day: a recruitment strategy for registered nurses.
The shortage of and demand for professional registered nurses is growing at an ever-increasing rate. Military facilities must consider alternative strategies for recruiting these professionals into their staffs even in the midst of worsening budget and personnel constraints. One idea is reported here that proved successful for a medical center overseas with no money expenditure. Recommendations for repetitions of a similar program are included.


History of leukemia-lymphoma cell lines.
We outline the near 50-year history of leukemia-lymphoma (LL) cell lines - a key model system in biomedicine. Due to the detailed documentation of their oncogenomic and transcriptional alterations via recent advances in molecular medicine, LL cell lines may be fitted to parent tumors with a degree of precision unattainable in other cancers. We have surveyed the corpus of published LL cell lines and found 637 examples that meet minimum standards of authentication and characterization. Alarmingly, the rate of establishment of new LL cell lines has plummeted over the last decade. Although the main hematopoietic developmental cell types are represented by cell lines, some LL categories stubbornly resist establishment in vitro. The advent of engineering techniques for immortalizing primary human cells that maintain differentiation means the time is ripe for renewed search for in vitro models from un(der)represented hematologic entities. Given their manifold applications in biomedicine, there is little doubt that LL-derived cell lines will continue to play a vital part well into the next half-century as well.


Cell surface hydrophobicity, adherence to HeLa cell cultures and haemagglutination pattern of pyelonephritogenic Escherichia coli strains.
Cell surface hydrophobicity, haemagglutination pattern and adherence to HeLa cells were examined in 230 strains of Escherichia coli collected from women (n = 61 strains) and children (n = 65 strains) with non-obstructive acute pyelonephritis and in 104 faecal control strains of E. coli from healthy adults (n = 71 strains) and children (n = 33 strains). Pyelonephritogenic E. coli strains showed a significantly increased incidence of hydrophobic properties (90%) and mannose resistant haemagglutination (MRHA) of human erythrocytes (83%) than faecal control strains (64 and 23% respectively, P less than 0.001 in both cases). Mannose sensitive haemagglutination (MSHA) was observed in 48% of the pyelonephritogenic E. coli strains and in 50% of the faecal control strains (NS). The incidence of adherence to HeLa cells was low both in pyelonephritogenic and faecal control strains, 6 and 7% respectively (NS). The bacterial phenotypes MRHA + MSHA + and MRHA + MSHA- appeared significantly more often in pyelonephritogenic E. coli strains (35 and 48% respectively) than in faecal control strains (5 and 17% respectively, P less than 0.001 in both cases). The phenotype MRHA- MSHA + occurred significantly more often in control strains (45%) than in pyelonephritogenic strains (13%, P less than 0.001). Eighty-three per cent of the pyelonephritogenic E. coli strains expressing hydrophobic properties showed MRHA and 50% of the hydrophobic strains showed MSHA. There were no significant correlations between cell surface hydrophobic properties and haemagglutination pattern or adherence to HeLa cells in pyelonephritogenic E. coli strains nor in faecal control strains.


Interaction of the v-Rel oncoprotein with NF-kappaB and IkappaB proteins: heterodimers of a transformation-defective v-Rel mutant and NF-2 are functional in vitro and in vivo.
The v-Rel oncoprotein of the avian Rev-T retrovirus is a member of the Rel/NF-kappa B family of transcription factors. The mechanism by which v-Rel malignantly transforms chicken spleen cells is not precisely known. To gain a better understanding of functions needed for transformation by v-Rel, we have now characterized the activities of mutant v-Rel proteins that are defective for specific protein-protein interactions. Mutant v-delta NLS, which has a deletion of the primary v-Rel nuclear localizing sequence, does not interact efficiently with I kappa B-alpha but still transforms chicken spleen cells approximately as well as wild-type v-Rel, indicating that interaction with I kappa B-alpha is not essential for the v-Rel transforming function. A second v-Rel mutant, v-SPW, has been shown to be defective for the formation of homodimers, DNA binding, and transformation. However, we now find that v-SPW can form functional DNA-binding heterodimers in vitro and in vivo with the cellular protein NF-kappa B p-52. Most strikingly, coexpression of v-SPW and p52 from a retroviral vector can induce the malignant transformation of chicken spleen cells, whereas expression of either protein alone cannot. Our results are most consistent with a model wherein Rel homodimers or heterodimers must bind DNA and alter gene expression in order to transform lymphoid cells.


A parameter-free prediction of simulated crystal nucleation times in the Lennard-Jones system: from the steady-state nucleation to the transient time regime.
Large scale simulations of crystal nucleation from the liquid are performed using the Lennard-Jones potential to determine the time required for nucleation. By considering both transient and finite-size effects, we for the first time successfully predict the nucleation time without any parameter fitting in the Lennard-Jones system. All necessary parameters are derived from separate, equilibrium simulations. At small undercoolings, large system size effects are observed. The required system size is not only determined by the size of the critical nuclei, but also the characteristic spacing between them. Two distinct nucleation regions are predicted by theory and observed by the simulations, which are dominated by the transient time and the steady-state nucleation time, respectively.


Self-dissolving microneedles for the percutaneous absorption of EPO in mice.
Erythropoietin (EPO) loaded microneedles were prepared using thread-forming polymer as a base for the percutaneous administration of EPO. The used polymers were dextrin, chondroitin sulfate and albumin. Under room temperature, EPO solution was added to high concentration of polymer solution and microneedles were prepared by forming thread with polypropylene tips. The mean weight of microneedle was 0.59 +/- 0.01 mg and length and basal diameter were 3.24 +/- 0.16 and 0.55 +/- 0.03 mm, respectively. Four microneedles were percutaneously (pc) administered to mice at the EPO dose levels of 100 IU/kg. After administration, blood samples were collected for 24 h and serum EPO levels were measured. Dextrin EPO microneedles were administered both pc and subcutaneously (sc) to mice. Serum EPO levels vs. time profiles showed Cmax of 138.6 +/- 16.1 and 146.5 +/- 8.0 mIU/ml, respectively. Tmax were 7.5 h. The values of bioavailability (BA) of EPO were 82.1 and 99.4%, respectively. By decreasing the dose from 100 to 50 and 25 IU/kg, dose-dependent serum EPO levels vs. time profiles were not clearly obtained. When chondroitin sulfate and albumin were used as the microneedle base, the serum EPO levels vs. time profiles showed almost the same pattern. Cmax of chondroitin sulfate and albumin microneedles were 96.3 +/- 8.8 and 132.2 +/- 18.9 mIU/ml, respectively. AUCs were 835.1 and 1098.7 mIU h/ml. Tmax were 8 and 6.8 h. These results suggest the usefulness of microneedles for the percutaneous administration of EPO.