Multielement Episodic Encoding in Young and Older Adults.
Previous research on age-related associative memory deficits has generally focused on memory for single associations. However, our real-world experiences contain a multitude of details that must be effectively integrated and encoded into coherent representations to facilitate subsequent retrieval of the event as a whole. How aging interferes with the processes necessary for multielement encoding is still unknown. We investigated this issue in the current fMRI study. While undergoing scanning, young and older adults were presented with an occupation and an object and were asked to judge how likely the two were to interact, either in general or within the context of a given scene. After scanning, participants completed recognition tasks for the occupation-object pairs and the sources/contexts with which the pairs were studied. Using multivariate behavioral partial least squares analyses, we identified a set of regions including anterior pFC and medial-temporal lobes whose activity was beneficial to subsequent memory for the pairs and sources in young adults but detrimental in older adults. An additional behavioral partial least squares analysis found that, although both groups recruited anterior pFC areas to support context memory performance, only in the young did this activity appear to reflect integration of the occupation, object, and scene features. This was also consistent with behavioral results, which found that young adults showed greater conditional dependence between pair and context memory compared with older adults. Together, these findings suggest that binding and/or retrieving multiple details as an integrated whole becomes increasingly difficult with age.


Predictors of self-rated health status among Texas residents.
The purpose of this study was to investigate the predictors of self-rated health status for Texas adults using the current 2003 Behavioral Risk Factor Surveillance System data. Self-rated health is generally accepted as a valid measure of health status in population studies, and understanding its correlates may help public health professionals prioritize health-promotion and disease-prevention interventions. The two research questions addressed by this study involved the predictors of self-rated health: 1) "Do demographic characteristics, health care coverage, leisure-time physical activity, and body mass index predict self-rated health status for Texas residents aged 18 to 64 years?" and 2) "Does choice of interview language (English vs Spanish) predict self-rated health status for Texas residents of Hispanic ethnicity aged 18 to 64 years?" Key analysis variables were identified, and descriptive statistics were used to describe the major variables and determine whether the number of respondents for each variable was sufficient for analysis. Multivariate regression analysis was used to assess the variables. Multiple logistic regression analysis (controlling for diabetes and arthritis) of the self-rated health predictors indicated that older age, lack of health care coverage, lack of a college education, being Hispanic, having a lower income, obesity, and not exercising explained 19.4% of the variance of fair and poor self-rated health. The interview language (English or Spanish), age, sex, education, income, obesity, health insurance coverage, and physical activity (controlling for chronic illness) explained 22.8% of the variance in fair and poor self-rated health for Hispanic respondents. The results of this study suggest that a college education, a lower body mass index, non-Hispanic ethnicity, and participation in physical activity are associated with good, very good, or excellent self-rated health status. The finding that the interview language significantly predicted fair and poor self-rated health substantiates previous research and emphasizes the importance of culturally sensitive approaches to health care services.


The neural substrates of affective processing in depressed patients treated with venlafaxine.
The purpose of this study was to use functional magnetic resonance imaging (fMRI) to probe the neural circuitry associated with reactivity to negative and positive affective stimuli in patients with major depressive disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine. Relations between baseline neural activation and response to treatment were also evaluated. Patients with major depressive disorder (N=12) and healthy comparison subjects (N=5) were scanned on three occasions, during which trials of alternating blocks of affective and neutral pictorial visual stimuli were presented. Symptoms were evaluated at each testing occasion, and both groups completed self-report measures of mood. Statistical parametric mapping was used to examine the fMRI data with a focus on the group-by-time interactions. Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response. The findings underscore the importance of the neural circuitry activated by negative affect in depression and indicate that components of this circuitry can be changed within 2 weeks of treatment with antidepressant medication.


Percutaneous endovascular treatment of aortic aneurysms: clinical evaluation and literature results.
In this study we aimed to evaluate the efficiency of percutaneous endovascular aortic aneurysm repair (p-EVAR). Anatomically selected patients treated with a single 10Fr Perclose Prostar XL vascular closure device (VCD) were examined. Primary success rate and common femoral artery (CFA) open conversion (OC) requirement per sheath size used were recorded. A literature review on p-EVAR results was also performed. One-hundred patients were enrolled. Successful p-EVAR was achieved in 183 of the 196 CFA access sites (93.4%), and was specifically 85.9% and 98.3% for sheaths ≥20Fr and ≤18Fr respectively. There were 13 periprocedural complications (bleeding = 10, arterial dissection and thrombosis = 1, pseudoaneurysm = 2) all leading to OC. Use of ≥20Fr sheaths had significantly higher OC rate (P < .05). Reconstruction was achieved with primary repair (N = 11) and patch angioplasty (N = 2). Mean hospital stay was 1.8 days. The literature review (vascular closure of 2921 CFA access sites) revealed an overall technical success rate of 92.3%. Device related- were more common than patient related-OCs (P < .05). p-EVAR procedures are safe and feasible. Sheath size is a significant predictor of OC rate and more OCs might be expected with very large (≥20Fr) sheath sizes.


Actionable reminders did not improve performance over passive reminders for overdue tests in the primary care setting.
Actionable reminders (electronic reminders linked to computerized order entry) might improve care by facilitating direct ordering of recommended tests. The authors implemented four enhanced actionable reminders targeting performance of annual mammography, one-time bone-density screening, and diabetic testing. There was no difference in rates of appropriate testing between the four intervention and four matched, control primary care clinics for screening mammography (OR 0.81, 95% CI 0.64 to 1.02), bone-density exams (OR 1.29, 95% CI 0.82 to 2.02), HbA1c monitoring (OR 0.91, 95% CI 0.58 to 1.42) and LDL cholesterol monitoring (OR 1.40, 95% CI 0.76 to 2.59). Of the survey respondents, 79% almost never used the system or were unaware of the functionality. In the 9/228 (3.9%) cases with indirect evidence of mammography reminder use, there was a significantly lower proportion with test performance. Our actionable reminders did not improve receipt of overdue testing, potentially due to limitations of workflow integration.


Improved morphology control using a modified two-step method for efficient perovskite solar cells.
A two-step wet chemical synthesis method for methylammonium lead(II) triiodide (CH3NH3PbI3) perovskite is further developed for the preparation of highly reproducible solar cells, with the following structure: fluorine-doped tin oxide (FTO)/TiO2 (compact)/TiO2 (mesoporous)/CH3NH3PbI3/spiro-OMeTAD/Ag. The morphology of the perovskite layer could be controlled by careful variation of the processing conditions. Specifically, by modifying the drying process and inclusion of a dichloromethane treatment, more uniform films could be prepared, with longer emission lifetime in the perovskite material and longer electron lifetime in solar cell devices, as well as faster electron transport and enhanced charge collection at the selective contacts. Solar cell efficiencies up to 13.5% were obtained.


Multiplex PCR assay and simple preparation method for stool specimens detect enterotoxigenic Escherichia coli DNA during course of infection.
Infection with enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrhea among travelers and residents of developing countries. ETEC produces either a heat-stable toxin or a heat-labile toxin, or both, encoded by plasmid-borne ST and LT genes, respectively. Diagnosis of infection with this subclass of E. coli can be performed with oligonucleotide hybridization probes; however, the sensitivity and specificity of this method are insufficient. A nonradioactive multiplex PCR assay that provides a sensitive and specific method for detecting the presence of either or both toxin genes has been developed. A simple procedure that removed inhibitors of the PCR while efficiently releasing ETEC DNA from stool specimens for subsequent amplification was used. The results for samples from a human volunteer study of ETEC infection indicated that this method of sample preparation results in greater clinical sensitivity than conventional total nucleic acid extraction and ethanol precipitation. Detection of ETEC by a multiplex PCR assay in stool specimens directly processed with a glass matrix and chaotropic solution had greater sensitivity than culture.


Trends in Hydrophilicity/Lipophilicity of Phosphonium Ionic Liquids As Determined by Ion-Transfer Electrochemistry.
Ionic liquids (ILs) have become valuable new materials for a broad spectrum of applications including additives or components for new hydrophobic/hydrophilic polymer coatings. However, fundamental information surrounding IL molecular properties is still lacking. With this in mind, the microinterface between two immiscible electrolytic solutions (micro-ITIES), for example, water|1,2-dichloroethane, has been used to evaluate the hydrophobicity/lipophilicity of 10 alkylphosphonium ILs. By varying the architecture around the phosphonium core, chemical differences were induced, changing the lipophilicity/hydrophilicity of the cations. Ion transfer (IT) within the polarizable potential window (PPW) was measured to establish a structure-property relationship. The Gibbs free energy of IT and the solubility of their ILs were also calculated. For phosphonium cations bearing either three butyl or three hydroxypropyl groups with a tunable fourth arm, the latter displayed a wide variety of easily characterizable IT potentials. The tributylphosphonium ILs, however, were too hydrophobic to undergo IT within the PPW. Utilizing a micro-ITIES (25 μm diameter) housed at the tip of a capillary in a uniquely designed pipet holder, we were able to probe beyond the traditional potential window and observe ion transfer of these hydrophobic phosphonium ILs for the first time. A similar trend in lipophilicity was determined between the two subsets of ILs by means of derived solubility product constants. The above results serve as evidence of the validation of this technique for the evaluation of hydrophobic cations that appear beyond the conventional PPW and of the lipophilicity of their ILs.


Mitoregulin: A lncRNA-Encoded Microprotein that Supports Mitochondrial Supercomplexes and Respiratory Efficiency.
Mitochondria are composed of many small proteins that control protein synthesis, complex assembly, metabolism, and ion and reactive oxygen species (ROS) handling. We show that a skeletal muscle- and heart-enriched long non-coding RNA, LINC00116, encodes a highly conserved 56-amino-acid microprotein that we named mitoregulin (Mtln). Mtln localizes to the inner mitochondrial membrane, where it binds cardiolipin and influences protein complex assembly. In cultured cells, Mtln overexpression increases mitochondrial membrane potential, respiration rates, and Ca2+ retention capacity while decreasing mitochondrial ROS and matrix-free Ca2+. Mtln-knockout mice display perturbations in mitochondrial respiratory (super)complex formation and activity, fatty acid oxidation, tricarboxylic acid (TCA) cycle enzymes, and Ca2+ retention capacity. Blue-native gel electrophoresis revealed that Mtln co-migrates alongside several complexes, including the complex I assembly module, complex V, and supercomplexes. Under denaturing conditions, Mtln remains in high-molecular-weight complexes, supporting its role as a sticky molecular tether that enhances respiratory efficiency by bolstering protein complex assembly and/or stability.


Treatment of Labial Fistula Communicating with the Duodenal Stump After Gastrectomy.
BACKGROUND Anastomotic failure after gastroenterological surgery is usually treated by intraperitoneal drainage and a mature ductal fistula. A ductal fistula may develop into a labial fistula. Although a ductal fistula is controllable, a labial fistula is intractable. We report a case of a labial fistula that communicated with the duodenal stump after gastrectomy. This condition was successfully treated by intraluminal drainage with continuous suction (IDCS) via a rectus abdominis musculocutaneous flap (RAMF). CASE REPORT A 70-year-old male underwent distal gastrectomy with intentional lymphadenectomy because of advanced gastric cancer. Digestive reconstruction was completed by the Billroth II method. Pancreatic leakage, intraperitoneal abscess, and anastomotic failure of gastrojejunostomy occurred after surgery. The duodenal stump was ruptured at postoperative day (POD) 26, and ductal fistula associated with the duodenum was observed. Unfortunately, this ductal fistula developed into a labial fistula at POD 90, and a high output of duodenal juice was observed. Additional surgery was proposed at POD 161. The broken stump and labial fistula were covered by a pedunculated RAMF, and a dual drainage system (a combination of a Penrose drain and a 2-way tube) travelled through the RAMF. The tip position of the drainage system was located in the duodenum, and the IDCS was effectively introduced. The secondary ductal fistula finally matured through the RAMF, and was subsequently closed at POD 231. The intractable labial fistula was successfully treated, and the patient was discharged at POD 235. CONCLUSIONS A high-output labial fistula, which communicated with the duodenal stump after gastrectomy, was refractory in our patient. Effective IDCS through an RAMF was useful for replacement of the labial fistula with a secondary ductal fistula.


Sublingual immunotherapy for latex allergy: tolerability and safety profile of rush build-up phase.
Sublingual immunotherapy represents an efficient therapeutic tool for the management of latex allergic patients. Local and systemic adverse reactions are reported, and risk factors for those reactions are poorly understood. The aim of this study is to compare two different rush induction protocols (2-day and 3-day) in terms of safety and tolerability and effectiveness in reaching the maintenance dose. Twenty-three outpatients (F/M = 18:5; 5-64 years of age), with latex allergy were randomly assigned to: Group 1 (2-day) and Group 2 (3-day). Adverse reactions were classified by their type and severity. Twenty-one subjects, 10 from Group 1 and 11 from Group 2, reached the maintenance dose, 70% of them without side effects. Seven adverse events were reported in Group 1: three were local (oral itching) and spontaneously remitted; four were systemic (Grade-2: two reactions; Grade-3: two reactions) and were effectively controlled with drugs. The protocol was interrupted in two cases because of recurrent reactions. No reactions were reported in Group 2. Age, gender, atopy, specific IgE, skin prick tests and sublingual challenge did not seem to influence the risk of side effects significantly. No significant modification of skin tests and specific IgE levels were reported in both groups. The cutaneous test turned negative in 16 patients, eight from Group 1 (80%) and eight from Group 2 (73%). The remaining patients (two from Group 1 and three from Group 2) showed a reduction of latex reactivity, in terms of symptom score (MIS: 2 vs. 0.5 in Group 1, 3 vs. 1 in Group 2). This study confirms the safety of rush induction. The 3-day protocol was better tolerated than the 2-day. Significant risk factors for the occurrence of adverse reactions were not identified. Only the type of protocol but not patient-related parameters seemed predictive of side-effects.


Drug-Resistant Epilepsy in Children with Juvenile Huntington's Disease: A Challenging Case and Brief Review.
Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder with a progressive decline in cognitive, motor, and psychological function. Chorea tends to be the most common associated movement disorder, although other variants of several abnormal movements are also seen. Adult-onset HD is the most common subtype. Juvenile Huntington's disease (JHD) accounts for 5%-10% of all HD cases and presents as a rapidly progressive disorder with a multitude of characteristics. We report on a 9-year-old male with JHD who presented with refractory epilepsy. His EEG findings, seizure type, and antiepileptic drug usage are discussed with a brief review of the currently available relevant literature. The currently reported case sheds light on antiepileptic drugs that proved effective in our patient and the importance of screening for JHD when a child presents with seizures that are difficult to control.


A comparative study on chirped-pulse upconversion and direct multichannel MCT detection.
A comparative study is carried out on two spectroscopic techniques employed to detect ultrafast absorption changes in the mid-infrared spectral range, namely direct multichannel detection via HgCdTe (MCT) photodiode arrays and the newly established technique of chirped-pulse up-conversion (CPU). Whereas both methods are meanwhile individually used in a routine manner, we directly juxtapose their applicability in femtosecond pump-probe experiments based on 1 kHz shot-to-shot data acquisition. Additionally, we examine different phase-matching conditions in the CPU scheme for a given mid-infrared spectrum, thereby simultaneously detecting signals which are separated by more than 200 cm(-1).


Acneiform eruption induced by cetuximab.
Cetuximab is a recombinant human/mouse chimeric monoclonal antibody that targets the extracellular domain of the epidermal growth factor receptor (EGFR). Cetuximab is approved by the US Food and Drug Administration for the treatment of EGFR-expressing metastatic colorectal cancer as monotherapy in patients who are intolerant to irinotecan-based chemotherapy, or in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy. Due to the important role of the EGFR in skin homeostasis, cutaneous reactions are a common adverse effect of cetuximab, mainly as acneiform follicular eruption seen in almost 85% of patients. We report on a 46-year-old female Caucasian patient with metastatic colorectal cancer, referred to our department for acneiform eruption induced by cetuximab in combination with irinotecan. Four days after the first infusion the patient developed intense acneiform eruption consisting of erythematous follicular papules and pustules spread to the face, neck and upper part of the trunk, accompanied by intense pruritus and fever (38.0 degrees C). There were no comedones. Biopsy specimen revealed superficial and florid neutrophilic suppurative folliculitis. She was treated with erythromycin tablet 600 mg, three times a day for 1 month, and topical clindamycin solution 3%. After 1 month of treatment, the lesions consistently faded, and the patient continued receiving immunochemotherapy.


Expression of flavonoid 3'-hydroxylase is controlled by P1, the regulator of 3-deoxyflavonoid biosynthesis in maize.
The maize (Zea mays) red aleurone1 (pr1) encodes a CYP450-dependent flavonoid 3'-hydroxylase (ZmF3'H1) required for the biosynthesis of purple and red anthocyanin pigments. We previously showed that Zmf3'h1 is regulated by C1 (Colorless1) and R1 (Red1) transcription factors. The current study demonstrates that, in addition to its role in anthocyanin biosynthesis, the Zmf3'h1 gene also participates in the biosynthesis of 3-deoxyflavonoids and phlobaphenes that accumulate in maize pericarps, cob glumes, and silks. Biosynthesis of 3-deoxyflavonoids is regulated by P1 (Pericarp color1) and is independent from the action of C1 and R1 transcription factors. In maize, apiforol and luteoforol are the precursors of condensed phlobaphenes. Maize lines with functional alleles of pr1 and p1 (Pr1;P1) accumulate luteoforol, while null pr1 lines with a functional or non-functional p1 allele (pr1;P1 or pr1;p1) accumulate apiforol. Apiforol lacks a hydroxyl group at the 3'-position of the flavylium B-ring, while luteoforol has this hydroxyl group. Our biochemical analysis of accumulated compounds in different pr1 genotypes showed that the pr1 encoded ZmF3'H1 has a role in the conversion of mono-hydroxylated to bi-hydroxylated compounds in the B-ring. Steady state RNA analyses demonstrated that Zmf3'h1 mRNA accumulation requires a functional p1 allele. Using a combination of EMSA and ChIP experiments, we established that the Zmf3'h1 gene is a direct target of P1. Highlighting the significance of the Zmf3'h1 gene for resistance against biotic stress, we also show here that the p1 controlled 3-deoxyanthocyanidin and C-glycosyl flavone (maysin) defence compounds accumulate at significantly higher levels in Pr1 silks as compared to pr1 silks. By virtue of increased maysin synthesis in Pr1 plants, corn ear worm larvae fed on Pr1; P1 silks showed slower growth as compared to pr1; P1 silks. Our results show that the Zmf3'h1 gene participates in the biosynthesis of phlobaphenes and agronomically important 3-deoxyflavonoid compounds under the regulatory control of P1.


Digital necroses and vascular thrombosis in severe spinal muscular atrophy.
Infantile spinal muscular atrophy (SMA) caused by homozygous SMN1 gene deletions/mutations is characterized by neuronal loss and axonopathy of motor neurons. We report two unrelated patients with severe SMA type I who had only one SMN2 copy and developed ulcerations and necroses of the fingers and toes. Sural nerve biopsy was normal in patient 1, whose affected skin displayed necroses and thrombotic occlusions of small vessels. Corresponding to a mouse model and other patients with similar findings, we believe that severe survival motor neuron (SMN) deficiency may present as vasculopathy.


Photonic crystal fibers.
Photonic crystal fibers guide light by corralling it within a periodic array of microscopic air holes that run along the entire fiber length. Largely through their ability to overcome the limitations of conventional fiber optics-for example, by permitting low-loss guidance of light in a hollow core-these fibers are proving to have a multitude of important technological and scientific applications spanning many disciplines. The result has been a renaissance of interest in optical fibers and their uses.


Steroids, aromatase and sex differentiation of the newt Pleurodeles waltl.
In the newt Pleurodeles waltl, genetic sex determination obeys female heterogamety (female ZW, male ZZ). In this species as in most of non-mammalian vertebrates, steroid hormones play a key role in sexual differentiation of gonads. In that context, male to female sex reversal can be obtained by treatment of ZZ larvae with estradiol. Male to female sex reversal has also been observed following treatment of ZZ larvae with testosterone, a phenomenon that was called the "paradoxical effect". Female to male sex reversal occurs when ZW larvae are reared at 32 degrees C during a thermosensitive period (TSP) that takes place from stage 42 to stage 54 of development. Since steroids play an important part in sex differentiation, we focussed our studies on the estrogen-producing enzyme aromatase during normal sex differentiation as well as in experimentally induced sex reversal situations. Our results based on treatment with non-aromatizable androgens, aromatase activity measurements and aromatase expression studies demonstrate that aromatase (i) is differentially active in ZZ and ZW larvae, (ii) is involved in the paradoxical effect and (iii) might be a target of temperature. Thus, the gene encoding aromatase might be one of the master genes in the process leading to the differentiation of the gonad in Pleurodeles waltl.


Efficiency enhancement in GaAs solar cells using self-assembled microspheres.
In this study we develop an efficient light harvesting scheme that can enhance the efficiency of GaAs solar cells using self-assembled microspheres. Based on the scattering of the microspheres and the theory of photonic crystals, the path length can be increased. In addition, the self-assembly of microspheres is one of the simplest and the fastest methods with which to build a 2D periodic structure. The experimental results are confirmed by the use of a simulation in which a finite-difference time-domain (FDTD) method is used to analyze the absorption and electric field of the 2D periodic structure. Both the results of the numerical simulations and the experimental results show an increase in the conversion power efficiency of GaAs solar cell of about 25% when 1 microm microspheres were assembled on the surface of GaAs solar cells.


Depressive symptoms in children and adolescents with dysthymic disorder.
This report examines clinical features of 'pure' dysthymic disorder (DD, without superimposed major depressive disorder, MDD) in a sample of children and adolescents. Profiles of symptomatology and comorbidity as a function of age and gender are described. The sample consisted of 48 subjects (22 males, 26 females, age range 7-18 years, mean age 12.1 years) screened from consecutively referred children and adolescents. All subjects were comprehensively diagnosed with structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School Age, Diagnostic Interview for Children and Adolescents-Revised), according to DSM-IV criteria. Depressed mood, irritability, loss of energy and fatigue, guilt and low self-esteem were present in more than 70% of the subjects. Differences in symptomatic profile between males and females were not significant. Children showed less symptoms than adolescents, but the symptomatic profile was comparable (only anhedonia was significantly more frequent in adolescents). Anxiety disorders were more commonly comorbid with DD, especially separation anxiety disorder in children (33%) and generalised anxiety disorder in adolescents (67%). Externalising disorders were less frequently represented in our sample (14%). An early diagnosis of 'pure' DD before the first episode of MDD is crucial for a timely intervention.


Global desertification: building a science for dryland development.
In this millennium, global drylands face a myriad of problems that present tough research, management, and policy challenges. Recent advances in dryland development, however, together with the integrative approaches of global change and sustainability science, suggest that concerns about land degradation, poverty, safeguarding biodiversity, and protecting the culture of 2.5 billion people can be confronted with renewed optimism. We review recent lessons about the functioning of dryland ecosystems and the livelihood systems of their human residents and introduce a new synthetic framework, the Drylands Development Paradigm (DDP). The DDP, supported by a growing and well-documented set of tools for policy and management action, helps navigate the inherent complexity of desertification and dryland development, identifying and synthesizing those factors important to research, management, and policy communities.


Ultraviolet optogalvanic laser spectroscopy of iron for reference wavelengths.
We present a preliminary study of a UV optogalvanic spectrum obtained by using a see-through iron hollow cathode and a tunable pulsed laser in the 240-260-nm range. The hollow cathode used and described is a homemade device that can be run in static- or dynamic-flow gas regimes. Spectra have been recorded with argon and neon buffer gases, and many classified Fe I lines have been identified. The accuracy of the measured wave numbers is limited at present to 0.05 cm(-1) by the spectral width of the UV laser. This iron optogalvanic spectrum is proposed for reference-wavelength calibration in UV laser spectroscopy, and an application to the study of Ba(+) Rydberg levels is reported. Possibilities for future developments of such a device are analyzed.


Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11).
Determining the structure of a protein by any method requires various contributions from experimental and computational sides. In a recent study, high-density cross-linking/mass spectrometry (HD-CLMS) data in combination with ab initio structure prediction determined the structure of human serum albumin (HSA) domains, with an RMSD to X-ray structure of up to 2.5 Å, or 3.4 Å in the context of blood serum. This paper reports the blind test on the readiness of this technology through the help of Critical Assessment of protein Structure Prediction (CASP). We identified between 201-381 unique residue pairs at an estimated 5% FDR (at link level albeit with missing site assignment precision evaluation), for four target proteins. HD-CLMS proved reliable once crystal structures were released. However, improvements in structure prediction using cross-link data were slight. We identified two reasons for this. Spread of cross-links along the protein sequence and the tightness of the spatial constraints must be improved. However, for the selected targets even ideal contact data derived from crystal structures did not allow modellers to arrive at the observed structure. Consequently, the progress of HD-CLMS in conjunction with computational modeling methods as a structure determination method, depends on advances on both arms of this hybrid approach.


The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase.
Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 microg/kg, 90 microg/kg, and 125 microg/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days. Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 microg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 microg/kg; P=0.757) and 60.0% (125 microg/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion. Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 microg/kg.


Your Path to Transplant: a randomized controlled trial of a tailored computer education intervention to increase living donor kidney transplant.
Because of the deceased donor organ shortage, more kidney patients are considering whether to receive kidneys from family and friends, a process called living donor kidney transplantation (LDKT). Although Blacks and Hispanics are 3.4 and 1.5 times more likely, respectively, to develop end stage renal disease (ESRD) than Whites, they are less likely to receive LDKTs. To address this disparity, a new randomized controlled trial (RCT) will assess whether Black, Hispanic, and White transplant patients' knowledge, readiness to pursue LDKT, and receipt of LDKTs can be increased when they participate in the Your Path to Transplant (YPT) computer-tailored intervention. Nine hundred Black, Hispanic, and White ESRD patients presenting for transplant evaluation at University of California, Los Angeles Kidney and Pancreas Transplant Program (UCLA-KPTP) will be randomly assigned to one of two education conditions, YPT or Usual Care Control Education (UC). As they undergo transplant evaluation, patients in the YPT condition will receive individually-tailored telephonic coaching sessions, feedback reports, video and print transplant education resources, and assistance with reducing any known socioeconomic barriers to LDKT. Patients receiving UC will only receive transplant education provided by UCLA-KPTP. Changes in transplant knowledge, readiness, pros and cons, and self-efficacy to pursue LDKT will be assessed prior to presenting at the transplant center (baseline), during transplant evaluation, and 4- and 8-months post-baseline, while completion of transplant evaluation and receipt of LDKTs will be assessed at 18-months post-baseline. The RCT will determine, compared to UC, whether Black, Hispanic, and White patients receiving YPT increase in their readiness to pursue LDKT and transplant knowledge, and become more likely to complete transplant medical evaluation and pursue LDKT. It will also examine how known patient, family, and healthcare system barriers to LDKT act alone and in combination with YPT to affect patients' transplant decision-making and behavior. Statistical analyses will be performed under an intent-to-treat approach. At the conclusion of the study, we will have assessed the effectiveness of an innovative and cost-effective YPT intervention that could be utilized to tailor LDKT discussion and education based on the needs of individual patients of different races in many healthcare settings. ClinicalTrials.gov, number NCT02181114.


A survey of the Th2R and Th3R allelic variants in the circumsporozoite protein gene of P. falciparum parasites from western Thailand.
Allelic variation in the Plasmodium falciparum circumsporozoite protein (CS) gene has been determined by sequencing the immunodominant T-cell epitopes, Th2R and Th3R, from 95 isolates from two malaria-endemic areas in the west of Thailand. Comparison with a reference sequence revealed only non-synonymous point mutations in the two epitope regions. Point mutations were found outside these epitopes in a minority of samples, and all but four were also non-synonymous. A relatively high number of variants, 11 Th2R and 9 Th3R, were detected and comprised some that had not been previously observed. However, the Th2R*05 and the Th3R*01 allelic variants predominated, as they were found in more than 70% of the 101 sequences obtained.


Synthesis and biological properties of cylindramide derivatives: evidence for calcium-dependent cytotoxicity of tetramic acid lactams.
To gain insight into the biological properties of tetramic acid lactam cylindramide 1, the analogues 4 a-d bearing a cyclopentane ring instead of the pentalene unit were prepared by tandem conjugate addition/enolate trapping of cyclopentenone 10; a Sonogashira or Stille coupling, followed by a Julia-Kocienski olefination, macrolactamisation and Lacey-Dieckmann cyclisation were the key steps. The previous NMR structure of cylindramide 1, which was based on NOE and J coupling restraints, could be refined by including residual dipolar coupling data measured for a sample of cylindramide that was aligned in polyacrylonitrile (18 %). Biological screening of cylindramide 1 and its analogues 2-epi-1, 20 and 4 revealed promising antiproliferative activity against several tumour cell lines. It turned out that the activity is strongly correlated to the functionalised pentalene system. The configuration of the cyclopentane ring and an intact tetramic acid lactam with the correct configuration seem to play an equal role in the cytotoxicity. The antiproliferative activity was found to be calcium dependent. Phenotypic characterisation of the mode of action showed vacuolisation and vesicle formation in the endoplasmic reticulum.


Oscillatory behavior of ventricular action potential duration in heart failure patients at respiratory rate and low frequency.
Oscillations of arterial pressure occur spontaneously at a frequency of approximately 0.1 Hz coupled with synchronous oscillations of sympathetic nerve activity ("Mayer waves"). This study investigated the extent to which corresponding oscillations may occur in ventricular action potential duration (APD). Fourteen ambulatory (outpatient) heart failure patients with biventricular pacing devices were studied while seated upright watching movie clips to maintain arousal. Activation recovery intervals (ARI) as a measure of ventricular APD were obtained from unipolar electrograms recorded from the LV epicardial pacing lead during steady state RV pacing from the device. Arterial blood pressure was measured non-invasively (Finapress) and respiration monitored. Oscillations were quantified using time frequency and coherence analysis. Oscillatory behavior of ARI at the respiratory frequency was observed in all subjects. The magnitude of the ARI variation ranged from 2.2 to 6.9 ms (mean 5.0 ms). Coherence analysis showed a correlation with respiratory oscillation for an average of 43% of the recording time at a significance level of p < 0.05. Oscillations in systolic blood pressure in the Mayer wave frequency range were observed in all subjects for whom blood pressure was recorded (n = 13). ARI oscillation in the Mayer wave frequency range was observed in 6/13 subjects (46%) over a range of 2.9 to 9.2 ms. Coherence with Mayer waves at the p < 0.05 significance level was present for an average of 29% of the recording time. In ambulatory patients with heart failure during enhanced mental arousal, left ventricular epicardial APD (ARI) oscillated at the respiratory frequency (approximately 0.25 Hz). In 6 patients (46%) APD oscillated at the slower Mayer wave frequency (approximately 0.1 Hz). These findings may be important in understanding sympathetic activity-related arrhythmogenesis.


The microRNA Machinery.
MicroRNAs (miRNAs) are short (~22 nucleotides) single-stranded RNA molecules that primarily function to negatively regulate gene expression at the post-transcriptional level. miRNAs have thus been implicated in the regulation of a wide variety of normal cell functions and pathophysiological conditions. The miRNA machinery consists of a series of protein complexes which act to: (1) cleave the precursor-miRNA hairpin from its primary transcript (i.e. DROSHA and DGCR8); (2) traffic the miRNA hairpin between nucleus and cytoplasm (i.e. XPO5); (3) remove the loop sequence of the hairpin by a second nucleolytic cleavage reaction (i.e. DICER1); (4) facilitate loading of the mature miRNA sequence into an Argonaute protein (typically AGO2) as part of the RNA-Induced Silencing Complex (RISC); (5) guide the loaded RISC complex to complementary, or semi-complementary, target transcripts and (6) facilitate gene silencing via one of several possible mechanisms.


Characterization of the Phd repressor-antitoxin boundary.
The P1 plasmid addiction operon (a classic toxin-antitoxin system) encodes Phd, an unstable 73-amino-acid repressor-antitoxin protein, and Doc, a stable toxin. It was previously shown by deletion analysis that the N terminus of Phd was required for repressor activity and that the C terminus was required for antitoxin activity. Since only a quarter of the protein or less was required for both activities, it was hypothesized that Phd might have a modular organization. To further test the modular hypothesis, we constructed and characterized a set of 30 point mutations in the third and fourth quarters of Phd. Four mutations (PhdA36H, V37A, I38A, and F44A) had major defects in repressor activity. Five mutations (PhdD53A, D53R, E55A, F56A, and F60A) had major defects in antitoxin activity. As predicted by the modular hypothesis, point mutations affecting each activity belonged to disjoint, rather than overlapping, sets and were separated rather than interspersed within the linear sequence. A final deletion experiment demonstrated that the C-terminal 24 amino acid residues of Phd (preceded by a methionine) retained full antitoxin activity.


First Report of Phytophthora palmivora Causing Root Rot of Cassava in China.
Cassava (Manihot esculenta) is an economically important crop grown widely in South China. Seventy percent of the cassava grown is used for starch and ethanol production and it has become the foundation of local food and bioenergy systems. In November 2010, a new root rot disease was found on cv. HuaNan205 from a cassava plantation in Danzhou, Hainan Province. Disease occurred on 30% or less of the plants. Initially, the upper leaves wilted at noon and recovered in the evening. Eventually, infected plants no longer recovered and the whole plant wilted and died. Root rot symptoms consisting of irregular brown patches occurred on the tuberous roots. Symptomatic root rot tissue was cut into 1-cm pieces, washed in distilled water, and soaked in a solution of 1% sodium hypochlorite for 3 min. A subsection was cut from each sterilized piece, placed on a plate of V8 agar medium, and incubated at 28°C for 7 days. Pathogenicity was established by following Koch's postulates. In July 2011, 10 plants of cassava cv. HuaNan205 were selected from a disease-free plantation in Danzhou. The pathogen was cultivated on V8 agar at 28°C for 14 days. Four holes were established 15 cm from the base of the cassava plants. Five plants were inoculated with 100 mL of the mycelial suspension in each of the four spots and covered by soil. The other five plants were treated with sterile water as control. Plants were maintained for 4 months. All five of the inoculated plants wilted and two died, while the control plants grew normally. Symptoms similar to the original root lesions were observed on tuberous roots of inoculated plants, while only scars formed on tuberous roots of control plants. The pathogen was reisolated from the lesions of inoculated plants. Microscopic examination showed the sporangia as papillate and ovoid with the widest part close to the base. They were easily washed off and each detached sporangium contained a short pedicel 1.2 to 6.9 μm long, average 2.9 μm. Chlamydospores were readily observed on diseased roots and observed in pure cultures on V8 agar. Morphological characteristics of the specimen were similar to the descriptions for Phytophthora palmivora (2). Genomic DNA of this isolate was extracted with a cetyltrimethylammoniumbromide protocol (3) from mycelium and used as a template for amplification of the internal transcribed spacer (ITS) region of rDNA with primer pair ITS1/ITS4 (1). The sequence (GenBank Accession No. HE580279) exactly matched several sequences (e.g., GenBank Accession Nos. HQ237481.1, AY745750, and AY745751) of P. palmivora. To our knowledge, this is the first report of root rot caused by P. palmivora on cassava in China. References: (1) D. E. L. Cooke et al. Fungal Genet. Biol. 30:17, 2000. (2) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St. Paul, MN, 1996. (3) J. R. Xu et al. Genetics 143:175, 1996.


Oral intake of Lactobacillus rhamnosus M21 enhances the survival rate of mice lethally infected with influenza virus.
Influenza viruses cause acute respiratory disease. Because of the high genetic variability of viruses, effective vaccines and antiviral agents are limited. Considering the fact that the site of influenza virus entry is the mucosa of the upper respiratory tract, probiotics that can enhance mucosal immunity as well as systemic immunity could be an important source of treatment against influenza infection. Mice were fed with Lactobacillus rhamnosus M21 or skim milk and were challenged with influenza virus. The resulting survival rate, lung inflammation, and changes in the cytokine and secretory immunoglobulin A (sIgA) levels were examined. Because of infection (influenza virus), all the mice in the control group and 60% of the mice in the L. rhamnosus M21 group died; however, the remaining 40% of the mice fed with L. rhamnosus M21 survived the infection. Pneumonia was severe in the control group but moderate in the group treated with L. rhamnosus M21. Although there were no significant changes in the proinflammatory cytokines in the lung lysates of mice collected from both groups, levels of interferon-γ and interleukin-2, which are representative cytokines of type I helper T cells, were significantly increased in the L. rhamnosus M21-treated group. An increase in sIgA as well as the diminution of inflammatory cells in bronchoalveolar lavage fluid was also observed in the L. rhamnosus M21-treated group. These results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection.


From virility to virtue: the psychology of apology in honor cultures.
In honor cultures, relatively minor disputes can escalate, making numerous forms of aggression widespread. We find evidence that honor cultures' focus on virility impedes a key conflict de-escalation strategy-apology-that can be successfully promoted through a shift in mindset. Across five studies using mixed methods (text analysis of congressional speeches, a cross-cultural comparison, surveys, and experiments), people from honor societies (e.g., Turkey and US honor states), people who endorse honor values, and people who imagine living in a society with strong honor norms are less willing to apologize for their transgressions (studies 1-4). This apology reluctance is driven by concerns about reputation in honor cultures. Notably, honor is achieved not only by upholding strength and reputation (virility) but also through moral integrity (virtue). The dual focus of honor suggests a potential mechanism for promoting apologies: shifting the focus of honor from reputation to moral integrity. Indeed, we find that such a shift led people in honor cultures to perceive apologizing more positively and apologize more (study 5). By identifying a barrier to apologizing in honor cultures and illustrating ways to overcome it, our research provides insights for deploying culturally intelligent conflict-management strategies in such contexts.


Sox18 and Sox7 play redundant roles in vascular development.
Mutations in SOX18 cause the human hypotrichosis-lymphedema-telangiectasia (HLT) syndrome. Their murine counterparts are the spontaneous ragged mutants, showing combined defects in hair follicle, blood vessel, and lymphatic vessel development. Mice null for Sox18 display only mild coat defects, suggesting a dominant-negative effect of Sox18/ragged mutations and functional redundancy between Sox18 and other Sox-F proteins. We addressed this point in zebrafish. The zebrafish homologs of Sox18 and of Sox7 are expressed in angioblasts and in the endothelial component of nascent blood vessels in embryos. Knockdown of either gene, using moderate doses of specific morpholinos, had minimal effects on vessels. In contrast, simultaneous knockdown of both genes resulted in multiple fusions between the major axial vessels. With combined use of transgenic lines and molecular markers, we could show that endothelial cells are specified, but fail to acquire a correct arteriovenous identity. Venous endothelial cell differentiation was more severely affected than arterial. Thus, sox7 and sox18 play redundant but collectively essential roles in the establishment of proper arteriovenous identity in zebrafish. Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT.


Serological diagnostics in the detection of IgG autoantibodies against human collagen VII in epidermolysis bullosa acquisita: a multicentre analysis.
Epidermolysis bullosa acquisita (EBA) is a rare, potentially devastating autoimmune disease of the skin. IgG autoantibodies directed against type VII collagen (Col7), the major component of anchoring fibrils, induce skin fragility leading to cutaneous and mucocutaneous blister formation, which is mostly of a scarring phenotype. Thus, powerful and reproducible diagnostic assays are critical to establish the diagnosis of EBA early to avoid irreversible sequelae. The present international, retrospective multicentre study included a large cohort of patients with EBA and evaluated the diagnostic power of four different diagnostic assays for the detection of anti-Col7 IgG autoantibodies. Overall, 95 EBA sera and 200 control sera consisting of 100 bullous pemphigoid sera, 50 pemphigus vulgaris sera and 50 sera of healthy controls were tested for anti-Col7 IgG autoantibodies using indirect immunofluorescence (IIF), two commercial enzyme-linked immunosorbent assay (ELISA) systems and Western blot (WB) analysis. EBA sera were taken from patients with positive direct immunofluorescence and IgG reactivity in at least one of the immunoserological assays (IIF, ELISA, WB). A Col7-NC1/NC2 ELISA (MBL, Nagoya, Japan) showed the highest sensitivity (97·9%), followed by a Col7-NC1 ELISA (Euroimmun, Lübeck, Germany) (89·5%), WB with Col7-NC1 (85·3%), and IIF on saline-split human skin (74·7%). The specificities of both ELISA systems were comparable (NC1 98·7%, NC1/NC2 99·3%). Furthermore, WB was more sensitive than IIF, which was more specific. The two commercially available ELISA systems allow for a highly sensitive and specific diagnosis of EBA. The sensitivity of the Col7-NC1/NC2 ELISA is significantly higher compared with the ELISA based on the Col7-NC1 domain only.


The investigation and management of unilateral nipple discharge.
Between 16,000 and 48,000 women are estimated to present to UK breast clinics with nipple discharge each year. The incidence of malignancy in these women is 2.7-24.2%. Currently, there is no consensus on the best way to investigate and manage these women. The aim of this study was to assess the rate of malignancy in women presenting with unilateral nipple discharge, and to evaluate the role of examination, imaging and cytology in reliably predicting outcome. Breast units were asked to prospectively collect data on all new patients with unilateral nipple discharge. Data collected included discharge colour, whether it was uniductal or multiductal, examination and imaging findings, cytology results and outcome. Complete datasets were submitted by 5 units on 228 patients. The incidence of malignancy was 4.4%. Clinical examination was valuable in detecting malignancy and multiductal discharge was not related to malignancy. The positive predictive value for detecting malignancy for an abnormality found on mammography was 53.5% and for ultrasonography, it was 65.2%. The role of cytology in detecting malignancy was inconclusive with positive predictive values of the presence of red blood cells and epithelial cells at 6.1% and 10.7% respectively. A large number of women are investigated for nipple discharge (with huge resource implications) but there is little reliable evidence on the best way to investigate and manage these patients. A larger study is needed to evaluate the role of investigations in nipple discharge to produce guidelines on optimal management.


A role for p38 MAPK in the regulation of ciliary motion in a eukaryote.
Motile cilia are essential to the survival and reproduction of many eukaryotes; they are responsible for powering swimming of protists and small multicellular organisms and drive fluids across respiratory and reproductive surfaces in mammals. Although tremendous progress has been made to comprehend the biochemical basis of these complex evolutionarily-conserved organelles, few protein kinases have been reported to co-ordinate ciliary beat. Here we present evidence for p38 mitogen-activated protein kinase (p38 MAPK) playing a role in the ciliary beat of a multicellular eukaryote, the free-living miracidium stage of the platyhelminth parasite Schistosoma mansoni. Fluorescence confocal microscopy revealed that non-motile miracidia trapped within eggs prior to hatching displayed phosphorylated (activated) p38 MAPK associated with their ciliated surface. In contrast, freshly-hatched, rapidly swimming, miracidia lacked phosphorylated p38 MAPK. Western blotting and immunocytochemistry demonstrated that treatment of miracidia with the p38 MAPK activator anisomycin resulted in a rapid, sustained, activation of p38 MAPK, which was primarily localized to the cilia associated with the ciliated epidermal plates, and the tegument. Freshly-hatched miracidia possessed swim velocities between 2.17 - 2.38 mm/s. Strikingly, anisomycin-mediated p38 MAPK activation rapidly attenuated swimming, reducing swim velocities by 55% after 15 min and 99% after 60 min. In contrast, SB 203580, a p38 MAPK inhibitor, increased swim velocity by up to 15% over this duration. Finally, by inhibiting swimming, p38 MAPK activation resulted in early release of ciliated epidermal plates from the miracidium thus accelerating development to the post-miracidium larval stage. This study supports a role for p38 MAPK in the regulation of ciliary-beat. Given the evolutionary conservation of signalling processes and cilia structure, we hypothesize that p38 MAPK may regulate ciliary beat and beat-frequency in a variety of eukaryotes.


Efficacy of ECT in severe obsessive-compulsive disorder with Parkinson's disease.
A man in his 60's was admitted following a serious suicide attempt secondary to severe obsession with bowel movements and severe depression. He had multiple previous admissions with similar presentations and responded partially to psychotropic medications. It was transpired that obsessive compulsive disorder preceded depression and being overwhelmed with this obsession related to bowel movement, he decided to end his life. Electro-convulsive therapy was commenced with good results. His obsessive-compulsive disorder came under control to a greater extent and there was an improvement in his mood.


MRI arterial enhancement fraction in hepatic fibrosis and cirrhosis.
Fibrosis leads to altered liver hemodynamics. The arterial enhancement fraction, which is defined as the ratio of hepatic arterial perfusion to the total hepatic perfusion, can provide noninvasive assessment of hepatic perfusion. The aim of this study was to show that the arterial enhancement fraction values correlate with histopathologic stage of liver fibrosis, thus providing a reliable noninvasive radiologic alternative to liver biopsy for the detection and staging of hepatic fibrosis. We evaluated hepatic fibrosis stage (denoted by Metavir score [F]) and arterial enhancement fraction of patients who underwent standard triphasic liver MRI and liver biopsy within 1 year from January 2005 to December 2010. Prototype software was used to calculate the arterial enhancement fraction. Statistical analysis included nonparametric tests and area under the receiver operating characteristic curve (AUC). One hundred fourteen patients (69 men and 45 women; median age, 52.5 years) were divided into groups according to the Metavir score. The mean arterial enhancement fraction was 24.2% ± 11.6% for F0, 35.2% ± 18.7% for F1, 30.2% ± 12.5% for F2, 37.5% ± 16.4% for F3, and 59.8% ± 16.6% for F4. The mean arterial enhancement fraction values differed significantly between Metavir scores (p < 0.001) and showed a positive correlation with Metavir score (r = 0.693; p < 0.001). The optimal mean arterial enhancement fraction cutoffs were 32.96% or more (AUC = 0.8343) for detection of mild fibrosis, 33.33% or more (AUC = 0.8524) for detection of moderate fibrosis, 38.43% or more (AUC = 0.8819) for detection of severe fibrosis, and 45.76% or more (AUC = 0.9161) for detection of cirrhosis. Arterial enhancement fraction using triple-phase MRI can provide a reliable noninvasive method to assess hepatic fibrosis.


Effect of and satisfaction with www.elearnSCI.org for training of nurse students: a submodule pilot study.
Interventional training session. To investigate the effect and satisfaction with didactic training using printed text of a submodule of www.elearnSCI.org for nurse students and to assess the answers of each question. A Peking University teaching hospital. Twenty-eight nurse students in two groups (14 in each) were involved. Only group A received a translated print-out of the slides from the 'Nursing management' submodule in www.elearnSCI.org for 1-h self-study before the class. At the beginning of class, both groups were tested using the self assessment questions. Then, a lecture according to the content of this submodule was carried out and afterwards both groups answered the self assessment questions again. Finally, both groups filled in a training course satisfaction questionnaire. At the beginning of the class, the mean score (max 9) of the self assessment in group A was 7.1 ± 1.1, which was significantly higher than that in group B (4.9 ± 1.7, P = 0.001). After the lecture, the mean score of the self assessment in group A had insignificantly increased to 7.4 ± 1.3, whereas in group B it increased significantly to 6.9 ± 0.8 (P < 0.001). The mean score (max 50) of the training course satisfaction questionnaire was 42.8 ± 5.2. Sixty-four percentage of the students indicated that they were very satisfied (overall score ⩾ 42) with the training and no students were unsatisfied (overall score < 30). Self-study and lecture presentation are effective methods for training the content of www.elearnSCI.org to nurse students. The training satisfaction of this submodule within the www.elearnSCI.org is favorable.


Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation.
We have examined the roles of Fc receptors and complement receptors in mediating the interaction of sensitized sheep erythrocytes (E) with activated and with nonactivated mouse peritoneal macrophages. Both activated and nonactivated macrophages ingest IgG-coated erythrocytes [E(IgG)]; activated cells intest 1.5-2 times as man E(IgG) as do nonactivated macrophages. Thus, there is a quantitative difference in Fc receptor-mediated ingestion between activated and nonactivated macrophages. There is, however, a qualitative difference in function of complement receptors of activated and nonactivated macrophages. Nonactivated macrophages avidly bind complement-coated E [E(IgM)Ia1, but do not ingest them to a significant degree. Activated macrophages, on the other hand, bind and ingest E(IgM)C. The possibility of Fc receptor participation in mediating ingestion of E(IgM)C by activated macrophages was eliminated by blocking Fc receptors with an antimacrophage IgG fraction. Activated macrophages treated with antimacrophage IgG did not ingest E(igG) but did ingest both E(IgM)C AND E(IgM)C. Nonactivated macrophages treated with antimacrophage IgG did not interact at all with E(IgG). These cells bound, but did not ingest, E(IgM)C and E(IgM)C. Complement receptor-mediated ingestion is a marker for macrophage activation and may be physiologically important in the elimination of complement-coated particles.


DNA binding, antioxidant and antimicrobial activities of homo- and heteronuclear copper(II) and nickel(II) complexes with new oxime-type ligands.
Some homo- and heteronuclear Cu(II) and Ni(II) complexes of new oxime-type ligands were tested against several pathogenic microorganisms to assess their antimicrobial potentials. The antimicrobial activities of complexes were evaluated in terms of minimum inhibitory concentration (MIC; μg/μL) and it was observed that the complexes possess moderate antimicrobial properties. The binding of the complexes with DNA were also investigated by using UV-Vis spectroscopy. It was seen that three of the complexes could bind to DNA through an intercalative mode while the other complexes could have other mechanisms. Furthermore, the antioxidant efficiencies of the metal complexes were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavening activities. Due to the observed IC(50) values, they are potential drugs to eliminate the radicals.


Acinetobacter species as model microorganisms in environmental microbiology: current state and perspectives.
Acinetobacter occupies an important position in nature because of its ubiquitous presence in diverse environments such as soils, fresh water, oceans, sediments, and contaminated sites. Versatile metabolic characteristics allow species of this genus to catabolize a wide range of natural compounds, implying active participation in the nutrient cycle in the ecosystem. On the other hand, multi-drug-resistant Acinetobacter baumannii causing nosocomial infections with high mortality has been raising serious concerns in medicine. Due to the ecological and clinical importance of the genus, Acinetobacter was proposed as a model microorganism for environmental microbiological studies, pathogenicity tests, and industrial production of chemicals. For these reasons, Acinetobacter has attracted significant attention in scientific and biotechnological fields, but only limited research areas such as natural transformation and aromatic compound degradation have been intensively investigated, while important physiological characteristics including quorum sensing, motility, and stress response have been neglected. The aim of this review is to summarize the recent achievements in Acinetobacter research with a special focus on strain DR1 and to compare the similarities and differences between species or other genera. Research areas that require more attention in future research are also suggested.


Calcium supplementation in clinical practice: a review of forms, doses, and indications.
Most Americans do not meet the adequate intake (AI) for calcium; calcium supplements can help meet requirements. Calcium supplementation has been found to be beneficial for bone health in children, young adults, and menopausal women. In addition to calcium, vitamin D is necessary for bone health and is generally deficient in the industrialized world. Calcium from carbonate and citrate are the most common forms of calcium supplements. Calcium carbonate, the most cost-effective form, should be taken with a meal to ensure optimal absorption. Calcium citrate can be taken without food and is the supplement of choice for individuals with achlorhydria or who are taking histamine-2 blockers or protein-pump inhibitors. Calcium lactate and calcium gluconate are less concentrated forms of calcium and are not practical oral supplements. Research on hydroxyapatite as a source of calcium is limited, so this form of calcium is not recommended. The maximum dose of elemental calcium that should be taken at a time is 500 mg. U.S. Pharmacopeia-verified calcium supplements meet vigorous manufacturing and quality requirements. Absorption from calcium-fortified beverages varies and in general is not equal to that of milk. Potential adverse effects of calcium supplementation include gastrointestinal complaints. Renal calculi in most studies have not been associated with calcium supplementation. The risk of advanced and fatal prostate cancer has been associated with calcium intakes from food or supplements in amounts >1500 mg/d.


Distribution of Aedes albopictus (Diptera, Culicidae) in southwestern Pacific countries, with a first report from the Kingdom of Tonga.
Aedes (Stegomyia) albopictus is currently one of the most notorious globally invasive mosquito species. Its medical importance is well documented, and its fast expansion throughout most continents is being monitored with concern. It is generally assumed that its expansion through the Western Pacific island countries has not progressed since its establishment in Fiji in 1989. However, the current status of Ae. albopictus in the Pacific region is largely unknown. According to data from the literature and our own observations, Ae. albopictus is currently present in the following countries of the southern Pacific region: Papua New Guinea, Solomon Islands, Fiji, and the Kingdom of Tonga, where it was first detected in July 2011. It is absent from New Caledonia and French Polynesia where routine entomological surveillance is carried out, and was not detected during entomological work in 2007, either on the Cook Islands or on the Wallis and Futuna Islands. The species was not reported from American Samoa in 2004, but it is mentioned as probably present in Vanuatu. This is the first report of Ae. albopictus in Tonga. The introduction and establishment of Ae. albopictus in Tonga was expected due to the geographical proximity of this country to Fiji where the species is strongly established. The pathway of introduction is unknown. The expansion of Ae. albopictus in the Pacific region poses an increasing threat to public health given the role this mosquito plays as primary vector of emerging infectious diseases such as Chikungunya fever.


Adipose-derived stromal cells overexpressing vascular endothelial growth factor accelerate mouse excisional wound healing.
Angiogenesis is essential to wound repair, and vascular endothelial growth factor (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein (GFP) using biodegradable poly (β-amino) esters (PBAE). Cells transfected using Lipofectamine 2000, a commercially available transfection reagent, were included as controls. ASCs transfected using PBAEs showed enhanced transfection efficiency and 12-15-fold higher VEGF production compared with cells transfected using Lipofectamine 2000 (*P < 0.05). When transplanted into a mouse wild-type excisional wound model, VEGF-overexpressing ASCs led to significantly accelerated wound healing, with full wound closure observed at 8 days compared to 10-12 days in groups treated with ASCs alone or saline control (*P < 0.05). Histology and polarized microscopy showed increased collagen deposition and more mature collagen fibers in the dermis of wound beds treated using PBAE/VEGF-modified ASCs than ASCs alone. Our results demonstrate the efficacy of using nonviral-engineered ASCs to accelerate wound healing, which may provide an alternative therapy for treating many diseases in which wound healing is impaired.


DNMT1 maintains progenitor function in self-renewing somatic tissue.
Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance, the role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unclear. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis showed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, UHRF1 (refs 9, 10), a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A and B, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue.


The Effect of Parental Medical History on the Prevalence of Cerebrovascular Diseases in Their Children in an Iranian Population.
Still a controversial issue, family history is known as a risk factor for the development of Cerebrovascular Diseases (CVD). In this study, we aimed to evaluate the relationship between parental history and risk of CVD in their offspring in Iranian population. Isfahan Cohort Study (ICS) included total 6504 healthy participants which were randomly selected through a two-stage cluster sampling method from three districts. The participants were followed prospectively for 10 years. The diagnosis of CVD were confirmed by expert panelist. Clinically validated history of CVD was established for definition of parental history of CVD. Types of history were categorized into paternal, maternal, both parents, and no history. The prevalence of CVD is generally higher among female offspring compared with male ones (P<0.001). The relative risk of CVD with maternal history was not significant (95%CI=0.95-2.29). By adjusted model analysis, history of CVD in both parents affected the risk of CVD in their male children (RR=2.13, P=0.033, 95%CI). By crude model analysis, maternal history of CVD (P=0.047), history of CVD in both parents (P=0.032), and maternal history of hypertension (P=0.005) were determined as risk factors of CVD in offspring. Indeed, the mean age of CVD in offspring decreases based on this order: history of hypertension in parents, paternal history of CVD in both parents, maternal history of CVD, and no history (P<0.001). Early and regular screening for CVD development is necessary in female offspring of the families with the present history of CVD from maternal side. This group are at risk and should be considered as the target group for screening and taking preventive measures.


A hierarchic approach to the design of hexameric helical barrels.
The design of large macromolecular assemblies is an endeavor with implications for protein engineering as well as nanotechnology. A hierarchic approach was used to design an antiparallel hexameric, tubular assembly of helices. In previous studies, a domain-swapped, dimeric three-helix bundle was designed from first principles. In the crystal lattice, three dimers associate around a 3-fold rotational axis to form a hexameric assembly. Although this hexameric assembly was not observed in solution, it was possible to stabilize its formation by changing three polar residues per monomer to hydrophobic (two Phe and one Trp) residues. Molecular models based on the crystallographic coordinates of DSD (PDB accession code 1G6U) show that these side-chains pack in the central cavity (the "supercore") of the hexameric bundle. Analytical ultracentrifugation, fluorescence spectroscopy, CD spectroscopy, and guanidine-HCl denaturation were used to determine the assembly of the hexamer. To probe the requirements for stabilizing the hexamer, we systematically varied the polarity and steric bulk of one of the Phe residues in the supercore of the hexamer. Depending on the nature of this side-chain, it is possible to modulate the stability of the hexamer in a predictable manner. This family of hexameric proteins may provide a useful framework for the construction of proteins that change their oligomeric states in response to binding of small molecules.


Vegetable oil hybrid films cross-linked at the air-water interface: formation kinetics and physical characterization.
Vegetable oil based hybrid films were developed thanks to a novel solvent- and heating-free method at the air-water interface using silylated castor oil cross-linked via a sol-gel reaction. To understand the mechanism of the hybrid film formation, the reaction kinetics was studied in detail by using complementary techniques: rheology, thermogravimetric analysis, and infrared spectroscopy. The mechanical properties of the final films were investigated using nano-indentation, whereas their structure was studied using a combination of wide-angle X-ray scattering, electron diffraction, and atomic force microscopy. We found that solid and transparent films form in 24 hours and, by changing the silica precursor to castor oil ratio, their mechanical properties are tunable in the MPa-range by about a factor of twenty. In addition to that, a possible optimization of the cross-linking reaction with different catalysts was explored, and finally cytotoxicity tests were performed on fibroblasts proving the absence of film toxicity. The results of this work pave the way to a straightforward synthesis of castor-oil films with tunable mechanical properties: hybrid films cross-linked at the air-water interface combine an easy and cheap spreading protocol with the features of their thermal history optimized for possible future micro/nano drug loading, thus representing excellent candidates for the replacement of non-environmentally friendly petroleum-based materials.


Cognitive and affective bases of opinion survey responses.
Two experiments investigated the determinants of agreement with propositions that advocated social privileges for either people in general or specific social groups. Liking for the group to which a group-specific proposition referred had a contrast effect on agreement with a related general proposition that was considered immediately after it, but had a positive influence on agreement with a general proposition that did not occur until several items later. The latter effect was eliminated by instructing Ss to base their judgments on the consequences of the policies described in the propositions. Instructions to base judgments on affective reactions to the propositions produced contrast effects of group-specific propositions on judgments of general ones regardless of whether these items were separated or together in the questionnaire.


Manual therapy: a critical assessment of role in the profession of physical therapy.
Interest in manual therapy appears to continue to grow among physical therapy clinicians and educators throughout the world even though the underlying concepts and techniques have not been justified by a knowledge base. The purposes of this article are to critically assess the role of manual therapy within the physical therapy profession and to provide an introduction to the other articles in this special issue. Eisner's model of explicit, implicit, and null curricula is used as a framework for our analysis and our discussion of manual therapy. The explicit area of manual therapy includes discussions of the definition and the role of manual therapy, the scientific rationale for manual therapy, and manual therapy in education and a comparison of manual therapy evaluative frameworks. The implicit area deals with the role of clinical decision making and critical thinking in manual therapy in education and rehabilitation. In the null (unaddressed) area of manual therapy, we suggest directions for future development and research.


Toward rational design of ribonuclease inhibitors: high-resolution crystal structure of a ribonuclease A complex with a potent 3',5'-pyrophosphate-linked dinucleotide inhibitor.
The crystal structure of ribonuclease A (RNase A) in complex with pdUppA-3'-p [5'-phospho-2'-deoxyuridine-3'-pyrophosphate (P'-->5') adenosine 3'-phosphate] has been determined at 1.7 A resolution. This dinucleotide is the most potent low molecular weight inhibitor of RNase A reported to date (K(i) = 27 nM) and is also effective against two major nonpancreatic RNases: eosinophil-derived neurotoxin and RNase-4; in all cases, tight binding in large part derives from the unusual 3',5'-pyrophosphate internucleotide linkage [Russo, N., and Shapiro, R. (1999) J. Biol. Chem. 274, 14902-14908]. The design of pdUppA-3'-p was based on the crystal structure of RNase A complexed with 5'-diphosphoadenosine 3'-phosphate (ppA-3'-p) [Leonidas, D. D., Shapiro, R., Irons, L. I., Russo, N., and Acharya, K. R. (1997) Biochemistry 36, 5578-5588]. The adenosine of pdUppA-3'-p adopts an atypical syn conformation not observed for standard adenosine nucleotides bound to RNase A. This conformation, which allows extensive interactions with Asn 67, Gln 69, Asn 71, and His 119, is associated with the placement of the 5'-beta-phosphate of the adenylate, rather than alpha-phosphate, at the site where substrate phosphodiester bond cleavage occurs. The contacts of the deoxyuridine 5'-phosphate portion of pdUppA-3'-p appear to be responsible for the 9-fold increased affinity of this compound as compared to ppA-3'-p: the uracil base binds to Thr 45 in the same manner as previous pyrimidine inhibitors, and the terminal 5'-phosphate is positioned to form medium-range Coulombic interactions with Lys 66. The full potential benefit of these added interactions is not realized because of compensatory losses of hydrogen bonds of Lys 7 and Gln 11 with the terminal 3'-phosphate and the adenylate 5'-alpha-phosphate, which were not predicted by modeling. The results reported here have important implications for the design of improved inhibitors of RNase A and for the development of therapeutic agents to control the activities of RNase homologues such as eosinophil-derived neurotoxin and angiogenin that have roles in human pathologies.


Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group.
There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine. The European Helicobacter Pylori Study Group therefore organised a meeting in Maastricht of H pylori experts, primary care physicians and representatives of National Societies of Gastroenterology from Europe to establish consensus guidelines on the management of H pylori at the primary care and specialist levels, and to consider general health care issues associated with the infection. As in previous guidelines, eradication therapy was recommended in all H pylori positive patients with peptic ulcer disease. Additionally, at the primary care level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis is recommended by non-invasive means (13C urea breath test, serology) and if H pylori positive the patient should be treated. Moreover, at the specialist level the indications for eradication of H pylori were also broadened to include H pylori positive patients with functional dyspepsia in whom no other possible causes of symptoms are identified by the specialist (after a full investigation including endoscopy, ultrasound and other necessary investigations), patients with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed in specialised centres) and those with gastritis with severe macro- or microscopic abnormalities. There was consensus that treatment regimens should be simple, well tolerated and achieve an eradication rate of over 80% on an intention to treat basis. It was strongly recommended, therefore, that eradication treatment should be with proton pump inhibitor based triple therapy for seven days, using a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin.


Pannexin1 contributes to pathophysiological ATP release in lipoapoptosis induced by saturated free fatty acids in liver cells.
Hepatocyte lipoapoptosis induced by saturated free fatty acids (FFA) contributes to hepatic inflammation in lipotoxic liver injury, and the cellular mechanisms involved have not been defined. Recent studies have shown that apoptosis in nonhepatic cells stimulates ATP release via activation of pannexin1 (panx1), and extracellular ATP functions as a proinflammatory signal for recruitment and activation of the inflammatory cells. However, it is not known whether lipoapoptosis stimulates ATP release in liver cells. We found that lipoapoptosis induced by saturated FFA stimulated ATP release in liver cells that increased extracellular ATP concentration by more than fivefold above the values observed in healthy cells. This sustained pathophysiological ATP release was not dependent on caspase-3/7 activation. Inhibition of c-Jun NH(2)-terminal kinase (JNK), a key mediator of lipoapoptosis, with SP600125 blocked pathophysiological ATP release in a dose-dependent manner. RT-PCR analysis indicated that panx1 is expressed in hepatocytes and multiple liver cell lines. Notably, inhibition of panx1 expression with short hairpin (sh)RNA inhibited in part pathophysiological ATP release. Moreover, lipoapoptosis stimulated uptake of a membrane impermeable dye YoPro-1 (indicative of panx1 activation), which was inhibited by panx1 shRNA, probenecid, and mefloquine. These results suggest that panx1 contributes to pathophysiological ATP release in lipoapoptosis induced by saturated FFA. Thus panx1 may play an important role in hepatic inflammation by mediating an increase in extracellular ATP concentration in lipotoxic liver injury.


Is there a role for workplaces in reducing employees' driving to work? Findings from a cross-sectional survey from inner-west Sydney, Australia.
The role of workplaces in promoting active travel (walking, cycling or using public transport) is relatively unexplored. This study explores the potential for workplaces to reduce employees' driving to work in order to inform the development of workplace interventions for promoting active travel. An analysis of a cross-sectional survey was conducted using data from parents/guardians whose children participated in the Central Sydney Walk to School Program in inner-west Sydney, Australia. A total of 888 parents/guardians who were employed and worked outside home were included in this analysis. The role of the workplace in regards to active travel was assessed by asking the respondents' level of agreement to eight statements including workplace encouragement of active travel, flexible working hours, public transport availability, convenient parking, shower and change rooms for employees and whether they lived or worked in a safe place. Self-reported main mode of journey to work and demographic data were collected through a self-administrated survey. Binary logistic regression modelling was used to ascertain independent predictors of driving to work. Sixty nine per cent of respondents travelled to work by car, and 19% agreed with the statement, "My workplace encourages its employees to go to and from work by public transport, cycling and/or walking (active travel)." The survey respondents with a workplace encouraging active travel to work were significantly less likely to drive to work (49%) than those without this encouragement (73%) with an adjusted odds ratio (AOR) of 0.41 (95% CI 0.23-0.73, P = 0.002). Having convenient public transport close to the workplace or home was also an important factor that could discourage employees from driving to work with AOR 0.17 (95% CI 0.09-0.31, P < 0.0001) and AOR 0.50 (95% CI 0.28-0.90, P = 0.02) respectively. In contrast, convenient parking near the workplace significantly increased the likelihood of respondents driving to work (AOR 4.6, 95% CI 2.8-7.4, P < 0.0001). There is a significant inverse association between the perception of workplace encouragement for active travel and driving to work. Increases in the number of workplaces that encourage their employees to commute to work via active travel could potentially lead to fewer employees driving to work. In order to make active travel more appealing than driving to work, workplace interventions should consider developing supportive workplace policies and environments.


Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.
During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.


Can improved prescription medication labeling influence adherence to chronic medications? An evaluation of the Target pharmacy label.
Prescription medication labels contain valuable health information, and better labels may enhance patient adherence to chronic medications. A new prescription medication labeling system was implemented by Target pharmacies in May 2005 and aimed to improve readability and understanding. We evaluated whether the new Target label influenced patient medication adherence. Using claims from two large health plans, we identified patients with one of nine chronic diseases who filled prescriptions at Target pharmacies and a matched sample who filled prescriptions at other community pharmacies. We stratified our cohort into new and prevalent medication users and evaluated the impact of the Target label on medication adherence. We used linear regression and segmented linear regression to evaluate the new-user and prevalent-user analyses, respectively. Our sample included 23,745 Target users and 162,368 matched non-Target pharmacy users. We found no significant change in adherence between new users of medications at Target or other community pharmacies (p = 0.644) after implementing the new label. In prevalent users, we found a 0.0069 percent reduction in level of adherence (95% CI -0.0138-0.0; p < 0.001) and a 0.0007 percent increase in the slope in Target users (the monthly rate of change of adherence) after implementation of the new label (95% CI 0.0001-0.0013; p = 0.001). We found no changes in adherence of chronic medication in new users, and small and likely clinically unimportant changes in prevalent users after implementation of the new label. While adherence may not be improved with better labeling, evaluation of the effect of labeling on safety and adverse effects is needed.


Electronic speckle photography: increased accuracy by nonintegral pixel shifting.
Electronic speckle photography offers a simple and fast technique for measuring in-plane displacement fields in solid and fluid mechanics. An improved algorithm is presented and analyzed by use of both computer-simulated speckle patterns and real experiments. The idea of the improved algorithm is to maximize the correlation between correlated subimages from different images by shifting one of them by nonintegral pixel values. The improved algorithm was found to determine displacement components with an uncertainty of less than 1% of a pixel and with negligible systematic errors in ideal experimental conditions.


Replication study of SNP associations for colorectal cancer in Hong Kong Chinese.
Recent genome-wide association studies of colorectal cancer (CRC) have identified common single-nucleotide polymorphisms (SNPs) mapping to 10 independent loci that confer modest increased risk. These studies have been conducted in European populations and it is unclear whether these observations generalise to populations with different ethnicities and rates of CRC. An association study was performed on 892 CRC cases and 890 controls recruited from the Hong Kong Chinese population, genotyping 32 SNPs, which were either associated with CRC in previous studies or are in close proximity to previously reported risk SNPs. Twelve of the SNPs showed evidence of an association. The strongest associations were provided by rs10795668 on 10p14, rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear association between CRC risk and the number of independent risk variants possessed by an individual (P=2.29 × 10(-5)). These results indicate that some previously reported SNP associations also impact on CRC risk in the Chinese population. Possible reasons for failure of replication for some loci include inadequate study power, differences in allele frequency, linkage disequilibrium structure or effect size between populations. Our results suggest that many associations for CRC are likely to generalise across populations.


Sex steroid hormone concentrations and risk of death in US men.
The association of sex hormone levels with mortality over a median of 16 years of follow-up was evaluated in a prospective cohort study. The study included 1,114 US men who participated in phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey Mortality Study and had no history of cardiovascular disease or cancer at baseline. Multivariable adjusted hazard ratios for all-cause mortality associated with a decrease in hormone concentration equal to the difference between the 90th and 10th percentiles of the sex hormone distributions were estimated by using proportional hazards regression. The hazard ratios associated with low free testosterone and low bioavailable testosterone levels were 1.43 (95% confidence interval (CI): 1.09, 1.87) and 1.52 (95% CI: 1.15, 2.02), respectively, for follow-up between baseline and year 9; they were 0.94 (95% CI: 0.51, 1.72) and 0.98 (95% CI: 0.56, 1.72), respectively, for follow-up between year 9 and year 18. Men with low free and bioavailable testosterone levels may have a higher risk of mortality within 9 years of hormone measurement. Future studies should be conducted to fully characterize the association of low free and bioavailable testosterone concentrations and mortality in men and to describe the mechanism underlying the association.


Gingival recession: epidemiology and risk indicators in a representative urban Brazilian population.
Gingival recession is a common manifestation of periodontal disease, but it is also associated with other risk factors. A few studies have investigated the epidemiology and risk factors of this condition. This study describes the epidemiology of gingival recession in a representative, urban Brazilian population and assesses various risk indicators. A representative sample of 1,460 subjects was selected using a multi-stage, probability, cluster sampling strategy. The subjects were interviewed using a structured questionnaire and had a full-mouth clinical examination in a mobile examination center. More than half (51.6%) and 22.0% of the individuals and 17.0% and 5.8% of teeth per individual showed gingival recession > or = 3 mm and > or = 5 mm, respectively. The prevalence, extent, and severity of recession correlated with age. Recession showed a nonlinear relationship with age, with 25 to 50 year olds showing the highest level of recession. Males aged > or = 30 years showed significantly higher prevalence and extent of gingival recession than females. The percentage of teeth with recession was significantly higher in the lower socioeconomic groups irrespective of age, and in subjects > or = 30 years of age with irregular dental care than in subjects with regular care. Using a multivariable model, cigarette smoking and presence of supragingival calculus were the factors most significantly associated with localized and generalized recession, whereas gender, dental visits, and socioeconomic status were not significant risk indicators. The high level of gingival recession in this Brazilian population may be primarily related to destructive periodontal disease and is significantly associated with a high level of supragingival dental calculus and cigarette smoking. Population-based programs aimed at the prevention of periodontal diseases may reduce the prevalence of severe gingival recession in this and similar populations.


[Novel biologically active compounds isolated from unexploited organisms, cellular sime molds].
Cellular slime molds are thought to be excellent model organisms for the study of cell and developmental biology because of their simple pattern of development. However, there have been few reports on secondary metabolites of them. We have focused on the utility of cellular slime molds as novel resources for natural product chemistry, and have studied the diversity of secondary metabolites produced by them as well as their physiological and pharmacological activities. We have recently isolated many novel compounds from the fruiting bodies of various species of Dictyostelium cellular slime molds. Total syntheses and biological evaluation of these compounds have been carried out. It was shown that dictyopyrones and dictyomedins may regulate Dictyostelium development. Amino sugar derivatives such as furanodictines and dictyoglucosamines induced neuronal differentiation of rat PC-12 cells. In addition, brefelamide inhibited the cellular proliferation of 1321N1 human astrocytoma cells. These results show that cellular slime molds are promising sources in natural product chemistry.


Double and triple in situ hybridization for coexpression studies: combined fluorescent and chromogenic detection of neuropeptide Y (NPY) and serotonin receptor subtype mRNAs expressed at different abundance levels.
Multiple fluorescence in situ hybridization is the method of choice for studies aimed at determining simultaneous production of signal transduction molecules and neuromodulators in neurons. In our analyses of the monoamine receptor mRNA expression of peptidergic neurons in the rat telencephalon, double tyramide-signal-amplified fluorescence in situ hybridization delivered satisfactory results for coexpression analysis of neuropeptide Y (NPY) and serotonin receptor 2C (5-HT2C) mRNA, a receptor subtype expressed at high-to-moderate abundance in the regions analyzed. However, expression of 5-HT1A mRNA, which is expressed at comparatively low abundance in many telencephalic areas, could not be unequivocally identified in NPY mRNA-reactive neurons due to high background and poor signal-to-noise ratio in fluorescent receptor mRNA detections. Parallel chromogenic in situ hybridization provided clear labeling for 5-HT1A mRNA and additionally offered the possibility to monitor the chromogen deposition at regular time intervals to determine the optimal signal-to-noise ratio. We first developed a double labeling protocol combining fluorescence and chromogenic in situ hybridization and subsequently expanded this variation to combine double fluorescence and chromogenic in situ hybridization for triple labelings. With this method, we documented expression of 5-HT2C and/or 5-HT1A in subpopulations of telencephalic NPY-producing neurons. The method developed in the present study appears suitable for conventional light and fluorescence microscopy, combines advantages of fluorescence and chromogenic in situ hybridization protocols and thus provides a reliable non-radioactive alternative to previously published multiple labeling methods for coexpression analyses in which one mRNA species requires highly sensitive detection.